Developing an Internal Quality Auditing Program

Transcription

1 Developing an Internal Quality Auditing Program SeerPharma Pty Lt Capsig August

2 Critical Success Factors Culture of Compliance Integrate quality systems and risk management principles Well defined and coordinated program (a system) Trained and competent auditors Integrated and effective problem solving practices Effective and efficient reporting processes Tracking system for effective close out of audits Regular reviews of the auditing process Capsig August

3 Audit Intent & Purpose The purpose of the internal quality auditing program is: To ensure that the requirements of cgmp, and product quality are met, To assess compliance with cgmps and company SOPs, To identify corrective and preventive actions. To communicate the current level of compliance, and any necessary remediation actions, to the senior management. HES Ver 8.5

4 Management Responsibility It is critical to establish clear compliance objectives. What are your compliance requirements? How complex is your business / your processes? What changes are you planning? Are you effectively managing risks? Create the Vision Capsig August

5 Establish a Compliance Framework 12 Building Blocks (From AS3806) 1 Top Management Commitment Commitment 4. Objectives Documented & Endorsed 2 Compliance Policy 6. Responsibilities Assigned Organisation & Standards 7. Competency & Training Needs Addressed 5. Compliance Obligations identified & Assessed 3. Appropriate Resources Allocated Organisation & Planning 8. Culture of Compliance Behaviour 9. Compliance Controls in Place Risk Assessment Conducted 10. Compliance Performance Monitored 11 Compliance Demonstrated & Documented Compliance Compliance Program Program Regularly Regularly Reviewed Reviewed and and Improved Improved Maintenance and Improvement Implementation Compliance Systems 06/09 5

6 New Era With New Challenges risk-based concepts and principles of ICH Ref: ICH Q8 Q9 Q10 Compliance Systems 06/09 6

7 MHRA Risk-based inspection process MHRA launched Risk-based inspection process 1 st April 2009 Participating sites are those UK sites that hold a Manufacturing Authorization and 3rd Country sites that are named on a UK Marketing Authorisation Sites will be required to complete a Compliance Report in advance of inspection must identify risks The inspector will identify a risk rating for the site, this will in turn equate to a future inspection frequency. Risk ratings identify the degree of surveillance required within the licensing and inspection program Compliance Systems 06/09 7

8 Well Defined (documented) Program Authority P A D C Competence of Auditors Capsig August

9 Audit Program Written Procedures Planning and scheduling audits; Assuring the competence of auditors and audit team leaders; Selecting audit teams assigning their roles and responsibilities; Conducting audits; Classifying deficiencies Conducting audit follow-up, if applicable; Maintaining audit program records; Monitoring performance/ effectiveness of the audit program; Reporting to top management on the overall achievements of the audit program. Note: For smaller organizations, the activities above can be addressed in a single procedure. Capsig August

10 Audit Program Records Records related to individual audits, such as audit plans, audit reports, nonconformity reports, corrective and preventive action reports, and audit follow-up reports, if applicable; Results of audit program review; Records related to audit personnel covering subjects such as: Auditor competence and performance evaluation, Audit team selection, and Maintenance and improvement of competence. Note: Records should be retained and suitably safeguarded. Capsig August

11 Key Steps for Effective Auditing Scope the system or process to review eg. Liquid filling, HVAC, water purification, change control, complaints etc Define the standards to be applied Determine key questions to seek answers to (audit objectives) Agree the approach Decide which documents and records to review and how many (sampling strategy) Conduct the audit seeking objective evidence for answers to your questions Check observations against the audit objectives HES 6015 Ver

12 Effective Audits: Planning Plan to audit the system / process, not the department or the person: Map the process before you start (from the SOPs) Look for potential weaknesses: Change in responsibilities Decision making steps Identification and documentation of the critical process controls Interfaces with other systems Map the process during the audit (from the auditee(s)) Focus on potential weaknesses HES 6015 Ver

13 Capsig August

14 Effective Audits: Conduct Include a review of electronic audit trails Are not be just a paper exercise: Speak with personnel and observe practices Verify that written procedures are followed Verify that SOP s accurately describe tasks that are performed. Include an evaluation as to the adequacy of laboratory and manufacturing deviations Verify that corrective actions have been implemented Capsig August

15 Audit Sampling Strategy I st /2 nd Sample Both OK OK? > 1 in Error Move on 1 in Error Any special Reason? No 1 in Error Increase Sampling Plan - # depends on significance Deficiency Move on HES 6015 Ver

16 Internal Audit Team Auditors must have appropriate qualifications, training and expertise to determine compliance with current good manufacturing practices. FDA cgmps Auditors must be able to: Identify critical control points and adequacy of manufacturing processes. Identify the cgmp issue(s) and not just present a shopping list of observations. Differentiate issues based on risk. Auditors should have leadership roles in ISO / GMP related activities. Auditors require initial training, regular participation in audits and (r)evaluation with feedback. Capsig August

17 Example FDA Audit Deficiency Employees are not given training in the particular operations they perform as part of their job function. The manufacturer of strongly recommended a training session for the operators. Operators were observed to be operating the equipment incorrectly. GMP training consists of reading the SOP s; employees are not required to demonstrate an understanding of the procedures. Capsig August

18 Example FDA Audit Deficiency There is no assurance that operators performing and verifying critical manufacturing steps are actually performing the checks. The addition of the incorrect drums of material was not detected by production operators who signed and verified that the correct blend was added to the batch. Line clearances were signed as completed prior to the completion of the line clearances. Capsig August

19 An Integrated Quality System HES CAPA Ver

20 Corrective and Preventive Action There should be a procedure for investigating non-compliance with the quality system and for prescribing and verifying corrective action. The procedures should include a description of how records of corrective actions are maintained. Capsig August

21 Investigation Documentation Description of problem/event Scope of problem (other lots/products) Cause of problem/event (if known) Recommendation & Corrective Action Conclusion & Follow-up Management Review & Approval of Investigation Documentation Implementation and Assessment of Corrective Action Plan Capsig August

22 Commitment Tracking Report HES CAPA Ver

23 Top 10 FDA 483s The responsibilities and procedures applicable to the quality control unit are not fully followed. CFR (d) Written production and process control procedures are not documented at the time of performance. CFR (b) Control procedures are not established which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of the drug product. CFR (a) There are no written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess. 21CFR (a) Capsig August

24 Top 10 FDA 483s (cont) Laboratory controls do not include the establishment of scientifically sound and appropriate specifications designed to assure that drug products conform to the appropriate standards of identity, strength, quality and purity. 21CFR.160(d) Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the final specifications prior to release. CFR (a) There is a failure to thoroughly review any unexplained discrepancy whether or not the batch has already been distributed. CFR Capsig August

25 Top 10 FDA 483s (cont) Batch production and control records do not include complete information relating to the production and control of each batch. CFR Employees are not given training in the particular operations they perform as part of their job function. CFR (e) Written procedures are not established for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product. CFR (b) Capsig August

26 Top EMEA Audit Deficiencies 2008 Documentation - quality system elements/procedures Documentation - manufacturing Design and maintenance of premises Documentation - specification and testing Status labelling - work in progress, facilities and equipment Contamination, microbiological - potential for Supplier and contractor audit and technical agreements In-process controls - control and monitoring of production operations Housekeeping - cleanliness, tidiness Environmental monitoring Capsig August

27 To Sum Up: Critical Success Factors Culture of Compliance Integrate quality systems and risk management principles Well defined and coordinated program (a system)trained and competent auditors Integrated and effective problem solving practices Tracking system for timely and effective close out of audits Effective and efficient reporting processes To Auditee(s) To QA To Executive Management Regular reviews of the auditing process Capsig August

28 Melbourne Level Prospect St Box Hill Vic. Ph Training & elearn Sydney Suite 2 level Bay St. Brighton Le Sands NSW 2216 Ph Singapore 10 Anson Road #27-10/11 International Plaza Singapore Ph Validation & CFR 11 Productivity & PAT Integrated solutions Automated QA system Risk Management United Kingdom PO Box 63 York YO61 1WY United Kingdom Ph GxP compliance South Korea #208 Hyosungintelian Kwanyang-dong, Korea Ph Compliance Systems 06/