Incorporate Domestic and International Regulations for Effective GMP Auditing
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Transcript of Incorporate Domestic and International Regulations for Effective GMP Auditing
Incorporate Domestic and International Regulations
for Effective GMP Auditing
Janeen SantarosaRegulatory (Affairs) Specialist II
Presentation Overview
• Best Practices for harmonization• Domestic and international guidances,
standards and regulations• Integrating valuable risk based and sustainable
practices• Supplier audit practice tools
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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
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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.
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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.
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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)
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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.
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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”.
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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.
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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
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Audits
Example: Supplier audits based on risk level – Action
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Level 1 ActionHigh risk supplier/service provider On-site audit
Level 3 ActionModerate risk supplier Written audit
Level 4 Action Low risk supplier Limited assessment / Audit not
applicable
Audits
Audit FrequencyAudit 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 findingsDependent on the status of third party certifications
Monitor supplier certifications = ensure qualification programs are maintained
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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
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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
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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.
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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”.
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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
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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.
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Integrating valuable risk based and sustainable practices
Example: Decision Tree
•EXAMPLE
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Risk Assessment for Calibration Subcontractor Action
Certified to ISO 17025? Yes= Obtain cert for fileNo= Written audit
Risk Assessment for Critical Component Action
Custom Built product? Yes=On-site auditNo= Go to next question
Certified to ISO? (applicable standard) Yes= Obtain cert for fileNo= Written audit
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
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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
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Questions?
Contact information: Janeen SantarosaNelson Laboratories , Inc.Phone: (801) [email protected]
Thank you!
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