Quality Agreements with CMO’s
Presented at ASQ Orange Empire Meeting May 13, 2014
By Luke FooSr. Director QA/QC
Spectrum Pharmaceuticals
FDA Guidance
• Contract Manufacturing Arrangements for Drugs: Quality Agreements, Draft Guidance, May 2013
FDA Guidance
• Delineates responsibilities between CMO and client for API, finished drug product, combination products and biologicals
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FDA Guidance
• Does not apply to Type A medicated articles and medicated feeds, medical devices, dietary supplements, and human tissue intended for transplantation.
FDA Guidance
• Applies to commercial manufacturing. Manufacturing includes processing, packing, holding, labeling, testing, and operations of the quality unit.
Definitions
• Owner = contract giver or client
• Contracted Facility = contract acceptor or contractor
Responsibilities
• Owner is responsible for assuring product introduced into interstate commerce is not adulterated or misbranded. Responsible for final product release. (can’t be delegated!) See also 211.22(a)
• Contract Facility is responsible for compliance to cGMPs.
Pop Quiz
• Does this mean that the contracted facility is not responsible for adulteration or misbranding?
Answer
• No, because the contractor is considered an extension of the owner. Both owner and contractor are responsible.
21 CFR Part 820.50
• Purchasing Controls - each manufacturer shall establish and maintain quality requirements that must be met by supplier, contractors, and consultants.
ICH Guidance Q7A GMPs for API’s
• Section XVI: Contract Manufacturers: there should be a written and approved contract or formal agreement between a company and its contractor that defines in details the responsibilities, including the quality measures, of each party.
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EU Guidelines for GMPsVolume 4
• Chapter 7: Outsourced Activities
• section 7.1 states “there shall be a written contract covering the outsourced activities...”
Pharmaceutical Inspection Convention Scheme (PIC/S)
• PE 009-11 (Part I) Guide on GMPs for Medicinal Products, March 2014
• Chapter 7: Contract Manufacture and Analysis states “there must be a written contract between the contract giver and the contract acceptor which clearly establishes the duties of each party”.
International Pharmaceutical Excipients Council (IPEC)
• IPEC Guide for Quality Agreements, 2009
• establishes best practices for Quality Agreements
ICH Q9 Risk Management
• recommends evaluation of suppliers and CMOs through audits and Quality Agreements.
Quality Agreement
• Scope
• Terms (including effective date)
• Dispute resolution
• Change control
• Responsibilities and contacts
Quality Agreement
• Deviations
• Audits by owner and regulatory agencies
• Preventing cross-contamination
• Facilities and equipment validation
Quality Agreement• Material management
• sampling, testing, quarantine, release, specifications, auditing & qualifying suppliers, storage, labeling
• Product
• specifications, release, expiration dating, batch numbering, storage, shipment
Quality Agreement• Laboratory Controls
• procedures for sampling and testing,
• method validation,
• equipment maintenance and calibration,
• stability, and reserve samples
• OOS investigations.
Quality Agreement
• Record retention
• Field alerts and recalls
• Complaints and adverse event reporting
• Subcontractors
• Man-in-the-plant
Quality Agreement
• Owner Responsibility
• transfer of knowledge
• to review and approve SOPs, MBRs, specifications, lab records, validation documents(not all cases), annual reports, investigations, and change controls(not all cases).
Pop Quiz
• If a MBR approved by the owner contains a step that is non-GMP compliant, is the contractor responsible?