Incorporate Domestic and International Regulations for Effective GMP Auditing


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In this presentation from, Janeen Santorosa discusses the best practices for harmonization of GMP auditing, domestic and international regulations for supplier auditing, integration of risk-based practices, and supplier audit practice tools.

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Incorporate Domestic and International Regulations for Effective GMP Auditing

  1. 1. Incorporate Domestic and International Regulations for Effective GMP Auditing Janeen Santarosa Regulatory (Affairs) Specialist II
  2. 2. Presentation Overview • Best Practices for harmonization • Domestic and international guidances, standards and regulations • Integrating valuable risk based and sustainable practices • Supplier audit practice tools Copyright Nelson Laboratories 2011 2
  3. 3. Harmonization Objectives FDA’s goals in participating in international harmonization include: • To safeguard U.S. public health • To assure that consumer protection standards and requirements are met • To facilitate the availability of safe and effective products • To develop and utilize product standards and other requirements more effectively • To minimize or eliminate inconsistent standards internationally Copyright Nelson Laboratories 2011 3
  4. 4. Benefits… • We are ultimately responsible for assuring the quality and compliance of our products. • Aligning goals = reaching high levels of performance without excessive costs or redundant or conflicting requirements. • Avoid the risk of service/product failures. • Ensure specifications match supplier capabilities to avoid issues. • Supplier Benefit: Increased knowledge and better understanding of customer expectations. Copyright Nelson Laboratories 2011 4
  5. 5. Harmonized Requirements • Comparison Chart outlining supplier qualification • Similarities but with different applications include: • ICH-Manufacturers of intermediates and/or API’s should have a system(s) in place for evaluating suppliers of critical material. Materials should be purchased against an agreed specification from supplier or suppliers approved by the quality units. • GHTF-When selecting potential suppliers the manufacturer should investigate their business and operational capability. Select potential suppliers according to predefined criteria and the results of capability investigations. Copyright Nelson Laboratories 2011 5
  6. 6. Best Practices • Developing a risk based sustainable approach • Systems for managing and controlling suppliers include: • Qualification • Audits (paper/onsite), third-party certification) • Assessments (intervals) • Agreements (quality/change) • Monitoring (continuous) Copyright Nelson Laboratories 2011 6
  7. 7. Audits • Comparison Chart outlining supplier audits • Similarities but with different applications include: • GHTF - Depending on the risk of the supplied product/service, the manufacturer may plan and perform periodic supplier re-evaluations, regardless of whether problems have been identified. • TGA - Period Review: As part of the qualification process a program for Periodic Review should be established. Copyright Nelson Laboratories 2011 7
  8. 8. Audits Base supplier audits on type of risk (e.g. service provided, supplies purchased, third party certifications). Definitions: • GHTF/SG4/N33 “critical supplier” is a supplier delivering materials, components, or services that may influence the safety and performance of the product. • ICH Q7: “Critical describes a process step, process condition, test requirement, or other relevant parameter or item that must be controlled within predetermined criteria to ensure that the API meets its specification”. • ICH Q9: “Risk is the combination of the probability of occurrence of harm and the severity of the harm to the patient or consumer”. Copyright Nelson Laboratories 2011 8
  9. 9. Audits • Rate supplier audits on risk-based process approach. • Risk level drives the relation of supply/supplier. The level of action addresses the supplier situation individually and provides measureable controls around the supplier. • Tailor internal resources: Identify supplier risk during receipt inspection, QC verification, in-process inspection and final inspection. Copyright Nelson Laboratories 2011 9
  10. 10. Audits Example of Risk Levels: • Level 1: The highest risk suppliers that have a critical impact on the quality or availability of your product • Level 2: Significant risk suppliers that have a direct impact on your product, alternatives are available • Level 3: Moderate risk suppliers that have an indirect impact on the product • Level 4: Low risk suppliers that have no product impact 10 Copyright Nelson Laboratories 2011
  11. 11. Audits Example: Supplier audits based on risk level – Action Copyright Nelson Laboratories 2011 11 Level 1 Action High risk supplier/service provider On-site audit Level 3 Action Moderate risk supplier Written audit Level 4 Action Low risk supplier Limited assessment / Audit not applicable
  12. 12. Audits Audit Frequency Audit frequency is established based on risk and performance (annual, biennial, triennial) Frequency may change based on detection inputs from assessment tools. Increase audit frequency for adverse findings Dependent on the status of third party certifications Monitor supplier certifications = ensure qualification programs are maintained Copyright Nelson Laboratories 2011 12
  13. 13. Assessments Copyright Nelson Laboratories 2011 13
  14. 14. Assessments • Comparison Chart outlining supplier assessments • Similarities but with different applications include: • ICH Q10-Monitor and review the performance of the contract acceptor or the quality of the material from the provider • EU Volume 4 Part II-Have system for evaluating suppliers of critical materials, monitor • GHTF-Depending on risk of suppliers may plan and perform periodic re-evaluations Copyright Nelson Laboratories 2011 14
  15. 15. Agreements • Agreements ensure the quality of purchased products/services. • Quality Agreements = Agree to the QMS expectations, define responsibility • Change Agreements = Notification requirements of changes in order to assess impact to your process/product. • Service Agreements • Purchase Order Copyright Nelson Laboratories 2011 15
  16. 16. Agreements • Comparison Chart outlining supplier agreements • Similarities but with different applications include: • EU Volume 4 Part II-Formal agreement that defines/details GMP responsibilities, quality measures of each party • 21 CFR 820.50-Establish and maintain purchasing data with specified requirements, notification of change agreements • Health Canada-Written agreement outlining the specific responsibilities of each party involved. Specify that the raw material vendor must inform the drug fabricator of any changes in the processing or specifications of the raw material. Copyright Nelson Laboratories 2011 16
  17. 17. Supplier Rating • Supplier Scorecard results in improved supplier performance, minimizes risk and sustains the supply base. • Develop scorecards with corporate goals/objectives in mind. • Quality, compliance, service, on-time delivery, cost • “Where performance is measured, performance improves”. Copyright Nelson Laboratories 2011 17
  18. 18. Supplier Rating • Supplier scorecards are used to measure and monitor supplier performance. • Identify attributes, agreements, factors and attribute ratings • Ensure the “highest factor” is what is most important to your business needs • Establish ratings: 90-100=Excellent, 75-89=Satisfactory, less than 75=Unsatisfactory • Identify corrective action if applicable Copyright Nelson Laboratories 2011 18
  19. 19. Supplier Rating Copyright Nelson Laboratories 2011 19
  20. 20. Integrating valuable risk based and sustainable practices • Ensure process is sustainable with growth of supplier base and adheres to standards necessary to support quality and compliance. • Pre-defined decision tree for consistent determinations and justifications • Risk based decision tree helps maintain consistency and provides justification as to why the audit type, or lack thereof is chosen. Copyright Nelson Laboratories 2011 20
  21. 21. Integrating valuable risk based and sustainable practices Example: Decision Tree •EXAMPLE Copyright Nelson Laboratories 2011 21 Risk Assessment for Calibration Subcontractor Action Certified to ISO 17025? Yes= Obtain cert for file No= Written audit Risk Assessment for Critical Component Action Custom Built product? Yes=On-site audit No= Go to next question Certified to ISO? (applicable standard) Yes= Obtain cert for file No= Written audit
  22. 22. Summary of Tools • Objectives and goals • Audits, assessments, agreements • Risk Management: Ongoing supplier monitoring • Audit selection based on supplier risk profile • Supplier rating (Scorecard) • Comparison tables • Domestic and international reference tool Copyright Nelson Laboratories 2011 22
  23. 23. Domestic and International References • GHTF/SG3/N17:2008- Control of Suppliers • GHTF/SG3/N15R8- Risk Management Principles in a QMS • GHTF/SG4/N84:2010 Guidelines for Regulatory Auditing of Quality Management Systems of Medical Device Manufacturers Part 5: Audits of Manufacturer Control of Suppliers • Health Canada - Good Manufacturing Practices (GMP) Guidelines GUI-001 • ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients • ICH Q10 Pharmaceutical Quality System • EU Guidelines to GMP Part II Basic Requirements for Active Substances used as Starting Materials • ISO 13485 (Harmonized quality system standard adopted in Europe for medical devices) • ISO 9000:2008 Principle 8: Mutually beneficial supplier relationships • Japan Pharmaceutical Affairs Law (JPAL Ordinance 169) • 21 CFR Part 210/211 21 CFR 820 Quality System Regulation(QSR) • FDA’s “Guidance for Industry Quality Systems Approach to Pharmaceutical cGMP Regulations, • Australian Government- Technical Guidance on the Interpretation of Manufacturing Standards • PIC/S Guide to Good Manufacturing Practice for Medicinal Products Copyright Nelson Laboratories 2011 23
  24. 24. Questions? Contact information: Janeen Santarosa Nelson Laboratories , Inc. Phone: (801) 290-7671 Thank you! Copyright Nelson Laboratories 2011 24