Quality Agreements: BIO Comments on Draft Guidance on Contract Manufacturing Agreements for Drugs

Dear Sir/Madam:

The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA) for the opportunity to submit comments on the “Draft Guidance for Industry on Contract Manufacturing Agreements: Quality Agreements.” 

BIO represents more than 1,100 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment. 

GENERAL COMMENTS:

BIO appreciates FDA’s release of this Draft Guidance to help manufacturers better utilize Quality Agreements when dealing with a Contracted Facility.

Definition of “Manufacturing” and “Owners”

BIO asks that for the purpose of consistency and clarity the term “manufacturing” should be used in the same way throughout the document.  Ideally, the definition should be consistent with 21 CFR 210.3(b)(12) defining manufacturing as “Manufacture, processing, packing, or holding of a drug product includes packaging and labeling operations, testing, and quality control of drug products.”

BIO asks the Agency to clarify the definition of “Owners” under the Guidance.  The Guidance defines Owner as any “party that introduces (or causes the introduction of) a drug into interstate commerce.”  (See lines 41-42.)  As currently drafted, this definition may be read to include distributors and therefore may affect manufacturer product guarantees permissible under the Federal Food Drug and Cosmetic Act (FFDCA) section 303(a).  BIO is concerned that there may be a conflict between FFDCA section 303(a) and lines 52-54 of the Guidance. FFDCA section 303(a) permits manufacturers to provide product guarantees that exempt distributors from the responsibility for distributing adulterated or misbranded products received in good faith.  However, Guidance lines 52-54 state that owners are “responsible for assuring that drugs introduced for interstate commerce are neither adulterated nor misbranded as a result of the action of their selected Contracted Facilities.”  BIO asks the Agency to please confirm that the Draft Guidance did not intend to sweep distributors into the definition of owners and that product guarantees provide adequate liability protections as intended by FFDCA section 303(a).

Scope of Guidance

The Draft Guidance applies to commercial manufacturing of product (line 24).  However, BIO notes that quality agreements are equally important during the development phase.  They are a useful tool to provide both thoughtful consideration of reasonable quality expectations based on the item being procured and to provide standards during development and manufacturing.  Limiting the guidance to commercial manufacturing may lead contract manufacturers to conclude that such agreements are unnecessary during drug development.  An important part of commercial approval is the quality of the product and the ability to withstand regulatory scrutiny of the development endeavor.  BIO notes that quality agreements have become an integral part of success in drug development.  We ask FDA to consider expanding the scope of the guidance to include quality agreements for investigational product during the development phase.

Contract manufacturing of drugs may also be subject to good laboratory practices (GLPs) as applicable.  While the Draft Guidance is appropriately focused on good manufacturing practices (GMPs), it does not appear to allow for a contract laboratory to perform certain tests in accordance with GLPs.  BIO asks that the Guidance recognize that manufacturing of drugs may also be subject to GLPs and therefore, are also included in the scope of the Guidance.

CONCLUSION:

BIO appreciates this opportunity to comment on the “Draft Guidance for Industry on Contract Manufacturing Agreements: Quality Agreements.”  Specific, detailed comments are included in the following chart.  We would be pleased to provide further input or clarification of our comments, as needed.