The FDA does not have specific guidelines for quality agreements between medical device companies and the CMOs that provide services to them. However, the FDA guidelines state that quality agreements should cover activities covered by Part 820 of the 21 CFR, the Quality System Regulation (QSR) for medical device companies, “where applicable.” Given the inclusion of Part 820 in the Guidelines, a quality agreement between a medical device company and a CMO should address the following aspects to varying degrees, depending on the nature of the relationship between the two parties and the products and services concerned: deviations and corrective and preventive measures (CAPA) are other potential points of disagreement. Deviations require the CMO and sponsor to understand the cause and impact of a QMS process or excursion. The primary responsibility for root cause investigations must be clearly stated in the quality agreement, as well as the question of when and how a drug sponsor may participate in an investigation. Often, large pharmaceutical and biotech companies have formalized investigative frameworks that must be applied to gaps, while the CMO can enable other approaches. The ability to reconcile two different sets of requirements is essential to avoid unnecessary disruption downstream of the commercial supply chain. This is another example where limiting the scope of advice to trade programs is a missed opportunity for the Agency. These guidelines are intended to build on the principles and recommendations of quality risk management outlined in the following FDA guidelines: The FDA makes it clear that it does not believe that provisions incorporated into trade agreements such as master service agreements or supply agreements are sufficient to define roles and responsibilities related to quality. Quality agreements are not only good business practices, there are also regulatory requirements for them.
ICH Industry Guide Q7 Good Manufacturing Practices Guide for Active Pharmaceutical Ingredients recommends that owners evaluate contract facilities to ensure contractors` sites are GMP compliant for specific operations. Written agreements should also set out subcontracting considerations. They should describe how changes to processes, equipment, methodologies and specifications are managed, and allow the owner to verify compliance with the PMCCs of their contractor`s facilities. According to the FDA, a quality agreement is a comprehensive written agreement between the parties involved in contract manufacturing that defines and determines each party`s manufacturing activities with respect to GMP compliance. The agreement should clearly indicate whether the owner or the procuring entity (or both) carries out certain GMP activities. (1) The Agreement should clearly define cases of routine, escalation and urgency and how they are dealt with. The agreement should also define what happens in the event of disputes that may be raised by both parties and should document the mechanism for the early and effective resolution of disputes. In particular, the guidelines set out how contractors report manufacturing deviations and how these issues are investigated and resolved to maintain GMP compliance. First, it is important to note that the new guidelines reflect the FDA`s current considerations on commercial manufacturing relationships, not research and development, and apply to the following categories: human drugs, veterinary drugs, certain combination products, biologics and biotechnology products, finished products, APIs, drug substances, process materials, and pharmaceutical ingredients of drugs.
combined / products. The guidelines do not cover the following product types: Type A drugs and medicated feed, medical devices, food supplements, or cells, tissues, or cellular or human tissue products regulated pursuant to Section 300 of the Public Health Services Act and Part 1271 of the 21 CFR. The quality contract must be drafted and mutually accepted by the CMO and the customer before the acceptance of the supply contract in order to ensure the identification of all items that will be invoiced and any functional limitations. Whenever an entrepreneur or marketing director is deployed, including agreements between different departments of the same company, regardless of the physical location of the parties involved, a quality agreement must be concluded. The agreement should cover all aspects of the project that affect the identity, quality, safety, efficacy and purity of a product. Elements that could affect the contractor`s or client`s compliance status should also be included. Companies should be aware that the FDA intends to review quality agreements during facility inspections, so the FDA (and we) recommend that quality agreements be separated from other contracts between owners and contracting entities. The guidelines require owners to review and approve most changes before they are implemented.
However, in some circumstances, contractors may make changes without notifying the owner. A quality agreement should define how all these changes are made and managed. In November 2016, the FDA issued new industry guidelines titled Contract Manufacturing Arrangements for Drugs: Quality Agreements. This forecast is timely given the rise of the virtual biotech company in the development landscape. Most development programs now include support from at least one contract service provider (CSP) for services ranging from early development contract research to commercial manufacturing and analytical support. In view of these changes, pharmaceutical manufacturers with existing quality agreements should review all existing quality agreements to ensure that outsourced suppliers and other contractual entities comply with those requirements. With this final guidance, the FDA has clarified its scope, particularly with respect to the parties to which it applies. Detailed background on this topic can be found in our blog post on the draft guideline (here). In the eyes of the FDA, any activity that is not documented may just as well not have occurred. A quality agreement gives the contractual facility and the owner the opportunity to set expectations as to who reviews and approves quality documents.
It shall describe protocols for modifying standard operating procedures (SOPs), manufacturing records, specifications, validation documentation and other essential documents related to the goods or services provided by the procuring entity. The role of both parties in creating and updating original GMP-compliant documents or actual copies should be clarified. The agreement should also specify how these records are to be readily available for inspection. It is beneficial to include a statement that electronic records are stored in accordance with GMP and kept in a recoverable state for the required registration periods specified in applicable regulations in accordance with FDA requirements. To learn how to streamline the coordination of quality agreements and other contract manufacturing capabilities with digital tools, read the trend letter “3 Ways Contract Manufacturing Organizations Are Turning to Digital Technology to Improve Collaboration.” .