PCI Pharmaceutical Consulting The Role of the QP: before & after Annex 16 Presented by: Karen Ginsbury For IFF, Denmark March 2016
Responsibility Authority
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
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
Responsibility vs Authority
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
Better do it now Quality Quality System
What sort of Organization do you work in / with? active and visible support
Grumpy Cat What has changed? What is your most challenging issue?
What s Troubling Me
Certification by a QP and Batch Release: Annex 16 Issued October 2015 Effective 15 APRIL, 2016 Reason for update: SUPPLY CHAIN
Certification by a QP and Batch Release: Annex 16 Reason for update: SUPPLY CHAIN and FALSIFIED MEDICINES ACT, ICH Q8, 9, 10
Let s look at Annex 16 What jumps out?
Annex 16 Batch release pre-requisites Supplier qualification and falsified medicines directive API and excipients: Audits quality agreements CMOs: Production Packaging Other service providers
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
Annex 16 Batch release pre-requisites QP discretion CAPA, investigations And before any of that process mapping and risk assessment!
Risk Assessment for Excipients
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)
GMP / GDP Inspectors Working Group
FDA Guidance Agenda 2015
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 2015 01 Mar 2015 01 Mar 2015 Annex 1 Annex 15 Annex 16 Annex 17 Concept paper on revision 01 Oct 2015 01 April 2016 Draft out
3 Premises and Equipment 3.6 as part of improved guidance on prevention of cross-contamination involving Cap 5
5 - Production
8 Complaints, Quality Defects and Product Recalls
Annex 15 Validation
Annex 17: Real Time Release Testing RTRT 26
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
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
Hot Topics Data Integrity
Data Integrity does your company have a data governance policy?
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
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)
Have you Heard About ISO 9001:2015?
Product control What is the difference Process control
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
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
Where does QP Responsibility Fit? Certification and Release 37
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
115 110 105 100 95 90 115 110 105 100 95 90 85 80 115 110 105 100 95 90 85 80 120 115 110 105 100 95 90 115 110 105 100 95 90 110 105 100 95 90 85 60 40 40 20 60 80 62 42 42 22 62 82 64 44 44 24 64 84 66 46 46 26 66 86 I Chart 68 70 72 Observation I Chart 48 50 52 Observation I Chart 48 50 52 Observation I Chart 28 30 32 Observation I Chart 68 70 72 Observation I Chart 88 90 92 Observation 74 54 54 34 74 94 76 56 56 36 76 96 78 58 58 38 78 98 80 60 60 40 80 100 UCL=111.55 _ X=99.63 LCL=87.71 UCL=112.65 _ X=97.94 LCL=83.23 UCL=112.65 _ X=97.94 LCL=83.23 UCL=116.68 _ X=102.37 LCL=88.05 UCL=111.55 _ X=99.63 LCL=87.71 UCL=111.17 _ 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 115 110 105 100 95 90 85 1 11 21 31 I Chart 41 51 61 Observation 71 81 91 UCL=114.17 _ X=99.95 LCL=85.72 Environment Adapted from slide by Moheb Naser, When at FDA 39 39
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
FDA Metrics
FDA Optional Metrics Related to Quality Culture and Process Capability/Performance
Optional metric #2
Optional metric #2
Optional metric #3
What Quality Data Would Be Reported
What Quality Data Would Be Reported
Measurement is the basis of the Quality Process What do we measure What could we measure What should we measure What can we measure
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
How many metrics BE CAREFUL if everything is important then nothing is important
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
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
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?
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
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
Dashboards
The Power of Walking the Floor Thoughts?
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
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
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
FIND ME AT: karen@pcipharma.com THANK YOU FOR PARTICIPATING