BioPharm

20 BioPharm International eBook March 2018 www.biopharminternational.com Outsourcing Resources Quality Agreements Rober t Iser, vice-president of PA RE X EL Consulting, spoke with BioPharm International about the role quality agreements play in outsourcing. BioPharm: What is a drug company's responsibility when it comes to ensuring the quality and safety of products or ingredients manufactured at a contract facility? Iser: Although a drug company (or an application sponsor or marketing authorization holder) is ultimately responsible for ensuring that products available for patients and caregivers meet quality and safety expectations, the assurance of quality and safety of products and ingredients manufactured at a contract facility is a shared responsibility between the drug company and any contracted facility. Both parties must adhere to the expectations set out by the appropriate regulations and guidance to ensure that the products are manufactured in accordance with current good manufacturing practices (CGMPs), meet the necessary quality standards, and are safe and effective throughout a product's lifecycle. As noted in the current FDA guidance on qualit y agreements (1),'when all parties clearly understand their CGMP-related roles and manufacturing responsibilities, the owner s who use contr ac t facilities, contr ac t facilities that provide services to owners, and, ultimately, patients who take the drugs manufactured under these arrangements may benefit in many ways … each party engaged in the manufacture of a drug is responsible for ensuring compliance with CGMP for the manufacturing activities it performs.' This demonstrates the importance of putting together a sound quality agreement and clearly defining roles and responsibilities of the company and the contract facility. BioPharm: What are the most important aspects of a quality agreement? Iser: There are a number of important aspects for quality agreements between a drug company and a contract manufacturer. It is vital that the following aspects are clearly stated and agreed upon: • The CGMP-related roles and responsibilities of the company and the contract manufacturer, including final approval for manufacturing activities • How deviations and out-of-specification results will be investigated, communicated, and resolved • How changes that may need to be made to the manufacturing process, equipment, analytical methods, specifications, etc., are managed. It is important to consider these aspects, along with other recommendations found in current guidance, when develop- ing and implementing agreements with contact facilities. BioPharm: What are FDA's expectations regarding quality agreements? Iser: FDA published a final guidance for industry in November 2016 on quality agreements with contract manufacturers (1). The guidance was developed as a collaborative effort with the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), the Center for Veterinary Medicine (CVM), and Office of Regulatory Affairs (ORA) and lays out the current thoughts and expectations that FDA has for quality agreements. It is strongly recommended that companies refer to this guidance when initiating a new quality agreement or if they are reviewing an existing quality agreement with a contract facility. It should also be noted that ICH [International Council for Harmonization] Q7 (2) includes helpful information regarding quality agreements with API manufacturing sites which is augmented by FDA's quality agreement guidance. Companies developing combination products should review the expectations found in the guidance on Current Good Manufacturing Practice Requirements for Combination Products, as it relates to contract facilities and quality agreements (3). BioPharm: What are the European expectations regarding quality agreements? Iser: The European Commission published a revision to the European Union Good Manufacturing Practices (GMPs) (Chapter 7) (4), effective in 2013, to provide expectations for outsourced GMP-regulated activities. The revised GMP guide includes many of the same topics as found in the current FDA guidance for industry including roles and responsibilities for contract giver (the drug company) and the contract acceptor (the contract facility), assessment of a facility to carry out outsourced activities, communication of information that is necessary to carry out the outsourced activities, change control expectations, etc. A company looking to enter into a quality agreement should utilize this guide. BioPharm: What mistakes are companies making when drafting quality agreements? Iser: There are some common mistakes that occur when companies are drafting quality agreements. First, roles and responsibilities of the drug company and the contract manufacturer are not always clear, especially when it comes Expectations in Quality Agreements

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