We found that our discussions on quality agreements were an insightful process that created a dialogue with our suppliers and CROs and established more meaningful relationships between the parties. For example, a measure of our quality agreement required reporting on all critical audit results of regulators or proponents in a contracted region with respect to a contracted service. The quality assurance representative of the respective clinical service provider stated that it could not accept this measure because of its obligation to maintain the confidentiality of its clients. This led to a discussion on the root of the measure, which should provide assurance that a rigorous process will be followed when assessing the potential impact of critical audit results on other programs in the region or other programs that use the same service. We explained to the QA representative what we expected from a robust process, and the clinical service provider assured us that it had SOPs and work practices (WPs) that governed the assessment of potential impacts on other programs. Although the essence of what we described was detailed in their SOPs and WPs, the Quality Assurance Representative agreed that their process could be improved to meet our expectations. This led to a revision of their SOPs and WPs. In today`s environment of virtual businesses and outsourced drug development, it is important to properly supervise and monitor regulators. With the publication of ICH/GCP Addendum E-6 (R2) 2016, proponents must also demonstrate adequate monitoring of CROs by suppliers, including those awarded by the ORC-SPONSORS to another party. A quality agreement is the ideal tool to define responsibilities and expectations. A quality agreement in the context of pharmaceutical development is an agreement that is mutually negotiated and concluded between the quality departments of a sponsor (pharmaceutical companies) and their suppliers (CRO, etc.). It is intended to define responsibilities with regard to quality tasks and to help ensure the development of safe products. Contractual partnerships inevitably have problems and quality agreements ensure that they are dealt with quickly and systematically.
As clinical research continues the trend of outsourcing more clinical trial activities to clinical service providers such as CROs or other providers, it is essential that sponsors ensure that the activities they outsource are conducted in accordance with the sponsor`s quality expectations. Due to short development times, often after a rigorous selection process, the clinical service provider immediately begins working on the project without both parties discussing their quality expectations. A quality agreement clarifies exactly what is expected of both parties and who will be responsible for virtually every aspect of the project. It also identifies specific aspects of project costs and can thus save time and money. A quality agreement is a document that defines both specific quality parameters for a project and which party is responsible for executing those parameters. The level of detail may vary depending on the development phase of the project. In early 2013, Chapter 7 of the EU GMP was revised and renamed „Outsourced Activities” to better align with ICH`s Q10 Pharmaceutical Quality System. The principle of Chapter 7 states: „Any activity covered by the GMP Guidelines that is outsourced must be adequately defined, agreed upon and controlled in order to avoid misunderstandings that could lead to a product or operation of unsatisfactory quality.
There must be a written contract between the customer and the order acceptor in which the obligations of each party are clearly defined. The contracting entity`s quality management system shall clearly indicate how the qualified person certifying each batch of the product with a view to its release shall exercise full responsibility. »; There are regulatory requirements for quality agreements. Although they are not currently needed by US GMPs for drugs, it is very likely that they will be soon. In 2016, the FDA released the guidance document „Contract Manufacturing Agreements for Drugs: Quality Agreements.” Adding a quality agreement requirement to 21 CFR 211 would bring U.S. GMPs into compliance with European Union (EU) GMPs and ICH guidelines accepted by the FDA (see below). Quality agreements are also set out in ICH quality documents. ICH Q7, 16.12, reads: „There should be a written and approved contract or formal agreement between a company and its contractors detailing each party`s GMP responsibilities, including quality measures.” One of the many important details of quality agreements is the time windows. If a CMO wants a processing time of five days to verify a record master batch (MBR), this can be useful because there is no need to verify the data. However, if the CMO wants five days to review a batch production record (OPI) executed, this is not appropriate in most cases. There is simply too much data that needs to be verified to be able to do a thorough job in five days.
Arvilla Trag, RAC, a consultant at BioProcess Technology Consultants, has 27 years of experience in the development of new drugs. As President and Senior Advisor of Midwest Consulting Services (MCS) from 1997 to 2016, she prepared dozens of INDs and several sections of Modules 3 and 2.3 for OCAs. In addition to detailed bid preparation, Trag has conducted more than 250 CGMP compliance audits of contract manufacturers and testing laboratories, conducted due diligence audits for mergers and acquisitions, created several quality manuals, and conducted a quality systems gap analysis. She has extensive experience in product types and has participated in more than two dozen product development programs, including monoclonal antibodies, vaccines, small molecules, and combination products. .