Issue link: https://www.e-digitaleditions.com/i/581434
Tablets & Capsules October 2015 32C cGMP requirements" [1]. Specifically, distributors were cited for failure to: • Establish specifications; • Establish written procedures for the responsibilities of quality control operations; • Document approval and release of products; • Establish and follow procedures for product complaints; • Establish and follow procedures for product returns; and, • Document employee training. The cGMP final rule, which states that a company must "comply with the cGMP requirements that apply to [its] operations related to manufacturing, packaging, labeling, and holding of dietary supplements" [2], has been miscon- strued by some to suggest that companies are responsible only for the cGMP regulations that apply to their in-house operations. But that's incorrect, because further down on the same page the regulation states [3]: In cases where a distributor contracts with a manu- facturer to manufacture a dietary supplement that the distributor then distributes under its own label, the distributor has an obligation to know what and how manufacturing activities are performed so that the dis- tributor can make decisions related to whether the packaged and labeled product conforms to its estab- lished specifications and whether to approve and release the product for distribution. In short, if your company's name is on the label, the FDA expects you to ensure compliance. Enter the quality agreement In a 2013 draft Guidance for Industry [4], the FDA offered recommendations for establishing quality agree- ments between label owners and CMOs that spell out the specific cGMP-compliance responsibilities of each party. The draft Guidance was issued with commercial phar- maceutical operations in mind, but it applies to dietary sup- plement operations, too. While the FDA doesn't require dietary supplement manufacturers or distributors to have Quality Agreements, they're nonetheless a good idea because they promote cGMP compliance, help to safeguard the quality of products entering the marketplace, and pro- tect distributors and CMOs from FDA enforcement action and/or other legal entanglements. The FDA defines a quality agreement as "a comprehen- sive written agreement that defines and establishes the obligations and responsibilities of the Quality Units of each of the parties involved in contract manufacturing of prod- ucts subject to cGMP" [5]. Table 1 summarizes what a qual- ity agreement should cover. In general, quality agreements should clarify which of the regulatory activities are to be carried out by each party. They are not to be construed as commercial or business agreements; that is, they don't address general terms and conditions, confidentiality, prices and costs, delivery terms, or limits on liability or liquidated damages. The FDA rec- ommends that quality agreements be separate documents, or at least severable, from commercial contracts, such as master service and supply agreements. The best quality agreements are drafted with the help of representatives from each party's quality assurance departments and key stakeholders. Bear in mind that while the FDA does not routinely request or review business documents or business agreements during inspections, the Agency does routinely request and review evidence of quality agreements or the lack thereof. Drilling down on quality specifications Per the FDA, "[Q]uality means that the dietary supple- ment consistently meets the established specifications for identity, purity, strength, and composition and limits on contaminants, and has been manufactured, packaged, labeled, and held under conditions to prevent adulteration" [6]. Therefore, the quality agreement must spell out the means by which you will ensure that: • Each ingredient is the one specified and that each supplement matches its specification and its label (identity); • The ingredients, finished product, and packaging are free of contaminants (purity); Table 1 What a quality agreement should cover • GMP verification • Communication and confidentiality • Roles and responsibilities • Definition of signatories • Client's (OLD's) right to audit • Documentation/record retention • Change control • Storage & shipping • Personnel • Labeling approval and management • Specifications • Supplier qualification • Raw-material and finished-product testing • Stability testing • Manufacturing and packaging records • Sample retention • Equipment and facilities • Deviations, unexpected occurrences, out-of-spec results • Reprocessing/disposals • Batch record review and batch release to client (OLD) • Final product release by client (OLD) • Use of third parties (labs, etc.) • Complaint handling • Recalls, market withdrawals, stock recovery • Notification of FDA inspections and regulatory activities