Regulatory Enforcement in Contract Manufacturing: An Emerging Normal

Regulations concerning the manufacture, packaging, holding and distribution of dietary supplements have been in effect for over a decade. They are codified in the Code of Federal Regulations (CFR), part 111 cGMPs (current good manufacturing practices), the “DS CGMP Rule.” Every step along the supply chain is covered by these regulations, and the emphasis on compliance with these regulations has never been more important. Contract manufacturers have the greatest burden regarding the application and enforcement of these regulations in large part because of the amount of involvement. The activities involved in co-packing products on behalf of another company are no less detailed, and the obligations out of these regulations are being reinforced through greater efforts on the part of FDA. The result of this reinforcement is the establishment of a new normal for the regulated.

Inspections that occur with increasing frequency by representatives of FDA (sometimes, inclusive of state regulatory agencies serving as surrogates for these inspections) involve deeper analysis of practices being employed. Deficiencies found during inspection are recorded on an inspectional observations sheet (form 483) and response detailing actions to be taken is required. Failure to respond appropriately, inclusive of actual implementation of corrective actions described in the response, can result in the issuance of a warning letter. This is effectively the potential for “strike two” in the regulatory at bat.

Now, there is a shift in the norm. In part as the result of authority granted to FDA by the Food Safety Modernization Act (FSMA), FDA is increasingly acting in a direct fashion after a second strike. The actions taken now involve enlisting the power and authority of the U.S. Department of Justice (DOJ) to mete out punishment for lack of compliance. This is usually a self-accepted punishment in the form of a consent decree. The terms of the decrees can effectively relegate a business to the ash-heap of history and prevent the current owners from participating in the industry in the future. This is a real threat and is part of the normal consequences of non-compliance.

The application of FDA’s administrative authority is a response to the history of recalcitrance on the part of some industry members (remember that decade that has passed since finalization of GMPs?). The targets for these actions fall mostly on contract manufacturers. Even in instances where activity from a business perspective is co-packing, the regulatory obligations found in GMPs remain, and the consequences are real and significant. In the best-case scenario, the contract manufacturer recognizes the requirements and fulfills its regulatory obligations, with specific emphasis on performing the right tests and examinations of products as required. Should there be an inspection finding by FDA regarding the operation, prompt, effective response and implementation of commitments within the response are mandatory. The seriousness of consequences in time, money and potential continuation of business is real in the emerging normal of enforcement. This should be considered a positive in many ways since this enforcement activity raises awareness, at a minimum, and delivers the message that compliance is the only way to continue moving forward. The threat, in most instances, is self-inflicted. The solution is to review procedures, processes and activities performed, and confirm operation complies.

Shortcuts to compliance are demonstrated in the most recent findings of the inspections occurring. Third-party GMP certification of the operation has little value when it comes to regulatory compliance. Confusion over obligations of the regulations and additionally imposed standards from these certifications do nothing to blunt the threat in this emerging normal. Contract manufacturers must be aware of all aspects of their operations, practices, testing and release of products, regardless of arrangements with their customers. No longer is enforcement less-than harmful.

The solution lies in preventive techniques and a proactive quality mindset. Re-evaluate the procedures in place for the operation, regardless of the activities performed. Re-assess the specifications established for each step where regulatory obligations require such specifications. Ensure appropriate testing against these specifications occurs and that components and products are controlled through proper release of the goods, once manufacturing is complete. As time passes, be assured that continually improving on the operations from a compliance perspective is mandatory as well. The consequences are not going to diminish and the level of detail in assessing compliance will only increase.

As chief operating officer, Jim Lassiter oversees all consulting operations at Ingredient Identity (ingredientidentity.com). He has more than four decades of experience in quality control (QC), and government and regulatory affairs throughout the pharmaceutical, dietary supplement and natural product industries with organizations such as Nutrilite, Robinson Pharma, Irwin Naturals, Chromadex, the American Herbal Products Association (AHPA) and the Council for Responsible Nutrition (CRN). A respected author and speaker, Lassiter has served on numerous industry and trade boards.