SPECIFIC REQUIREMENTS FOR MODULES OF MARKETING AUTHORIZATION APPLICATION DOSSIERS
Requirements for marketing authorization application dossier of generic medicinal products
a) Applications for essentially similar (generic) medicinal products shall be submitted in accordance with this section and taking into account the Rules of performing bioequivalence studies of medicinal products in the Eurasian Economic Union subject to approval by the Commission.
The choice of the reference product for bioequivalence studies shall be made in accordance with the Rules of performing bioequivalence studies of medicinal products in the Eurasian Economic Union subject to approval by the Commission.
Bioequivalence of a generic medicinal product with the original medicinal product shall be demonstrated by appropriate bioavailability studies in accordance with the Rules of performing bioequivalence studies of medicinal products in the Eurasian Economic Union subject to approval by the Commission.
The summary of product characteristics and medication guide of a generic medicinal product shall correspond to the summary of product characteristics and medication guide of the original medicinal product. Where additional therapeutic indications, posology or routes of administrations are claimed in the medication guide of the generic medicinal product in comparison with that of original medicinal product, appropriate clinical data shall be provided.
6.1. Module 1
Applicant shall provide in Module 1.8.2 a concise document (up to 5 pages), summarizing the grounds and evidence used for demonstrating that the medicinal product for which an application is submitted, is a ‘generic’ of a reference medicinal product. This summary should include details on the medicinal product, its qualitative and quantitative composition in active substance(s), its pharmaceutical form and its safety/efficacy profile of the active substance(s) in comparison to the active substance(s) of the reference medicinal product, as well as details related to the bio-‐availability and bio-‐equivalence, where necessary, of the medicinal product concerned.
In specific cases, Risk Management Plan might be necessary.
When certain elements are not included, a justification for its absence should be provided in the respective section of the marketing authorization application dossier.
6.2. Module 2
1 The non-‐clinical and clinical overviews should particularly focus on the following elements:
2-‐ A summary of impurities present in batches of the active substance(s) (and where relevant decomposition products arising during storage) as proposed for use in the product to be marketed;
3‐ An evaluation of the bioequivalence studies or a justification why studies were not performed;
4 -‐ An update of published literature relevant to the substance and the present application. It may be acceptable for articles in "peer review" journals to be annotated for this purpose;
5-‐ Every claim in the Summary of Product Characteristics (SPC) not known from or inferred from the properties of the medicinal product and/or its therapeutic group should be discussed in the non-‐clinical/clinical overviews/summaries and substantiated by published literature and/or additional studies;
6-‐ When different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of the active substance of the reference medicinal product are used, additional information providing proof that their safety and/or efficacy profile is not different from the one of the reference medicinal product should be submitted.
6.3. Module 3
A complete Module 3 should be submitted.
MODULE 3: QUALITY
3.1. Table of contents of Module
3 3.2. Basic principles and requirements
3.2.S. Active substance (API); for medicinal products containing more than one active substance, the full information shall be provided for each substance
3.2.S.1. General information and information related to the starting and raw materials
3.2.S.1.1 Nomenclature of the API
3.2.S.1.2 Structure of the API
3.2.S.1.3 General Properties of the API
3.2.S.2. Manufacturing process of the active substance
3.2.S.2.1 Manufacturer
3.2.S.2.2 Description of Manufacturing Process and Process Controls
3.2.S.2.3 Control of Materials
3.2.S.2.4 Controls of Critical Steps and Intermediates
3.2.S.2.5 Process Validation and/or Evaluation
3.2.S.2.6 Manufacturing Process Development
3.2.S.3. Characterization of the API
3.2.S.3.1 Elucidation of Structure and other Characteristics
3.2.S.3.2 Impurities
3.2.S.4 Control of the API
3.2.S.4.1 Specification
3.2.S.4.2 Analytical Procedures
3.2.S.4.3 Validation of Analytical Procedures
3.2.S.4.4 Batch Analyses
3.2.S.4.5 Justification of Specification
3.2.S.5 Reference Standards or Materials
3.2.S.6 Container Closure System
3.2.S.7. Stability
3.2.S.7.1 Stability Summary and Conclusions
3.2.S.7.2 Post-‐approval Stability Protocol and Stability Commitment
3.2.S.7.3 Stability Data
3.2.P. Finished medicinal product
3.2.P.1. Description and composition of the finished medicinal product
3.2.P.2. Pharmaceutical development
3.2.P.2.1 Components of the Finished Medicinal Product
3.2.P.2.1.1 Active Substance
3.2.P.2.1.2 Excipients
3.2.P.2.2 Finished Medicinal Product
3.2.P.2.2.1 Formulation Development
3.2.P.2.2.2 Overages
3.2.P.2.2.3 Physicochemical and Biological Properties
3.2.P.2.3 Manufacturing Process Development
3.2.P.2.4 Container Closure System
3.2.P.2.5 Microbiological Attributes
6 3.2.P.2.6 Compatibility
3.2.P.3 Manufacture of the Finished Medicinal Product
3.2.P.3.1 Manufacturers
3.2.P.3.2 Batch Formula
3.2.P.3.3 Description of Manufacturing Process and Process Controls
3.2.P.3.4 Controls of Critical Steps and Intermediates
3.2.P.3.5 Process Validation and/or Evaluation
3.2.P.4 Control of Excipients
3.2.P.4.1 Specifications
3.2.P.4.2 Analytical Procedures
3.2.P.4.3 Validation of Analytical Procedures
3.2.P.4.4 Justification of Specifications
3.2.P.4.5 Excipients of Human or Animal Origin
3.2.P.4.6 Novel Excipients
3.2.P.5 Control of Drug Product
3.2.P.5.1 Specifications
3.2.P.5.2 Analytical Procedures. A draft normative document drawn up in accordance with recommendations subject to approval by the Eurasian Economic Commission
3.2.P.5.3 Validation of Analytical Procedures
3.2.P.5.4 Batch Analyses
3.2.P.5.5 Characterization of Impurities
3.2.P.5.6 Justification of Specifications
3.2.P.6 Reference Standards or Materials
3.2.P.7 Container Closure System
3.2.P.8 Stability
3.2.P.8.1 Stability Summary and Conclusion
3.2.P.8.2 Post-‐approval Stability Protocol and Stability Commitment
3.2.P.8.3 Stability Data
3.2.A Appendices
3.2.A.1 Facilities and Equipment
3.2.A.2 Adventitious Agents Safety Evaluation 3.2.A.3 Excipients
3.2.R Regional Information
3.3. Literature References
6.4. Module 4 and Module 5
The results of the bioequivalence studies performed where appropriate shall be included in section 5.3.1. Equivalence demonstration data for biowaiver shall be included in section
5.3.1.2. Method validation report shall also be submitted. Concentration, pharmacokinetics, and statistical data shall also be provided.
-Investigator’s details including employer, study site and study dates shall be provided in a bioequivalence study report.
-Audit certificates shall be attached to the report, where available.
-In a bioequivalence study report or separate letter, justification for reference product choice shall be provided in accordance the Rules of performing bioequivalence studies of medicinal products in the Eurasian Economic Union subject to approval by the Commission.
Following reference product information shall also be submitted:
-‐ Brand name;
-‐ Strength;
-‐ Dosage form;
-‐ marketing authorization holder;
-‐ Date of marketing authorization;
-‐ Certificate of a marketing authorization number;
-‐ Member State where the reference product is authorized for marketing;
-‐ Batch number;
-‐ Manufacturer’s name
-‐ Shelf life;
-‐ Country where the product has been purchased.
The recommendation of the Expert Committee for Medicinal Products on the reference product choice shall be submitted, where available.
The name and composition of test product, batch size, date of manufacture, and where available expiry data shall be provided.
In an annex to the study report, certificates of analysis of the reference product and test product used in the bioequivalence study shall be included.
An official letter signed by the qualified person on quality and declaring that the quantitative composition and manufacturing process of a test product identical
to the quantitative composition and manufacturing process of the product to be marketed.
When different chemical forms (salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives) of the active substance of the reference medicinal product are used, additional information providing proof that their safety and/or efficacy profile is not different from the one of the reference medicinal product should be submitted following the Common Technical Document structure.
Non-‐clinical and clinical data on generic medicinal product generated where necessary shall be included in the appropriate sections of
Module 4 & Module 5.
Bioavailability studies shall be conducted where a generic medicinal product fulfils criteria provided in the Rules of performing bioequivalence studies of medicinal products in the Eurasian Economic Union subject to approval by the Commission.
Where the active substance of an essentially similar medicinal product contains the same therapeutic moiety as the authorized product associated with a different salt/ester complex/derivative, additional data (bibliographic overview) or non-‐clinical and/or clinical data (bioavailability data) demonstrating that there is no change in the pharmacokinetics, pharmacodynamics and/or in toxicity shall be provided. Should this not be the case, this association shall be considered as a new active substance.
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