An unintended consequence of limiting the scope of the Guidelines is that it allows CDMOs to use them as a pretext to limit the distribution of quality tasks up to the trade programme. This certainly facilitates the work of the CDMO because it has to juggle the differences between the QMS of each client. At a time when accelerated clinical plans are the norm rather than the exception, the need to maintain a practical division of quality responsibility during development is critical to a drug sponsor/owner`s ability to ensure a robust CMC and clinical program. The staff of the contracting entity should be properly trained and monitored in order to ensure performance in accordance with the quality system. Make sure everyone is on the same page. When the CMO manufactures a product for the company to its specifications, “it`s nice to think that you have your own quality systems or our own GMP SOPs. But this is your product, and the quality systems of contractors and subcontractors should not conflict,” Minsk stressed. This guide describes the FDA`s current considerations for defining, defining, and documenting the manufacturing activities of parties involved in contract manufacturing of drugs that are subject to current Good Manufacturing Practices (GMPC) requirements. In particular, we describe how parties involved in the contract manufacturing of pharmaceuticals can use quality agreements to delineate their manufacturing activities to ensure GMP compliance. The FDA states in the guidelines using two hypothetical scenarios that both owners and contract facilities are responsible for current GMP and regulatory compliance. A quality agreement does not relieve the parties of their legal or regulatory responsibilities.
However, the application holder remains ultimately responsible for ensuring that its products are manufactured in accordance with the MPMC or the Quality Systems Regulations (QSR), even if the quality agreement delegates certain manufacturing activities to the contract facility. 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. It`s not easy to keep up with the FDA`s ever-changing regulatory requirements.
In November 2016, the FDA finalized its guidance on contract manufacturing agreements for drugs and detailed its expectations for quality agreements. The final document outlines the specific steps manufacturers should take to ensure that their contracting bodies meet a higher standard of compliance. In addition, the guidelines give entrepreneurs a better understanding of what they really need at the end of a quality agreement, which helps them better position themselves as a viable partner. Finally, it gives both parties a roadmap to potential inspection/audit points to keep in mind. Minsk shared part of the FDA`s quality agreement guideline, which included important points that needed to be strengthened (Figure 1). It defines roles, responsibilities and procedures between the parties` respective regulatory issues or quality assurance groups. A standard operating procedure should be in place to indicate which types of suppliers and services require a quality agreement. At the very least, an agreement must be reached every time a CMO is used, as well as with all suppliers of critical materials. They are recommended for suppliers of large quantities of raw materials or components. The implementation of a written quality agreement can facilitate compliance with GMP and in particular 21 CFR 211.22(d), according to which the activities and procedures of the quality unit must be in writing.
The FDA recommends that owners and contracting entities enter into a written quality agreement to describe their respective roles, responsibilities, and activities related to GMP in drug manufacturing. The agreement must not include certain points such as general conditions, pricing and indexation clauses, forecasts, delivery conditions, confidentiality obligations and limitations of liability. These elements belong to the supply contract, which is a separate document. The quality agreement may be incorporated by reference into the supply contract. If both documents are created as a single document, the approval list may include people who have no reason or time to consider issues that have nothing to do with their area of expertise. The ICH Guidelines for the Industry Pharmaceutical Quality System Q10 recommend that, as part of a pharmaceutical grade system, the owner is ultimately responsible for ensuring that “processes are in place to ensure the control of outsourced activities and the quality of materials purchased.” It should be noted that these processes should include quality risk management and include core activities, such as: this section should have been at the heart of the guidelines, but consists of only two paragraphs. One of the biggest challenges with using a CMO is defining how the quality units of the two organizations will work together and interact with each other. While it is true that the drug sponsor cannot delegate responsibility for GMP compliance, the complexity associated with harmonizing a drug sponsor`s quality management system (QMS) with that of a CMO is palpable. For example, the person in the factory (PIP) is a point of relationship where friction can arise between a CMO and a sponsor. Rights and responsibilities for notification, frequency, access and communication are elements that must be clearly defined in a quality agreement.
A CMO has multiple clients, and each PIP requires hosting and management, which adds an extra layer of organizational management to the CMO`s operations. 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: The FDA reminds industry that quality agreements should be available for review by the agency, when the Agency carries out operational inspections. The FDA regularly requests proof of a quality agreement or lack thereof. On the other hand, the new guidelines give a general overview of the areas that should be included in a quality agreement. It contains sections on the following elements related to manufacturing activities: The quality agreement must be specific to specific products. One size fits all is not for everyone. Often, companies will ask for a model agreement, or companies will often have their own model agreement, Minks said.
It`s good to start with that, but you don`t end with a pattern of agreement. While this contributes to profitability, there is no reason to reinvent the wheel. Every project is different. A quality agreement is a comprehensive document that describes both the specific quality parameters of a project and the party responsible for executing those parameters. The level of detail of a quality agreement varies depending on the stage of development of the project. The quality agreements between pharmaceutical companies and the contract manufacturing organizations (CMOs) they employ have been the subject of controversy and FDA scrutiny for many years, leading to the development and publication of FDA guidelines on the subject in 2016. .