FDA Guidance Clarifies Quality Agreement Expectations for Drugmakers

A newly-finalized guidance leaves no doubt as to what FDA expects to see in quality agreements between drugmakers and contract facilities––the documents used to maintain compliance with current good manufacturing practices (cGMP).

In light of these changes, drugmakers with existing quality agreements should review all existing quality agreements to ensure outsourced suppliers and other contract facilities comply with these requirements.

The guidance – a clarified version of a May 2013 draft – lays out the broader goal of a quality agreement: define manufacturing roles and responsibilities and establish expectations for communication between parties.

In particular, the guidance establishes how contractors will report manufacturing deviations and how those issues will be investigated and resolved in order to maintain cGMP compliance.

We've highlighted the key components of this new guidance in the summary below:

1. The End of Quality-Related Commercial Agreement Provisions

FDA makes clear that they do not believe provisions built into commercial agreements such as master services agreements or supply agreements are sufficient in establishing roles and responsibilities related to quality.

Discreet Quality Agreements should clearly state which party is responsible for carrying out specific cGMP activities, covering those mentioned in section 501(a)(2)(B) of the FD&C Act and, as applicable, those in 21 CFR parts 210, 211, 600-680, 820, and 1271, and all other applicable statutory or regulatory requirements.

2. Quality Agreements Cannot Be Used to Delegate Regulatory Responsibilities

Quality agreements are not to be used to "delegate statutory or regulatory responsibilities to comply with CGMP."

Rather, they are comprehensive written agreements that define and establish each party’s manufacturing activities in terms of how each will comply with cGMP.

This is important to keep in mind when structuring and phrasing the elements of your agreements. Each party's roles and manufacturing activities can be documented with charts, matrices, and/or narratives, however the agreement should clearly state which party is responsible for particular activities related to the quality unit, facilities and equipment, material management, product-specific considerations, laboratory controls, and documentation.

3. Most Quality Agreements Should Contain Five Core Components

Regulators outline five particular sections that should be included – in "clear language" – within a typical quality agreement:

1. Purpose/Scope — to cover the nature of the contract manufacturing services to be provided
   
   
2. Definitions — to ensure that the owner and contract facility agree on precise meaning of terms in the quality agreement
   
   
3. Resolution of disagreements — to explain how the parties will resolve disagreements about product quality issues or other problems
   
   
4. Manufacturing activities — to document quality unit and other activities associated with manufacturing processes as well as control of changes to manufacturing processes
   
   
5. Life cycle of, and revisions to, the quality agreement

Along with this, FDA suggests including the contract facility's established processes and procedures as part of the agreement in order to "reduce the risk of misrepresentation or error during manufacturing."

4. Contracting Research and Development Arrangements Are Not Included

Although many in the industry have asked for it, FDA has decided not to expand these rules to include contracted R&D, clarifying that the provisions are limited only to "commercial manufacturing facilities."

The guidance does acknowledge its potential use as a resource in crafting quality agreements for other activities, but doesn't offer itself as a definitive guide in those applications.

5. Quality Systems and Quality Agreements Go Hand-in-Hand

Since those who use a quality systems model to ensure CGMP compliance likely use contract facilities, quality agreements have become a common component of most quality systems in general.

This guidance is intended to build upon the quality risk management principles and recommendations described in the following FDA guidances:

• Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients

• Q9 Quality Risk Management

• Q10 Pharmaceutical Quality System

Want to learn more about crafting an effective quality agreement? Register for our free webinar: Qualifying Suppliers & Managing Quality in FDA-Regulated Industries.