Generated Narrative: CodeSystem 200000003964 version: 5.0.0; Last updated: 2023-08-03 11:35:00+0000 This case-sensitive code system http://spor.ema.europa.eu/v1/lists/200000003964 defines the following codes: Code Display 200000004202 A declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application as responsible for batch release. 200000004203 A declaration by the Qualified Person (QP) responsible for batch certification stating that the active substance manufacturer(s) referred to in the marketing authorisation operate in compliance with the detailed guidelines on good manufacturing practice for starting materials. A single declaration may be acceptable under certain circumstances — see the note under variation No B.II.b.1. 200000004204 A declaration from the marketing authorisation holder or the ASMF holder as appropriate that the changes to the manufacturing methods are only those necessitated by scale-up or downscaling, e.g. use of different-sized equipment, that the change does not adversely affect the reproducibility of the process, that it is not the result of unexpected events arising during manufacture or because of stability concerns and that the specifications of the active substance/intermediates remain the same. 200000004205 A declaration from the marketing authorisation holder or the ASMF holder as appropriate that the required stability studies have been started under ICH/VICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. 200000004206 A declaration from the marketing authorisation holder or the ASMF holder, where applicable, that the synthetic route quality control procedures and specifications of the active substance and of the starting material/reagent/intermediate in the manufacturing process of the active substance (if applicable) are the same as those already approved. 200000004207 A declaration from the marketing authorisation holder or the ASMF Holder, where applicable, that there is no change in qualitative and quantitative impurity profile or in physico-chemical properties, that the synthetic route remains the same and that the specifications of the active substance or intermediates are unchanged. 200000004208 A declaration that the proposed Summary of Product Characteristics, Labelling and Package Leaflet is identical for the concerned sections to that annexed to the Commission Decision or to the agreement reached by the CMDh (as applicable). 200000004209 A declaration that the required stability studies have been started under ICH/VICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. 200000004210 A declaration that the required stability studies have been started under ICH/VICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. 200000004211 A document including the identification (name and address) of the current PMF Holder (transferor) and the identification (name and address) of the person to whom the transfer is to be granted (transferee) together with the proposed implementation date — signed by both companies. 200000004212 A formal document from a relevant official body (e.g. Chamber of Commerce) in which the new name and/or address is mentioned. 200000004213 Amendment of product information (where applicable). 200000004214 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate) including revised product information as appropriate. 200000004215 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), and of the approved Active Substance Master File (where applicable), including a direct comparison of the present process and the new process. 200000004216 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate). 200000004217 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), if applicable. 200000004218 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a description of the analytical methodology and a summary of validation data. 200000004219 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a description of the analytical methodology, a summary of validation data, revised specifications for impurities (if applicable). 200000004220 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a detailed drawing of the current and proposed situation, and including revised product information as appropriate. 200000004221 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a detailed drawing or written description of the current and new appearance, and including revised product information as appropriate. 200000004222 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a direct comparison of the present process and the new process. 200000004223 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including description, detailed drawing and composition of the container or closure material, and including revised product information as appropriate. 200000004224 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including description, detailed drawing and composition of the device material and supplier where appropriate, and including revised product information as appropriate. 200000004225 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including identification method for any new colorant, where relevant, and including revised product information as appropriate. 200000004226 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including revised product information as appropriate. 200000004227 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate). 200000004228 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate). This must contain results of appropriate real time stability studies (covering the entire shelf life) conducted in accordance with the relevant stability guidelines on at least two pilot scale batches of the finished product in the authorised packaging material and/or after first opening or reconstitution, as appropriate. 200000004229 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate). This must contain results of appropriate real time stability studies, conducted in accordance with the relevant stability guidelines on at least two pilot or production scale batches of the active substance in the authorised packaging material and covering the duration of the requested retest period or requested storage conditions. 200000004230 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format). 200000004231 Amendment of the relevant section(s) of the dossier. 200000004232 Amendment of the relevant section(s) of the dossiers including the introduction of the new studies to investigate the capability of manufacturing steps to inactivate/reduce adventitious agents. 200000004233 Amendment of the relevant section(s) of the dossiers. 200000004234 An expert statement outlining all the changes introduced with the certified PMF and evaluating their potential impact on the finished products including product specific risk assessments. 200000004235 An expert statement outlining all the changes introduced with the certified VAMF and evaluating their potential impact on the finished products including product specific risk assessments. 200000004236 Appropriate data on the new packaging (comparative data on permeability, e.g. for O 2 , CO 2 moisture). 200000004237 Appropriate data on the new packaging (e.g. comparative data on permeability, e.g. for O 2 , CO 2 moisture), including a confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic materials and objects in contact with foodstuffs. 200000004238 Assurance on GMP or ISO compliance of the site where the sterilisation of the containers is performed. 200000004239 Attached to the cover letter of the variation application: A reference to the agreement of the competent authority (in the case of marketing authorisations granted under the centralised procedure, the CHMP). 200000004240 Attached to the cover letter of the variation application: a reference to the Commission Decision concerned or to the agreement reached by the CMDh (as applicable) with the annexed Summary of Product Characteristics, Labelling or Package Leaflet. 200000004241 Attached to the cover letter of the variation application: A reference to the Commission Decision concerned. 200000004242 Attached to the cover letter of the variation application: A reference to the list of medicinal products that are subject to additional monitoring. 200000004243 Attached to the cover letter of the variation application: A reference to the relevant decision of the competent authority. 200000004244 Attached to the cover letter of the variation application: EMA/NCA request, if applicable. 200000004245 Attached to the cover letter of the variation application: proof of authorisation of the legal status change (e.g. reference to the Commission Decision concerned). 200000004246 Attached to the cover letter of the variation application: reference to the agreement/assessment of the competent authority. 200000004247 Attached to the cover letter of the variation application: The relevant decision of the competent authority. 200000004248 Batch analysis data (in a comparative tabular format) for at least two batches (minimum pilot scale) of the active substance from the current and proposed manufacturers/sites. 200000004249 Batch analysis data (in a comparative tabulated format) of at least two batches (minimum pilot scale) of the excipient manufactured according to the old and the new process. 200000004250 Batch analysis data (in a comparative tabulated format) on a minimum of one batch manufactured to both the currently approved and the proposed process. Batch data on the next two full production batches should be made available upon request and reported by the marketing authorisation holder if outside specification (with proposed action). 200000004251 Batch analysis data (in a comparative tabulated format) on a minimum of one production batch manufactured to both the currently approved and the proposed sizes. Batch data on the next two full production batches should be made available upon request and reported by the MAH if outside specifications (with proposed action). 200000004252 Batch analysis data (in a comparative tabulated format) on a minimum of one production batch of the active substance or intermediate as appropriate, manufactured to both the currently approved and the proposed sizes. Batch data on the next two full production batches should be made available upon request and reported by the marketing authorisation holder if outside specification (with proposed action). 200000004253 Batch analysis data (in a comparative tabulated format) on two production batches of the relevant substance for all tests in the new specification and additionally, where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch. For herbal medicinal products, comparative disintegration data may be acceptable. 200000004254 Batch analysis data (in comparative tabular format) of at least two batches (minimum pilot scale) manufactured according to the currently approved and proposed process. 200000004255 Batch analysis data on one production batch and two pilot-scale batches simulating the production process (or two production batches) and comparative data on the last three batches from the previous site; batch data on the next two production batches should be available on request or reported if outside specifications (with proposed action). 200000004256 Batch analysis data on two batches of the immediate packaging for all specification parameters. 200000004257 Batch analysis data on two production batches (3 production batches for biological excipients) of the excipient for all specification parameters. 200000004258 Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the active substance for all specification parameters. 200000004259 Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the finished product for all specification parameters. 200000004260 Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the relevant substance for all specification parameters. 200000004261 Batch analysis data on two production batches for all tests in the new specification. 200000004262 Change management protocol related to the active substance. 200000004263 Change management protocol related to the finished product. 200000004264 Comparative dissolution data on at least one pilot batch of the current and proposed dimensions (no significant differences regarding comparability see the relevant (Human or Veterinary) guidance on Bioavailability). For herbal medicinal product comparative disintegration data may be acceptable. 200000004265 Comparative table of current and proposed in-process tests and limits. 200000004266 Comparative table of current and proposed in-process tests. 200000004267 Comparative table of current and proposed specifications. 200000004268 Comparative table of current and proposed specifications, if applicable. 200000004269 Comparative table of the current and proposed immediate packaging specifications, if applicable. 200000004270 Comparative validation results or if justified comparative analysis results showing that the current test and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new test procedure. 200000004271 Comparison of the current and proposed immediate packaging specifications, if applicable. 200000004272 Confirmation of the transfer of the complete PMF documentation since the initial PMF certification to the transferee — signed by both companies. 200000004273 Confirmation that stability studies have been done to the currently approved protocol. The studies must show that the agreed relevant specifications are still met. 200000004274 Copy of approved and new (if applicable) specifications of the excipient. 200000004275 Copy of approved end of shelf life finished product specification and where applicable, specifications after dilution/reconstitution or first opening. 200000004276 Copy of approved release and end-of-shelf life specifications if relevant. 200000004277 Copy of approved release and end-of-shelf life specifications. 200000004278 Copy of approved specifications of the active substance (and of the intermediate, if applicable). 200000004279 Copy of approved specifications of the active substance. 200000004280 Copy of approved specifications of the finished product. 200000004281 Copy of the current (updated) Ph. Eur. Certificate of Suitability. 200000004282 Copy of the EMA letter of acceptance of the new (invented) name. 200000004283 Copy of the latest PMF Certificate page ‘EMA Plasma Master File (PMF) Certificate of compliance with Community legislation’. 200000004284 Copy of the modified manufacturing authorisation, if available; or a formal document from a relevant official body (e.g. Chamber of Commerce, or if not available, from a Regulatory Agency) in which the new name and/or address is mentioned. 200000004285 Data to demonstrate accuracy, precision and compatibility of the device. 200000004286 Data to demonstrate that the new excipient does not interfere with the finished product specification test methods, if appropriate. 200000004287 Data to demonstrate the suitability of the monograph to control the substance, e.g. a comparison of the potential impurities with the transparency note of the monograph. 200000004288 Declaration from the manufacturer or the marketing authorisation holder of the material that it is purely of vegetable or synthetic origin. 200000004289 Declaration that any change should be within the range of currently approved limits. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 200000004290 Declaration that relevant stability studies have been started under ICH/VICH conditions, as appropriate, (with indication of the batch numbers concerned) and relevant stability parameters have been assessed in at least one pilot scale or industrial scale batch and at least 3 months satisfactory stability data are at the disposal of the applicant at time of notification and that the stability profile is similar to the currently registered situation. 200000004291 Declaration that stability studies will be conducted in accordance with the relevant guidelines for products where stability parameters could be affected. Data to be reported only if outside specifications (with proposed action). 200000004292 Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 200000004293 Declaration that the PMF Certificate and Evaluation Report are fully applicable for the authorised product, PMF holder has provided the PMF Certificate, Evaluation report and PMF dossier to the MAH (where the MAH is different to the PMF holder), the PMF Certificate and Evaluation Report replace the previous PMF documentation for this Marketing Authorisation. 200000004294 Declaration that the remaining pack-size(s) is/are consistent with the dosage regimen and duration of treatment and adequate for the dosing instructions as approved in the summary of product characteristics. 200000004295 Declaration that the remaining product presentation(s) are adequate for the dosing instructions and treatment duration as mentioned in the summary of product characteristics. 200000004296 Declaration that the VAMF Certificate and Evaluation Report are fully applicable for the authorised product, VAMF holder has submitted the VAMF Certificate, Evaluation report and VAMF dossier to the MAH (where the MAH is different to the VAMF holder), the VAMF Certificate and Evaluation Report replace the previous VAMF documentation for this Marketing Authorisation. 200000004297 Demonstration of GMP approval of the changes, which should be available at the time of implementation. 200000004298 Description of the design space in tabular format, including the variables (material attributes and process parameters, as appropriate) and their proposed ranges. 200000004299 Detailed description for the proposed change. 200000004300 Details of any new analytical method and summary of validation data. 200000004301 Details of any new analytical method and validation data, where relevant. 200000004302 Details of any new non-pharmacopoeial analytical method and validation data, where relevant. 200000004303 Details of the sterilisation method should be provided and in the event that the method does not use the reference conditions stated in the Ph. Eur., validation data should be provided. 200000004304 Either a Ph. Eur. Certificate of Suitability for any new component of animal susceptible to TSE risk or where applicable, documentary evidence that the specific source of the TSE risk material has been previously assessed by the competent authority and shown to comply with the scope of the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathies via Human and Veterinary Medicinal Products. 200000004305 Either a TSE Ph. Eur. Certificate of Suitability for any new source of material or, where applicable, documentary evidence that the specific source of the TSE risk material has previously been assessed by the competent authority and shown to comply with the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products. 200000004306 Epidemiological data for viral markers related to the blood/plasma collection centre covering the last 3 years. For newly opened centre(s) or in case no data are yet available, a declaration that epidemiological data will be provided at the time of the next annual update(s). 200000004307 For a site within the EU/EEA: Attach copy of manufacturing authorisation(s) or where no manufacturing authorisation exists a certificate of GMP compliance issued within the last 3 years by the relevant competent authority. For a manufacturing site outside the EEA where an operational GMP mutual recognition agreement (MRA) exists between the country concerned and the EU: a GMP certificate, issued within the last 3 years by the relevant competent authority. 200000004308 For centralised procedure only: contact details of new contact person in the EU/EEA for product defects and recalls, if applicable. 200000004309 For changes to process parameter(s) that have been considered to have no impact on the quality of the finished product, declaration to this effect reached in the context of the previously approved risk assessment. 200000004310 For devices for medicinal products for human use, proof of CE marking. 200000004311 For semi-solid and liquid formulations in which the active substance is present in non-dissolved form, appropriate validation data including microscopic imaging of particle size distribution and morphology or any other appropriate imaging technique. 200000004312 For semi-solid and liquid products in which the active substance is present in non-dissolved form: appropriate validation of the change including microscopic imaging of particles to check for visible changes in morphology; comparative size distribution data by an appropriate method. 200000004313 For solid dosage forms, comparative dissolution profile data of at least two pilot scale batches of the finished product in the new and old composition. For herbal medicinal products, comparative disintegration data may be acceptable. 200000004314 For solid dosage forms: dissolution profile data of one representative production batch and comparative data of the last three batches from the previous process; data on the next two full production batches should be available on request or reported if outside specification (with proposed action). For herbal medicinal products, comparative disintegration data may be acceptable. 200000004315 For veterinary medicines intended for use in food producing animal species, proof that the excipient is classified according to Article 14(2)(c) of Regulation (EC) No 470/2009 or, if not, justification that the excipient does not have pharmacological activity at the dose at which it is administered to the target animal. 200000004316 i) If the new manufacturing site uses the active substance (AS) as a starting material - A declaration by the QP at the site responsible for batch release that the AS is manufactured in accordance with GMP for starting materials. ii) In addition, if the new manufacturing site is located within the EU/EEA and uses the AS as a starting material - A declaration by the QP of the new manufacturing site that the AS used is manufactured in accordance with GCP for starting materials. 200000004317 If applicable, amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including revised product information as appropriate. 200000004318 If the manufacturing site and the primary packaging site are different, conditions of transport and bulk storage should be specified and validated. 200000004319 In case of a change in the headspace or a change in the surface/volume ratio, a declaration that the required stability studies have been started under ICH/VICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation for a Type IA notification and time of submission of a Type IB notification, and that the available data did not indicate a problem. 200000004320 In case of an addition of a manufacturing site, the variation application form should clearly outline the ‘present’ and ‘proposed’ manufacturers as listed in section 2.5 of the application form. 200000004321 In case of change in the name of the holder of the Active Substance Master File holder, updated ‘letter of access’. 200000004322 Justification for change in name. 200000004323 Justification for not submitting a new bioequivalence study according to the current Note for Guidance on The Investigation of Bioavailability and Bioequivalence. 200000004324 Justification for not submitting a new bioequivalence study according to the relevant (Human or Veterinary) guidance on Bioavailability. 200000004325 Justification for not submitting a new bioequivalence study according to the relevant (Human, Veterinary) Guideline on Bioavailability, if appropriate. 200000004326 Justification for the change/choice of excipients etc. must be given by appropriate development pharmaceutics (including stability aspects and antimicrobial preservation where appropriate). 200000004327 Justification for the deletion of the device. 200000004328 Justification for the deletion of the target species. 200000004329 Justification for the deletion, including a statement regarding alternative means to obtain the solvent/diluent as required for the safe and effective use of the medicinal product. 200000004330 Justification for the new specification parameter and the limits. 200000004331 Justification for the new/remaining pack-size, showing that the new/remaining size is/are consistent with the dosage regimen and duration of treatment as approved in the summary of product characteristics. 200000004332 Justification for the proposed change(s). 200000004333 Justification for the proposed deletion. 200000004334 Justification from the MAH or ASMF Holder as appropriate for the new in-process test and limits. 200000004335 Justification from the MAH or ASMF Holder as appropriate of the new specification parameter and the limits. 200000004336 Justification from the marketing authorisation holder or the ASMF Holder, as appropriate, of the new specification parameter and the limits. 200000004337 Justification of the new in-process test and limits. 200000004338 Justification of the new specification parameter and the limits. 200000004339 Justification that the studies do not modify the risk assessment. 200000004340 Justification/risk assessment from the marketing authorisation holder or the ASMF Holder, as appropriate, that the in-process parameter is non-significant, or that the in-process parameter is obsolete. 200000004341 Justification/risk assessment from the marketing authorisation holder or the ASMF Holder, as appropriate, that the in-process tests are non-significant, or that the in-process tests are obsolete. 200000004342 Justification/risk assessment showing that the in-process test is non-significant or that it is obsolete. 200000004343 Justification/risk assessment showing that the parameter is non-significant or that it is obsolete. 200000004344 Latest version of the DDPS and, where applicable, latest version of the product specific addendum. These should include for changes to the QPPV a) summary CV of the new QPPV, b) proof of QPPV EudraVigilance registration, and c) a new statement of the MAH and the QPPV regarding their availability and the means for notification of adverse reactions signed by the new QPPV and the MAH, and reflecting any other consequential changes, e.g. to the organisation chart. 200000004345 Letter of Authorisation including contact details of the person responsible for communication between the competent authority and the PMF holder — signed by the transferee. 200000004346 Letter of Undertaking to fulfil all open and remaining commitments (if any) — signed by the transferee. 200000004347 List of testing centre(s) where the kit is currently used and a list of testing centre(s) where the kit will be used. 200000004348 List of testing site(s) where the kit is used. 200000004349 PMF Certificate and Evaluation Report. 200000004350 Proof of acceptance (by WHO) or copy of the ATC (Vet) Code list. 200000004351 Proof of acceptance by WHO or copy of the INN list. If applicable, proof that the change is in line with the Ph. Eur. For herbal medicinal product, declaration that the name is in accordance with the Note for Guidance on Quality of Herbal Medicinal Products, and with the guideline on declaration of herbal substances and herbal preparations in (traditional) herbal medicinal products. 200000004352 Proof of CE marking and if a measuring function is intended the proof of CE marking should also include the 4 digit notified body number. 200000004353 Proof of establishment of the new holder (Excerpt of the commercial register and the English translation of it) — signed by both companies. 200000004354 Proof of GMP approval of the changes, which should be available at the time of implementation. 200000004355 Proof that the proposed site is appropriately authorised for the pharmaceutical form or product concerned. 200000004356 Proof that the proposed site is appropriately authorised for the pharmaceutical form or product or manufacturing operation concerned. 200000004357 PSMF number (if available) 200000004358 Reference of the application/procedure and product in which the change(s) were accepted. 200000004359 Reference to an assessment / Copy of assessment document from a previous procedure where the temperature of use has been agreed. 200000004360 Reference to the application/procedure and product in which the DDPS was assessed previously. 200000004361 Reference to the approved change management protocol. 200000004362 Results from product and process development studies (including risk assessment and multivariate studies, as appropriate) demonstrating that a systematic mechanistic understanding of material attributes and process parameters to the critical quality attributes of the finished product has been achieved. 200000004363 Results of the appropriate Ph. Eur tests demonstrating equivalence in characteristics/correct dosing. 200000004364 Results of the studies performed in accordance with the approved change management protocol. 200000004365 Revalidation studies have been performed in case of sterile products terminally sterilised. The batch numbers of the batches used in the revalidation studies should be indicated, where applicable. 200000004366 Revised frequency and/or date of submission of the PSUR (for medicinal products authorised via the centralised procedure, the full set of annexes, including the revised Annex II should be provided). 200000004367 Revised Product Information (and Annex A, if applicable). 200000004368 Revised product information. 200000004369 Sample of the new product, where applicable (see Notice to Applicants Requirements for samples in the Member States). 200000004370 Samples of the finished product where applicable (see NTA, Requirements for samples in the Member States). 200000004371 Samples of the new container/closure where applicable (see NTA, Requirements for samples in the Member States/EMA). 200000004372 Samples of the new device where applicable (see NTA, Requirements for samples in the Member States). 200000004373 Signed declaration that the change does not involve a change of the quality system within the blood establishment. 200000004374 Signed declaration that there is no change in the list of the collection centres. 200000004375 Statement that the centre is working under the same conditions as the other centres belonging to the blood establishment, as specified in the standard contract between blood establishment and PMF holder. 200000004376 Statement that the storage centre is working following the same SOPs as the already accepted establishment. 200000004377 Statement that the testing is performed following the same SOPs and/or test methods as already accepted. 200000004378 Study of equivalence of the materials and the impact on production of the final material and impact on behaviour (e.g. dissolution characteristics) of the finished product. 200000004379 Suitable evidence to confirm compliance of the water used in the final steps of the synthesis of the active substance with the corresponding requirements on quality of water for pharmaceutical use. 200000004380 Summary of the pharmacovigilance system, or update of the relevant elements (as applicable): - Proof that the applicant has at his disposal a qualified person responsible for pharmacovigilance and a statement signed by the applicant to the effect that the applicant has the necessary means to fulfil the tasks and responsibilities listed in Title IX of Directive 2001/83/EC. - Contact details of the QPPV, Member States in which the QPPV resides and carries out his/her tasks - PSMF location 200000004381 The batch numbers of the tested batches having the proposed batch size. 200000004382 The change should not lead to substantial amendments of the product information. 200000004383 The changes introduced during the referral procedure should be clearly highlighted in the submission. 200000004384 The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies demonstrating where relevant that a systematic mechanistic understanding of material attributes and process parameters to the critical quality attributes of the active substance has been achieved. 200000004385 The medicinal product can still be accurately delivered. 200000004386 The new Detailed Description of the Pharmacovigilance System (DDPS). 200000004387 The new device is compatible with the medicinal product. 200000004388 The proposed measuring or administration device must accurately deliver the required dose for the product concerned in line with the approved posology and results of such studies should be available. 200000004389 The results of stability studies that have been carried out under ICH/VICH conditions, on the relevant stability parameters, on at least one pilot or industrial scale batch, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action). 200000004390 The results of stability studies that have been carried out under ICH/VICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved retest period (with proposed action). 200000004391 The results of stability studies that have been carried out under ICH/VICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action). 200000004392 The section “present/proposed” is filled out completely and correctly. 200000004393 The updated ASMF must be submitted by the ASMF holder (open and closed part to NCA, open part to MAH), the variation as such has to be submitted by the marketing authorisation holder. 200000004394 The validation results should be provided. 200000004395 The variation application form should clearly outline the ‘present’ and ‘proposed’ finished product manufacturers as listed in section 2.5 of the application form. 200000004396 The variation application form should clearly outline the ‘present’ and ‘proposed’ finished product manufacturers, importer, batch control/testing and batch release sites as listed in section 2.5 of the application form for marketing authorisation. 200000004397 The variation application form should clearly outline the ‘present’ and ‘proposed’ manufacturers as listed in section 2.5 of the application form for marketing authorisations. 200000004398 The variation application form should clearly outline the ‘present’ and ‘proposed’ PMF EMA Certificate (code number) in the MA dossier. When applicable, the variation application form should clearly list also all the other PMFs to which the medicinal product refers even if they are not the subject of the application. 200000004399 The variation application form should clearly outline the ‘present’ and ‘proposed’ VAMF EMA Certificate (code number) in the MA dossier. When applicable, the variation application form should clearly list also all the other VAMFs to which the medicinal product refers even if they are not the subject of the application. 200000004400 Update of the relevant section of the dossier. 200000004401 Updated relevant sections and annexes of the PMF dossier, including a list of all the blood establishments using this transport organisation, a summary of the system in place to ensure that the transport is performed under appropriate conditions (time, temperature and GMP compliance) and confirmation that transport conditions are validated. 200000004402 Updated relevant sections and annexes of the PMF dossier, including detailed description of the new conditions, confirmation of validation of storage/transport conditions and the name of the blood establishment(s) where the change takes place (if relevant). 200000004403 Updated relevant sections and annexes of the PMF dossier, including the name of container, manufacturer, anticoagulant solution specification, confirmation of CE-mark and the name of the blood establishments where the container is used. 200000004404 Updated relevant sections and annexes of the PMF dossier, including updated information on testing as requested in the ‘Guideline on the scientific data requirements for a PMF’. 200000004405 Updated relevant sections and annexes of the PMF dossier. 200000004406 Updated relevant sections of the PMF dossier, including the rationale for introduction or extension of inventory hold period, the sites where the inventory hold takes place and for changes to procedure, a decision tree including new conditions. 200000004407 Updated relevant sections of the PMF dossier. 200000004408 VAMF Certificate and Evaluation Report. 200000004409 Where applicable, a document providing information of any materials falling within the scope of the Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products including those which are used in the manufacture of the active substance/excipient. 200000004410 Where applicable, for active substance, a declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the QP of each of the manufacturing authorisation holders listed in the application as responsible for batch release. 200000004411 Where appropriate, comparative dissolution profile data for the finished product of at least two batches (minimum pilot scale). For herbal medicinal products, comparative disintegration data may be acceptable. 200000004412 Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch complying with the current and proposed specification. For herbal medicinal products, comparative disintegration data may be acceptable. 200000004413 Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch containing the active substance complying with the current and proposed specification. For herbal medicinal products, comparative disintegration data may be acceptable. 200000004414 Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch containing the excipient complying with the current and proposed specification. For herbal medicinal products comparative disintegration data may be acceptable. 200000004415 Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch manufactured using the current and new in-process tests. For herbal medicinal products, comparative disintegration data may be acceptable. 200000004416 Where appropriate, proof must be provided that no interaction between the content and the packaging material occurs (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic material and objects in contact with foodstuffs. 200000004417 Where relevant the batch numbers, corresponding batch size and the manufacturing date of batches (≥ 3) used in the validation study should be indicated or validation protocol (scheme) be submitted. 200000004418 Where relevant, a commitment of the manufacturer of the active substance to inform the MA holder of any changes to the manufacturing process, specifications and test procedures of the active substance. 200000004419 Where relevant, the batch numbers, corresponding batch size and the manufacturing date of batches (≥ 3) used in the validation study should be indicated and the validation data presented, or validation protocol (scheme) to be submitted. 200000004420 Written confirmation from the manufacturer of the finish product stating verification of compliance of the manufacturer of the active substance with principles and guidelines of good manufacturing practices. 200000023186 Written confirmation from the manufacturer of the finished product stating verification of compliance of the manufacturer of the active substance with principles and guidelines of good manufacturing practices. 200000023187 A declaration from the marketing authorisation holder or the ASMF holder that the synthetic route quality control procedures and specifications of the active substance and of the starting material/reagent/intermediate in the manufacturing process of the active substance are the same as those already approved. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023189 The variation application form should clearly outline the “present” and “proposed” manufacturers as listed in the application form for marketing authorisation. 200000023190 Proof that the proposed site is appropriately authorised for the pharmaceutical form or product or manufacturing operation concerned (SEE FULL DESCRIPTION IN GUIDELINE) 200000023191 Amendment of the approved Active Substance Master File, including a direct comparison of the present process and the new process. 200000023194 A declaration from the ASMF Holder that there is no change in qualitative and quantitative impurity profile or in physico-chemical properties, that the synthetic route remains the same and that the specifications of the active substance or intermediates are unchanged. 200000023198 Comparative table of current and proposed in-process tests. 200000023199 Details of any new non-pharmacopoeial analytical method and validation data, where relevant. 200000023200 Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the active substance for all specification parameters. 200000023201 Justification from the MAH or ASMF Holder as appropriate for the new in-process test and limits. 200000023202 Comparative table of current and proposed specifications. 200000023203 Details of any new analytical method and validation data, where relevant. 200000023204 Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the relevant substance for all specification parameters. 200000023205 Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch containing the active substance complying with the current and proposed specification. For herbal medicinal products, comparative disintegration data may be acceptable. 200000023206 Justification from the MAH or ASMF Holder as appropriate of the new specification parameter and the limits. 200000023207 Description of the analytical methodology, a summary of validation data, revised specifications for impurities (if applicable). 200000023208 Comparative validation results, or if justified comparative analysis results showing that the current test and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new test procedure. 200000023209 Appropriate data on the new packaging (e.g. comparative data on permeability e.g. for O2, CO2 moisture), including a confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic materials and objects in contact with foodstuffs. 200000023210 Where appropriate, proof must be provided that no interaction between the content and the packaging material occurs (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeia requirements or legislation of the Union on plastic material and objects in contact with foodstuffs. 200000023211 The results of stability studies that have been carried out under VICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved retest period (with proposed action). 200000023212 Comparison of the current and proposed immediate packaging specifications, if applicable. 200000023213 Batch analysis data on two batches of the immediate packaging for all specification parameters. 200000023214 Justification from the marketing authorisation holder or the ASMF Holder, as appropriate, of the new specification parameter and the limits. 200000023215 Results of appropriate real time stability studies, conducted in accordance with the relevant stability guidelines on at least two (three for biological medicinal products) pilot or production scale batches of the active substance in the authorised packaging material and covering the duration of the requested re-test period or requested storage conditions. 200000023216 Confirmation that stability studies have been done to the currently approved protocol. The studies must show that the agreed relevant specifications are still met. 200000023217 The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies demonstrating where relevant that a systematic mechanistic understanding of material attributes and process parameters to the critical quality attributes of the active substance has been achieved. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023218 Description of the Design space in tabular format, including the variables (material attributes and process parameters, as appropriate) and their proposed ranges. 200000023219 Detailed description for the proposed change. 200000023220 Change management protocol related to the active substance. 200000023221 Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 200000023222 Detailed drawing or written description of the current and new appearance. 200000023223 Samples of the finished product where applicable. 200000023224 Detailed drawing of the current and proposed situation. 200000023225 Comparative dissolution data on at least one pilot batch of the current and proposed dimensions (no significant differences regarding comparability see the relevant guidance on bioavailability/bioequivalence). For herbal medicinal product comparative disintegration data may be acceptable. 200000023226 Justification for not submitting a new bioequivalence study according to the relevant guidance on Bioavailability/bioequivalence. 200000023227 Identification method for any new colorant, where relevant. 200000023228 Sample of the new product, where applicable. 200000023229 Either a Ph. Eur. Certificate of Suitability for any new component of animal susceptible to TSE risk or where applicable, documentary evidence that the specific source of the TSE risk material has been previously assessed by the competent authority and shown to comply with the scope of the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathies via Human and Veterinary Medicinal Products. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023230 For solid dosage forms, comparative dissolution profile data of at least two pilot scale batches of the finished product in the new and old composition. For herbal medicinal products, comparative disintegration data may be acceptable. 200000023231 If intended for use in food producing animal species, proof that the excipient is classified according to Article 14(2)(c) of Regulation (EC) No 470/2009 of the European Parliament and the Council of 6 May 2009 laying down Community procedures for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin, or, if not, justification that the excipient does not have pharmacological activity at the dose at which it is administered to the target animal. 200000023232 Proof that the proposed site is appropriately authorised for the pharmaceutical form or product or manufacturing operation concerned. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023233 Where relevant, the batch numbers, corresponding batch size and the manufacturing date of batches (larger than/equal to 3) used in the validation study should be indicated and the validation data presented, or validation protocol (scheme) to be submitted. 200000023234 The variation application form should clearly outline the “present” and “proposed” finished product manufacturers as listed in the application form. 200000023235 Copy of approved release and end-of-shelf life specifications if relevant. 200000023236 Batch analysis data on one production batch and two pilot-scale batches simulating the production process (or two production batches) and comparative data on the last three batches from the previous site; batch data on the next two production batches should be available on request or reported if outside specifications (with proposed action). 200000023237 For semisolid and liquid formulations in which the active substance is present in non-dissolved form, appropriate validation data including microscopic imaging of particle size distribution and morphology or any other appropiate imaging technique. 200000023238 Declaration by the Qualified Person. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023239 Direct comparison of the present process and the new process. 200000023240 For semi-solid and liquid products in which the active substance is present in non-dissolved form: appropriate validation of the change including microscopic imaging of particles to check for visible changes in morphology; comparative size distribution data by an appropriate method. 200000023241 For solid dosage forms: dissolution profile data of one representative production batch and comparative data of the last three batches from the previous process; data on the next two full production batches should be available on request or reported if outside specification (with proposed action). For herbal medicinal products, comparative disintegration data may be acceptable. 200000023242 For changes to process parameter(s) that have been considered to have no impact on the quality of the finished product, declaration to this effect reached in the context of the previously approved risk assessment. 200000023243 Copy of approved release and end-of-shelf life specifications. 200000023244 Batch analysis data (in a comparative tabulated format) on a minimum of one batch manufactured to both the currently approved and the proposed process. Batch data on the next two full production batches should be made available upon request and reported by the marketing authorisation holder if outside specification (with proposed action). 200000023245 Declaration that relevant stability studies have been started under VICH conditions, as appropriate, (with indication of the batch numbers concerned) and relevant stability parameters have been assessed. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023246 Batch analysis data (in a comparative tabulated format) on a minimum of one production batch manufactured to both the currently approved and the proposed sizes. Batch data on the next two full production batches should be made available upon request and reported by the MAH if outside specifications (with proposed action). 200000023247 Where relevant the batch numbers, corresponding batch size and the manufacturing date of batches (larger than/equal to 3) used in the validation study should be indicated or validation protocol (scheme) be submitted. 200000023248 The validation results should be provided. 200000023249 The results of stability studies that have been carried out under VICH conditions. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023250 Comparative table of current and proposed in-process tests and limits. 200000023251 Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the finished product for all specification parameters. 200000023252 Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch manufactured using the current and new in-process tests. For herbal medicinal products, comparative disintegration data may be acceptable. 200000023253 Justification of the new in-process test and limits. 200000023254 Batch analysis data on two production batches (3 production batches for biological excipients) of the excipient for all specification parameters. 200000023255 Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch containing the excipient complying with the current and proposed specification. For herbal medicinal products comparative disintegration data may be acceptable. 200000023256 Justification for not submitting a new bioequivalence study according to the relevant Guidance on bioavailability/bioequivalence, if appropriate. 200000023257 Justification of the new specification parameter and the limits. 200000023258 Description of the analytical methodology, a summary of validation data, revised specification for impurities (if applicable). 200000023259 Comparative validation results or if justified comparative analysis results showing that the current test and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new test procedure. 200000023260 Declaration from the manufacturer or the marketing authorisation holder of the material that it is purely of vegetable or synthetic origin. 200000023261 Study of equivalence of the materials and the impact on production of the final material and impact on behaviour (e.g. Dissolution characteristics) of the finished product. 200000023262 Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch complying with the current and proposed specification. For herbal medicinal products, comparative disintegration data may be acceptable. 200000023263 Justification of the new specification parameter and the limits. 200000023264 Appropriate data on the new packaging (comparative data on permeability e.g. for O2, CO2 moisture). 200000023265 Comparative table of the current and proposed immediate packaging specifications, if applicable. 200000023266 Samples of the new container/closure where applicable. 200000023267 Description, detailed drawing and composition of the container or closure material. 200000023268 Re-validation studies have been performed in case of sterile products terminally sterilised. The batch numbers of the batches used in the re-validation studies should be indicated, where applicable. 200000023269 In case of a change in the headspace or a change in the surface/volume ratio, a declaration that the required stability studies have been started under VICH conditions. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023270 Justification for the new pack-size, showing that the new size is consistent with the dosage regimen and duration of treatment as approved in the summary of product characteristics. 200000023271 Declaration that stability studies will be conducted in accordance with the relevant guidelines for products where stability parameters could be affected. Data to be reported only if outside specifications (with proposed action). 200000023272 Results of appropriate real time stability studies (covering the entire shelf life) conducted in accordance with the relevant stability guidelines on at least two pilot scale batches of the finished product in the authorised packaging material and/or after first opening or reconstitution, as appropriate; where applicable, results of appropriate microbiological testing should be included. 200000023273 Copy of approved end of shelf life finished product specification and where applicable, specifications after dilution/reconstitution or first opening. 200000023274 Results from product and process development studies (including risk assessment and multivariate studies, as appropriate) demonstrating that a systematic mechanistic understanding of material attributes and process parameters to the critical quality attributes of the finished product has been achieved. 200000023275 Change management protocol related to the finished product. 200000023276 Declaration that any change should be within the range of currently approved limits. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products. 200000023277 Copy of approved specifications of the finished product. 200000023279 In case of an addition of a manufacturing site, the variation application form should clearly outline the “present” and “proposed” manufacturers as listed in the application form. 200000023280 Where applicable, a document providing information of any materials falling within the scope of the Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products including those which are used in the manufacture of the active substance/excipient. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023281 Where applicable, for active substance, a declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the QP of each of the manufacturing authorisation holders listed in the application as responsible for batch release. (SEE FULL DESCRIPTION IN GUIDELINE) 200000023283 Description, detailed drawing and composition of the device material and supplier where appropriate. 200000023284 Data to demonstrate accuracy, precision and compatibility of the device. 200000023285 Samples of the new device where applicable. 200000023286 Details of any new analytical method and summary of validation data. 200000023287 Batch analysis data on two production batches for all tests in the new specification. 200000023291 The variation application form should clearly outline the “present” and “proposed” VAMF EMA Certificate (code number) in the MA dossier. When applicable, the variation application form should clearly list also all the other VAMFs to which the medicinal product refers even if they are not the subject of the application. 200000023292 Attached to the cover letter of the variation application: a reference to the Commission Decision concerned with the annexed Summary of Product Characteristics, Labelling or Package Leaflet. 200000023293 A declaration that the proposed Summary of Product Characteristics, Labelling and Package Leaflet is identical for the concerned sections to that annexed to the Commission Decision. 200000023294 Attached to the cover letter of the variation application: a reference to the agreement/assessment of the competent authority. 200000023295 Attached to the cover letter of the variation application: a reference to the procedure where the wording for one of the active substances was approved. 200000023296 Attached to the cover letter of the variation application: proof of authorisation of the legal status change (e.g. reference to the Commission Decision concerned) 200000023297 Justification for the deletion of the target species 200000032254 A confirmation that the related signal has been submitted in the Union Pharmacovigilance database, in the module for Veterinary Signal Management (VSM) submissions (IRIS). The procedure number for the VSM submission in IRIS (e.g. EMA/VS/XXXXXXXXXX) will suffice. 200000032255 The veterinary signal assessment report for MAHs in line with the relevant template available on the EMA website, and any references or supporting documentation. 200000051923 Amendment of the relevant section(s) of the dossier, including revised product information as appropriate. 200000051924 A declaration by the qualified person (QP) of each of the manufacturing authorisation holders listed in the application, where the active substance is used as a starting material, and a declaration by the gualified person of each of the manufacturing authorisation holders listed in the application as responsible for batch release. These declarations should state that the active substance manufacturer(s) referred to in the application operate in compliance with the detailed ... 200000051925 A declaration by the qualified person (QP) responsible for batch certification stating that the active substance manufacturer(s) referred to in the marketing authorisation operate in compliance with the detailed guidelines on good manufacturing practice for starting materials. A single declaration may be acceptable under certain circumstances (see the note under variation no. Q.II.b.1). 200000051926 A declaration from the marketing authorisation holder (and the ASMF holder as appropriate) that the changes to the manufacturing methods are only those necessitated by scale-up or downscaling, e.g. use of different-sized equipment, that the change does not adversely affect the reproducibility of the process, that it is not the result of unexpected events arising during manufacture or because of stability concerns and that the specifications of the active substance/intermediates remain the same. 200000051927 A declaration from the marketing authorisation holder (and the ASMF holder, where applicable) that the starting material (specifications and analytical procedures) and that the synthetic route, quality control procedures and specifications of the active substance and of the intermediate used in the manufacturing process of the active substance are the same as those already approved. For herbal active substances, a declaration that the geographical source, production ... 200000051928 A declaration from the marketing authorisation holder or the ASMF holder as appropriate that the required stability studies have been started under ICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. Assurance should also be given that the studies will be finalised and ... 200000051929 A declaration from the marketing authorisation holder that an evaluation has been performed and the minor changes do not impact the quality, safety or efficacy of the active substance/finished product (e.g. minor amendments to process description without actual process change, such as details of reagents (e.g. buffers, media preparation). For herbal starting materials/active substances, this evaluation should include a detailed comparison regarding quality determining process characteristics ... 200000051930 A declaration from the marketing authorisation holder that an evaluation of the concerned manufacturing step(s) has been performed and the minor change does not impact the quality, safety or efficacy of the finished product. 200000051931 A declaration that the required stability studies have been started under ICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. Assurance should also be given that the studies will be finalised and that data will be provided immediately to the competent authorities if ... 200000051932 A declaration that the required stability studies have been started under ICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. Assurance should also be given that the studies will be finalised and that data will be provided immediately to the competent authorities if... 200000051933 A formal document from a relevant official body (e.g. Chamber of Commerce) in which the new name or new address is mentioned. 200000051934 A formal document from a relevant official body (e.g. Chamber of Commerce, or if not available, from a competent authority) in which the new name and/or address is mentioned, or a copy of the modified manufacturing authorisation, if available. 200000051935 A summary and justification of the proposed change(s), clearly describing the present and proposed situation and supporting documentation. 200000051936 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format) including revised product information as appropriate. 200000051937 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), and revised product information as appropriate. 200000051938 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), as appropriate. 200000051939 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a description of the analytical methodology, a summary of validation data, revised specifications. 200000051940 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a description of the analytical methodology, a summary of validation data. 200000051941 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a description of the manufacturing and qualification of the new in-house reference standard. 200000051942 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a detailed drawing of the current and proposed situation, and including revised product information as appropriate. 200000051943 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a detailed drawing or written description of the current and new appearance, and including revised product information as appropriate. 200000051944 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a direct comparison of the present process and the new process. 200000051945 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including description, detailed drawing and composition of the container or closure material, and including revised product information as appropriate. 200000051946 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including revised product information, as appropriate. 200000051947 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format). This must contain results of appropriate real time stability studies, conducted in accordance with the relevant stability guidelines on three pilot or production scale batches of the active substance or intermediate in the authorised packaging material. 200000051948 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format). This must contain results of appropriate stability studies conducted in accordance with the relevant stability guidelines on three pilot scale batches(*) of the finished product in the authorised packaging material and/or two batches after first opening or reconstitution, as appropriate. Where applicable, results of appropriate microbiological testing should be included. 200000051949 Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format). This should include: Updated consolidated holder/finished product manufacturer list of manufacturers of the active substance (section 3.2.S.2.1); Updated single compiled holder/finished product manufacturer active substance specification, including analytical methods and method validation (where the finished product manufacturer uses analytical procedures which are different from the Ph. Eur. ... 200000051950 Amendment of the relevant section(s) of the dossier, as appropriate. 200000051951 Amendment of the relevant section(s) of the dossier, including description, drawing and composition of the device material, compatibility and usability studies as appropriate. 200000051952 Amendment of the relevant section(s) of the dossier, including revised product information as appropriate. 200000051953 An updated product lifecycle management document (PLCM) with relevant sections modified. 200000051954 Appropriate data on the new packaging (comparative data on permeability, e.g. for O2, CO2 moisture). Where appropriate, proof must be provided that no adverse interaction between the content and the packaging material occurs (e.g. data on migration of components of the proposed material into the content and loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeial requirements or legislation of ... 200000051955 Appropriate data on the new packaging (e.g. comparative data on permeability e.g. for O2, CO2 moisture). Where appropriate, proof must be provided that no interaction between the content and the packaging material has no impact on the active substance quality (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeia requirements or ... 200000051956 Attached to the cover letter of the variation application: A reference to the relevant decision of the competent authorities. 200000051957 Attached to the cover letter of the variation application: reference to the agreement/assessment of the competent authoritiesies. 200000051958 Batch analysis data (in a comparative tabular format) for at least two batches (minimum pilot scale) [or 3 batches (unless otherwise justified) for biologicals] of the active substance/starting material from the current and proposed manufacturers/sites. 200000051959 Batch analysis data (in a comparative tabulated format) of at least two batches (minimum pilot scale) [or 3 production batches (unless otherwise justified) for biological excipients] of the excipient manufactured according to the present and proposed process, or by the present and proposed manufacturer, as applicable. 200000051960 Batch analysis data (in a comparative tabulated format) on a minimum of two batches] manufactured to both the currently approved and the proposed process. 200000051961 Batch analysis data (in a comparative tabulated format) on a minimum of two production batches manufactured to both the currently approved and the proposed sizes. Batch analysis data of 3 batches (unless otherwise justified) for biological finished product should be available for the proposed batch size. 200000051962 Batch analysis data (in a comparative tabulated format) on a minimum of two production batches of the active substance or intermediate, as appropriate, manufactured to both the currently approved and the proposed sizes. Batch analysis data of 3 batches (unless otherwise justified) for biological active substance, should be available for the proposed batch size. 200000051963 Batch analysis data (in a comparative tabulated format) on two production batches of the relevant substance for all analytical procedures in the new specification and additionally, where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch. For herbal finished products, comparative disintegration data may be acceptable. 200000051964 Batch analysis data on one production batch and two pilot scale batches simulating the production process (or two production batches) and comparative data on the last three batches from the previous site; batch data on the next two production batches should be available on request or reported if outside specifications (with proposed action). Batch analysis data of 3 batches (unless otherwise justified) of the biological finished product, manufactured from the current and ... 200000051965 Batch analysis data (in comparative tabular format) of at least two batches (minimum pilot scale), of the active substance or intermediate as appropriate, manufactured according to the currently approved and proposed process. 200000051966 Batch analysis data on two production batches [3 production batches (unless otherwise justified) for biologicals] of the finished product for all specification attributes. 200000051967 Batch analysis data on two production batches [3 production batches (unless otherwise justified) for biologicals]) of the relevant substance for all specification attributes. 200000051968 Batch analysis data on two production batches of the active substance for all specification attributes. 200000051971 Batch analysis data on two production batches of the excipient for all specification attributes [3 production batches (unless otherwise justified) for biological excipients or novel excipients]. 200000051972 Batch analysis data on two production of the finished product for all specification attributes. 200000051973 Comparative batch analysis data and comparative dissolution profile data of at least two pilot scale batches of the finished product in the current and proposed formulation. For herbal medicinal products where dissolution testing may not be feasible, comparative disintegration data should be provided. 200000051974 Comparative dissolution data on at least one pilot batch of the current and proposed dimensions (no significant differences regarding comparability see the relevant guideline on Investigation of Bioequivalence). For herbal medicinal product comparative disintegration data may be acceptable. 200000051975 Comparative study results or comparative analysis results showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure. 200000051976 Comparative table of current and proposed in-process controls and limits. 200000051977 Comparative test results, showing that the current in-house reference standard and the proposed one are equivalent. 200000051978 Comparative validation results (or, if justified, comparative analysis results) showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure unless the new analytical procedure is added as an alternative procedure to a current one. 200000051979 Comparative validation results or if justified comparative analysis results showing that the current analytical and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure. 200000051980 Comparative validation results or if justified comparative analysis results showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure. 200000051981 Comparative validation results, or if justified comparative analysis results showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure unless the new analytical procedure is added as an alternative procedure to a current one. 200000051982 Confirmation and data demonstrating compliance with equivalent quality standard as CE-mark as requested in the ‘Guideline on the scientific data requirements for a PMF’. 200000051983 Confirmation no changes other than administrative (Type IA) have been implemented. 200000051984 Confirmation of equivalence of the materials and that there is no impact on the quality of the finished product. 200000051985 Confirmation of the transfer of the complete PMF documentation since the initial PMF certification to the transferee - signed by both companies. 200000051986 Confirmation that any anticoagulant solution complies with Ph. Eur. requirements. 200000051987 Confirmation that standard contract between blood establishment/centre and PMF holder is in place. 200000051988 Confirmation that the proposed summary of product characteristics, labelling and package leaflet is identical for the concerned sections to that annexed to the Commission Decision or to the agreement reached by the CMDh (as applicable). 200000051989 Copy of approved and new (if applicable) specifications of the excipient (as annex to the application form). 200000051990 Copy of approved end of shelf life finished product specification and where applicable, specifications after dilution/reconstitution or first opening (as annex to the application form). 200000051991 Copy of approved release and end-of-shelf life specifications (as annex to the application form). 200000051992 Copy of approved release and end-of-shelf life specifications if relevant (as annex to the application form). 200000051993 Copy of approved specifications of the active substance (as annex to the application form). 200000051994 Copy of the current (updated) Ph. Eur. certificate of suitability (CEP) and the letter of access (where available). 200000051995 Data to demonstrate performance, safety and compatibility of the device, as appropriate. 200000051996 Data to demonstrate that the new excipient does not interfere with the finished product specification analytical procedures, if appropriate. 200000051997 Data to demonstrate the suitability of the monograph to control the substance (e.g. a comparison of the potential impurities with the transparency note of the monograph). 200000051998 Data to validate the proposed change in holding time and/or storage conditions of the intermediate or bulk product (minimum of two batches at pilot or commercial scale). Composition of the intermediate or bulk container should be described and its specification stated. If pilot scale batches are provided, a commitment to verify these data on commercial scale batches. Declaration that the finished product shelf life is set in accordance with ... 200000051999 Declaration of changes introduced, and variation applications submitted. 200000052000 Declaration that relevant stability studies have been started under ICH conditions, as appropriate, (with indication of the batch numbers concerned) and relevant stability parameters have been assessed in at least one pilot scale or industrial scale batch. Assurance is given that these studies will be finalised and that the data will be provided immediately to the competent authorities if outside specifications or ... 200000052001 Declaration that the change is in accordance with the post-approval change management protocol and that the study results meet the acceptance criteria specified in the protocol(*). 200000052002 Declaration that the change is in accordance with the approved change management protocol and that the study results meet the acceptance criteria specified in the protocol.(*) 200000052003 Declaration that the changes do not change the overall strategy defined in the protocol and are not broader than the currently approved protocol. 200000052004 Declaration that the serotype, strain, antigen or coding sequence is no longer appropriate in relation to the epidemiological evolution of the human virus of concern. 200000052005 Declaration that the finished product specification has only been updated in respect of weight and dimensions. 200000052006 Declaration that the PMF Certificate and Evaluation Report are fully applicable for the authorised product, PMF holder has provided the PMF Certificate, Evaluation report and PMF dossier to the holder (where the marketing authorisation holder is different to the PMF holder), the PMF Certificate and Evaluation Report replace the previous PMF documentation for this marketing authorisation. 200000052007 Declaration that the remaining product presentation(s) are adequate for the dosing instructions and duration as mentioned in the summary of product characteristics, and the deletion has been agreed in principle with the Agency. 200000052008 Declaration that the VAMF Certificate and Evaluation Report are fully applicable for the authorised product, VAMF holder has submitted the VAMF Certificate, Evaluation report and VAMF dossier to the holder (where the marketing authorisation holder is different to the VAMF holder), the VAMF Certificate and Evaluation Report replace the previous VAMF documentation for this marketing authorisation. 200000052009 Declaration that, while the establishment(s)/centre(s) has remained in non-operational, the epidemiology data have been submitted annually. 200000052010 Description of the design space in tabular format, and/or in the form of mathematical equation, as relevant, including the variables (material attributes and process parameters, as appropriate) with their proposed ranges and limits. 200000052011 Description of the sterilisation method and sterilisation cycle. Validation of the sterilisation cycle should be provided if it does not use the reference conditions stated in Ph. Eur.. 200000052012 Description of the sterilisation method and sterilisation cycle. Validation of the sterilisation cycle should be provided if the sterilisation cycle does not use the reference conditions stated in the Ph. Eur. 200000052015 Details of any new analytical procedure and validation data, where relevant. 200000052016 Details of any new analytical procedure and validation, where relevant. 200000052017 Either a Ph. Eur. certificate of suitability for any new component of animal susceptible to TSE risk or where applicable, documentary evidence that the specific source of the TSE risk material has been previously assessed by the competent authority and shown to comply with the scope of the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathies via Human and Veterinary Medicinal Products... 200000052018 Either a TSE Ph. Eur. certificate of suitability for any new source of material or, where applicable, documentary evidence that the specific source of the TSE risk material has previously been assessed by the competent authority and shown to comply with the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products. The information should include the following:... 200000052019 Epidemiological data for viral markers related to the blood/plasma collection centre to be provided as requested in the Guideline on epidemiological data on blood transmissible infections. 200000052020 Evidence that the sterilisation has been conducted and validated in accordance with GMP and/or relevant ISO standards, as per guideline on the sterilisation of the medicinal product, active substance, excipient and primary container. 200000052021 For active substance and excipients, proof of acceptance by WHO or copy of the INN list. If applicable, proof that the change is in line with the Ph. Eur.. For herbal medicinal product, declaration that the name is in accordance with the guideline on declaration of herbal substances and herbal preparations in (traditional) herbal medicinal products. 200000052022 For biological active substance, a justification that an assessment of comparability is not required. 200000052059 For biological finished products, a justification that an assessment of comparability is not required. 200000052060 For herbal active substances a detailed comparison regarding specifications and critical quality attributes (e.g. for extracts: reference to the herbal starting material (incl. scientific binominal name and plant part), physical state, extraction solvent (nature and concentration), drug extract ratio (DER) and manufacturing process (including a stepwise comparison of all manufacturing steps in tabular format). 200000052063 For herbal active substances/herbal starting materials a detailed comparison regarding their characteristics (e.g. for extracts: reference to the herbal starting material (incl. scientific binominal name and plant part, physical state extraction solvent (nature and concentration), drug extract ratio (DER) and the manufacturing process) should be provided. 200000052064 For herbal starting material supplier, a GACP declaration from the new supplier (and updated QP declaration if the new supplier is also involved in the herbal active substance manufacture). 200000052065 For herbal starting material, a detailed comparison regarding specifications and critical quality attributes of the herbal starting material. For herbal active substance, a detailed comparison regarding specifications and critical quality attributes (e.g. for extracts: reference to the herbal starting material (incl. scientific binominal name and plant part), physical state, extraction solvent (nature and concentration), drug extract ratio (DER) and manufacturing process... 200000052066 For medical devices, updated CE certificate and/or declaration of conformity, if available. 200000052067 For semisolid and liquid formulations in which the active substance is present in non-dissolved form, appropriate validation data including microscopic imaging of particle size distribution and morphology or any other appropriate imaging technique. 200000052068 For semi-solid and liquid products in which the active substance is present in non-dissolved form: appropriate validation of the change including microscopic imaging of particles to check for visible changes in morphology; comparative size distribution data by an appropriate method. 200000052069 For solid dosage forms: dissolution profile data of one representative production batch and comparative data of the last three batches from the previous process; data on the next two full production batches should be available on request or reported if outside specification (with proposed action). For herbal medicinal products, comparative disintegration data may be acceptable. 200000052070 For the addition or replacement of a co-packaged medical device, evidence that relevant standards have been met e.g. EU declaration of conformity or, where applicable, EU certificate, or other appropriate documentation such as summary information confirming compliance with relevant General Safety and Performance Requirements. 200000052071 For the biosimilar medicinal product aligning the product information with an indication of the reference medicinal product: a justification that the comparability exercise performed for the biosimilar medicinal product is valid for the applied indication. 200000052072 If the manufacturing site and the immediate packaging site are different, conditions of transport and bulk storage should be specified and validated. 200000052074 In case of a change in the headspace or a change in the surface/volume ratio, a declaration that the required stability studies have been started under ICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data (at least three months stability data for at least one pilot scale or industrial scale batches) were at the disposal of the applicant at time of implementation for a Type IA notification and time of submission of 200000052075 In case of change in the name of the holder of the Active Substance Master File, updated “letter of access”. 200000052076 In the case of herbal starting materials, an updated GACP declaration and a declaration from the marketing authorisation holder that the manufacturing process of the herbal active substance remains the same. 200000052077 Justification for not submitting a new bioequivalence study according to the current guideline on Investigation of Bioequivalence. 200000052078 Justification for not submitting a new bioequivalence study according to the relevant guidance on Investigation of Bioequivalence. 200000052079 Justification for not submitting a new bioequivalence study according to the relevant guideline on Investigation of Bioequivalence. 200000052080 Justification for not submitting a new bioequivalence study according to the relevant Guideline on The Investigation of Bioequivalence, if appropriate. 200000052081 Justification for the absence of a Notified Body opinion/EU certificate/EU declaration of conformity, based on the risk-assessment performed, which concluded that the proposed change has no significant impact on the medicinal product. 200000052082 Justification for the deletion, including a statement regarding alternative means to obtain the solvent / diluent as required for the safe and effective use of the finished product. 200000052083 Justification from the holder for the change in the testing of specification attribute. A change from routine testing to skip/periodic testing is warranted when the manufacturing process is under control and supported by a sufficient amount of historical data compliant with the specification. A change from skip/periodic testing to routine testing should be supported by analytical data demonstrating failure to meet the approved acceptance criteria for the skip tested specification. 200000052084 Justification from the holder or ASMF holder as appropriate for the new in-process control and limits. 200000052085 Justification from the marketing authorisation holder or ASMF holder as appropriate of the new specification attribute and the acceptance criteria. 200000052086 Justification from the marketing authorisation holder or the ASMF holder for the change in the testing of specification attribute. A change from routine testing to skip/periodic testing is warranted when the manufacturing process is under control and supported by sufficient amount of historical data compliant with the specification or as foreseen by relevant guidelines. A change from skip/periodic testing to routine testing should be supported by analytical data demonstrating failure to meet the 200000052087 Justification from the marketing authorisation holder or the ASMF Holder, as appropriate, of the new specification attribute and the acceptance criteria. 200000052088 Justification of the new in-process control and limits. 200000052089 Justification of the new specification attribute and the acceptance criteria. 200000052090 Justification of the specification attribute and its acceptance criteria. 200000052091 Justification that the studies modify the risk assessment resulting in equivalent or lower risk. 200000052092 Justification that there is no impact on the quality criteria of the blood in the container. 200000052093 Justification/risk assessment from the marketing authorisation holder or the ASMF holder, as appropriate, that the in-process controls are non-significant, or that the in-process controls are obsolete. 200000052094 Justification/risk assessment from the marketing authorisation holder or the ASMF Holder, as appropriate, that the specification attribute is non-significant, or obsolete. 200000052095 Justification/risk assessment from the marketing authorisation holder or the ASMF holder, as appropriate, that the specification attribute is non-significant, or that the specification attribute is obsolete. 200000052096 Justification/risk assessment showing that the attribute is non-significant or that it is obsolete. 200000052097 Justification/risk assessment showing that the in-process control is non-significant or that it is obsolete. 200000052098 Letter of Authorisation including contact details of the person responsible for communication between the competent authority and the PMF holder - signed by the transferee. 200000052099 Letter of Undertaking to fulfil all open and remaining commitments (if any) - signed by the transferee. 200000052100 List of testing site(s) where the test is currently used and a list of testing centre(s) where the kit will be used. 200000052101 Proof of acceptance (by WHO) or copy of the ATC Code list. 200000052102 Proof of establishment of the new holder (Excerpt of the commercial register and the English translation of it) - signed by both companies. 200000052103 Results of consultation with target patient groups (user test or bridging report). 200000052104 Results of the studies performed and any other supporting documentation in accordance with the post-approval change management protocol. 200000052105 Re-validation studies have been performed in case of sterile products. The batch numbers of the batches used in the re-validation studies should be indicated, where applicable. 200000052106 Revised product information, as appropriate. 200000052107 Statement that the testing is performed following the same SOPs and/or analytical procedures as already accepted. 200000052108 Suitable evidence to confirm compliance of either the water used in the final steps of the synthesis of the active substance, or the active substance, itself with the corresponding requirements of the guideline on quality of water for pharmaceutical use regarding bacterial endotoxins and microbiological quality. 200000052109 The analytical procedure transfer protocols in accordance with Eudralex Volume 4 Chapter 6 article 6.39 (which pre-define the acceptance criteria), from the old site to the new site (or new test laboratory). 200000052110 The content of the product lifecycle management document has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies (e.g. interaction of the different parameters, including risk assessment and multivariate studies, as appropriate) demonstrating where relevant that a systematic understanding of how material attributes and process parameters impact the critical ... 200000052111 The content of the product lifecycle management document has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies (including risk assessment and multivariate studies, as appropriate) demonstrating where relevant that a systematic understanding of how material attributes and process parameters impact the critical quality attributes of the finished product has been achieved. 200000052112 The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product and process development studies (including risk assessment and multivariate studies, as appropriate) demonstrating that a systematic understanding of material attributes and process parameters to the critical quality attributes of the finished product has been achieved. 200000052113 The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies including risk assessment and multivariate studies or process modelling, as appropriate, demonstrating where relevant that a systematic understanding of how material attributes and process parameters impact the critical quality attributes of the active substance has been achieved. 200000052114 The product lifecycle management document includes a description of the material attributes, quality attributes and process parameters (or analytical procedure parameters), their proposed limits and ranges, and future variation reporting categories, in a tabular format. 200000052115 The results of stability studies that have been carried out under ICH conditions, on the relevant stability parameters, on at least one pilot or industrial scale batch, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action). 200000052116 The results of stability studies that have been carried out under ICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved retest period (with proposed action). 200000052117 The results of stability studies that have been carried out under ICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action). 200000052121 Updated affected sections of the dossier for the medicinal product. 200000052122 Updated epidemiological data for viral markers related to the blood/plasma collection centre. 200000052123 Updated product information whenever this is required by the relevant national legislation. 200000052124 Updated relevant sections and annexes of the PMF dossier including also inspections and audit information. 200000052125 Updated relevant sections and annexes of the PMF dossier including inspections and audit information, as needed. 200000052128 Updated relevant sections and annexes of the PMF dossier including inspections and audit information. 200000052129 Updated relevant sections and annexes of the PMF dossier, including detailed description of the new conditions, confirmation of validation of storage/transport conditions and the name of the blood establishment(s) where the change takes place (if relevant). 200000052131 Updated relevant sections and annexes of the PMF dossier, including updated information on testing as requested in the 'Guideline on the scientific data requirements for a PMF'. 200000052133 Valid proof that the proposed site is GMP compliant for the manufacturing and/or testing operation(s) concerned: For a site within the EU/EEA: a copy of manufacturing authorisation(s) or where no manufacturing authorisation exists a certificate of GMP compliance issued within the last 3 years by the relevant competent authority. A reference to the EudraGMP database will suffice. For a third country site where a GMP mutual recognition agreement (MRA) or other relevant agreement... 200000052135 Valid proof that the proposed site is GMP compliant for the manufacturing and/or testing operation(s) concerned: For a site within the EU/EEA: a copy of the current manufacturing authorisation or where no manufacturing authorisation exists a certificate of GMP compliance issued within the last 3 years by the relevant competent authority. A reference to the EudraGMP database will suffice. For a third country site where a GMP mutual recognition agreement (MRA) or other relevant agreement on GMP is 200000052139 Where applicable, a document providing information of any materials falling within the scope of the Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products, including those which are used in the manufacture of the active substance/excipient. The following information should be included for each such material: Name of manufacturer, species and tissues from which the material is a derivative... 200000052141 Where applicable, for active substance, a declaration by the qualified person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the QP of each of the manufacturing authorisation holders listed in the application as responsible for batch release. 200000052143 Where appropriate, proof must be provided that no interaction between the medicinal product and the device (part) occurs (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the device), including confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic material and objects in contact with foodstuffs. 200000052145 Where relevant the batch numbers, corresponding batch size and the manufacturing date of batches (³3) used in the validation study should be indicated or validation protocol (scheme) be submitted. 200000052146 Where relevant, a commitment of the manufacturer of the active substance to inform the marketing authorisation holder of any changes to the manufacturing process, specifications and analytical procedures of the active substance. 200000052211 A declaration from the marketing authorisation holder (and the ASMF holder, where applicable) that there is no change in qualitative and quantitative impurity profile or in physico-chemical properties, that the synthetic route remains the same and that the specifications of the active substance or intermediates are unchanged 200000052212 Valid proof that the proposed site is GMP compliant for the manufacturing and/or testing operation(s)concerned: For a manufacturing site within the EU/EEA: a copy of the current manufacturing authorisation. A reference to the EudraGMP database will suffice; For a third country site where a GMP mutual recognition agreement (MRA) or other relevant agreement is in place between the country concerned and the EU: a proof of GMP compliance issued within the last 3 years...
A declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application as responsible for batch release.
A declaration by the Qualified Person (QP) responsible for batch certification stating that the active substance manufacturer(s) referred to in the marketing authorisation operate in compliance with the detailed guidelines on good manufacturing practice for starting materials. A single declaration may be acceptable under certain circumstances — see the note under variation No B.II.b.1.
A declaration from the marketing authorisation holder or the ASMF holder as appropriate that the changes to the manufacturing methods are only those necessitated by scale-up or downscaling, e.g. use of different-sized equipment, that the change does not adversely affect the reproducibility of the process, that it is not the result of unexpected events arising during manufacture or because of stability concerns and that the specifications of the active substance/intermediates remain the same.
A declaration from the marketing authorisation holder or the ASMF holder as appropriate that the required stability studies have been started under ICH/VICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem.
A declaration from the marketing authorisation holder or the ASMF holder, where applicable, that the synthetic route quality control procedures and specifications of the active substance and of the starting material/reagent/intermediate in the manufacturing process of the active substance (if applicable) are the same as those already approved.
A declaration from the marketing authorisation holder or the ASMF Holder, where applicable, that there is no change in qualitative and quantitative impurity profile or in physico-chemical properties, that the synthetic route remains the same and that the specifications of the active substance or intermediates are unchanged.
A declaration that the proposed Summary of Product Characteristics, Labelling and Package Leaflet is identical for the concerned sections to that annexed to the Commission Decision or to the agreement reached by the CMDh (as applicable).
A declaration that the required stability studies have been started under ICH/VICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem.
A document including the identification (name and address) of the current PMF Holder (transferor) and the identification (name and address) of the person to whom the transfer is to be granted (transferee) together with the proposed implementation date — signed by both companies.
A formal document from a relevant official body (e.g. Chamber of Commerce) in which the new name and/or address is mentioned.
Amendment of product information (where applicable).
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate) including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), and of the approved Active Substance Master File (where applicable), including a direct comparison of the present process and the new process.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate).
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), if applicable.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a description of the analytical methodology and a summary of validation data.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a description of the analytical methodology, a summary of validation data, revised specifications for impurities (if applicable).
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a detailed drawing of the current and proposed situation, and including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a detailed drawing or written description of the current and new appearance, and including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including a direct comparison of the present process and the new process.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including description, detailed drawing and composition of the container or closure material, and including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including description, detailed drawing and composition of the device material and supplier where appropriate, and including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including identification method for any new colorant, where relevant, and including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate). This must contain results of appropriate real time stability studies (covering the entire shelf life) conducted in accordance with the relevant stability guidelines on at least two pilot scale batches of the finished product in the authorised packaging material and/or after first opening or reconstitution, as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate). This must contain results of appropriate real time stability studies, conducted in accordance with the relevant stability guidelines on at least two pilot or production scale batches of the active substance in the authorised packaging material and covering the duration of the requested retest period or requested storage conditions.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format).
Amendment of the relevant section(s) of the dossier.
Amendment of the relevant section(s) of the dossiers including the introduction of the new studies to investigate the capability of manufacturing steps to inactivate/reduce adventitious agents.
Amendment of the relevant section(s) of the dossiers.
An expert statement outlining all the changes introduced with the certified PMF and evaluating their potential impact on the finished products including product specific risk assessments.
An expert statement outlining all the changes introduced with the certified VAMF and evaluating their potential impact on the finished products including product specific risk assessments.
Appropriate data on the new packaging (comparative data on permeability, e.g. for O 2 , CO 2 moisture).
Appropriate data on the new packaging (e.g. comparative data on permeability, e.g. for O 2 , CO 2 moisture), including a confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic materials and objects in contact with foodstuffs.
Assurance on GMP or ISO compliance of the site where the sterilisation of the containers is performed.
Attached to the cover letter of the variation application: A reference to the agreement of the competent authority (in the case of marketing authorisations granted under the centralised procedure, the CHMP).
Attached to the cover letter of the variation application: a reference to the Commission Decision concerned or to the agreement reached by the CMDh (as applicable) with the annexed Summary of Product Characteristics, Labelling or Package Leaflet.
Attached to the cover letter of the variation application: A reference to the Commission Decision concerned.
Attached to the cover letter of the variation application: A reference to the list of medicinal products that are subject to additional monitoring.
Attached to the cover letter of the variation application: A reference to the relevant decision of the competent authority.
Attached to the cover letter of the variation application: EMA/NCA request, if applicable.
Attached to the cover letter of the variation application: proof of authorisation of the legal status change (e.g. reference to the Commission Decision concerned).
Attached to the cover letter of the variation application: reference to the agreement/assessment of the competent authority.
Attached to the cover letter of the variation application: The relevant decision of the competent authority.
Batch analysis data (in a comparative tabular format) for at least two batches (minimum pilot scale) of the active substance from the current and proposed manufacturers/sites.
Batch analysis data (in a comparative tabulated format) of at least two batches (minimum pilot scale) of the excipient manufactured according to the old and the new process.
Batch analysis data (in a comparative tabulated format) on a minimum of one batch manufactured to both the currently approved and the proposed process. Batch data on the next two full production batches should be made available upon request and reported by the marketing authorisation holder if outside specification (with proposed action).
Batch analysis data (in a comparative tabulated format) on a minimum of one production batch manufactured to both the currently approved and the proposed sizes. Batch data on the next two full production batches should be made available upon request and reported by the MAH if outside specifications (with proposed action).
Batch analysis data (in a comparative tabulated format) on a minimum of one production batch of the active substance or intermediate as appropriate, manufactured to both the currently approved and the proposed sizes. Batch data on the next two full production batches should be made available upon request and reported by the marketing authorisation holder if outside specification (with proposed action).
Batch analysis data (in a comparative tabulated format) on two production batches of the relevant substance for all tests in the new specification and additionally, where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch. For herbal medicinal products, comparative disintegration data may be acceptable.
Batch analysis data (in comparative tabular format) of at least two batches (minimum pilot scale) manufactured according to the currently approved and proposed process.
Batch analysis data on one production batch and two pilot-scale batches simulating the production process (or two production batches) and comparative data on the last three batches from the previous site; batch data on the next two production batches should be available on request or reported if outside specifications (with proposed action).
Batch analysis data on two batches of the immediate packaging for all specification parameters.
Batch analysis data on two production batches (3 production batches for biological excipients) of the excipient for all specification parameters.
Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the active substance for all specification parameters.
Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the finished product for all specification parameters.
Batch analysis data on two production batches (3 production batches for biologicals, unless otherwise justified) of the relevant substance for all specification parameters.
Batch analysis data on two production batches for all tests in the new specification.
Change management protocol related to the active substance.
Change management protocol related to the finished product.
Comparative dissolution data on at least one pilot batch of the current and proposed dimensions (no significant differences regarding comparability see the relevant (Human or Veterinary) guidance on Bioavailability). For herbal medicinal product comparative disintegration data may be acceptable.
Comparative table of current and proposed in-process tests and limits.
Comparative table of current and proposed in-process tests.
Comparative table of current and proposed specifications.
Comparative table of current and proposed specifications, if applicable.
Comparative table of the current and proposed immediate packaging specifications, if applicable.
Comparative validation results or if justified comparative analysis results showing that the current test and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new test procedure.
Comparison of the current and proposed immediate packaging specifications, if applicable.
Confirmation of the transfer of the complete PMF documentation since the initial PMF certification to the transferee — signed by both companies.
Confirmation that stability studies have been done to the currently approved protocol. The studies must show that the agreed relevant specifications are still met.
Copy of approved and new (if applicable) specifications of the excipient.
Copy of approved end of shelf life finished product specification and where applicable, specifications after dilution/reconstitution or first opening.
Copy of approved release and end-of-shelf life specifications if relevant.
Copy of approved release and end-of-shelf life specifications.
Copy of approved specifications of the active substance (and of the intermediate, if applicable).
Copy of approved specifications of the active substance.
Copy of approved specifications of the finished product.
Copy of the current (updated) Ph. Eur. Certificate of Suitability.
Copy of the EMA letter of acceptance of the new (invented) name.
Copy of the latest PMF Certificate page ‘EMA Plasma Master File (PMF) Certificate of compliance with Community legislation’.
Copy of the modified manufacturing authorisation, if available; or a formal document from a relevant official body (e.g. Chamber of Commerce, or if not available, from a Regulatory Agency) in which the new name and/or address is mentioned.
Data to demonstrate accuracy, precision and compatibility of the device.
Data to demonstrate that the new excipient does not interfere with the finished product specification test methods, if appropriate.
Data to demonstrate the suitability of the monograph to control the substance, e.g. a comparison of the potential impurities with the transparency note of the monograph.
Declaration from the manufacturer or the marketing authorisation holder of the material that it is purely of vegetable or synthetic origin.
Declaration that any change should be within the range of currently approved limits. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products.
Declaration that relevant stability studies have been started under ICH/VICH conditions, as appropriate, (with indication of the batch numbers concerned) and relevant stability parameters have been assessed in at least one pilot scale or industrial scale batch and at least 3 months satisfactory stability data are at the disposal of the applicant at time of notification and that the stability profile is similar to the currently registered situation.
Declaration that stability studies will be conducted in accordance with the relevant guidelines for products where stability parameters could be affected. Data to be reported only if outside specifications (with proposed action).
Declaration that the change is in accordance with the approved change management and that the study results meet the acceptance criteria specified in the protocol. In addition, declaration that an assessment of comparability is not required for biological/immunological medicinal products.
Declaration that the PMF Certificate and Evaluation Report are fully applicable for the authorised product, PMF holder has provided the PMF Certificate, Evaluation report and PMF dossier to the MAH (where the MAH is different to the PMF holder), the PMF Certificate and Evaluation Report replace the previous PMF documentation for this Marketing Authorisation.
Declaration that the remaining pack-size(s) is/are consistent with the dosage regimen and duration of treatment and adequate for the dosing instructions as approved in the summary of product characteristics.
Declaration that the remaining product presentation(s) are adequate for the dosing instructions and treatment duration as mentioned in the summary of product characteristics.
Declaration that the VAMF Certificate and Evaluation Report are fully applicable for the authorised product, VAMF holder has submitted the VAMF Certificate, Evaluation report and VAMF dossier to the MAH (where the MAH is different to the VAMF holder), the VAMF Certificate and Evaluation Report replace the previous VAMF documentation for this Marketing Authorisation.
Demonstration of GMP approval of the changes, which should be available at the time of implementation.
Description of the design space in tabular format, including the variables (material attributes and process parameters, as appropriate) and their proposed ranges.
Detailed description for the proposed change.
Details of any new analytical method and summary of validation data.
Details of any new analytical method and validation data, where relevant.
Details of any new non-pharmacopoeial analytical method and validation data, where relevant.
Details of the sterilisation method should be provided and in the event that the method does not use the reference conditions stated in the Ph. Eur., validation data should be provided.
Either a Ph. Eur. Certificate of Suitability for any new component of animal susceptible to TSE risk or where applicable, documentary evidence that the specific source of the TSE risk material has been previously assessed by the competent authority and shown to comply with the scope of the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathies via Human and Veterinary Medicinal Products.
Either a TSE Ph. Eur. Certificate of Suitability for any new source of material or, where applicable, documentary evidence that the specific source of the TSE risk material has previously been assessed by the competent authority and shown to comply with the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products.
Epidemiological data for viral markers related to the blood/plasma collection centre covering the last 3 years. For newly opened centre(s) or in case no data are yet available, a declaration that epidemiological data will be provided at the time of the next annual update(s).
For a site within the EU/EEA: Attach copy of manufacturing authorisation(s) or where no manufacturing authorisation exists a certificate of GMP compliance issued within the last 3 years by the relevant competent authority. For a manufacturing site outside the EEA where an operational GMP mutual recognition agreement (MRA) exists between the country concerned and the EU: a GMP certificate, issued within the last 3 years by the relevant competent authority.
For centralised procedure only: contact details of new contact person in the EU/EEA for product defects and recalls, if applicable.
For changes to process parameter(s) that have been considered to have no impact on the quality of the finished product, declaration to this effect reached in the context of the previously approved risk assessment.
For devices for medicinal products for human use, proof of CE marking.
For semi-solid and liquid formulations in which the active substance is present in non-dissolved form, appropriate validation data including microscopic imaging of particle size distribution and morphology or any other appropriate imaging technique.
For semi-solid and liquid products in which the active substance is present in non-dissolved form: appropriate validation of the change including microscopic imaging of particles to check for visible changes in morphology; comparative size distribution data by an appropriate method.
For solid dosage forms, comparative dissolution profile data of at least two pilot scale batches of the finished product in the new and old composition. For herbal medicinal products, comparative disintegration data may be acceptable.
For solid dosage forms: dissolution profile data of one representative production batch and comparative data of the last three batches from the previous process; data on the next two full production batches should be available on request or reported if outside specification (with proposed action). For herbal medicinal products, comparative disintegration data may be acceptable.
For veterinary medicines intended for use in food producing animal species, proof that the excipient is classified according to Article 14(2)(c) of Regulation (EC) No 470/2009 or, if not, justification that the excipient does not have pharmacological activity at the dose at which it is administered to the target animal.
i) If the new manufacturing site uses the active substance (AS) as a starting material - A declaration by the QP at the site responsible for batch release that the AS is manufactured in accordance with GMP for starting materials. ii) In addition, if the new manufacturing site is located within the EU/EEA and uses the AS as a starting material - A declaration by the QP of the new manufacturing site that the AS used is manufactured in accordance with GCP for starting materials.
If applicable, amendment of the relevant section(s) of the dossier (presented in the EU-CTD format or NTA volume 6B format for veterinary products, as appropriate), including revised product information as appropriate.
If the manufacturing site and the primary packaging site are different, conditions of transport and bulk storage should be specified and validated.
In case of a change in the headspace or a change in the surface/volume ratio, a declaration that the required stability studies have been started under ICH/VICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation for a Type IA notification and time of submission of a Type IB notification, and that the available data did not indicate a problem.
In case of an addition of a manufacturing site, the variation application form should clearly outline the ‘present’ and ‘proposed’ manufacturers as listed in section 2.5 of the application form.
In case of change in the name of the holder of the Active Substance Master File holder, updated ‘letter of access’.
Justification for not submitting a new bioequivalence study according to the current Note for Guidance on The Investigation of Bioavailability and Bioequivalence.
Justification for not submitting a new bioequivalence study according to the relevant (Human or Veterinary) guidance on Bioavailability.
Justification for not submitting a new bioequivalence study according to the relevant (Human, Veterinary) Guideline on Bioavailability, if appropriate.
Justification for the change/choice of excipients etc. must be given by appropriate development pharmaceutics (including stability aspects and antimicrobial preservation where appropriate).
Justification for the deletion of the device.
Justification for the deletion of the target species.
Justification for the deletion, including a statement regarding alternative means to obtain the solvent/diluent as required for the safe and effective use of the medicinal product.
Justification for the new specification parameter and the limits.
Justification for the new/remaining pack-size, showing that the new/remaining size is/are consistent with the dosage regimen and duration of treatment as approved in the summary of product characteristics.
Justification for the proposed change(s).
Justification for the proposed deletion.
Justification from the MAH or ASMF Holder as appropriate for the new in-process test and limits.
Justification from the MAH or ASMF Holder as appropriate of the new specification parameter and the limits.
Justification from the marketing authorisation holder or the ASMF Holder, as appropriate, of the new specification parameter and the limits.
Justification of the new in-process test and limits.
Justification of the new specification parameter and the limits.
Justification that the studies do not modify the risk assessment.
Justification/risk assessment from the marketing authorisation holder or the ASMF Holder, as appropriate, that the in-process parameter is non-significant, or that the in-process parameter is obsolete.
Justification/risk assessment from the marketing authorisation holder or the ASMF Holder, as appropriate, that the in-process tests are non-significant, or that the in-process tests are obsolete.
Justification/risk assessment showing that the in-process test is non-significant or that it is obsolete.
Justification/risk assessment showing that the parameter is non-significant or that it is obsolete.
Latest version of the DDPS and, where applicable, latest version of the product specific addendum. These should include for changes to the QPPV a) summary CV of the new QPPV, b) proof of QPPV EudraVigilance registration, and c) a new statement of the MAH and the QPPV regarding their availability and the means for notification of adverse reactions signed by the new QPPV and the MAH, and reflecting any other consequential changes, e.g. to the organisation chart.
Letter of Authorisation including contact details of the person responsible for communication between the competent authority and the PMF holder — signed by the transferee.
Letter of Undertaking to fulfil all open and remaining commitments (if any) — signed by the transferee.
List of testing centre(s) where the kit is currently used and a list of testing centre(s) where the kit will be used.
List of testing site(s) where the kit is used.
Proof of acceptance (by WHO) or copy of the ATC (Vet) Code list.
Proof of acceptance by WHO or copy of the INN list. If applicable, proof that the change is in line with the Ph. Eur. For herbal medicinal product, declaration that the name is in accordance with the Note for Guidance on Quality of Herbal Medicinal Products, and with the guideline on declaration of herbal substances and herbal preparations in (traditional) herbal medicinal products.
Proof of CE marking and if a measuring function is intended the proof of CE marking should also include the 4 digit notified body number.
Proof of establishment of the new holder (Excerpt of the commercial register and the English translation of it) — signed by both companies.
Proof of GMP approval of the changes, which should be available at the time of implementation.
Proof that the proposed site is appropriately authorised for the pharmaceutical form or product concerned.
Proof that the proposed site is appropriately authorised for the pharmaceutical form or product or manufacturing operation concerned.
Reference of the application/procedure and product in which the change(s) were accepted.
Reference to an assessment / Copy of assessment document from a previous procedure where the temperature of use has been agreed.
Reference to the application/procedure and product in which the DDPS was assessed previously.
Reference to the approved change management protocol.
Results from product and process development studies (including risk assessment and multivariate studies, as appropriate) demonstrating that a systematic mechanistic understanding of material attributes and process parameters to the critical quality attributes of the finished product has been achieved.
Results of the appropriate Ph. Eur tests demonstrating equivalence in characteristics/correct dosing.
Results of the studies performed in accordance with the approved change management protocol.
Revalidation studies have been performed in case of sterile products terminally sterilised. The batch numbers of the batches used in the revalidation studies should be indicated, where applicable.
Revised frequency and/or date of submission of the PSUR (for medicinal products authorised via the centralised procedure, the full set of annexes, including the revised Annex II should be provided).
Revised Product Information (and Annex A, if applicable).
Sample of the new product, where applicable (see Notice to Applicants Requirements for samples in the Member States).
Samples of the finished product where applicable (see NTA, Requirements for samples in the Member States).
Samples of the new container/closure where applicable (see NTA, Requirements for samples in the Member States/EMA).
Samples of the new device where applicable (see NTA, Requirements for samples in the Member States).
Signed declaration that the change does not involve a change of the quality system within the blood establishment.
Signed declaration that there is no change in the list of the collection centres.
Statement that the centre is working under the same conditions as the other centres belonging to the blood establishment, as specified in the standard contract between blood establishment and PMF holder.
Statement that the storage centre is working following the same SOPs as the already accepted establishment.
Statement that the testing is performed following the same SOPs and/or test methods as already accepted.
Study of equivalence of the materials and the impact on production of the final material and impact on behaviour (e.g. dissolution characteristics) of the finished product.
Suitable evidence to confirm compliance of the water used in the final steps of the synthesis of the active substance with the corresponding requirements on quality of water for pharmaceutical use.
Summary of the pharmacovigilance system, or update of the relevant elements (as applicable): - Proof that the applicant has at his disposal a qualified person responsible for pharmacovigilance and a statement signed by the applicant to the effect that the applicant has the necessary means to fulfil the tasks and responsibilities listed in Title IX of Directive 2001/83/EC. - Contact details of the QPPV, Member States in which the QPPV resides and carries out his/her tasks - PSMF location
The batch numbers of the tested batches having the proposed batch size.
The change should not lead to substantial amendments of the product information.
The changes introduced during the referral procedure should be clearly highlighted in the submission.
The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies demonstrating where relevant that a systematic mechanistic understanding of material attributes and process parameters to the critical quality attributes of the active substance has been achieved.
The medicinal product can still be accurately delivered.
The new Detailed Description of the Pharmacovigilance System (DDPS).
The new device is compatible with the medicinal product.
The proposed measuring or administration device must accurately deliver the required dose for the product concerned in line with the approved posology and results of such studies should be available.
The results of stability studies that have been carried out under ICH/VICH conditions, on the relevant stability parameters, on at least one pilot or industrial scale batch, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action).
The results of stability studies that have been carried out under ICH/VICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved retest period (with proposed action).
The results of stability studies that have been carried out under ICH/VICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action).
The section “present/proposed” is filled out completely and correctly.
The updated ASMF must be submitted by the ASMF holder (open and closed part to NCA, open part to MAH), the variation as such has to be submitted by the marketing authorisation holder.
The validation results should be provided.
The variation application form should clearly outline the ‘present’ and ‘proposed’ finished product manufacturers as listed in section 2.5 of the application form.
The variation application form should clearly outline the ‘present’ and ‘proposed’ finished product manufacturers, importer, batch control/testing and batch release sites as listed in section 2.5 of the application form for marketing authorisation.
The variation application form should clearly outline the ‘present’ and ‘proposed’ manufacturers as listed in section 2.5 of the application form for marketing authorisations.
The variation application form should clearly outline the ‘present’ and ‘proposed’ PMF EMA Certificate (code number) in the MA dossier. When applicable, the variation application form should clearly list also all the other PMFs to which the medicinal product refers even if they are not the subject of the application.
The variation application form should clearly outline the ‘present’ and ‘proposed’ VAMF EMA Certificate (code number) in the MA dossier. When applicable, the variation application form should clearly list also all the other VAMFs to which the medicinal product refers even if they are not the subject of the application.
Update of the relevant section of the dossier.
Updated relevant sections and annexes of the PMF dossier, including a list of all the blood establishments using this transport organisation, a summary of the system in place to ensure that the transport is performed under appropriate conditions (time, temperature and GMP compliance) and confirmation that transport conditions are validated.
Updated relevant sections and annexes of the PMF dossier, including detailed description of the new conditions, confirmation of validation of storage/transport conditions and the name of the blood establishment(s) where the change takes place (if relevant).
Updated relevant sections and annexes of the PMF dossier, including the name of container, manufacturer, anticoagulant solution specification, confirmation of CE-mark and the name of the blood establishments where the container is used.
Updated relevant sections and annexes of the PMF dossier, including updated information on testing as requested in the ‘Guideline on the scientific data requirements for a PMF’.
Updated relevant sections and annexes of the PMF dossier.
Updated relevant sections of the PMF dossier, including the rationale for introduction or extension of inventory hold period, the sites where the inventory hold takes place and for changes to procedure, a decision tree including new conditions.
Updated relevant sections of the PMF dossier.
Where applicable, a document providing information of any materials falling within the scope of the Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products including those which are used in the manufacture of the active substance/excipient.
Where applicable, for active substance, a declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the QP of each of the manufacturing authorisation holders listed in the application as responsible for batch release.
Where appropriate, comparative dissolution profile data for the finished product of at least two batches (minimum pilot scale). For herbal medicinal products, comparative disintegration data may be acceptable.
Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch complying with the current and proposed specification. For herbal medicinal products, comparative disintegration data may be acceptable.
Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch containing the active substance complying with the current and proposed specification. For herbal medicinal products, comparative disintegration data may be acceptable.
Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch containing the excipient complying with the current and proposed specification. For herbal medicinal products comparative disintegration data may be acceptable.
Where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch manufactured using the current and new in-process tests. For herbal medicinal products, comparative disintegration data may be acceptable.
Where appropriate, proof must be provided that no interaction between the content and the packaging material occurs (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic material and objects in contact with foodstuffs.
Where relevant the batch numbers, corresponding batch size and the manufacturing date of batches (≥ 3) used in the validation study should be indicated or validation protocol (scheme) be submitted.
Where relevant, a commitment of the manufacturer of the active substance to inform the MA holder of any changes to the manufacturing process, specifications and test procedures of the active substance.
Where relevant, the batch numbers, corresponding batch size and the manufacturing date of batches (≥ 3) used in the validation study should be indicated and the validation data presented, or validation protocol (scheme) to be submitted.
Written confirmation from the manufacturer of the finish product stating verification of compliance of the manufacturer of the active substance with principles and guidelines of good manufacturing practices.
Written confirmation from the manufacturer of the finished product stating verification of compliance of the manufacturer of the active substance with principles and guidelines of good manufacturing practices.
A declaration from the marketing authorisation holder or the ASMF holder that the synthetic route quality control procedures and specifications of the active substance and of the starting material/reagent/intermediate in the manufacturing process of the active substance are the same as those already approved. (SEE FULL DESCRIPTION IN GUIDELINE)
The variation application form should clearly outline the “present” and “proposed” manufacturers as listed in the application form for marketing authorisation.
Proof that the proposed site is appropriately authorised for the pharmaceutical form or product or manufacturing operation concerned (SEE FULL DESCRIPTION IN GUIDELINE)
Amendment of the approved Active Substance Master File, including a direct comparison of the present process and the new process.
A declaration from the ASMF Holder that there is no change in qualitative and quantitative impurity profile or in physico-chemical properties, that the synthetic route remains the same and that the specifications of the active substance or intermediates are unchanged.
Description of the analytical methodology, a summary of validation data, revised specifications for impurities (if applicable).
Comparative validation results, or if justified comparative analysis results showing that the current test and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new test procedure.
Appropriate data on the new packaging (e.g. comparative data on permeability e.g. for O2, CO2 moisture), including a confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic materials and objects in contact with foodstuffs.
Where appropriate, proof must be provided that no interaction between the content and the packaging material occurs (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeia requirements or legislation of the Union on plastic material and objects in contact with foodstuffs.
The results of stability studies that have been carried out under VICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved retest period (with proposed action).
Results of appropriate real time stability studies, conducted in accordance with the relevant stability guidelines on at least two (three for biological medicinal products) pilot or production scale batches of the active substance in the authorised packaging material and covering the duration of the requested re-test period or requested storage conditions.
The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies demonstrating where relevant that a systematic mechanistic understanding of material attributes and process parameters to the critical quality attributes of the active substance has been achieved. (SEE FULL DESCRIPTION IN GUIDELINE)
Description of the Design space in tabular format, including the variables (material attributes and process parameters, as appropriate) and their proposed ranges.
Detailed drawing or written description of the current and new appearance.
Samples of the finished product where applicable.
Detailed drawing of the current and proposed situation.
Comparative dissolution data on at least one pilot batch of the current and proposed dimensions (no significant differences regarding comparability see the relevant guidance on bioavailability/bioequivalence). For herbal medicinal product comparative disintegration data may be acceptable.
Justification for not submitting a new bioequivalence study according to the relevant guidance on Bioavailability/bioequivalence.
Identification method for any new colorant, where relevant.
Sample of the new product, where applicable.
Either a Ph. Eur. Certificate of Suitability for any new component of animal susceptible to TSE risk or where applicable, documentary evidence that the specific source of the TSE risk material has been previously assessed by the competent authority and shown to comply with the scope of the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathies via Human and Veterinary Medicinal Products. (SEE FULL DESCRIPTION IN GUIDELINE)
If intended for use in food producing animal species, proof that the excipient is classified according to Article 14(2)(c) of Regulation (EC) No 470/2009 of the European Parliament and the Council of 6 May 2009 laying down Community procedures for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin, or, if not, justification that the excipient does not have pharmacological activity at the dose at which it is administered to the target animal.
Proof that the proposed site is appropriately authorised for the pharmaceutical form or product or manufacturing operation concerned. (SEE FULL DESCRIPTION IN GUIDELINE)
Where relevant, the batch numbers, corresponding batch size and the manufacturing date of batches (larger than/equal to 3) used in the validation study should be indicated and the validation data presented, or validation protocol (scheme) to be submitted.
The variation application form should clearly outline the “present” and “proposed” finished product manufacturers as listed in the application form.
For semisolid and liquid formulations in which the active substance is present in non-dissolved form, appropriate validation data including microscopic imaging of particle size distribution and morphology or any other appropiate imaging technique.
Declaration by the Qualified Person. (SEE FULL DESCRIPTION IN GUIDELINE)
Direct comparison of the present process and the new process.
Declaration that relevant stability studies have been started under VICH conditions, as appropriate, (with indication of the batch numbers concerned) and relevant stability parameters have been assessed. (SEE FULL DESCRIPTION IN GUIDELINE)
Where relevant the batch numbers, corresponding batch size and the manufacturing date of batches (larger than/equal to 3) used in the validation study should be indicated or validation protocol (scheme) be submitted.
The results of stability studies that have been carried out under VICH conditions. (SEE FULL DESCRIPTION IN GUIDELINE)
Justification for not submitting a new bioequivalence study according to the relevant Guidance on bioavailability/bioequivalence, if appropriate.
Description of the analytical methodology, a summary of validation data, revised specification for impurities (if applicable).
Study of equivalence of the materials and the impact on production of the final material and impact on behaviour (e.g. Dissolution characteristics) of the finished product.
Appropriate data on the new packaging (comparative data on permeability e.g. for O2, CO2 moisture).
Samples of the new container/closure where applicable.
Description, detailed drawing and composition of the container or closure material.
Re-validation studies have been performed in case of sterile products terminally sterilised. The batch numbers of the batches used in the re-validation studies should be indicated, where applicable.
In case of a change in the headspace or a change in the surface/volume ratio, a declaration that the required stability studies have been started under VICH conditions. (SEE FULL DESCRIPTION IN GUIDELINE)
Justification for the new pack-size, showing that the new size is consistent with the dosage regimen and duration of treatment as approved in the summary of product characteristics.
Results of appropriate real time stability studies (covering the entire shelf life) conducted in accordance with the relevant stability guidelines on at least two pilot scale batches of the finished product in the authorised packaging material and/or after first opening or reconstitution, as appropriate; where applicable, results of appropriate microbiological testing should be included.
In case of an addition of a manufacturing site, the variation application form should clearly outline the “present” and “proposed” manufacturers as listed in the application form.
Where applicable, a document providing information of any materials falling within the scope of the Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products including those which are used in the manufacture of the active substance/excipient. (SEE FULL DESCRIPTION IN GUIDELINE)
Where applicable, for active substance, a declaration by the Qualified Person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the QP of each of the manufacturing authorisation holders listed in the application as responsible for batch release. (SEE FULL DESCRIPTION IN GUIDELINE)
Description, detailed drawing and composition of the device material and supplier where appropriate.
Samples of the new device where applicable.
The variation application form should clearly outline the “present” and “proposed” VAMF EMA Certificate (code number) in the MA dossier. When applicable, the variation application form should clearly list also all the other VAMFs to which the medicinal product refers even if they are not the subject of the application.
Attached to the cover letter of the variation application: a reference to the Commission Decision concerned with the annexed Summary of Product Characteristics, Labelling or Package Leaflet.
A declaration that the proposed Summary of Product Characteristics, Labelling and Package Leaflet is identical for the concerned sections to that annexed to the Commission Decision.
Attached to the cover letter of the variation application: a reference to the agreement/assessment of the competent authority.
Attached to the cover letter of the variation application: a reference to the procedure where the wording for one of the active substances was approved.
Attached to the cover letter of the variation application: proof of authorisation of the legal status change (e.g. reference to the Commission Decision concerned)
Justification for the deletion of the target species
A confirmation that the related signal has been submitted in the Union Pharmacovigilance database, in the module for Veterinary Signal Management (VSM) submissions (IRIS). The procedure number for the VSM submission in IRIS (e.g. EMA/VS/XXXXXXXXXX) will suffice.
The veterinary signal assessment report for MAHs in line with the relevant template available on the EMA website, and any references or supporting documentation.
Amendment of the relevant section(s) of the dossier, including revised product information as appropriate.
A declaration by the qualified person (QP) of each of the manufacturing authorisation holders listed in the application, where the active substance is used as a starting material, and a declaration by the gualified person of each of the manufacturing authorisation holders listed in the application as responsible for batch release. These declarations should state that the active substance manufacturer(s) referred to in the application operate in compliance with the detailed ...
A declaration by the qualified person (QP) responsible for batch certification stating that the active substance manufacturer(s) referred to in the marketing authorisation operate in compliance with the detailed guidelines on good manufacturing practice for starting materials. A single declaration may be acceptable under certain circumstances (see the note under variation no. Q.II.b.1).
A declaration from the marketing authorisation holder (and the ASMF holder as appropriate) that the changes to the manufacturing methods are only those necessitated by scale-up or downscaling, e.g. use of different-sized equipment, that the change does not adversely affect the reproducibility of the process, that it is not the result of unexpected events arising during manufacture or because of stability concerns and that the specifications of the active substance/intermediates remain the same.
A declaration from the marketing authorisation holder (and the ASMF holder, where applicable) that the starting material (specifications and analytical procedures) and that the synthetic route, quality control procedures and specifications of the active substance and of the intermediate used in the manufacturing process of the active substance are the same as those already approved. For herbal active substances, a declaration that the geographical source, production ...
A declaration from the marketing authorisation holder or the ASMF holder as appropriate that the required stability studies have been started under ICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. Assurance should also be given that the studies will be finalised and ...
A declaration from the marketing authorisation holder that an evaluation has been performed and the minor changes do not impact the quality, safety or efficacy of the active substance/finished product (e.g. minor amendments to process description without actual process change, such as details of reagents (e.g. buffers, media preparation). For herbal starting materials/active substances, this evaluation should include a detailed comparison regarding quality determining process characteristics ...
A declaration from the marketing authorisation holder that an evaluation of the concerned manufacturing step(s) has been performed and the minor change does not impact the quality, safety or efficacy of the finished product.
A declaration that the required stability studies have been started under ICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. Assurance should also be given that the studies will be finalised and that data will be provided immediately to the competent authorities if ...
A declaration that the required stability studies have been started under ICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data were at the disposal of the applicant at time of implementation and that the available data did not indicate a problem. Assurance should also be given that the studies will be finalised and that data will be provided immediately to the competent authorities if...
A formal document from a relevant official body (e.g. Chamber of Commerce) in which the new name or new address is mentioned.
A formal document from a relevant official body (e.g. Chamber of Commerce, or if not available, from a competent authority) in which the new name and/or address is mentioned, or a copy of the modified manufacturing authorisation, if available.
A summary and justification of the proposed change(s), clearly describing the present and proposed situation and supporting documentation.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format) including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), and revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a description of the analytical methodology, a summary of validation data, revised specifications.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a description of the analytical methodology, a summary of validation data.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a description of the manufacturing and qualification of the new in-house reference standard.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a detailed drawing of the current and proposed situation, and including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a detailed drawing or written description of the current and new appearance, and including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including a direct comparison of the present process and the new process.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including description, detailed drawing and composition of the container or closure material, and including revised product information as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format), including revised product information, as appropriate.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format). This must contain results of appropriate real time stability studies, conducted in accordance with the relevant stability guidelines on three pilot or production scale batches of the active substance or intermediate in the authorised packaging material.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format). This must contain results of appropriate stability studies conducted in accordance with the relevant stability guidelines on three pilot scale batches(*) of the finished product in the authorised packaging material and/or two batches after first opening or reconstitution, as appropriate. Where applicable, results of appropriate microbiological testing should be included.
Amendment of the relevant section(s) of the dossier (presented in the EU-CTD format). This should include: Updated consolidated holder/finished product manufacturer list of manufacturers of the active substance (section 3.2.S.2.1); Updated single compiled holder/finished product manufacturer active substance specification, including analytical methods and method validation (where the finished product manufacturer uses analytical procedures which are different from the Ph. Eur. ...
Amendment of the relevant section(s) of the dossier, as appropriate.
Amendment of the relevant section(s) of the dossier, including description, drawing and composition of the device material, compatibility and usability studies as appropriate.
An updated product lifecycle management document (PLCM) with relevant sections modified.
Appropriate data on the new packaging (comparative data on permeability, e.g. for O2, CO2 moisture). Where appropriate, proof must be provided that no adverse interaction between the content and the packaging material occurs (e.g. data on migration of components of the proposed material into the content and loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeial requirements or legislation of ...
Appropriate data on the new packaging (e.g. comparative data on permeability e.g. for O2, CO2 moisture). Where appropriate, proof must be provided that no interaction between the content and the packaging material has no impact on the active substance quality (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the pack), including confirmation that the material complies with relevant pharmacopoeia requirements or ...
Attached to the cover letter of the variation application: A reference to the relevant decision of the competent authorities.
Attached to the cover letter of the variation application: reference to the agreement/assessment of the competent authoritiesies.
Batch analysis data (in a comparative tabular format) for at least two batches (minimum pilot scale) [or 3 batches (unless otherwise justified) for biologicals] of the active substance/starting material from the current and proposed manufacturers/sites.
Batch analysis data (in a comparative tabulated format) of at least two batches (minimum pilot scale) [or 3 production batches (unless otherwise justified) for biological excipients] of the excipient manufactured according to the present and proposed process, or by the present and proposed manufacturer, as applicable.
Batch analysis data (in a comparative tabulated format) on a minimum of two batches] manufactured to both the currently approved and the proposed process.
Batch analysis data (in a comparative tabulated format) on a minimum of two production batches manufactured to both the currently approved and the proposed sizes. Batch analysis data of 3 batches (unless otherwise justified) for biological finished product should be available for the proposed batch size.
Batch analysis data (in a comparative tabulated format) on a minimum of two production batches of the active substance or intermediate, as appropriate, manufactured to both the currently approved and the proposed sizes. Batch analysis data of 3 batches (unless otherwise justified) for biological active substance, should be available for the proposed batch size.
Batch analysis data (in a comparative tabulated format) on two production batches of the relevant substance for all analytical procedures in the new specification and additionally, where appropriate, comparative dissolution profile data for the finished product on at least one pilot batch. For herbal finished products, comparative disintegration data may be acceptable.
Batch analysis data on one production batch and two pilot scale batches simulating the production process (or two production batches) and comparative data on the last three batches from the previous site; batch data on the next two production batches should be available on request or reported if outside specifications (with proposed action). Batch analysis data of 3 batches (unless otherwise justified) of the biological finished product, manufactured from the current and ...
Batch analysis data (in comparative tabular format) of at least two batches (minimum pilot scale), of the active substance or intermediate as appropriate, manufactured according to the currently approved and proposed process.
Batch analysis data on two production batches [3 production batches (unless otherwise justified) for biologicals] of the finished product for all specification attributes.
Batch analysis data on two production batches [3 production batches (unless otherwise justified) for biologicals]) of the relevant substance for all specification attributes.
Batch analysis data on two production batches of the active substance for all specification attributes.
Batch analysis data on two production batches of the excipient for all specification attributes [3 production batches (unless otherwise justified) for biological excipients or novel excipients].
Batch analysis data on two production of the finished product for all specification attributes.
Comparative batch analysis data and comparative dissolution profile data of at least two pilot scale batches of the finished product in the current and proposed formulation. For herbal medicinal products where dissolution testing may not be feasible, comparative disintegration data should be provided.
Comparative dissolution data on at least one pilot batch of the current and proposed dimensions (no significant differences regarding comparability see the relevant guideline on Investigation of Bioequivalence). For herbal medicinal product comparative disintegration data may be acceptable.
Comparative study results or comparative analysis results showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure.
Comparative table of current and proposed in-process controls and limits.
Comparative test results, showing that the current in-house reference standard and the proposed one are equivalent.
Comparative validation results (or, if justified, comparative analysis results) showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure unless the new analytical procedure is added as an alternative procedure to a current one.
Comparative validation results or if justified comparative analysis results showing that the current analytical and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure.
Comparative validation results or if justified comparative analysis results showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure.
Comparative validation results, or if justified comparative analysis results showing that the current analytical procedure and the proposed one are equivalent. This requirement is not applicable in case of an addition of a new analytical procedure unless the new analytical procedure is added as an alternative procedure to a current one.
Confirmation and data demonstrating compliance with equivalent quality standard as CE-mark as requested in the ‘Guideline on the scientific data requirements for a PMF’.
Confirmation no changes other than administrative (Type IA) have been implemented.
Confirmation of equivalence of the materials and that there is no impact on the quality of the finished product.
Confirmation of the transfer of the complete PMF documentation since the initial PMF certification to the transferee - signed by both companies.
Confirmation that any anticoagulant solution complies with Ph. Eur. requirements.
Confirmation that standard contract between blood establishment/centre and PMF holder is in place.
Confirmation that the proposed summary of product characteristics, labelling and package leaflet is identical for the concerned sections to that annexed to the Commission Decision or to the agreement reached by the CMDh (as applicable).
Copy of approved and new (if applicable) specifications of the excipient (as annex to the application form).
Copy of approved end of shelf life finished product specification and where applicable, specifications after dilution/reconstitution or first opening (as annex to the application form).
Copy of approved release and end-of-shelf life specifications (as annex to the application form).
Copy of approved release and end-of-shelf life specifications if relevant (as annex to the application form).
Copy of approved specifications of the active substance (as annex to the application form).
Copy of the current (updated) Ph. Eur. certificate of suitability (CEP) and the letter of access (where available).
Data to demonstrate performance, safety and compatibility of the device, as appropriate.
Data to demonstrate that the new excipient does not interfere with the finished product specification analytical procedures, if appropriate.
Data to demonstrate the suitability of the monograph to control the substance (e.g. a comparison of the potential impurities with the transparency note of the monograph).
Data to validate the proposed change in holding time and/or storage conditions of the intermediate or bulk product (minimum of two batches at pilot or commercial scale). Composition of the intermediate or bulk container should be described and its specification stated. If pilot scale batches are provided, a commitment to verify these data on commercial scale batches. Declaration that the finished product shelf life is set in accordance with ...
Declaration of changes introduced, and variation applications submitted.
Declaration that relevant stability studies have been started under ICH conditions, as appropriate, (with indication of the batch numbers concerned) and relevant stability parameters have been assessed in at least one pilot scale or industrial scale batch. Assurance is given that these studies will be finalised and that the data will be provided immediately to the competent authorities if outside specifications or ...
Declaration that the change is in accordance with the post-approval change management protocol and that the study results meet the acceptance criteria specified in the protocol(*).
Declaration that the change is in accordance with the approved change management protocol and that the study results meet the acceptance criteria specified in the protocol.(*)
Declaration that the changes do not change the overall strategy defined in the protocol and are not broader than the currently approved protocol.
Declaration that the serotype, strain, antigen or coding sequence is no longer appropriate in relation to the epidemiological evolution of the human virus of concern.
Declaration that the finished product specification has only been updated in respect of weight and dimensions.
Declaration that the PMF Certificate and Evaluation Report are fully applicable for the authorised product, PMF holder has provided the PMF Certificate, Evaluation report and PMF dossier to the holder (where the marketing authorisation holder is different to the PMF holder), the PMF Certificate and Evaluation Report replace the previous PMF documentation for this marketing authorisation.
Declaration that the remaining product presentation(s) are adequate for the dosing instructions and duration as mentioned in the summary of product characteristics, and the deletion has been agreed in principle with the Agency.
Declaration that the VAMF Certificate and Evaluation Report are fully applicable for the authorised product, VAMF holder has submitted the VAMF Certificate, Evaluation report and VAMF dossier to the holder (where the marketing authorisation holder is different to the VAMF holder), the VAMF Certificate and Evaluation Report replace the previous VAMF documentation for this marketing authorisation.
Declaration that, while the establishment(s)/centre(s) has remained in non-operational, the epidemiology data have been submitted annually.
Description of the design space in tabular format, and/or in the form of mathematical equation, as relevant, including the variables (material attributes and process parameters, as appropriate) with their proposed ranges and limits.
Description of the sterilisation method and sterilisation cycle. Validation of the sterilisation cycle should be provided if it does not use the reference conditions stated in Ph. Eur..
Description of the sterilisation method and sterilisation cycle. Validation of the sterilisation cycle should be provided if the sterilisation cycle does not use the reference conditions stated in the Ph. Eur.
Details of any new analytical procedure and validation data, where relevant.
Details of any new analytical procedure and validation, where relevant.
Either a Ph. Eur. certificate of suitability for any new component of animal susceptible to TSE risk or where applicable, documentary evidence that the specific source of the TSE risk material has been previously assessed by the competent authority and shown to comply with the scope of the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathies via Human and Veterinary Medicinal Products...
Either a TSE Ph. Eur. certificate of suitability for any new source of material or, where applicable, documentary evidence that the specific source of the TSE risk material has previously been assessed by the competent authority and shown to comply with the current Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products. The information should include the following:...
Epidemiological data for viral markers related to the blood/plasma collection centre to be provided as requested in the Guideline on epidemiological data on blood transmissible infections.
Evidence that the sterilisation has been conducted and validated in accordance with GMP and/or relevant ISO standards, as per guideline on the sterilisation of the medicinal product, active substance, excipient and primary container.
For active substance and excipients, proof of acceptance by WHO or copy of the INN list. If applicable, proof that the change is in line with the Ph. Eur.. For herbal medicinal product, declaration that the name is in accordance with the guideline on declaration of herbal substances and herbal preparations in (traditional) herbal medicinal products.
For biological active substance, a justification that an assessment of comparability is not required.
For biological finished products, a justification that an assessment of comparability is not required.
For herbal active substances a detailed comparison regarding specifications and critical quality attributes (e.g. for extracts: reference to the herbal starting material (incl. scientific binominal name and plant part), physical state, extraction solvent (nature and concentration), drug extract ratio (DER) and manufacturing process (including a stepwise comparison of all manufacturing steps in tabular format).
For herbal active substances/herbal starting materials a detailed comparison regarding their characteristics (e.g. for extracts: reference to the herbal starting material (incl. scientific binominal name and plant part, physical state extraction solvent (nature and concentration), drug extract ratio (DER) and the manufacturing process) should be provided.
For herbal starting material supplier, a GACP declaration from the new supplier (and updated QP declaration if the new supplier is also involved in the herbal active substance manufacture).
For herbal starting material, a detailed comparison regarding specifications and critical quality attributes of the herbal starting material. For herbal active substance, a detailed comparison regarding specifications and critical quality attributes (e.g. for extracts: reference to the herbal starting material (incl. scientific binominal name and plant part), physical state, extraction solvent (nature and concentration), drug extract ratio (DER) and manufacturing process...
For medical devices, updated CE certificate and/or declaration of conformity, if available.
For semisolid and liquid formulations in which the active substance is present in non-dissolved form, appropriate validation data including microscopic imaging of particle size distribution and morphology or any other appropriate imaging technique.
For the addition or replacement of a co-packaged medical device, evidence that relevant standards have been met e.g. EU declaration of conformity or, where applicable, EU certificate, or other appropriate documentation such as summary information confirming compliance with relevant General Safety and Performance Requirements.
For the biosimilar medicinal product aligning the product information with an indication of the reference medicinal product: a justification that the comparability exercise performed for the biosimilar medicinal product is valid for the applied indication.
If the manufacturing site and the immediate packaging site are different, conditions of transport and bulk storage should be specified and validated.
In case of a change in the headspace or a change in the surface/volume ratio, a declaration that the required stability studies have been started under ICH conditions (with indication of the batch numbers concerned) and that, as relevant, the required minimum satisfactory stability data (at least three months stability data for at least one pilot scale or industrial scale batches) were at the disposal of the applicant at time of implementation for a Type IA notification and time of submission of
In case of change in the name of the holder of the Active Substance Master File, updated “letter of access”.
In the case of herbal starting materials, an updated GACP declaration and a declaration from the marketing authorisation holder that the manufacturing process of the herbal active substance remains the same.
Justification for not submitting a new bioequivalence study according to the current guideline on Investigation of Bioequivalence.
Justification for not submitting a new bioequivalence study according to the relevant guidance on Investigation of Bioequivalence.
Justification for not submitting a new bioequivalence study according to the relevant guideline on Investigation of Bioequivalence.
Justification for not submitting a new bioequivalence study according to the relevant Guideline on The Investigation of Bioequivalence, if appropriate.
Justification for the absence of a Notified Body opinion/EU certificate/EU declaration of conformity, based on the risk-assessment performed, which concluded that the proposed change has no significant impact on the medicinal product.
Justification for the deletion, including a statement regarding alternative means to obtain the solvent / diluent as required for the safe and effective use of the finished product.
Justification from the holder for the change in the testing of specification attribute. A change from routine testing to skip/periodic testing is warranted when the manufacturing process is under control and supported by a sufficient amount of historical data compliant with the specification. A change from skip/periodic testing to routine testing should be supported by analytical data demonstrating failure to meet the approved acceptance criteria for the skip tested specification.
Justification from the holder or ASMF holder as appropriate for the new in-process control and limits.
Justification from the marketing authorisation holder or ASMF holder as appropriate of the new specification attribute and the acceptance criteria.
Justification from the marketing authorisation holder or the ASMF holder for the change in the testing of specification attribute. A change from routine testing to skip/periodic testing is warranted when the manufacturing process is under control and supported by sufficient amount of historical data compliant with the specification or as foreseen by relevant guidelines. A change from skip/periodic testing to routine testing should be supported by analytical data demonstrating failure to meet the
Justification from the marketing authorisation holder or the ASMF Holder, as appropriate, of the new specification attribute and the acceptance criteria.
Justification of the new in-process control and limits.
Justification of the new specification attribute and the acceptance criteria.
Justification of the specification attribute and its acceptance criteria.
Justification that the studies modify the risk assessment resulting in equivalent or lower risk.
Justification that there is no impact on the quality criteria of the blood in the container.
Justification/risk assessment from the marketing authorisation holder or the ASMF holder, as appropriate, that the in-process controls are non-significant, or that the in-process controls are obsolete.
Justification/risk assessment from the marketing authorisation holder or the ASMF Holder, as appropriate, that the specification attribute is non-significant, or obsolete.
Justification/risk assessment from the marketing authorisation holder or the ASMF holder, as appropriate, that the specification attribute is non-significant, or that the specification attribute is obsolete.
Justification/risk assessment showing that the attribute is non-significant or that it is obsolete.
Justification/risk assessment showing that the in-process control is non-significant or that it is obsolete.
Letter of Authorisation including contact details of the person responsible for communication between the competent authority and the PMF holder - signed by the transferee.
Letter of Undertaking to fulfil all open and remaining commitments (if any) - signed by the transferee.
List of testing site(s) where the test is currently used and a list of testing centre(s) where the kit will be used.
Proof of acceptance (by WHO) or copy of the ATC Code list.
Proof of establishment of the new holder (Excerpt of the commercial register and the English translation of it) - signed by both companies.
Results of consultation with target patient groups (user test or bridging report).
Results of the studies performed and any other supporting documentation in accordance with the post-approval change management protocol.
Re-validation studies have been performed in case of sterile products. The batch numbers of the batches used in the re-validation studies should be indicated, where applicable.
Revised product information, as appropriate.
Statement that the testing is performed following the same SOPs and/or analytical procedures as already accepted.
Suitable evidence to confirm compliance of either the water used in the final steps of the synthesis of the active substance, or the active substance, itself with the corresponding requirements of the guideline on quality of water for pharmaceutical use regarding bacterial endotoxins and microbiological quality.
The analytical procedure transfer protocols in accordance with Eudralex Volume 4 Chapter 6 article 6.39 (which pre-define the acceptance criteria), from the old site to the new site (or new test laboratory).
The content of the product lifecycle management document has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies (e.g. interaction of the different parameters, including risk assessment and multivariate studies, as appropriate) demonstrating where relevant that a systematic understanding of how material attributes and process parameters impact the critical ...
The content of the product lifecycle management document has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies (including risk assessment and multivariate studies, as appropriate) demonstrating where relevant that a systematic understanding of how material attributes and process parameters impact the critical quality attributes of the finished product has been achieved.
The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product and process development studies (including risk assessment and multivariate studies, as appropriate) demonstrating that a systematic understanding of material attributes and process parameters to the critical quality attributes of the finished product has been achieved.
The design space has been developed in accordance with the relevant European and international scientific guidelines. Results from product, process and analytical development studies including risk assessment and multivariate studies or process modelling, as appropriate, demonstrating where relevant that a systematic understanding of how material attributes and process parameters impact the critical quality attributes of the active substance has been achieved.
The product lifecycle management document includes a description of the material attributes, quality attributes and process parameters (or analytical procedure parameters), their proposed limits and ranges, and future variation reporting categories, in a tabular format.
The results of stability studies that have been carried out under ICH conditions, on the relevant stability parameters, on at least one pilot or industrial scale batch, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action).
The results of stability studies that have been carried out under ICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved retest period (with proposed action).
The results of stability studies that have been carried out under ICH conditions, on the relevant stability parameters, on at least two pilot or industrial scale batches, covering a minimum period of 3 months, and an assurance is given that these studies will be finalised, and that data will be provided immediately to the competent authorities if outside specifications or potentially outside specifications at the end of the approved shelf life (with proposed action).
Updated affected sections of the dossier for the medicinal product.
Updated epidemiological data for viral markers related to the blood/plasma collection centre.
Updated product information whenever this is required by the relevant national legislation.
Updated relevant sections and annexes of the PMF dossier including also inspections and audit information.
Updated relevant sections and annexes of the PMF dossier including inspections and audit information, as needed.
Updated relevant sections and annexes of the PMF dossier including inspections and audit information.
Updated relevant sections and annexes of the PMF dossier, including updated information on testing as requested in the 'Guideline on the scientific data requirements for a PMF'.
Valid proof that the proposed site is GMP compliant for the manufacturing and/or testing operation(s) concerned: For a site within the EU/EEA: a copy of manufacturing authorisation(s) or where no manufacturing authorisation exists a certificate of GMP compliance issued within the last 3 years by the relevant competent authority. A reference to the EudraGMP database will suffice. For a third country site where a GMP mutual recognition agreement (MRA) or other relevant agreement...
Valid proof that the proposed site is GMP compliant for the manufacturing and/or testing operation(s) concerned: For a site within the EU/EEA: a copy of the current manufacturing authorisation or where no manufacturing authorisation exists a certificate of GMP compliance issued within the last 3 years by the relevant competent authority. A reference to the EudraGMP database will suffice. For a third country site where a GMP mutual recognition agreement (MRA) or other relevant agreement on GMP is
Where applicable, a document providing information of any materials falling within the scope of the Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products, including those which are used in the manufacture of the active substance/excipient. The following information should be included for each such material: Name of manufacturer, species and tissues from which the material is a derivative...
Where applicable, for active substance, a declaration by the qualified person (QP) of each of the manufacturing authorisation holders listed in the application where the active substance is used as a starting material and a declaration by the QP of each of the manufacturing authorisation holders listed in the application as responsible for batch release.
Where appropriate, proof must be provided that no interaction between the medicinal product and the device (part) occurs (e.g. no migration of components of the proposed material into the content and no loss of components of the product into the device), including confirmation that the material complies with relevant pharmacopoeial requirements or legislation of the Union on plastic material and objects in contact with foodstuffs.
Where relevant the batch numbers, corresponding batch size and the manufacturing date of batches (³3) used in the validation study should be indicated or validation protocol (scheme) be submitted.
Where relevant, a commitment of the manufacturer of the active substance to inform the marketing authorisation holder of any changes to the manufacturing process, specifications and analytical procedures of the active substance.
A declaration from the marketing authorisation holder (and the ASMF holder, where applicable) that there is no change in qualitative and quantitative impurity profile or in physico-chemical properties, that the synthetic route remains the same and that the specifications of the active substance or intermediates are unchanged
Valid proof that the proposed site is GMP compliant for the manufacturing and/or testing operation(s)concerned: For a manufacturing site within the EU/EEA: a copy of the current manufacturing authorisation. A reference to the EudraGMP database will suffice; For a third country site where a GMP mutual recognition agreement (MRA) or other relevant agreement is in place between the country concerned and the EU: a proof of GMP compliance issued within the last 3 years...