Quality Agreement（part Ⅰ）

The quality agreement is between the pharma product owner & manufacturing contractor to implement quality in each process, intermediate product stages and the resultant final product being manufactured at the contractor’s site. The quality agreement is distinct from the generic or user requirement specification, including the process specifications, pricing, etc. It is a highly technical document that only covers the scope of quality and must be prepared separately. Like other agreements made for a specific purse, quality agreements are made to ensure the quality.

Much like the pharma product owner, who is responsible for implementing quality practices in its manufacturing site, quality is also required when a product is manufactured at the contractor's site, and a quality agreement helps define the responsibilities and goals of the two parties in terms of quality

The quality agreement defines the cGMP responsibilities between the pharma product owner and contract manufacturing when the product owner chooses CDMO for its production process. It establishes explicitly the quality techniques and what party is responsible for quality related activities. It includes the entire scope of the work, which can directly impact product quality and safety.

Outsourcing a pharma process or product to the contractor often becomes risky regarding implementing quality in their processes and the final product, and there must be a mechanism for enforcing quality and preventing deviations in the quality.  A quality agreement is among the many tools used to offset these risks.

Regulatory Guidelines

The United States FDA also defines the quality agreement as a requirement when outsourcing manufacturing operations to contractors. Failure to comply could result in regulatory actions. 

Some FDA guidelines that outline the importance of Quality Agreement, as mentioned below

Contract Manufacturing Arrangements for Drugs: Quality Agreements Guidance for Industry

This FDA guideline describes the importance of defining, establishing, and documenting manufacturing activities for the parties involved in contract manufacturing w.r.to cGMP requirements. It describes each party's responsibilities for implementing cGMP in the manufacturing process and product.

It describes 

• What is a quality agreement 

• Responsibilities of parties involved in contract manufacturing

• documentation, including

               ◆ What is a Quality Agreement           

               ◆ Element of Quality Agreement i,e, what should be included in a quality agreement 

The 21 CFR 211.22 Responsibilities of Quality Control Unit

The CFR 211.22 describes the importance of quality agreement as 

211.20 (a) -  responsibility of the quality control unit, and in its part

"There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labelling, and drug products, and the authority to review production records to ensure that no errors have occurred or if errors have occurred, that they have been fully investigated. The quality control unit shall approve or reject drug products manufactured, processed, packed, or held under contract by another company".

211.20 (d) - written agreement

"The responsibilities and procedures applicable to the quality control unit shall be in writing; such written procedures shall be followed."

21 CFR 200.10 Contract facilities (including consulting laboratories) utilized as external facilities by pharmaceutical manufacturers.

These guidelines describe the association between the contract manufacturer and the product owner.

"The Food and Drug Administration is aware that many manufacturers of pharmaceutical products utilize extramural independent contract facilities, such as testing laboratories, contract packers or labellers, and custom grinders, and regards extramural facilities as an extension of the manufacturer's facility."

ICH Guideline

In addition to the FDA mentioned above guidelines, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ( ICH) also has guidelines related to the quality agreement mentioned in the FDA guidelines. 

Following is the reference to the guidelines

• Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients 

• Q9 Quality Risk Management

• Q10 Pharmaceutical Quality System

How do you write a quality agreement? 

A well-written quality agreement covers the entire scope of manufacturing activities related to cGMP. 

According to the FDA guidelines, a well-written quality agreement includes the following section.

Purpose/Scope

This section defines the nature of contract manufacturing services that a pharma product owner expects from the contractor. 

Definitions 

This section describes the detailed meaning of every technical and non-technical term used in the quality agreement. Its primary purpose is to prevent confusion at any stage of the manufacturing activities.

Resolution of disagreements

Like every cooperation & collaboration, disputes can occur in quality agreements requiring strong written and documentation support to resolve. 

This section guides how disagreements related to product quality or other problems are managed and solved.

Manufacturing activities 

This section describes documentation related to manufacturing activities, including the quality unit. It also includes changes to manufacturing processes, if any.

Then manufacturing activities includes, but are not limited to 

• Formulation

• Fill and finish

• Chemical synthesis

• Cell culture and fermentation, including for biological products 

• Analytical testing and other laboratory services 

• Packaging and labelling • Sterilization or terminal sterilization

The life cycle of, and revisions to, the quality agreement

This section includes a series of changes in the quality agreement to prevent deviation in the product & process and final product.