GMP Track 1 Day 2 Session 1 Vendor Assurance

Transcription

1 GMP Track 1 Day 2 Session 1 Vendor Assurance 11 August _POUT

2 This session Three presentations Chapter 6 and 7 - Trevor Schoerie Quality Control Out sourced Activities Draft - FDA Quality Metrics Eoin Hanley Auditing tips / ISO Trevor Schoerie Slide 2 PharmOut 2015

3 Chapter 6 & 7 Quality Control & Outsourced Activities Update Presented by Trevor Schoerie 11 August _POUT

4 Falsified Medicines Directive (FMD) Falsified medicines (the term 'falsified' is used to distinguish the issue from IP violations, so-called 'counterfeits') are a major threat to public health and safety. As falsifications become more sophisticated, the risk that falsified medicines reach patients in the EU increases every year. Falsified medicines represent a serious threat to global health and call for a comprehensive strategy both at European and international level. Slide 4 PharmOut 2015

5 Falsified Medicines Directive (FMD) New measures include: An obligatory authenticity feature on the outer packaging of the medicines : serialisation; Strengthened requirements for control and inspections of plants manufacturing active pharmaceutical ingredients; Strengthened record-keeping requirements for wholesale distributors; Strengthened rules on inspections; The obligation for manufacturers and distributors to report any suspicion of falsified medicines. Slide 5 PharmOut 2015

6 Chapter 6: Quality Control Quality Control is not confined to laboratory operations, but must be involved in all decisions which may concern the quality of the product. The independence of quality control from production is considered fundamental to the satisfactory operations of Quality Control. Also refer to CFR Responsibilities of quality control unit Slide 6 PharmOut 2015

7 Chapter 6: Quality Control The reasons for changes: Inclusion of a new section on technical transfer of testing methods and other items such as Out Of Specification results. Slide 7 PharmOut 2015

8 Chapter 6: Quality Control QC Testing Controls for laboratory reagents, standards and equipment should be based on their use and available stability data Introduced to cover requirements for reference standards These should be suitable for use, certification fully documented and preferably from an officially recognised source Slide 8 PharmOut 2015

9 Chapter 6: Quality Control Standards and media Can use secondary standards if traceable to the primary standard They should be used as per appropriate monographs unless approved otherwise by the national authority Controls for culture media required Micro media and strains should be decontaminated to not pose a crosscontamination risk Media shelf life should be determined and documented Slide 9 PharmOut 2015

10 Chapter 6: Quality Control Technical Transfer Original validation method should be compliant with ICH requirements A gap analysis should be performed to identify additional validation requirements Transfer should be described in a written protocol Slide 10 PharmOut 2015

11 Chapter 6: Quality Control Technical Transfer Specific requirements for Tech Transfer Protocol, including training requirements & transport requirements Acceptance criteria defined and based on current validation study Requirements of other European Guidelines should be addressed if appropriate (e.g. NIR) Protocol deviations should be investigated as per validation deviation methods and technical transfer not closed until complete Slide 11 PharmOut 2015

12 PIC/S PE vs Eudralex Vol. 4 PE 009-8: Ch. 6 Quality Control Sections are generally aligned Sec 6.8 states QC documents to be kept for 1 year after expiry of the batch EU Vol. 4: Ch. 6 Quality Control Sec 6.5 includes cross contamination measures for lab equipment and micro labs Sec 6.7, 6.9 include a requirement for procedures for OOS/OOT Sec 6.8 general reference to Ch. 4 Documentation for batch record retention Slide 12 PharmOut 2015

13 PIC/S PE vs Eudralex Vol. 4 PE 009-8: Ch. 6 Quality Control Sec 6.14 reference sample size for 1 full retest EU Vol. 4: Ch. 6 Quality Control Sec 6.12 includes using QRM for the sampling plan 6.14 diverts to Annex 19 and requires reference sample size for minimum 2 full retests Sec 6.15 distinguishes between validation and verification of methods Slide 13 PharmOut 2015

14 PIC/S PE vs Eudralex Vol. 4 PE 009-8: Ch. 6 Quality Control Sec 6.31 refers to Authorised Person EU Vol. 4: Ch. 6 Quality Control Sec 6.20 is new for reference standard suitability Sec new sections on receipt of reagents, culture media use and prevention of cross contamination of micro media Sec 6.34 refers to Qualified Person Slide 14 PharmOut 2015

15 Chapter 6: Quality Control Independent group responsible for product testing All products and materials are tested as necessary No product is released to customers until its quality is judged as satisfactory Slide 15 PharmOut 2015

16 Chapter 6: Quality Control Good Laboratory Practices (GLP) Stability Quality Control Subject Matter Experts Testing Sampling Slide 16 PharmOut 2015

17 Quality Control Functions Good Quality Control Laboratory Practice The personnel, premises, and equipment in the laboratories should be appropriate to the tasks imposed by the nature and the scale of the manufacturing operations. Contract Analysis can be accepted as per Chapter 7, but should be stated in the Quality Control Records. Slide 17 PharmOut 2015

18 Quality Control Functions Laboratory Documentation should meet the requirements of Chapter 4 and include: Specifications Sampling and testing procedures Analytical Reports Environmental Monitoring data Validation Records for test methods Procedures for and records of the calibration of instruments and maintenance of equipment. Slide 18 PharmOut 2015

19 Documentation Performed in accordance with written procedures detailing methods, equipment, collection containers, storage conditions and special considerations (ie sterile or hazardous materials) Sample containers should have clear labelling of contents Reference samples kept in appropriate conditions Slide 19 PharmOut 2015

20 On-Going Stability Programme Monitoring Stability of medicinal products should be monitored according to a continuous programme will permit the detection of any stability issue. Storage conditions Purpose is to monitor the product over its shelf life and to determine if it will remain within specifications under the labelled storage conditions. Handling OOS Out of specification or significant atypical trends should be investigated and if confirmed, should be reported to the relevant competent authorities. Slide 20 PharmOut 2015

21 Testing Analytical methods should be validated and performed as described in Marketing Authorisations Testing materials should be prepared in accordance with written procedures Calculations should be critically examined Records of testing should be retained Slide 21 PharmOut 2015

22 Technical Transfer Specific requirements for Tech Transfer Protocol, including training requirements & transport requirements Acceptance criteria defined and based on current validation study Requirements of other European Guidelines should be addressed if appropriate (e.g. NIR) Protocol deviations should be investigated as per validation deviation methods and technical transfer not closed until complete Slide 22 PharmOut 2015

23 What does this mean in the QC Lab? Transfer of Testing between: R&D to QC QC lab to other internal QC lab To contract manufacturer To contract test laboratory All require a detailed, documented technical transfer protocol and a completed report before test use in manufacturing Slide 23 PharmOut 2015

24 Why add these requirements? Industry performance poor in: Test transfers poorly documented Assessment of Test transfer not considered Consideration of sample logistics not addressed Protocol deviations not assessed prior to test implementation Assessment of the transfer validation results insufficient Identification of further validation and revalidation requirements not addressed Slide 24 PharmOut 2015

25 Chapter 7 Outsourced Activities In view of the ICH Q10 guideline on the Pharmaceutical Quality System, Chapter 7 of the GMP Guide has been revised in order to provide updated guidance on outsourced GMP regulated activities beyond the current scope of contract manufacture and analysis operations. The title of the Chapter has been changed to reflect this. 4 sections 1. General 2. The Contract Giver 3. The Contract Acceptor 4. The Contract Slide 25 PharmOut 2015

26 Chapter 7 Outsourced Activities General Section 7.3 Where the marketing authorization holder and the manufacturer are not the same, appropriate arrangements should be in place, taking into account the principles described in this chapter. Australia Manufacturer is broad, Labs, Warehousing; Manufacturer, Agent, Sponsor, Distributer Slide 26 PharmOut 2015

27 Chapter 7 Outsourced Activities The Contract Giver From 7.3. The Contract Giver is responsible for assessing the competence of the Contract Acceptor to carry out successfully the work required and for ensuring by means of the contract that the principles and Guidelines of GMP as interpreted in this Guide are followed. To 7.4 The pharmaceutical quality system of the Contract Giver should include the control and review of any outsourced activities. The Contract Giver is ultimately responsible to ensure processes are in place to assure the control of outsourced activities. These processes should incorporate quality risk management principles and notably include: Slide 27 PharmOut 2015

28 Chapter 7 Outsourced Activities The Contract Giver 7.8 The Contract Giver should be responsible for reviewing and assessing the records and the results related to the outsourced activities. He should also ensure, either by himself, or based on the confirmation of the Contract Acceptor s Qualified Person, that all products and materials delivered to him by the Contract Acceptor have been processed in accordance with GMP and the marketing authorisation. Slide 28 PharmOut 2015

29 Chapter 7 Outsourced Activities The Contract Acceptor 7.13 The Contract Acceptor should understand that outsourced activities, including contract analysis, may be subject to inspection by the competent authorities. PIC/S PE009-8 Same In case of contract analysis, the Contract Acceptor should understand that he is subject to inspection by the competent Authorities. Slide 29 PharmOut 2015

30 Chapter 7 Outsourced Activities The Contract Content very similar Technical Agreement, GMP agreement Quality Agreement Slide 30 PharmOut 2015

31 Thank you for your time. Trevor Schoerie Managing Director Slide 31 PharmOut 2015