M 4 QCommon Technical Document for the …

1 European Medicines Agency 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 85 75 Fax (44-20) 75 23 70 40 E-mail: EMEA 2006 Reproduction and/or distribution of this Document is authorised for non commercial purposes only provided the EMEA is acknowledged July 2003 CPMP/ICH/2887/99 - quality ICH Topic M 4 Q common Technical Document for the registration of Pharmaceuticals for Human Use - quality Step 5 common Technical Document FOR THE registration OF PHARMACEUTICALS FOR HUMAN USE quality OVERALL SUMMARY OF MODULE 2 AND MODULE 3: quality (CPMP/ICH/2887/99 - quality ) TRANSMISSION TO CPMP July 2000 RELEASE FOR CONSULTATION July 2000 DEADLINE FOR COMMENTS September 2000 TRANSMISSION TO CPMP FOR INFORMATION November 2000 RELEASE FOR INFORMATION November 2000 NUMBERING AND SECTION HEADERS EDITED FOR CONSISTENCY AND USE IN E-CTD AS AGREED BY ICH STEERING COMMITTEE September 2002 TRANSMISSION TO CPMP AND RELEASE FOR INFORMATION February 2003 DATE FOR IMPLEMENTATION July 2003 Note: The sequence of M4 common Technical Document for the registration of Pharmaceuticals for Human Use is: M4 - Organisation of common Technical Document M4 quality - quality overall summary of Module 2 and Module 3.

2 quality M4 Safety - Nonclinical Overview and Nonclinical Summaries of Module 2 and Organisation of Module 4 M4 Efficacy - Clinical overview and Clinical summary of Module 2 and Module 5: Clinical Study reports EMEA 2006 2 The Document as presented may be subject to further editorial changes and is for information only. Details on how to prepare a submission dossier based on the CTD format including information on the content of Module I are included in the revision of the Notice to Applicants. EMEA 2006 3 common Technical Document FOR THE registration OF PHARMACEUTICALS FOR HUMAN USE: quality quality OVERALL SUMMARY OF MODULE 2 MODULE 3: quality TABLE OF CONTENTS MODULE 2: common Technical Document SUMMARIES ..7 : quality OVERALL SUMMARY (QOS).

3 7 INTRODUCTION ..7 DRUG SUBSTANCE (NAME, MANUFACTURER) ..7 General Information (name, manufacturer) ..7 Manufacture (name, manufacturer) ..7 Characterisation (name, manufacturer) ..8 Control of Drug Substance (name, manufacturer)..8 Reference Standards or Materials (name, manufacturer) ..8 Container Closure System (name, manufacturer)..8 Stability (name, manufacturer) ..8 DRUG PRODUCT (NAME, DOSAGE FORM)..8 Description and Composition of the Drug Product (name, dosage form) ..8 Pharmaceutical Development (name, dosage form) ..9 Manufacture (name, dosage form)..9 Control of Excipients (name, dosage form)..9 Control of Drug Product (name, dosage form) ..9 Reference Standards or Materials (name, dosage form).

4 9 Container Closure System (name, dosage form) ..9 Stability (name, dosage form) ..9 Facilities and Equipment (name, manufacturer)..9 Adventitious Agents Safety Evaluation (name, dosage form and manufacturer) ..9 Excipients ..10 REGIONAL MODULE 3 : quality ..11 TABLE OF CONTENTS OF MODULE 3 ..11 BODY OF EMEA 2006 4 DRUG SUBSTANCE (NAME, MANUFACTURER)..11 General Information (name, manufacturer) ..11 Nomenclature (name, manufacturer) ..11 Structure (name, manufacturer) ..11 General Properties (name, manufacturer) ..12 Manufacture (name, manufacturer) ..12 Manufacturer(s) (name, manufacturer) ..12 Description of Manufacturing Process and Process Controls (name, manufacturer).

5 12 Control of Materials (name, manufacturer) ..13 Controls of Critical Steps and Intermediates (name, manufacturer)..14 Process Validation and/or Evaluation (name, manufacturer) ..14 Manufacturing Process Development (name, manufacturer)..14 Characterisation (name, manufacturer) ..15 Elucidation of Structure and other Characteristics (name, manufacturer) ..15 Impurities (name, manufacturer)..15 Control of Drug Substance (name, manufacturer)..15 Specification (name, manufacturer) ..15 Analytical Procedures (name, manufacturer)..15 Validation of Analytical Procedures (name, manufacturer) ..16 Batch Analyses (name, manufacturer).

6 16 Justification of Specification (name, manufacturer) ..16 Reference Standards or Materials (name, manufacturer) ..16 Container Closure System (name, manufacturer)..16 Stability (name, manufacturer) ..16 Stability Summary and Conclusions (name, manufacturer) ..16 Post-approval Stability Protocol and Stability Commitment (name, manufacturer) ..16 Stability Data (name, manufacturer) ..16 DRUG PRODUCT (NAME, DOSAGE FORM) ..17 Description and Composition of the Drug Product (name, dosage form) ..17 Pharmaceutical Development (name, dosage form) ..17 Components of the Drug Product (name, dosage form) ..17 Drug Substance (name, dosage form).

7 17 Excipients (name, dosage form) ..17 Drug Product (name, dosage form) ..18 EMEA 2006 5 Formulation Development (name, dosage form) ..18 Overages (name, dosage form) ..18 Physicochemical and Biological Properties (name, dosage form) ..18 Manufacturing Process Development (name, dosage form) ..18 Container Closure System (name, dosage form)..18 Microbiological Attributes (name, dosage form)..18 Compatibility (name, dosage form) ..18 Manufacture (name, dosage form)..18 Manufacturer(s) (name, dosage form)..18 Batch Formula (name, dosage form)..19 Description of Manufacturing Process and Process Controls (name, dosage form) 19 Controls of Critical Steps and Intermediates (name, dosage form) ..19 Process Validation and/or Evaluation (name, dosage form).

8 19 Control of Excipients (name, dosage form)..19 Specifications (name, dosage form) ..19 Analytical Procedures (name, dosage form) ..19 Validation of Analytical Procedures (name, dosage form) ..20 Justification of Specifications (name, dosage form) ..20 Excipients of Human or Animal Origin (name, dosage form)..20 Novel Excipients (name, dosage form) ..20 Control of Drug Product (name, dosage form) ..20 Specification(s) (name, dosage form) ..20 Analytical Procedures (name, dosage form) ..20 Validation of Analytical Procedures (name, dosage form) ..20 Batch Analyses (name, dosage form)..20 Characterisation of Impurities (name, dosage form)..20 Justification of Specification(s) (name, dosage form) ..20 Reference Standards or Materials (name, dosage form).

9 21 Container Closure System (name, dosage form) ..21 Stability (name, dosage form) ..21 Stability Summary and Conclusion (name, dosage form) ..21 Post-approval Stability Protocol and Stability Commitment (name, dosage form)..21 Stability Data (name, dosage form) ..21 Facilities and Equipment (name, manufacturer)..21 EMEA 2006 6 Adventitious Agents Safety Evaluation (name, dosage form, manufacturer) ..22 Excipients ..23 REGIONAL INFORMATION ..23 LITERATURE REFERENCES ..23 EMEA 2006 7 MODULE 2: common Technical Document SUMMARIES : quality OVERALL SUMMARY (QOS) The quality Overall Summary (QOS) is a summary that follows the scope and the outline of the Body of Data in Module 3. The QOS should not include information, data or justification that was not already included in Module 3 or in other parts of the CTD.

10 The QOS should include sufficient information from each section to provide the quality reviewer with an overview of Module 3. The QOS should also emphasise critical key parameters of the product and provide, for instance, justification in cases where guidelines were not followed. The QOS should include a discussion of key issues that integrates information from sections in the quality Module and supporting information from other Modules ( qualification of impurities via toxicological studies discussed under the CTD-S module), including cross-referencing to volume and page number in other Modules. This QOS normally should not exceed 40 pages of text, excluding tables and figures. For biotech products and products manufactured using more complex processes, the Document could be longer but normally should not exceed 80 pages of text (excluding tables and figures).