Content of the BPTF Quality Agreement Templates
Both of SOCMA's BPTF Quality Agreement Templates provide guidance for drafting agreements relating to the manufacture and
release of APIs regulated by FDA. The templates are based on the collective experience of API industry members as well as
the knowledge gained from executing quality agreements with drug manufacturers and reviews of these agreements by FDA inspectors.
Specifically, the BPTF Quality Agreement Templates contain the following sections:
- Legalities (e.g., agreement parties, scope, effective date, terms, amendments, survival cause, resolution of quality issues)
- Manufacturing location(s), including third parties
- Responsibility (a table that addresses key CGMP and filing issues)
- Appendix 1: Products covered under the agreement
- Appendix 2: Contacts and responsible parties for the agreement
- Appendix 3: Product specifications.
Parties signing the agreement may spend a significant amount of time negotiating the legal language. From a US perspective,
common language in this section should be acceptable to both signatories. If there is a conflict between the quality agreement
and another agreement that may already be in place (e.g., a supply agreement), it is recommended that the quality agreement
prevail to avoid any potential quality concerns. It is important to include this type of language in the supply agreement.
In the Responsibility section of the BPTF Quality Agreement Template, BPTF provided its recommendations for each requirement
such as change control, who will file regulatory documents, and who will manage stability programs. It is expected that a
supplier would develop its own recommendations for this section (preassigned checked boxes are included in each section of
the template based on best practices and experience) and start the negotiation process with their customer. The goal is to
have a minimal number of changes to the document which will help minimize the impact on the supplier's existing processes,
procedures, and quality system.
Change-control requirements tend to vary considerably in quality agreements. The definition of the term "significant," for
example, is an important part of a quality agreement. A practical, yet regulatory-compliant model, is needed for change control.
The supplier cannot practically notify a customer about every change, however, significant regulatory changes should be reported
to the customer and approved. Additionally, it is not feasible for a supplier to have a different change-control and notification
standard for each customer. These processes should be standardized.
Additional considerations for custom API manufacturing
Although the BPTF Quality Templates for general API manufacturing and custom API manufacturing have common elements, quality
agreements with custom manufacturing organizations tend to contain more options and are therefore more complex. Again, there
is a big advantage to both parties (i.e, the API manufacturer and the custom manufacturer) to keep the same standards for
The BPTF Custom Manufacturing Organization Quality Agreement Template provides for key differences betwee custom API manufacturing
and routine API manufacturing. In custom contract manufacturing business, each project may have a different customer, and
the project may only involve a few batches. The custom template, therefore, incorporates flexibility in CGMP responsibilities
and filing requirements. For example, the customer may have developed or own the manufacturing process, in which case the
manufacturing process may be transferred from the customer, and the customer may own the intellectual property (IP). In standard
manufacturing, on the other hand, the supplier typically has developed and owns the manufacturing process, and thus owns and
controls the IP and related drug master file (DMF) for the process.
If the IP is owned by the customer, the quality agreement needs to reflect that fact. For CMOs, the batch records, analytical
method validations, stability, and even the process validation may be the responsibility of the customer rather than the supplier.
Additionally, filing requirements such as product-label codes can be submitted by the customer. Using a DMF or chemistry,
manufacturing, and controls (CMC) filing information in the drug submission must be defined for custom manufacturing organization.
The BPTF Custom Quality Agreement Template accounts for these differences and, in many cases, one just needs to click on the
appropriate box when using the templates.
A standardized quality agreement is crucial for API manufacturers. An API manufacturer cannot use different sets of requirements
and quality system processes for each of its customers. BPTF Quality Templates offer a regulatory-compliant quality approach
to API producers and their customers.
*BPTF was organized in 2002 as an affiliate group under SOCMA. BPTF is focused on facilitating CGMP compliance and addressing
related CGMP issues that affect chemical manufacturers. The members of BPTF currently include: Albemarle, Ash Stevens, BASF,
Chattem Chemicals, Cherokee Pharmaceuticals, Copperhead Chemical Company, ISP Chemicals, Lonza, and SAFC.
1. FDA, ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (Rockville, MD, 2001).
WEB: To view and download SOCMA's BPTF Quality Agreement Templates in PDF format, visit
Brant Zell is chair of the Bulk Pharmaceutical Task Force for the Society for Chemical Manufacturers and Affiliates (SOCMA), a member
of the FDA Industry Coalition, and vice-president of quality and environmental, health, and safety for Cherokee Pharmaceuticals
LLC, 1835 Market Street, Suite 1100, Philadelphia, PA 19103, tel. 215.988.8986, fax 215.569.1925, Brant.Zell@Cherokee-pharma.com