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

Copyright Nelson Laboratories 2011

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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

10Copyright Nelson Laboratories

2011

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


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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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Supplier Rating


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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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Health & Medicine

Incorporate Domestic and International Regulations for Effective GMP Auditing