We’ve no need to look beyond the headlines of the daily news to understand the significant role the pharma and biotechnology industries play in the detection and combat of deadly diseases. As many more players enter this space, all parties (owners, contract facilities and regulators) in the industry need to agree on the best practices to guide processes and behaviours, especially in the manufacturing of pharmaceutical products (active ingredients and finished products). Contract manufacturing organizations (CMOs) play an increasingly pivotal role in the active pharmaceutical ingredients (APIs) and finished product pharmaceutical drug manufacturing processes, which prompted a November 2016 FDA Guidance on defining appropriate roles and responsibilities of the manufacturer and sponsor. The resulting work, entitled “Contract Manufacturing Arrangements for Drugs: Quality Agreements Guidance for Industry”, is a 16-page document outlining the use of Quality Agreements in Pharma to ensurecompliance with Current Good Manufacturing Practices (cGMP).
What is a Quality Agreement?
A Quality Agreement is a legally-binding written agreement that broadly defines and establishes the various manufacturing activities involved in a contract manufacturing of drugs. One of the most important elements is to clearly define roles of each party. The aim is to ensure that services performed in support of pharmaceutical manufacturing are in compliance with cGMP. The requirements have their basis in sections US FD&C Act r501(a)(2)(B) and in 21 CFR parts 210, 211, 600-680, 820, and 1271.
A Quality Agreement is document specifying the roles, responsibilities, and Quality-related business activities as a means to ensure that regulated products are manufactured in a safe and compliant manner. It is developed jointly between a supplier and sponsor and defines mutually agreed upon matters for executing all quality tasks including specifications, Quality requirements, notification procedures, and the like. Both Supply Agreement and Quality Agreement should exist independently and complement one another.
Benefits of a Quality Agreement
In addition to formalizing the sharing of responsibility, the Quality Agreement serves to clearly define many of the business processes to be performed in the regulated environment.
The value of instituting Quality Agreements is great and directly benefits patients who use the drugs that have been manufactured. By specifying what each party to the agreement ‘brings to the table’, a transparency and clear accountability emerges. This clarity ensures everybody stays on track. The enhanced efficiency results in speed of operation in an industry for which speed to market can have a profound effect on public health.
As a Pharmaceutical Manufacturer, an owner in a Quality Agreement, you are empowered with the authority to either approve or reject the drugs that have been manufactured by a contract facility. This oversight prevents the circulation of adulterated and/or mis-branded drugs. The Quality Agreement details expectations of both parties and assures the high standard of the production processes and controls.
Characteristics and Elements of Quality Agreements
Though not currently a Regulatory requirement, FDA recognizes the complicated nature of contract drug manufacturing. Taken from the FDA’s website: “[FDA]…recommends that owners and contract facilities implement written quality agreements as tools to delineate manufacturing activities for ensuring compliance with cGMP.”
In many cases, pharmaceutical companies enter into contract with a third-party facility to produce a drug or provide active ingredients in a drug. This process is called Contract Manufacturing. Thus, the former becomes known as the “owner” while the latter becomes the “contract facility”.
Most quality agreements clearly outline the detailed activities involved in a contract manufacturing of drugs. Among these are the roles, and responsibilities of parties, as well as communication between parties. Also, it outlines which products and/or services the owner expects from the contract facility as well as which party or parties have the final approval for various activities.
Key Elements of Quality Agreements
The quality agreement should comply with cGMP regulations, by including the following sections or elements commonly used in most quality agreements.
• Purpose/Scope: This entails the nature of the contract manufacturing services to be provided.
• Definitions: Definitions ensure that the owner and contract facility agree on the precise meaning of terms in the quality agreement.
• Resolution of disagreements: Should there be any disagreements about product quality issues or other problems, this section outlines the most appropriate ways to resolve them.
• Manufacturing activities: Very essential parts of the manufacturing processes such as quality unit and other activities
• Control of changes: routine quality monitoring and reporting and continuous improvement efforts in manufacturing will inevitably lead to process changes over time. One of the most critical elements of the Quality Agreement is the articulation of change notification and Regulatory assessment procedures
• Life cycle of, and revisions to, the Quality Agreement: the issuance of the Quality Agreement is the start of the business relationship. The QA is periodically reviewed to determine if changes are required to reflect changes in regulations or business practices.
What is cGMP?
cGMP stands for Current Good Manufacturing Practices and provide assurance of proper design, monitoring, and control of manufacturing processes and facilities by all parties involved in the drug manufacturing process. The Food & Drug Administration (FDA) is charged with enforcing the regulations. By requiring that manufacturers of medications adequately control manufacturing operations, the FDA is able to assure the identity, strength, quality, and purity of drug products. Some aspects of the cGMP include establishing strong quality management systems and obtaining appropriate quality raw materials. Still others focus on establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories.
By convention, any drug product and/or service (including active pharmaceutical ingredients) that do not comply with cGMP are described as “compromised” or “adulterated”. Furthermore, the FDA forbids any person or pharmaceutical company from introducing and/or administering adulterated or mis-branded drugs unto the market.
ICH Guidances Supporting Quality Agreements
With respect to contract manufacturing arrangements, the following are three ICH guidance in CGMP compliance by way of recommendations:
• Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients. This Guidance offers recommendations for the evaluation of contract facilities by owners to ensure that cGMP best manufacturing practices are observed. It includes prescriptive detail on how subcontracting and changes by the contractor would be handled, managed, and monitored throughout the manufacturing process.
• Q9 Quality Risk Management. The systematic approach to an effective quality risk management program is a key component of drug manufacturing.
• Q10 Pharmaceutical Quality System: As an owner, you assume the ultimate responsibility by ensuring that all the necessary processes for manufacturing are both in place, safe and proven. The assessment of competence of potential contractors must be performed prior to outsourcing. This includes defining the detailed manufacturing responsibilities and communication processes and monitoring and reviewing of performance of contract facilities and incoming ingredients.
Though not required, the FDA recommends that registration owners institute agreements with their contractors outlining all aspects of the quality considerations from processes, methods, equipment, and specification changes within the CGMP framework. This is an extension of the ICH Guidance of Industry Q7 for Good Manufacturing Practice Guidance for APIs. Despite Quality Agreements not being an FDA requirement, though they are an Implementation of Quality Agreements in the European Union as a Regulatory statute according to European Union cGMP, Chapter 7.
In conclusion, as the regulatory agency chartered with safeguarding public health related to drug products, the FDA recommends all parties involved in a pharmaceutical product manufacturing process (especially owners) to adhere to Current Good Manufacturing Practices. The scope of process includes outsourcing through manufacturing to handling and delivery of drug products and active pharmaceutical ingredients. Comprehensive Quality Agreements specifying all manufacturing activities and roles are essential to ensure drugs manufactured are safe for the market.
About Our Template
The downloadable Quality Agreement template, found here: https://freeprojectmanagementtemplates.com/all-templates/ is based on Bulk Pharmaceutical Task Force (BPTF), an affiliate organization of the Society of Chemical Manufacturers and Affiliates (SOCMA). It is a guide for drafting a Quality Agreement relating to the manufacture and release of substances regulated by the Food and Drug Administration. The template has been enhanced with some additions and captioning to allow linked Table of Contents. Wishing you much project success!