Vendor Audits and cGMPs

Industries are taking ongoing actions in their response efforts to COVID-19 and this includes being prepared for Regulatory Authority CGMP requirements which include Vendor Audits.

FDA through inspections, recalls, and more can have a significant impact up and down the vendor supply chain. Consequently, companies need to monitor their outsourced operations to ensure they are operating within a defined and documented state of control throughout their vendor supply chain. Uncertainty in the supply chain can increase the risk to product and to patient.  

Vendor audits give more visibility to your company’s supply chain and help to identify potential areas of risk. Audits also provide a level of assurance that your quality standards are being met which in turn protects your brand reputation. All companies, virtual or otherwise, are ultimately responsible for the products they introduce, cause to be introduced or delivered into interstate commerce that may be adulterated or misbranded.

What are some of the high visibility areas that require Vendor Audits?

Contract Manufacturers such as API manufacturers and Contract Testing Laboratories. Both owner and contract manufacturer/testing laboratory are responsible to comply with the cGMPs.  When an owner uses a contract facility, the owner’s quality unit is legally responsible for approving or rejecting drug products manufactured by the contract facility, including final release. 

What are the cGMP regulations regarding Vendors Audits?

Some regulations include 21 CFR parts 210 and 211 e.g. 211.22 (a) which highlights the responsibility of quality control unit (QCU) for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company, and 211.22 (d) which requires that QCU responsibilities shall be in writing and shall be followed.  Additional references are listed below in reference section.

Why are vendor audits a high priority at FDA?

Drug manufacturing encompasses many different operations and activities. One manufacturer may perform all operations and activities or may engage an outside party or parties to perform some or all of the operations and activities under contract. Vendor Audits help to ensure, through review, there is a comprehensive quality system in place to ensure compliance with cGMPs.  

What are some critical elements companies should consider for the assessment and monitoring of Vendors (raw material suppliers, contract manufacturers and testing laboratories, API manufacturers)?

• Establish SOPs for the Assessment and Monitoring of Vendors to include responsibilities of owner and vendor/supplier, criteria for qualification, requalification, and disqualification, and actions to be taken if deviations occur or changes are required.
• Furthermore, implement an approved written quality agreement between parties involved in the contract manufacturing/testing, that can facilitate compliance with cGMP particularly with 21 CFR 211.22 which requires that Quality Unit activities and procedures should be in writing.

What are some key elements of a Quality Agreement?

Per FDA guidance¹ A quality agreement is a comprehensive written agreement between parties involved in the contract manufacturing of drugs that defines and establishes each party’s manufacturing activities in terms of how each will comply with CGMP.  The quality agreement should clearly state which party (the owner or the contract facility or both) carries out specific cGMP activities.  Key elements to be included in a Quality Agreement are;

• Defined Roles and Responsibilities, especially with regards to the Quality Control Unit
• Identification of how Deviations and OOS will be reported, investigated, documented, and resolved in compliance with cGMP including those related to product batches/lot release.
• Identification of how changes that may need to be made to the manufacturing process, equipment, analytical methods, specifications, etc., are managed
• Identification of how data and information will be shared/transferred between owner and contract site in a manner that ensures its integrity. Is there a secure means of transmission of this data?
• Mechanism to periodically assess and revise the Quality Agreement

A robust vendor audit program can identify common problems in contract manufacturing arrangements and consequently can identify ways in which both owners and contract facilities can improve product quality by resolving problems quickly and effectively.

References

• 211.22 Responsibilities of the Quality Control Unit
• 21CFR 211.180(f) General Requirements
• Contract Manufacturing Arrangements for Drugs: Quality Agreements¹ November Guidance for Industry 2016
• Guidance for the Industry; Q10 Pharmaceutical Quality System (ICH) April 2009
• Guidance for Industry; Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (ICH) April 2018
• Expectations in Quality Agreements, Pharmaceutical Technology, Volume 42 Issue 3, March 02, 2018 by Robert Iser VP PAREXEL Consulting