Supplier Qualification and Regulatory Compliance in International Biopharm Logistics. November 19 th, Copenhagen, 2015

Transcription

1 Supplier Qualification and Regulatory Compliance in International Biopharm Logistics November 19 th, Copenhagen, 2015

2 Pharmaceutical Quality Management Partner Selection and Qualification Outsourcing and Potential Pitfalls 2

3 Pharmaceutical Quality Management The world has changed The area of quality management is undergoing a significant change in the pharmaceutical industry: Spotlight is falling on the PQS (Pharmaceutical Quality System) Drive for efficiency within companies Modern science and risk-based thinking and guidance (e.g. ICH* Q8/9/10) instead of one-dimensional compliance focus 3 *International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)

4 Pharmaceutical Quality Management It s not only about the GxP s GMP is only a part of the lifecycle of a medicinal product and only a part of an overall effective Pharmaceutical Quality Management System. Other quality standards are: ISO 9000 ISO 9000 series on general Quality Management ISO 1348 ISO 13485/21CFR820 for Medical Devices ICH Q10 ICH Q10 defining a Pharmaceutical Quality System 4

5 Pharmaceutical Quality Management How the regulators see it Quality assurance is a wide ranging concept which covers all matters which individually or collectively influence the quality of the product. It is the sum total of the organized arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use. Quality assurance therefore incorporates GMP plus other factors outside the scope of the GMP Guide such as CONFIDENTIAL

6 Pharmaceutical Quality Management How the regulators see it Formalised business practices that define management responsibilities for organisational structure, processes, procedures and resources needed to fulfil product/service requirements, customer satisfaction and continual improvement CONFIDENTIAL

7 Pharmaceutical Quality Management Design of a state-of-the-art QMS A Quality Management System has to always to look at the big picture. Is is the sum of all the management arrangements and the top management s total approach to quality. PLAN what they need to do DO what they need to do CHECK that it has been done correctly ACT on the information and results to improve the way it does things 7

8 Pharmaceutical Quality Management Where are we currently? Evolution of regional GMPs 1970s Evolution of ISO 9000 approaches 1980s FDA 21 st Century initiative 2002 ICH Quality Vision / Q8, Q9, Q FDA Quality Systems guide 2006 ICH Q10 Pharmaceutical Quality System 2005/2008 8

9 Pharmaceutical Quality Management Purpose of ICH Q10 ICH Q10 aims to promote a paradigm shift from discrete GMP compliance procedures at each stage of the product lifecycle to a comprehensive quality systems approach over the lifecycle of the product. The objective is to: - Achieve product realizations - Establish and maintain a state of control - Facilitate continual improvement 9

10 Pharmaceutical Quality Management ICH Q10 and GMP s How do they go together? ICH Q10 Will expand existing GMPs with specific PQS elements and management responsibilities Encourage science and risk based approaches Be used together with existing GMPs Cover all stages of the product lifecycle as defined (beyond GMPs) Outsourced activities/purchased materials should be within the scope of the PQS 10

11 Pharmaceutical Quality Management What are the key elements? GMP ISO 9000 ICH Q10 GMP s Management Responsibility Continual Improvement Knowledge Management Quality Risk Management Lifecycle Approach Opportunities 11

12 Why GxP A short history of how GMP evolved Important dates 12

13 GDP Enters the Scene The quality of pharmaceutical products can be affected by a lack of adequate control over the numerous activities which occur during the distribution process. Courier/Transport companies are therefore the (weakest?) link in the supply chain between Manufacturer and point of dispense/use From the Introduction: WHO Technical Report No. 937 Annex 5 (2006) 40 years on meanwhile superseded by No. 957 (2010) 13

14 The Shifting Focus in GDP Distribution is an important activity in the integrated supply-chain management of pharmaceutical products. The nature of risks involved is likely to be similar to that for risks encountered in the Manufacturing environment Counterfeit pharmaceutical products are a real threat to public health and safety. Consequently, it is essential to protect the pharmaceutical supply chain against the penetration of such products. Every activity in the distribution of pharmaceutical products should be carried out according to the principles of GMP, ( ), GSP ( ) and GDP ( ). From the Introduction: WHO Technical Report No. 957 Annex 5 (2010) 14

15 European Changes Original GDP Guideline 94/C 63/03 (1994) Guidelines on Good Distribution Practice of Medicinal Products for Human Use General Guideline with less than 4 pages Legal Basis: Article 10 of Council Directive 92/25/EEC GDP Guideline (2013/C 343/01) - November 23 rd 2013 Greatly expanded 10 Chapters Legal Basis: Article 84 & 85b subs. 3 of Directive 2001/83/EC New Directive 2011/62/EU to fight Counterfeit Medication GDP Guideline (2015/C 95/01) for active substances - March19 th 2015 Good Distribution Practice of active substances for medicinal products for human use Legal Basis: Article 47of Council Directive 2001/83/EC 15

16 The Shifting Focus European changes GDP Guideline Quality Management QMS/Risk Mgt/Mgt Review/Change Control 2. Personnel Responsibilities/Training/Hygiene Key Concept Responsible Person similar to the QP function in GMP (Ch. 2.5) 3. Premises and Equipment Handling/e-Systems/Qualification Ireland United Kingdom Belgium Netherlands France Denmark Germany Luxemburg Austria Sweden Slovenia Poland Czech Republik Hungary Finland Lithuania Estonia Latvia Slovakia Romania 4. Documentation Signatures/Archiving/SOPs Spain Italy Bulgaria 5. Operations Storage/Separation/Destruction FEFO replaces FIFO Portugal Malta Greece Cyprus 16

17 The Shifting Focus European changes GDP Guideline Complaints, Returns, Suspected Falsified Medicinal Products and Medicinal Products Recalls Training for Increased Awareness 7. Outsourced Activities New Chapter/Qualification 8. Self-Inspections New Requirement (3rd Party Audits allowed) Ireland United Kingdom Belgium Netherlands France Denmark Germany Luxemburg Austria Sweden Slovenia Poland Czech Republik Hungary Finland Lithuania Estonia Latvia Slovakia Romania 9. Transportation Risk based approached/ Ship as stored Spain Italy Bulgaria 10. Specific Provisions for Brokers New/Broker Activities defined Portugal Malta Greece Cyprus 17

18 The Shifting Focus European changes GDP Guideline 2013 Clarification Documents regarding Temporary storage and Holding refrigerated goods (August 2014) MHRA:* 36 hours HPRA:** (formerly IMB) 48 hours For longer holds and for any holds of Refrigerated Product a WDA is required Ireland United Kingdom Belgium Netherlands France Denmark Germany Luxemburg Austria Sweden Slovenia Poland Czech Republik Hungary Finland Lithuania Estonia Latvia Slovakia Romania Spain Italy Bulgaria * Medicines & Healthcare products Regulatory Agency ** Health Products Regulatory Authority Portugal Malta Greece Cyprus 18

19 The Shifting Focus European changes GMP Updates Already Implemented 31 January 2013 Chapter 7 EU GMP Guideline revised (Published 11 September 2012) Review and Control of all Outsourced Activities (Risk based approach) Responsibility to assess Legality, Suitability and Competence of subcontractor Continuous assessment of Quality and Performance (identify and implement improvements) -> Audits! Ireland Portugal United Kingdom Spain Belgium Netherlands France Denmark Germany Luxemburg Austria Slovenia Malta Sweden Czech Republik Italy Poland Hungary Finland Lithuania Estonia Latvia Slovakia Romania Bulgaria Greece Cyprus Review of Records and Results and Conformity of Services rendered. 19

20 Pharmaceutical Quality Management Partner Selection and Qualification Outsourcing and Potential Pitfalls 20

21 Partner Selection and Qualification The Holistic Approach of a PQS and nearly all regulatory guidelines agreed upon that the management of outsourced activities and purchased materials must have processes in place which: Assess suitability of contractors / suppliers before use Ensure use of approved suppliers and a defined supply chain Define responsibilities and communication processes for quality related activities Review performance and make improvements 21

22 Partner Selection and Qualification Stepwise approach 1. Define selection parameters 2. Establish weighting criteria for selection parameters 3. Gather information from LSP s via questionnaire 4. Rate LSP on selection parameters 5. Calculate overall weighted score and overall rank 6. Generate short-list of candidates 7. Perform evaluation audit(s) 8. Appoint LSP 22

23 Partner Selection and Qualification Definition of selection parameters (example) Selection Parameter Description Scoring criteria Compliance Certification (SQAS, ISO 9001/14001, CT-PAT, GDP(?), FCPA*) Pharma reference customers Competency Cold Chain, DGR/ADR, Narcotics Customs Dedicated pharma organization QMS available & implemented in organization Certificate # of references # of accounts Own vs. contracted agencies Type of setup Dedicated, shared, none Commercial Offer Completeness of offer # of covered routes Quality of data received 1 to 10 Range of possible services Management by KPIs # of service modes Existing, planned, no Implementation & Development Implementation readyness Timeframe IT Compatibility Track & Trace Capabilities / Milestone reporting Innovation / Drive to change 1 to 10 Full, partly, no Company Size Turnover Global Network Financial situation Own tool, outsourced, none # of sites Profitable, break-even, non-profitable Foreign Corrupt Practices Act GDP Compliance exception for logistics companies Irish Exporters Association / Life Sciences 23

24 Partner Selection and Qualification Gather information via questionnaire Question Supplier 1 Supplier 2 1. Compliance 1. Compliance 1. Compliance 1.1. Have you already been certified (SQAS, ISO 9001/14001, CT-PAT, CEP, GxP etc.) and audited by an offical body in Germany? By whom? Certificates are still valid? 1.2. Which pharmaceutical references do you have for distribution out of Germany? May [company] get in contact with them in order to get convinced from your pharmaceutical experience? 1.3. What is the longest duration of an pharmaceutical customer relationship/contract? 1.4. What is your competence in Cold Chain, DGR/ADR, Narcotics and Legalization? Please state the number of accounts per commodity as mentioned before

25 Partner Selection and Qualification Establish weighting factors Score 1-10 (10 highest) Scoring Selection Criteria Overall Weighting Compliance No Partial Yes 35% Commercial Offer No Partial Yes 30% Implementation / Future Development No Partial Yes 20% Company No Partial Yes 15% Total 100% 25

26 Partner Selection and Qualification Weighted score and overall rank LSP Qualification by Selection Criteria (weighted rating) Company Compliance Commercial Offer Supplier 1 Supplier 2 Supplier 3 Supplier 4 Supplier 5 Supplier 6 Supplier 7 Supplier 8 Implementation/Future Development 26

27 Partner Selection and Qualification Perform evaluation audit Audit shall be carried out at both headquarters and branch office Involve contracted GHA s if applicable Main observations are: - Lack of training - Missing/incomplete documentation >No/not adequate change control > No process for deviation of handling - Non-qualified premises (for GHA s) Establish GDP-compliance plan Make sure that any departure & intermediate hubs are integrated as well! 27

28 Partner Selection and Qualification Areas for pre-go live qualification Quality Agreement Documentation of processes and workflows Change control Deviation handling Training 28

29 Partner Selection and Qualification Documentation of processes and workflows Topics that should be covered include: Contact details Hours of operation Public and company holidays Products and special requirements Packaging components Documentation Labeling Pickup Re-icing Special requirements at origin and destination Pre-alerts Irregularities Tracking & tracing 29

30 Partner Selection and Qualification Training Develop training modules for the specific needs Make sure that both parties talk the same language Include all staff levels for the trainings Keep the ball rolling every change could result in lack of knowledge 30

31 Partner Selection and Qualification Ongoing performance management: deviations 31

32 Complaints Partner Selection and Qualification Monthly performance monitoring (examples) Supplier 1 Supplier 2 Supplier 3 Supplier 4 Supplier 5 Supplier 6 Supplier 7 Supplier 8 other Crosslabelling Customs Damage Handlingtime Loss (partial) Loss (temporarily) Loss (total) Notification other Splitting Wrong destination Measurement per reason code/carrier Measurement of response time 0 =< 5 working days =< 10 working days =< 15 working days =< 20 working days > 20 working days open 32

33 Pharmaceutical Quality Management Partner Selection and Qualification Outsourcing and Potential Pitfalls 33

34 Outsourcing Logistics Services - Pitfalls Quality should not only be done by the Q-Team The selection and qualification of LSP has to involve several departments i.e. logistics, clinical, production, project management, etc. Be aware if outsourced activities are sourced out Most audits of potential vendors are performed at headquarters or nearest branches but clinical trials are conducted across the world and in remote countries or locations. It is necessary to evaluate the suitability also of international branches, agents or drivers. 34

35 Outsourcing Logistics Services - Pitfalls Don t get too obsessed with details Sometimes companies are trying to integrate all details into a Quality Agreement or are pushing for a shipment/transport qualification/validation. If requirements are too tightly defined or get too strict, there is a risk of being unable to react if setups change during trials or irregularities occur during transportation. Don t be too general either Although regulatory requirements are seen as largely compulsory, it is not enough to qualify a vendor once and for all potential tasks. Each project and trial is different or has changed requirements and therefore one should consider to re-qualify vendors for new projects. 35

36 Outsourcing Logistics Services - Pitfalls A questionnaire is no real involvement It is crucial to involve the LSP in project details during the selection and qualification process. Clinical trials get more and more complex these days (i.e. patient recruitment, sample drawing, sensitivity of the shipped commodities, etc.) and require a good understanding of the details at an early stage (example regenerative medicine). Misunderstandings or unclear requirements often result in costly delays of the project. Are all necessary parties (Sponsor/CRO/Lab/CMO/Packer/etc.) directly involved in the selection and qualification process? 36

37 Outsourcing Logistics Services - Pitfalls Share your thoughts and performance reviews Often performance reviews are not frequently shared with the LSP except deviations which require a feedback, i.e. CAPAs. Continuous improvement is only possible by open and frequent exchange among the partners. Set up a frequent exchange process for reports and quarterly or half year reviews 37

38 Choosing the right Supplier Moving towards GxP compliance 1. Quality Systems: Processes and SOPs 2. People: Education/Training/ Experience 3. Technology: Packaging and Monitoring 38

39 Thank you for your attention Michael Fleischer Director, Quality Transport GMP Compliance and QA Manager Certified Lead Auditor

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