Wirkstoffdokumentation & CEP- Verfahren

Transcription

1 Wirkstoffdokumentation & CEP- Verfahren Dr. Wolfgang Herzog AGES PharmMed, Institut Zulassung & Lifecycle Management AGES-Gespräch Am Pulsschlag des Arzneimittelwesens Das Institut LCM Österreichische Agentur für Gesundheit und Ernährungssicherheit GmbH

2 Documentation of Drug Substance Guideline of requirements for active substances in the quality part of the dossier (CHMP/QWP/297/97 Rev. 1): -Classification of active substances - Feasible ways to submit the required information 2

3 Documentation of Drug Substance New active substances Existing active substances not described in Ph. Eur./pharmacopoeia of EU member state Existing active substances described in Ph. Eur./ pharmacopoeia of EU member state 3

4 Documentation of Drug Substance Inorganic substances Herbal drugs and herbal drug preparations Organic substances (isolated from material of animal/human origin) Organic substances (synthetic or semi-synthetic or isolated from herbal sources or microorganism) 4

5 Documentation of Drug Substance Certificate of Suitability (CoS/CEP) Active Substance Master File (ASMF): Full Documentation as part of the MA application 5

6 Documentation of Drug Substance Chemistry of Active Substances (3AQ5A) Chemistry of New Active Substances (CPMP/QWP/130/96 Rev. 1) 6

7 Documentation of Drug Substance 3.2.S Drug Substance 3.2.S.1 General Information 3.2.S.2 Manufacture 3.2.S.3 Characterisation 3.2.S.4 Control of Drug Substance 3.2.S.5 Reference Standards or Materials 3.2.S.6 Container Closure System 3.2.S.7 Stability 7

8 Active Substance Master File (ASMF): - Nfg on ACTIVE SUBSTANCE MASTER FILE CPMP/QWP/227/02 Rev. 1 Date for coming into operation: "Applicants Part " (AP) and "Restricted Part " (RP) - Structure of the ASMF o human: in CTD format (since 1 st January 2005) o veterinary: according to NtA veterinary format or CTD 8

9 Active Substance Master File (ASMF): Scope: - New active substances - Existing active substances not included in the Ph. Eur. or pharmacopoeia of an EU Member State - Pharmacopoeial active substances Not in the Scope: Biological Substances!!!!! 9

10 Active Substance Master File (ASMF): The EDMF holder should submit to the Applicant: - A copy of the latest version of the AP - A copy of the QOS/ER on the latest version of the AP - Letter of access where this letter has not been sumitted earlier for the product concerned 10

11 Active Substance Master File (ASMF): The EDMF holder should submit to the Competent Authorities: - The EDMF accompanied by a covering letter - Letter of access where this letter has not been sumitted earlier for the product concerned 11

12 Common Technical Document (CTD): 3.2.S Drug Substance S.1 General Information o 3.2.S.1.1 Nomenclature rinn, compendial (Ph. Eur.) name, national approved names (Company or laboratory code) Reference CPMP Guideline: Chemistry of the Active Substance o 3.2.S.1.2 Structure Structural formula, rel. molecular mass o 3.2.S.1.3 General Properties Physicochemical properties (solubility, isomerism, ) 12

13 Common Technical Document (CTD): 3.2.S Drug Substance S.2 Manufacture o 3.2.S.2.1 Manufacturer(s) Name, Address o 3.2.S.2.2 Description of the Manufacturing Process Flow diagram Sequential procedural narrative Alternative processes, reprocessing Operating conditions Yield 13

14 Common Technical Document (CTD): 3.2.S Drug Substance S.2 Manufacture o 3.2.S.2.3 Control of Materials Starting material, solvents, reagents, catalysts, etc. Specifications should be submitted o 3.2.S.2.4 Control of critical steps and intermediates Tests und Acceptance criteria 14

15 Common Technical Document (CTD): 3.2.S Drug Substance S.2 Manufacture o 3.2.S.2.5 Process validation and/or Evaluation aseptic processing sterilisation o 3.2.S.2.6 Manufacturing Process Development Description of any significant changes 15

16 Common Technical Document (CTD): 3.2.S Drug Substance S.3 Characterisation o 3.2.S.3.1 Elucidation of Structure and other Characteristica Unequivocal proof of structure (Elemental analysis, UV/VIS Maxima, IR, 1 H/ 13 C NMR, MS, ) Information regarding Isomerism, Polymorphism (melting point, X-Ray powder diffraction, see EP 5.9), etc. 16

17 Common Technical Document (CTD): 3.2.S Drug Substance S.3 Characterisation o 3.2.S.3.2 Impurities Impurity profile: Starting material By-products Degradation products Reagents, ligands and catalysts Residual solvents Inorganic impurities 17

18 Common Technical Document (CTD): 3.2.S Drug Substance S.4 Control of the Active Substance (see EP-Monograph Substances for Pharmaceutical Use 01/2008:2034) o 3.2.S.4.1 Specification o 3.2.S.4.2 Analytical Procedures o 3.2.S.4.3 Validation of Analytical Procedures 18

19 Common Technical Document (CTD): 3.2.S Drug Substance S.4.1 Specification: minimum requirements o o o o o o o Description Identification Assay and/or potency Impurities - identified Impurities - unidentified Impurities -total Impurities 19

20 Common Technical Document (CTD): 3.2.S Drug Substance S.4.1 Specification additional Parameters - (see ICH Q6A- decision trees ) o Physicochemical properties o Particle size o Polymorphic forms (CPMP/ICH/2738/99 does not apply) o Tests for chiral substance (CPMP/ICH/2738/99 does not apply) o Water content o Inorganic impurities o Microbial limits (TAMC/TYMC see EP 5.1.4) 20

21 Common Technical Document (CTD): 3.2.S Drug Substance S.4 Control of the Active Substance o 3.2.S.4.4 Batch Analysis Recent consecutive batches (at least 3 pilot batches) Date of manufacture Batch size and number Place of manufacture Results of analytical determination o 3.2.S.4.5 Justification of Specification 21

22 Common Technical Document (CTD): 3.2.S Drug Substance S.5 Reference standards o Information on the reference standards used for testing of the active substance o Establishing of the reference standards (Primary and Secondary) o Specification 22

23 Common Technical Document (CTD): 3.2.S Drug Substance S.5 Reference standards o A European Pharmacopoeia reference standard is an integral and essential part of the monograph and as such is an official standard that is alone authoritative in case of doubt or disbute (see also chapter 5.12) 23

24 Common Technical Document (CTD): 3.2.S Drug Substance S.6 Container Closure System o Primary packaging material (see CPMP/QWP/4359/03) Details of the materials of construction Chemical name of the material Specification (EP-conformity if applicable) o Secondary packaging material 24

25 Common Technical Document (CTD): 3.2.S Drug Substance S.7 Stability o 3.2.S.7.1 Stability Summary and Conclusion o CPMP/QWP/122/02 Rev. 1 corr o CPMP/ICH/2736/99 (ICH Q1A (R2)) o CPMP/ICH/279/95 (ICH Q1B) 25

26 Common Technical Document (CTD): 3.2.S Drug Substance S.7 Stability o 3.2.S.7.2 Post-approval Stability Protocol and Stability Commitment o 3.2.S.7.3 Stability Data 26

27 Council of Europe 27

28 Certificate of Suitability (CoS/CEP)* Purpose of the procedure Facilitating and simplifying exchanges between the partners to ensure that the quality of substances is guaranteed These substances comply with the European Pharmacopoeia Promotefreemovementof medicines 28

29 Certificate of Suitability (CoS/CEP)* Excluded from the Application: Direct gene products (proteins) Products obtained from human tissues, vaccines and blood products and preparations other biological substances (see list of CMD(h)) 29

30 Application types - Simple certificate (chemical or TSE or herbal product) - Certificate for chemical purity and sterility - Double certificate (chemical and TSE) - Double certificate (chemical and TSE) covering also sterility 30

31 Overview of the procedure - Submission of the dossier - Acknowledgement of receipt - Designation of a rapporteur - Assessment - Notification of the decision - Follow up the Certification of Suitability 31

32 Assessment - Preparation of a report in three parts: - Report A or Confidential report - Report B or Request for revision of the monograph - Report C or Comments for the inspectors 32

33 Certificate of Suitability (CoS/CEP)* Documentation in the MA application: - Copy of the CoS has to be enclosed - Declaration of Access (not mandatory!) - GMP Declaration from the Qualified Person of the Batch Releaser and Manufacturer - Specification of the Applicant (with additional Parameters e.g. physical-chemical characteristics such as particle size) 33

34 Certificate of Suitability (CoS/CEP)* Ländervergleich DE AT ES UK NL BE *CH* FR IT DK FI 4 SE IS CZ HU 6 IE *Canada* 4 4 Gutachter Gutachtertage Quelle: EDQM 34

35 Thank You! Österreichische Agentur für Gesundheit und Ernährungssicherheit GmbH