Regulatory Focus™ > News Articles > New FDA Guidance Recommends Use of Quality Agreements to Define Contract Responsibilities

New FDA Guidance Recommends Use of Quality Agreements to Define Contract Responsibilities

Posted 28 May 2013 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) has released a new draft guidance regarding contract manufacturing arrangements, establishing the responsibilities of each entity involved in the manufacture of a pharmaceutical product in adherence to current good manufacturing practices (CGMPs).


The draft guidance, Contract Manufacturing Arrangements for Drugs: Quality Agreements, comes just as FDA has been identifying lapses in contract manufacturing arrangements. In May 2013, for example, the agency sent at least five Warning Letters to dietary supplement manufacturers, citing their failure to ensure the final quality of their products, which had been manufactured by a third party.

"Although your firm may contract out certain dietary supplement manufacturing operations, it cannot, by the same token, contract out its ultimate responsibility to ensure that the dietary supplement it places into commerce (or causes to be placed into commerce) is not adulterated for failure to comply with dietary supplement CGMP requirements," FDA wrote.

While those letters were aimed specifically at dietary supplements, FDA's new draft guidance seems to adhere to similar principles for intermediate and finished pharmaceutical and biological products, including combination products and veterinary products.

The Guidance

The guidance is applicable to all those involved in manufacturing, such as those entities that package, hold, label, test, produce or assure the quality of products. FDA further notes that contract manufacturing operations can include formulation, filling and finishing products, chemical synthesis, and cell culture and fermentation.

While regulators wrote that this can be beneficial to all parties involved, the owner is "in all cases" responsible for making sure that the products that are introduced into interstate commerce are neither adulterated nor misbranded, particularly as the result of failing to meet CGMPs. The guidance clarifies that FDA considers contract facilities an "extension of the manufacturer's own facility"-something clearly evident by the aforementioned May 2013 Warning Letters to the five supplement distributors.

"With respect to contract manufacturing, both Owners and Contracted Facilities must also work together to establish and maintain quality oversight of contracted manufacturing operations and the materials produced under contracted manufacturing arrangements," FDA explained.

The Quality Agreements

The guidance goes on to explain that one of the most important elements of any arrangement between an entity and a contract manufacturer is a quality agreement. Such agreements must require the manufacturer to comply with CGMP regulations, while making clear that it is ultimately the distributing entity that must ensure the products are in actuality manufactured to those standards. All responsibilities for both parties should be explicitly stated in the quality agreements, FDA recommended.

Per FDA's recommendations, the quality agreements should contain the following sections at a minimum:

  • the purpose and scope of the contract agreement
  • the terms of the agreement, including its effective dates
  • terms for dispute resolution
  • responsibility of each respective party, including an overview of the subparts of the CGMP regulations
  • change control and revision practices

FDA wrote that, "From a CGMP perspective, the most critical elements of a quality agreement are the sections delineating the parties' respective responsibilities and the discussion of change control." The format used by the parties is of their choosing, but should be clear as to the delineation of responsibilities, FDA explained.

Of particular interest to FDA is how each party will define the responsibilities of the Quality/Compliance Units, the facility and its equipment, the materials used in the manufacture of a product, laboratory controls, documentation of production, and change controls.

The agency added that such agreements should be separate or severable from other business documents, as it will regularly request these documents for inspection. If they are combined, that could pose confidentiality problems.

FDA added that the quality agreements are "not explicitly required under existing CGMP regulations," but that they are recommended by FDA and should prove useful to companies wishing to better manage their contracting operations.

Comments on the draft guidance will be accepted by FDA until 29 July 2013.

Contract Manufacturing Arrangements for Drugs: Quality Agreements

Federal Register

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