The choice of a contract manufacturer is long term orientated. Shane Killian, moderator of the Quality Agreement Session at the PDA/FDA Joint Regulatory Conference, compared the relationship between contract giver and acceptor to a marriage.
Everybody who has been married for a long time knows that a relationship goes through good times and bad times. That being said, there must be reliability, trust and willingness to cooperate on both sides.
The conference session in Washington was not about marriage but was focused on the quality agreements necessary in a partnership to produce drugs.
What is the needed framework when a company wants to outsource manufacturing steps? Paula Katz, FDA Acting Branch Chief, Regulatory Policy & Collaboration, FDA, and Rebecca A. Devine, Ph.D., Consultant, presented their views and experiences on this important topic. This article covers the presentation of Paula Katz.
The title of Paula Katz’s presentation was “Putting the ‘Quality’ in Quality Agreements for Contract Manufacturing Operations“. The reasons for outsourcing are quite diverse:
And today for nearly every step of drug manufacturing you can find external resources in all parts of the world.
As a lawyer by training Paula Katz made clear regulatory references to this topic:
501(a)(2)(B): A drug is adulterated if […] methods used in, or facilities or controls used for, manufacturing, processing, packing, or holding do not conform with CGMP.
FDASIA § 711: “CGMP” includes “the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products.”
This demonstrates that you cannot ‘contract around’ CGMP and that a quality oversight concerning the procedures at a contractor´s site is a must.
Paula Katz stated that the CGMP regulations do not explicitly require a written quality agreement, but:
In Europe the situation is different from the U.S. There is a requirement for a written quality agreement. (EU Guide to GMP, Sec. 7.1).
In the FDA and ICH guidelines are many references for the necessity of quality agreements.
Paula Katz described the key elements of the FDA draft guidance ‘Contract Manufacturing Arrangements for Drugs: Quality Agreements’ that was published in May 2013.
The scope of the draft is:
She also mentioned the topics that are not covered in the draft guideline:
The document outlines critical roles that are played by both product owners and contracted facility. It further explains how manufacturers should use quality agreements to define, establish and document their responsibilities. The draft emphasizes that quality agreements should
For that reason a quality agreement is a comprehensive document that defines and establishes obligations and responsibilities of quality units of both parties (contract giver, contract acceptor). There should be a clear interface to ‘supply agreements’ or ‘technical agreements’.
Here Paula Katz gave helpful and practical tips to the auditorium
There should be a clear language to define key quality roles and responsibilities:
There should be described communication expectations and involvement in procedures:
Change control can be implemented by the contracted facility
Important is the question: What risks might the type of change contemplated present to product quality?
It should also be discussed, agreed upon, and procedures should be documented for validation activities required to implement any changes.
Paula Katz stated that there are no new rules at play. The FDA continues to inspect based on FDCA & CGMP regulations, and all parties should continue to be subject to the same requirements
The FDA already routinely requests and reviews evidence of quality agreements (or the lack of quality agreements). In doing so Paula Katz wondered how difficult it is to engage in compliant contract drug manufacturing without a written quality agreement.
At the end of her presentation Paula Katz showed a lot of excerpts from FDA warning letters that referenced to a lack of compliance between contract giver and contract acceptor.
Some examples of the references:
In one of our next LOGFILES we will feature part II of this session and present the industries perspective as detailed by Rebecca Devine.
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