EMPROVE For Raw and Starting Materials & For Filtration Devices and Single Use Systems. Jan Thomsen Warsaw, November 15 th, 2016

Transcription

1 EMPROVE For Raw and Starting Materials & For Filtration Devices and Single Use Systems Jan Thomsen Warsaw, November 15 th, 2016

2 2

3 Content Emprove - An Introduction Emprove for Raw and Starting Materials Emprove for Filtration Devices and Single Use Easy Access through Emprove Suite Outlook Backup 3 lemprove

4 Content Emprove - An Introduction Emprove for Raw and Starting Materials Emprove for Filtration Devices and Single Use Easy Access through Emprove Suite Outlook Backup 4 TiEmorove

5 Emprove - An Introduction From chemicals supplier to thought leader in pharma raw materials regulations Organized in CTD format for easy use Based on: A robust quality management system (QMS) Thorough supplier qualification 2015: Emprove Evolution 2004: Merck launches Emprove 2003: CTD format becomes binding for drug registration in Europe 5 Emprove

6 Emprove for pharmaceutical raw materials Evolving and Compounding Regulatory Expectations 6 Emprove

7 Content Emprove - An Introduction Emprove for Raw and Starting Materials Emprove for Filtration Devices and Single Use Easy Access through Emprove Suite Outlook Backup 7 Title of Presentation DD.MM.YYYY

8 Qualification program covers all chapters of the EMPROVE dossier Our quality department comprises: Specification Test monograph Safety data sheet Origin Manufacturing process Impurities Manufacturing process Quality management system Packaging material Stability Analytical data. Certificates TSE/ BSE Allergen Aflatoxin GMO Halal, Kosher 8 EMPROVE

9 Qualification principle Change Control Teams (Purchasing, QC, QA, Product manager) Supplier specifications, batch definition and traceability, production risk details. GMP questionnaires Complete testing according to specification parameter of each batch during entrance control Comprehensive check of impurities, incl. res. solvents, residual metal catalysts. Audits 9 Title of Presentation DD.MM.YYYY

10 Transparency Results of the qualification process (1) Supply chain information Validated change notification system Transparancy about production filling labelling release of product. 1 2 Validated change information system, reflecting quality agreements with customers. Quality self assessment Reflecting qualified GMP Standard Excipients: GMP according to IPEC PQG GMP Guide 3 4 Supplier audit report summary Present basic information of supplier qualification audit. Process materials: DIN ISO 9001 or equivalent API: GMP certificate 10 EMPROVE

11 Transparency Results of the qualification process (2) 1 e-omt 3 Excipact certificate First online online batch specific original manufacturer traceability. Fulfills FDA requirements. EU Falsified Medicines Directive (FMD) 2011/62EU: the holder of the manufacturing authorization shall ensure that the excipients are suitable for use... by verifying the appropriate GMP 2 Stability studies 4 Validation report open part Long term stability studies supporting customer by defining their testing strategy and definition of in use stability. Complete transparency of about release of testing of multiple pharmacopoeial grade material. 11 EMPROVE

12 Quality data Support of currently upcoming guidelines 1 Elemental impurities 2 Product quality report ICH Q3D will come in force in 2016, 2017 and 2018 in EU US and Japan for new and final drugs. ICH Q3D The applicants risk assessment can be facilitated with information about potential elemental imouritites e.g. by supplier of drug substance and excipients. The Emprove Operational Excellence Dossier provide extensive data of 3 batches to facilitate applicant s risk assessment and to optimize applicant s testing strategy. Product quality review process is required for APIs and drugs. On a voluntary base Merck offers an extract of internal product quality process for Emprove products. Formalized risk assessment EU 2015/C 95/02, After having implemented the appropriate GMP, this has to be continuously verified, this can be done e.g. with trend analysis. The Emprove Operational Excellence Dossier provide trend analysis within the product quality report. 12 EMPROVE

13 Drug Substance and Excipients: Reporting of Elemental Impurities No guidance is given on reporting of EI for starting materials Information of supplier may be utilized: The applicant s risk assessment can be facilitated with information about the potential elemental impurities provided by suppliers of drug substances, excipients, container closure systems, and manufacturing equipment. Section 5.5 Evaluation (ICH Q3D) i June 2015 Copyright Merck KGaA, Darmstadt Germany

14 Our approach to ICH Q3D Elemental Impurity information Impurity Profile Information on intentionally added elements Shows all 24 elements of ICH Q3D Tested on 3 batches Levels above option one limit (calculated to a daily intake of ten gram of drug) will be implemented in our specification Example 15 Emprove

15 Elemental Impurities CoA and Specification Materials with Elemental Impurities not above Option 1 limit need no additional justification for use. 16 Emprove update status

16 Emprove Product Quality Report Demonstrated consistent product quality Content Survey about quality and selected results over defined period. Summary information about batches Trend analysis (minimum 5 batches) Trend in Ongoing stability studies Changes Diagrams of significant parameters Fits to: e.g. EU Guideline for the formalized risk assessment for excipient GMP Chapter 4.1 proposed activities: III. Survey and trend analysis 17 Emprove

17 Why a new Emprove? Suitability and GMP About 400 products in three usage categories: EMPROVE exp suitable for use as excipient /2016 EU 2015/C 95/02 Formalized risk assessement to ascertain appropriate GMP for Excipients used in human drugs EMPROVE bio suitable for use in biopharmaceutical production EMPROVE api suitable for use as an active pharmaceutical ingredient. 2 Only pharmaceutical producer can define appropriate GMP. 3 Evaluation EMPROVE Adapting portfolio 18 EMPROVE Products Dr. Erhard Lührs September 2014

18 Emprove for chemicals Addressing different risk levels ESSENTIAL Designed for moderate risk levels Former EMPROVE exp EXPERT Addresses higher risk applications Former EMPROVE bio Lowest microbiological and endotoxin levels specified API All products produced in Europe according to the ICH Q7 standard 19 Emprove

19 Emprove for chemicals The three pillars of the new Emprove program Supporting customers risk assessment Customer convenience Portfolio Dossiers Suite 20 Emprove

20 Emprove for chemicals Dossier library Material Qualification Dossier Free of charge In line with CTD chapter 3 quality (adapted for excipients) [2.3*] General information Manufacture Characterization Control of drug substance Reference standard Materials Container closure system Stability Information to start a material qualification Quality Management Dossier Quality Self Assessment [2.6*] Audit report summary [2.6*] Supply chain Information [2.3*] Stability data [2.3*] Operational Excellence Dossier Answers questions during risk assessment Quality Management + Operational Excellence Dossiers can be purchased together for Product quality report [4.1 *] Elemental impurity information Analytical procedure Supports process optimization Full Access to all dossiers of the Emprove Library One time registration Up to 5 addresses per company Access for two years 23 Emprove [*] No. of supported chapter of Guideline on formalized risk assessment for excipients EU/C 95/

21 Content Emprove - An Introduction Emprove for Raw and Starting Materials Emprove for Filtration Devices and Single Use Easy Access through Emprove Suite Outlook Backup 24 Title of Presentation DD.MM.YYYY

22 Emprove for Filtration and Single-Use Evolving and Compounding Regulatory Expectations UPCOMING: ICH Q12 Technical and Regulatory Considerations for Lifecycle and Change Management USP <661.3> Plastic Components and Systems Used in Pharmaceutical Manufacturing 25 Webinar: Risk Based Assessment of Sterilizing Grade Filters

23 Emprove for Filtration and Single-Use Pricing 26 Material Qualification Dossier General information Manufacturing flow chart Product characterization and qualification Specification, release criteria Materials of construction Extractables summary Residual solvents statement Elem. Impurities statement Regulatory statements (AO, Allergens ) Information to start a material qualification 26 Quality Management Dossier (coming soon) Operational Excellence Dossier (coming soon) Free of charge Available for Expres SHC and Express SHC SHC Cartrige filters Quality Self Assessment Audit report summary Supplier and CMO management Shelf life testing and results Critical raw materials Answers questions during risk assessment Quality Management + Operational Excellence Dossiers can be purchased together for 7500 Full Extractables profile Elemental impurity information Analytical procedure Supports process optimization Full Access to all dossiers of the EMPROVE library 20,000 One time registration Up to 5 adressses per company Access for two years

24 Emprove Whats in it for You? Internationally recognized structured format CTD Format Access to Emprove Suite Access to all dossiers in one place Excipact and RX- 360 reports Multi-compendial specs and method validation Third Party Audit Reports Crossvalidated compendial methods Convenience Largest portfolio in Industry Supplier audit report Supply chain & mfg process info Ensuring appropriate GMP at our suppliers Chain of custody and manufacturing flow chart ICH Q3D + product consistency Elemental Impurity + Product quality report eomt Online information of original manufacturers 27

25 Thank You! Any Questions?

26 Content Emprove - An Introduction Emprove for Raw and Starting Materials Emprove for Filtration Devices and Single Use Easy Access through Emprove Suite Outlook Backup 29 Title of Presentation DD.MM.YYYY

27 Emprove Suite Request for Access Go to EMD Millipore.com/emp rove Fill the form and process will be initiated. You will get a contract by separate from to be signed. 30 Emprove

28 Emprove Suite Enter the Emprove Suite 2 Alternatives after Login 1 Go to my account 2 Enter product name or code 31 Emprove

29 Emprove Suite Search your product 2 Find available dossiers 32 Emprove

30 Additional Questions?

31 EMPROVE Backup

32 Regulatory Background Latest Requests from Authorities Falsified Medicine Directive ICH Q3D Elemental Impurities 35

33 Falsified Medicine Directive (FMD) Guidelines on Formalized Risk Assessment Published by the EU Commission on March 21, 2015 Provide guidelines on the formalized risk assessment to ascertain the appropriate good manufacturing practice for excipients of medicinal products for human use Deadline for implementation: March 21,

34 Risk assessment guidelines for excipients The guideline is split into three sections: Determination of appropriate GMP based on the use and type of the excipient Determination of Excipient Manufacturer s Risk Profile Confirmation of Application of appropriate GMP 37

35 Appropriate GMP for excipients Drug Product Manufacturer Determine and assess appropriate GMP for each excipient Internal: Consider use and type Use of excipient Route of administration Function in the formulation Potential impact on critical quality attributes of the drug product Quantity, daily intake Type: Composite excipients Known quality defects External: Excipient Manufacturer Assess potential for contamination Impurities TSE, viral safety microbiological or endotoxin/pyrogens Use of dedicated equipment and / or facilities Environmental control and storage conditions Stability of Excipients Supply chain complexity 38

36 Finalized Finalized Valid Current Regulations on Elemental Impurities Europe EMEA/CHMP/SWP/4446/2000 In force since Sept 2008 (for new drug products) USA USP chapter <232>, <233>, Applicable as of 1 Jan International EU: June 2016 new DP Dec 2017 existing DP ICH Q3D: Finalized Dec 2014 To be implemented for new drug products; Transitional period 36 M for exist. products

37 Scope of ICH Q3D draft guideline ICH Q3D Elemental Impurities include additional contaminants that occur naturally or are introduced by interaction -> Risk Assessment Elements added intentionally (reagents, catalysts) already in the scope of the EMA guideline 40 New aspect: Elemental impurities may occur naturally (e.g. starting materials from natural sources) Scope of ICH Q3D New aspect: Elements introduced by interaction (e.g. with process materials, equipment)

38 New Obligations to Drug Product Manufacturers Prepare a risk assessment Develop risk based controls for Elemental Impurities Consider max daily dose and route of administration of drug product 41

39 Our approach to ICH Q3D Elemental Impurity information Impurity Profile Information on intentionally added elements Shows all 24 elements of ICH Q3D Tested on 3 batches Levels above option one limit (calculated to a daily intake of ten gram of drug) implemented in our specification Example 42 Emprove

40 Elemental Impurities CoA and Specification Materials with Elemental Impurities not above Option 1 limit need no additional justification for use. 43 Emprove update status

41 The new EMPROVE

42 Emprove for chemicals Suitability and GMP About 400 products in three usage categories: EMPROVE exp suitable for use as excipient /2016 EU 2015/C 95/02 Formalized risk assessement to ascertain appropriate GMP for Excipients used in human drugs EMPROVE bio suitable for use in biopharmaceutical production EMPROVE api suitable for use as an active pharmaceutical ingredient. 2 Only pharmaceutical producer can define appropriate GMP. 3 Evaluation EMPROVE Adapting portfolio 45 EMPROVE Products Dr. Erhard Lührs September 2014

43 Emprove portfolio Addressing different risk levels ESSENTIAL Designed for moderate risk levels Former EMPROVE exp EXPERT Addresses higher risk applications Former EMPROVE bio Lowest microbiological and endotoxin levels specified API All products produced in Europe according to the ICH Q7 standard 46

44 Emprove for chemicals Dossier library Material Qualification Dossier Free of charge In line with CTD chapter 3 quality (adapted for excipients) [2.3*] General information Manufacture Characterization Control of drug substance Reference standard Materials Container closure system Stability Information to start a material qualification Quality Management Dossier Quality Self Assessment [2.6*] Audit report summary [2.6*] Supply chain Information [2.3*] Stability data [2.3*] Operational Excellence Dossier Answers questions during risk assessment Quality Management + Operational Excellence Dossiers can be purchased together for Product quality report [4.1 *] Elemental impurity information Analytical procedure Supports process optimization Full Access to all dossiers of the Emprove Library One time registration Up to 5 addresses per company Access for two years 47 Emprove [*] No. of supported chapter of Guideline on formalized risk assessment for excipients EU/C 95/

45 Emprove for Filtration and Single-Use Pricing 48 Material Qualification Dossier General information Manufacturing flow chart Product characterization and qualification Specification, release criteria Materials of construction Extractables summary Residual solvents statement Elem. Impurities statement Regulatory statements (AO, Allergens ) Information to start a material qualification 48 Quality Management Dossier (coming soon) Operational Excellence Dossier (coming soon) Free of charge Available for Expres SHC and Express SHC SHC Cartrige filters Quality Self Assessment Audit report summary Supplier and CMO management Shelf life testing and results Critical raw materials Answers questions during risk assessment Quality Management + Operational Excellence Dossiers can be purchased together for 7500 Full Extractables profile Elemental impurity information Analytical procedure Supports process optimization Full Access to all dossiers of the EMPROVE library 20,000 One time registration Up to 5 adressses per company Access for two years

46 Emprove Suite Convenient 24/7 access Online access to all dossiers of the full Emprove portfolio One time registration up to 5 addresses per company Access for two years Facilitates your effort to collect information. 49

47 Emprove Benefits are Available for a Large Portfolio Internationally recognized structured format CTD Format Access to Emprove Suite Access to all dossiers in one place Excipact and RX- 360 reports Multi-compendial specs and method validation Third Party Audit Reports Crossvalidated compendial methods Convenience Largest portfolio in Industry Supplier audit report Supply chain & mfg process info Ensuring appropriate GMP at our suppliers Chain of custody and manufacturing flow chart ICH Q3D + product consistency Elemental Impurity + Product quality report eomt Online information of original manufacturers 50