A Comprehensive Guide For Supplier Quality Agreements

By Alexander K. Aust, M.S., MBA, Aust Business Solutions

When selecting a CDMO to manufacture a clinical or commercial material or product, the quality operations at the manufacturing facility are just as important to take into consideration as the technical capability and expertise of the supplier.

Before manufacturing any material that will be used to treat patients, you must establish a supplier quality agreement (SQA) to govern the cGMP activities of each party involved in the manufacturing activities of the supply chain. The parties, in this case, are the biopharma company (drug sponsor) and the supplier (CDMO/CMO).

An SQA is a written agreement that is mutually approved by the biopharma company and the supplier establishing cGMP responsibilities that each group is specifically responsible for. A quality agreement is not a confidentiality agreement, and it does not govern the business operations like pricing, liability, delivery terms, etc. These terms will be included in the individual contracts signed between the supplier and the biopharma company, such as a master service agreement (MSA) and supply agreement.

The quality agreement should take into consideration International Council for Harmonisation (ICH) industry guidance as well as the regulations specified by the FDA and those from any other applicable regulatory authorities (RA). Consider referencing the following:

• Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients
• Q9 Quality Risk Management
• Q10 Pharmaceutical Quality System
• Section 501(1)(2)(B) of the FD&C Act
• 21 CFR Parts 210, 211, 600-680, 820, and 1271

If you are a biopharma company that is going for an IND, you will more than likely need to partner with a CDMO to help with your formulation and process development requirements that will enable clinical activity. After you screen the suppliers for their technical capabilities, your quality and operations team should visit the supplier’s facility to “kick the tires” and conduct a cGMP audit of the to-be supplier’s quality system.

By being on-site, the supplier’s sales and marketing teams are taken out of the equation, and you, the biopharma company, can get a better sense of what kind of partner the supplier will be. If everything checks out from a quality perspective and it seems like a good fit, you will select the CDMO by executing a contract, which may take the form of an individual work order or an overall MSA. If the supplier is being chosen to manufacture a commercial material, instead of an IND, then a supply agreement will be the vehicle to capture the business terms and conditions.

After executing the contract with the supplier, you will need to focus on getting the SQA in place as soon as possible, and before the manufacture of any cGMP material. At the most basic level, the SQA will include the scope, definitions, and processes for conducting cGMP manufacturing activities, resolution of disagreements/discrepancies, and for updating documents — including the SQA – in the future. The FDA recommends that biopharma companies include delineation of responsibilities when dealing with a supplier in the following sections:

• Manufacturing quality operations
• Facilities and equipment
• Materials management
• Quality control (laboratory testing controls)
• Document control
• Change control
• Material-specific considerations

Responsibility Matrix Template

A quality agreement should be put in place prior to the manufacture of any cGMP materials. This responsibility matrix applies to relationships between biopharma companies and cGMP suppliers and vendors. This document can be used to help detail the responsibilities of each party. The responsibility matrix can be inserted as an exhibit into the quality agreement, which exists to outline the terms and conditions relating to the quality operations and coordination of activities between the two parties.

The supplier will be responsible for all operations that are marked with "X" in the column titled "Supplier,” and the biopharma company will be responsible for all operations that are marked with "X" in the column titled “Biopharma Company.” In the table, the "material" referenced can be thought of as any starting material, raw material, component, drug substance (DS), or drug product (DP) required to be manufactured according to cGMP standards.

Click here to download the matrix template.

References:

1. Contract Manufacturing Arrangements for Drugs: Quality Agreements Guidance for Industry https://www.fda.gov/regulatory-information/search-fda-guidance-documents/contract-manufacturing-arrangements-drugs-quality-agreements-guidance-industry#:~:text=Contract%20Manufacturing%20Arrangements%20for%20Drugs:%20Quality%20
   Agreements,for%20Industry%20Guidance%20for%20Industry%20November%202016.&text=
   manufacturing%20activities%20to%20ensure%20compliance%20with%20cGMP
2. FD&C Act, section 501(1)(2)(B) https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=225.1
3. 21 CFR parts 210, 211, 600-680, 820, and 1271 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211&showFR=1
4. ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q7-good-manufacturing-practice-guidance-active-pharmaceutical-ingredients-guidance-industry
5. ICH Q9(R1) Quality Risk Management https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q9r1-quality-risk-management
6. ICH Q10 Pharmaceutical Quality System https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q10-pharmaceutical-quality-system

About The Author:

Alexander Aust, M.S., MBA, is the cofounder and owner of Aust Business Solutions, a pharmaceutical consultancy based in Maryville, TN, where he focuses on strategic planning and partnerships and technical support. The firm provides CMC and project management services, assists with regulatory submissions, and helps to implement new technology. Aust serves as a senior project manager for the Parenteral Drug Association. He earned his MBA from Ball State University and an M.S. degree from Purdue University in molecular and cellular biology.