PCI Pharmaceutical Consulting

Transcription

1 PCI Pharmaceutical Consulting The Role of the QP: before & after Annex 16 Presented by: Karen Ginsbury For IFF, Denmark March 2016

2 Responsibility Authority

3 Responsibility Authority Having the duty to perform a task Being accountable for performing that task Having control over the performance of the task Without additional authorization The power or right to give orders, make decisions, and enforce obedience Within the framework of a company or organization

4 Responsibility YOUR duty to: Keep management informed Request and insist on appropriate resources Take action if authority is not granted Authority must be granted by: Owner Board of directors General manager / CEO Your boss if other than the above AND they must allow you to perform your responsibilities without interference and with appropriate resources

5 Responsibility vs Authority

6 The behaviors, beliefs and values characteristic of a particular group Culture is: Transmitted actively by defining: Mission Goals Metrics Transmitted passively and often subconsciously by behavior, body language, facial expressions and other actions

7 Better do it now Quality Quality System

8 What sort of Organization do you work in / with? active and visible support

9 Grumpy Cat What has changed? What is your most challenging issue?

10 What s Troubling Me

11 Certification by a QP and Batch Release: Annex 16 Issued October 2015 Effective 15 APRIL, 2016 Reason for update: SUPPLY CHAIN

12 Certification by a QP and Batch Release: Annex 16 Reason for update: SUPPLY CHAIN and FALSIFIED MEDICINES ACT, ICH Q8, 9, 10

13 Let s look at Annex 16 What jumps out?

14 Annex 16 Batch release pre-requisites Supplier qualification and falsified medicines directive API and excipients: Audits quality agreements CMOs: Production Packaging Other service providers

15 Annex 16 Batch release pre-requisites Validation and qualification (annex 15) in or out of scope? Computerized systems (annex 11) especially for batch release and inventory in or out of scope? Batch record review and data integrity

16 Annex 16 Batch release pre-requisites QP discretion CAPA, investigations And before any of that process mapping and risk assessment!

17 Risk Assessment for Excipients

18 What s Troubling the Inspector 2015 #1 Data integrity #2 Quality Culture (???) (attitude of most senior management??) leadership? #3 Quality Metrics #4 Drug Shortages #5 Supply chain and falsified medicines (although ties in with #1 closely)

19 GMP / GDP Inspectors Working Group

20 FDA Guidance Agenda 2015

21 What changes in last 12 months EU GMPs Part 1 Cap 3: Premises and Equipt Cap 5: Production Cap 8: Complaints, Recalls Effective: 01 Mar Mar Mar 2015 Annex 1 Annex 15 Annex 16 Annex 17 Concept paper on revision 01 Oct April 2016 Draft out

22 3 Premises and Equipment 3.6 as part of improved guidance on prevention of cross-contamination involving Cap 5

23 5 - Production

24 8 Complaints, Quality Defects and Product Recalls

25 Annex 15 Validation

26 Annex 17: Real Time Release Testing RTRT 26

27 Other US GMPs: 21CFR parts 210, 211, part 11 and part 820 FDA guidances: Draft guidance on quality metrics Quality system guidance vs ICH Q8, 9, 10 Process validation guidance Contract Manufacture

28 Other MHRA Compliance Report program and FDA on quality metrics WHO Guidances PIC/s Guidances USP, European Pharmacopoeia Pulling together the threads and staying updated

29 Hot Topics Data Integrity

30 Data Integrity does your company have a data governance policy?

31 What is Quality Meeting requirements all of them all the time and that means defining the requirements Annex 16 defines requirements for batch certification and release

32 Waivers the act of intentionally [and voluntarily] relinquishing or abandoning a known right, claim, or privilege So a planned deviation or temporary change or special release is a waiver of quality which is meeting requirements (all of them all the time)

33 Have you Heard About ISO 9001:2015?

34 Product control What is the difference Process control

35 Product vs Process Control Product Is controlled at the end of the process and you can do nothing about it you have already made the quality so you test and if it is ok release and if it is not ok you SHOULD reject but you probably get into an OOS fight Process Is controlled through understanding where the variability is and controlling critical process parameters such that all three cakes come out the same even when baked by three different students in three different ovens

36 My bread is fresh and tasty Quality control: the process of producing the product (or service) with the intent of eliminating problems that might result in defects The use of techniques and activities to achieve, sustain and improve the quality of a product

37 Where does QP Responsibility Fit? Certification and Release 37

38 CPPs and CQAs (Critical) Quality Attribute (CQA): A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality [= safety, efficacy, performance] (Critical) Process Parameter (CPP): A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality 38

39 I Chart Observation I Chart Observation I Chart Observation I Chart Observation I Chart Observation I Chart Observation UCL= _ X=99.63 LCL=87.71 UCL= _ X=97.94 LCL=83.23 UCL= _ X=97.94 LCL=83.23 UCL= _ X= LCL=88.05 UCL= _ X=99.63 LCL=87.71 UCL= _ X=98.76 LCL=86.35 CPPs affect CQAs: Reliable / Predictable Known variation / Reduce Variation I N P U T S (X) Individual Value People Equipment Individual Value Measurement Individual Value Individual Value Process y = ƒ(x) Inputs to the process control variability of the Output y Individual Value OUTPUT Materials Individual Value Individual Value I Chart Observation UCL= _ X=99.95 LCL=85.72 Environment Adapted from slide by Moheb Naser, When at FDA 39 39

40 George Bernard Shaw The only man I know who behaves sensibly is my tailor - he takes my measurements anew each time he sees me. The rest go on with their old measurements and expect me to fit them

41 FDA Metrics

42 FDA Optional Metrics Related to Quality Culture and Process Capability/Performance

43 Optional metric #2

44 Optional metric #2

45 Optional metric #3

46 What Quality Data Would Be Reported

47 What Quality Data Would Be Reported

48 Measurement is the basis of the Quality Process What do we measure What could we measure What should we measure What can we measure

49 Data Collection Plans (Protocols) What data NEEDS to be collected (if all data is important then none is important) HOW should it be collected? HOW should it be analyzed? HOW should it be presented? And by who and to whom? 49

50 How many metrics BE CAREFUL if everything is important then nothing is important

51 About Measurement Measurement is the first step that leads to control and eventually to improvement If you can t measure something, you can t understand it If you can t understand it, you can t control it If you can t control it, you can t improve it. H. James Harrington

52 Measureable But Meaningful If a measurement matters at all, it is because it must have some conceivable effect on decisions and behavior If we can't identify a decision that could be affected by a proposed measurement and how it could change those decisions, then the measurement simply has no value Douglas W. Hubbard, How to Measure Anything: Finding the Value of Intangibles in Business

53 Data Collection Plans Who decides what data to collect? How do they make that decision? How do they COMMUNICATE the decision? (what are the tools) How do they educate for compliance with the data collection plan?

54 The toolbox Fabulous 14 Tools Process flow diagram Cause and effect (fishbone) Pareto chart Check sheets Location diagrams Tally count Time plot Scatter diagram Histogram Stem and Leaf Box and Whisper plot Regression analysis Control Chart Conformance chart

55 Dashboards Dashboards are reporting tools that consolidate and arrange numbers, metrics and sometimes scorecards on a single screen Usually tailored for a specific role Display metrics targeted for a single point of view or department

56 Dashboards

57 The Power of Walking the Floor Thoughts?

58 The Power of Walking the Floor You see but you do not observe Just stand and watch a production operation and ask questions about what you see Talk to operators and LISTEN to their comments You must understand the processes you are certifying

59 In Conclusion GMP isn t enough even if c Keep it Simple: Define requirements Use Risk Management to identify risks and prevent them from happening Monitor and improve in a PDCA cycle

60 In Conclusion Stay up to date Stay cool, calm and collected Ask for and make sure you get data and information in order to make informed decisions Have process maps and regularly audit or have links in the chain audited by people you trust Investigate and participate in significant deviations, changes and quality defects / complaints Refuse to be brushed aside with an it s ok Use RISK MANAGEMENT not just take risks

61 FIND ME AT: THANK YOU FOR PARTICIPATING