cgmp Update Presented by: Karen Ginsbury For IFF, Denmark November 2016

Transcription

1 cgmp Update Presented by: Karen Ginsbury For IFF, Denmark November 2016

2 Trainer quiz 10 quickies

3 Grumpy Cat Last IFF Update: March 2016 What has changed? What is your most challenging issues related to GMP compliance / audit / inspection findings OR Related to your company s quality system write them down and share ONE of them initially

4 My Grumpy Cat Data Integrity and governance Learning management for competency (training / training effectiveness / competency / on the job coaching / qualification less lecturing more tailored teaching of individuals / needs) HUMAN RESOURCES should be responsible (Karen s opinion) There should be a skills / knowledge / functions matrix for every employee in the company identify: what they bring to the company (new hire) with respect to education (academic); work experience and what training they have had and then based on the job description assigned to them, a learning matrix is prepared and filled. Effectiveness of CAPAs and changes we know we aren t that effective, the regulators have started to drive us nuts about effectiveness checks and we don t really know how to do that - for CAPA: recurrence is one measure, indicating I failed; BUT also tie in some kind of check after corrective action has been taken e.g. increased review, oversight and checking - for changes: comparability protocol with acceptance criteria and CPV we carry on our process validation to show no statistically significant change

5 My Grumpy Cat Supply chain overview (pedigree) for QPs where did the starting material for the starting material of the starting material come from and how is it transported and how is it secured from bad people who want to forge it. The LOGISTICS/SUPPLY CHAIN/PURCHASING dept are responsible (Karen s opinion) for providing the pedigree rather than the QP chasing after it

6 What are the 9 chapters of Part 1 1. Pharmaceutical Quality System 2. Personnel and Organization 3. Facilities and Equipment 4. Documentation 5. Production and Packaging 6. Quality Control 7. Outsourced Operations 8. Complaints, Product Quality Defects and Recalls 9. Self Inspection

7 What s Troubling the Inspector Based on warning letters and what Karen hears at conferences and based on IWG Workplan and FDA guidance agenda #1 Data integrity #2 Quality Culture (???) (attitude of most senior management??) leadership? #3 Quality Metrics? #4 Drug Shortages

8 EU GMPs What changed in last 12 months Part 1 Cap 3: Premises and Equipt Cap 5: Production Cap 8: Complaints, Recalls Effective: 01 Mar Mar Mar 2015 Annex 15 Annex 16 Annex 17 RTRT Excipients Risk Assessment 01 Oct Apr 2016 Draft for comments through Dec Mar 2016

9 EU GMPs What changed in last 12 months Concept paper on MAH responsibilities Concept paper on revision of annex 1 Data integrity Q&A + PICs + WHO

10 NEW NEW NEW MAH responsibilities concept paper

11 NEW NEW but implemented? Excipients Directive

12 Not so NEW GDP for Active Substances

13 GMP / GDP Inspectors Working Group

14 FDA Guidance Agenda 2016

15 3 Premises and Equipment 3.6 as part of improved guidance on prevention of cross-contamination involving Cap 5

16 5 - Production

17 8 Complaints, Quality Defects and Product Recalls

18 Quality Catastrophe Scale Costs of Quality Least costly Most costly Implement appropriate controls for prevention of catastrophes = effective quality system Prevent receipt of a batch of starting material which does not meet specs Reject a batch of starting material (incoming) Rejection of in-process material / deviation handling Quality defect discovered in-house no impact on previously released batches Complaints defect discovered by customer OR defect discovered inhouse impacts marketed product Recalls

19 Annex 15 Validation

20 Validation and Qualification Grumpy Cats ageing equipment: changing spare parts (obsolence); POLICY decision on the anticipated and reasonable lifetime of equipment in our facilities and a BUDGET and REPLACEMENT schedule. In addition to which we need planned and PREVENTIVE maintenance which cannot be postponed 30 times. The schedule must allow for the AGE of the equipment and have more frequent planned maintenance ageing or dead but won t lie down process stick a KPI for process capability on the PQR and if it is below 1.3 it HAS to undergo troubleshooting Criteria for revalidation transferred from site to site and then new site made changes and had to go back to old process should that process be revalidated? Criteria or process for ongoing verification or demonstrating that you have maintained the validated state

21 Validation and Qualification Grumpy Cats Design of experiments and the time invested effective design of validation and qualification protocols Risk assessments before qualification not good enough Report reviewed / approved far too late! Stick a KPI on number of days till approval and have meetings rather than sending the file from procrastinator to procrastinator

22 Annex 16 final QP Release

23 Let s look at Annex 16 What jumps out?

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

25 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

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

27 Annex 17 Draft RTRT

28 Excipients GMP RA

29 Other US GMPs: 21CFR parts 210, 211, part 11 and part 820 FDA guidances: Quality system guidance vs ICH Q8, 9, 10 Process validation guidance Contract Manufacture QUALITY METRICS

30 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

31 Hot Topics Data Integrity

32 Data Integrity does your company have a Data Governance Policy? MHRA is focused on laboratory Data integrity goes to the heart of a company s culture

33 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

34 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

35 Responsibility vs Authority

36 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

37 What is Quality Meeting requirements all of them all the time and that means defining the requirements = URS / specifications / other

38 Quality is Meeting all the requirements all the time Therefore not meeting the requirements at any time is not quality Don t use high or low quality it cheapens the term

39 What is a Quality System

40 Define Roles President / Chairman of BOD / GM / CEO VP VP Quality and Quality Dept / Unit Everyone

41 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)

42 Have you Heard About ISO 9001:2015? FINAL Sept. 2015

43 Metrics What are metrics define? A metric is measurement of some parameter which provides an indication of the state of control and should allow us to improve / change the process or behavior If you are not going to do anything with the metric please don t measure it

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

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

46 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

47 ICH Q10 PQS Objectives of an Effective QS 1. Facilitate product realization

48 What is Quality Quality is meeting all the requirements all the time which means defining the requirements

49 What is a Quality System Fighting the chaos Investing energy to create an organized, methodical system to ensure we achieve requirements The sum total of the organized arrangements made with the intention of ensuring that product meets all the requirements all the time

50 What is the role of Production Support within the Quality System Product realization is my responsibility a major part of my every day life Implement GMP in our procedures Procedures are followed in real life

51 What is the Role of the Quality Unit within the Quality System To ensure compliance with external and internal guidelines and requirements this is not only the responsibility of the quality unit this is the goal of the QUALITY SYSTEM Batch disposition

52 What is the Role of the Quality Unit within the Quality System Set-up the system Maintain the system Monitor the state of control collect and analyze data Report to management who then need to act in order to ensure improvement

53 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

54 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

55 FDA Metrics

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

57 Optional metric #2

58 Optional metric #2

59 Optional metric #3

60 What Quality Data Would Be Reported

61 What Quality Data Would Be Reported

62 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?

63 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

64 Dashboards

65 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

66 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

67 The Power of Walking the Floor Thoughts?

68 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

69 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

70 In Conclusion Few KEY metrics Define data collection, analysis and presentation in a Data Collection Plan with standardized templates Management review and leadership of the program Follow up and feedback Walk the floor and LISTEN

71 Find me: THANK YOU FOR LISTENING!

72 A metric for internal audits An objective which will change MANAGEMENT behavior (dept heads and VPS) with respect to fixing findings from internal audits [For QA: How long until the report is issued goal: not more than 3 days after the audit] How long to respond to findings How long to implement corrections How effective are the corrections (Recurrent findings)

73 A quality metric for internal audits 1. Time taken from performance of audit until issuance of report I want audit reports to be issued in a more timely manner 2. How many times is an audit postponed before performance I want the department head to take audits seriously 3. Time from report issuance to receipt of CAPAs As above (#2) 4. Number of repeat observations I want effective CAPAs and I don t want unintended consequences of 3 above (rapid responses which are not implemented) REPORT ON ALL OF THE ABOVE IN MANAGEMENT REVIEW MEETING