11/02/2011 EUGMP the ICH and a "how to" guide on integrating ICH Q9 and Q10 within your current QMS Mark Dignum Contract QP Limited ICH Q9 and Q10 • • • • What is the ICH? What are Q9 and Q10? What do they mean to us? What do we have to do? 1 11/02/2011 The ICH? • International Conference on Harmonisation • EU, USA and Japan • Four areas - Quality, Safety, Efficacy, Multidisciplinary. ICH - Quality • • • • • • • • • • • Q1 Stability Q2 Analytical Validation Q3 Impurities Q4 Pharmacopoeias Q5 Quality of Biotechnology Products Q6 Specification Q7 GMP for Active Pharmaceutical Ingredients Q8 Pharmaceutical Development Q9 Quality Risk Management Q10 Pharmaceutical Quality System Q11 Development and manufacture of drug substance 2 11/02/2011 EU GMP and ICH? • Some ICH Guidelines are already more than a little familiar • For Example – ICH Q1 defines the stability conditions and requirements that we are familiar with. – ICH Q2 analytical method validation has been the accepted standard for some considerable time. – ICH Q7 has been transposed into EU GMP Part II • Adoption of ICH guidelines is well chartered in the EU. – ICH Q9 is Annex 20 of EU GMP – ICH Q10 incorporated into Part I / GMP Part III ? ICH Q9 • • • • Where is it? What should we do with it? Examples of implementation. Key points 3 11/02/2011 ICH Q9 Quality Risk Management • Annex 20 – Direct transcript of ICH Q9 • Amendment to Chapter 1 of EU GMP Quality Risk Management 1.5 Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively. 1.6 The quality risk management system should ensure that: the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient the level of effort, formality and documentation of the quality risk management process is commensurate with the level of risk Examples of the processes and applications of quality risk management can be found inter alia in Annex 20. ICH Q9 Quality Risk Management • Looks fantastic ... What is it? • What do I need to do? • What can this do for me? 4 11/02/2011 ICH Q9 Quality Risk Management • “The quality risk management system should ensure that…” • Implication here is that a system is required – an SOP would be a good start – What about a smarter approach – A Quality Risk Management Policy – Integrating risk management into our existing forms and processes. ICH Q9 Quality Risk Management 5 11/02/2011 ICH Q9 Quality Risk Management • We already do this ... More or less. • It could be as simple as calling some of the things that we already do risk assessments. – May seem a little petty though it does affect the culture or mind set of the organisation. ICH Q9 EU GMP Chapter 1 1.6 The quality risk management system should ensure that: • the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient • the level of effort, formality and documentation of the quality risk management process is commensurate with the level of risk 6 11/02/2011 ICH Q9 - FMEA • FMEA a worked example: Component Severity Risk of Occurrence Risk of NonDetection Score Reconcilliation Required Carton Labels PILS TE Seal Syringe Labels Packing Tube Labels Filled Syringe Packing tubes Plugs Cartons Shipping Box ICH Q9 - FMEA • Rules and Caveats – Note 0 is not acceptable. – Printed components and components scoring higher than 125 should be reconciled. • Why 125? – 5x5x5=125 Could this be smarter? See later. 7 11/02/2011 ICH Q9 - FMEA Component Carton Labels PILS TE Seal Syringe Labels Packing Tube Labels Filled Syringe Packing tubes Plugs Cartons Shipping Box Severity 9 9 6 9 9 9 9 9 9 5 Risk of Occurence 5 3 4 3 2 1 1 1 1 1 Risk of NonDetection Score 8 360 8 216 4 96 2 54 2 36 1 9 1 9 1 9 1 9 1 5 Reconcilliation Required X X X X X ICH Q9 - FMEA Acceptability Score – Another Approach. Conclude to schedule an audit when, – – – – Compliance/Severity: Safety & Efficacy = medium (3) or more Compliance/Severity: Availability = major (4) or more Complexity: Probability = indirect use for patient (2) or more History: Detectability = 3 years ago (4) or more This would result in 3 x 4 x 2 x 4 = 96 Basically Have a rationale that you can support – Scientific Knowledge 8 11/02/2011 ICH Q9 Risk Management Techniques • Their are lots of techniques. • Fishbone, HACCP and FMEA are good examples. – Probably enough for many situations • Lots of guidance and examples – Annex to Q9 – ICH Q9 Briefing Pack ICH Q9 – Key Points • It is here!!! • It can be used to your and your companies advantage – integration. • Level of effort is commensurate with the level of risk – Keep it simple when you can. • Think of your company culture – think and practice risk assessment as routine. 9 11/02/2011 ICH Q10 Pharmaceutical Quality System • • • • What is it? Quality Manual CAPA Knowledge Management ICH Q10 Pharmaceutical Quality System 10 11/02/2011 ICH Q10 • The objective is to describe a model for an effective quality management system for the pharmaceutical industry, referred to as the pharmaceutical quality system, that: • Ensures the realization of a quality drug product • Establishes and maintains a state of control • Facilitates continual improvement over the product lifecycle ICH Q10 • Q10 will: – Augment existing GMPs – Provide a bridge between different regional regulations – Complement and facilitate implementation of Q8 “Pharmaceutical Development” and Q9 “Quality Risk Management” 11 11/02/2011 ICH Q10 – Site Master File? 1.8 Quality Manual • A Quality Manual or equivalent documentation approach should be established and should contain the description of the pharmaceutical quality system. The description should include: – (a) The quality policy (see Section 2); – (b) The scope of the pharmaceutical quality system; – (c) Identification of the pharmaceutical quality system processes, as well as their sequences, linkages and interdependencies. Process maps and flow charts can be useful tools to facilitate depicting pharmaceutical quality system processes in a visual manner; – (d) Management responsibilities within the pharmaceutical quality system (see Section 2). ICH Q10 • CAPA System 12 11/02/2011 Q10 - CAPA Pharma industry definition Corrective Action – Fix the batch. Preventative Action - Fix the system. ISO ICH Definitions of CAPA • Corrective Action – Action to eliminate the cause of a detected non-conformity or other undesirable situation. • Preventive Action – Action to eliminate the cause of a potential non-conformity or other undesirable situation. • ISO 9001 has an Additional Category – Correction – Action to eliminate a detected non conformity. • In other words Fix the batch 13 11/02/2011 Q10 - CAPA • Corrective action – Amend SOP – Review System/Process. • Preventive action – Proactively look for things that may go wrong in the future. – Self inspection / trending of incidents. Enablers • Knowledge Management – Deviation systems generally log failure – Near Miss? 14 11/02/2011 Incident Report • Objective of this is to capture the noise and to apply a filter to detect the signals within the noise. • Health and Safety are well ahead of us on this. • Empower department managers to manage quality in their departments. • Resource is deployed were it is going to be required. INCIDENT REPORT - INTERNAL; Part A Incident Number Customer / Supplier: Product (if applicable including strength): Work Order: For Clinical Trials Only: Cubicle / machine Component Batch Number / Lot: Job Batch Number: Leg No: CTS No: Protocol No: DESCRIPTION OF INCIDENT (What, where, when, Qty affected, how discovered etc) IMMEDIATE ACTIONS TAKEN (What, where, who) Reported by: Date: FURTHER INFORMATION Completed by (sign): Date: Incident Categorisation: (what was issue (not root cause)) Pre Production 1 Production 2 Post Production 3 e.g. Pre-production, Low risk, Materials = 1aB Medium b High c Paperwork A Materials B Low Process C a Handling D Equipment E Personnel F Incident category: Further assessment required – Incident Risk Assessment / Corrections Part B required Department Manager: Sign Date YES / NO QA: Sign (delete as applicable) Date A copy of the completed document to be attached to the Batch Documentation if applicable. The original document to be retained by the Quality Assurance Department 15 11/02/2011 Incident Report • Don’t get worked up about root cause – You will not have the resource – Sometimes it isn’t worth the effort. • Trend your incidents – Act on the warning signs – Deploy resources were the knowledge tells you it is required. • Empower the department manager to manage quality in their department. – Maintain a QA oversight. 16 11/02/2011 Knowledge Management • Filter the information from the data. • Act on the information. ICH Q10 • Bring your site master file in from the cold. – Integrate it into your QMS • CAPA – Preventive Action – Proactively looking for continual improvement – Not just waiting for or acting on things that go wrong. • Self inspection • Incident Report • Enablers – Knowledge and Risk Management 17