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• Contract Manufacturing Arrangements for Drugs: Quality Agreements, Draft Guidance, May 2013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 211.22(d)

• States that the responsibilities of the quality unit must be in writing

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.

Pop Quiz

• Are Quality Agreements subject to FDA review?

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?

Answer

• Both owner and contractor are responsible.

Gospel According to Luke

• GMP Training

• Bi-lingual documents

Sample QAA

Thank You!

• You’ve been a wonderful audience!

Luke.foo@sppirx.com