BioPharm

www.biopharminternational.com March 2018 BioPharm International eBook 17 Outsourcing Resources Quality Agreements In talk ing about t he par t ies involved in contract manufactur- ing of drugs, the term "owner" is used to mean manufacturers of APIs, drug substances, in-process materials, and finished drug prod- ucts, including biological products and combination products. This excludes retail pharmacies, drug stores, supermarkets, discount ware- house stores, or other retailers who purchase finished drug products to sell over the counter (OTC) as a store brand. "Contract facilities" refers to parties that perform one or more manufacturing operations on behalf of an owner or owners. The guidance document empha- sizes the need for good communica- tion between owners and contract facilities. It also emphasizes the shared nature of the responsibil- ity to comply with CGMP. Neither party can blame the other for its failure to meet CGMP. SCOPE OF QUALITY AGREEMENTS GUIDANCE I n C o n t r a c t M a n u f a c t u r i n g Ar rangements for Dr ugs: Qualit y Agreements, FDA describes its current thinking on defining, establishing, and documenting manufacturing activities for all the parties involved in contract drug manufacturing. The drug product types include: • Human drugs • Veterinary drugs • Certain combination products • Biological and biotechnolog y products • Finished products • APIs • Drug substances • In-process materials • D r u g c o n s t i t u e n t s o f c o m b i n a t i o n d r u g / d e v i c e products. T he s c op e of t he g u id a nc e is limited to CGMP-related roles, responsibilities, and manufacturing activities between owners and con- tract facilities. The scope includes activities such as processing, pack- ing, holding, labeling operations, testing, and quality unit operations. Owners and contract facilities interact in a variety of ways. An owner could be a product sponsor or an entity that decides to make and market products. An owner could contract out all the man- ufact uring activ ities, but when an owner uses a contract facility, the owner's quality unit remains r e s p o n s i b l e u nd e r C G M P f o r approving or rejecting drug prod- ucts manufactured by the contract facility, including for final release. There are numerous reasons for owners to turn to contract facili- ties to outsource portions or all manufacturing activities. Owners typically benefit in terms of exper- tise, cost, efficiency, or capacity. To ensure CGMP conformance, product quality, and successful collaboration, all parties must clearly understand their CGMP-related roles and man- ufacturing responsibilities. Failure to define roles for manufacturing activities can lead to misunderstand- ings or misinterpretation by the owner and contract facility. These misunderstandings or erroneous assumptions can have significant consequences for product quality. Each party engaged in the manu- facture of a drug is responsible for ensuring compliance with CGMP for the manufacturing activities it performs. Delineating the CGMP- related roles, responsibilities, and manufacturing activities to be per- formed by each party is paramount in assuring product quality. Above all, remember that quality agree- ments cannot be used to delegate responsibility to comply with CGMP. A f ter an ow ner and contract facility establish a quality agree- ment, they may find they need to adapt to changes that affect their manufacturing activities. Either pa r t y shou ld b e able to i n it i- ate a conversation as change can originate from various sources— changes to facilities, raw material sources, processes, test methods, specifications, or the site of pro- duction. The quality agreement should address how changes made by eit her pa r t y a re com mu n i- cated and agreed upon and which changes will require prior approval to implement. Although periodic reviews are useful to ensure the agreement remains current, these periodic reviews do not replace essential real-time communication of changes between the parties. Owners and contract facilities are responsible for ensuring that their quality agreements are work- ing for them. Issues arise from poor com mu n icat ion, m isinter preta- tion, assumptions on the scope of work or activities to be performed, terminolog y, escalation/notifica- tion procedures, and control of change over the project/product's life cycle. To assure product qual- ity, owners must take steps to fully understand the contract facility's scope of activities and capabilities. Similarly, contract facilities should not over-promise or make assump- tions about a client's expectation. Quality agreements are not only a way of meeting CGMP require- ments; they make sound business sense to assure all parties involved understand their role in producing a compliant product. LEGAL BACKGROUND Drugs not manufactured in con- formance with CGMP are deemed adulterated under Section 501(a)(2) (B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Under this statute, a drug is adulterated "if the methods used in, or facilities or controls used for, manufactur- ing, processing, packing, or hold- ing do not conform with CGMP."

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