A high percentage of dietary supplements sold in the United States are manufactured by contract manufacturers. FDA regulations (21 CFR Part 111, Good Manufacturing Practice [GMPs] in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements) were published in 2007. GMPs provide extensive detail regarding what controls, records and testing must be done when manufacturing a dietary supplement, and apply to all manufacturers. Contract manufacturers have no different responsibilities than manufacturers that make and distribute products under their own label, and are responsible for compliance with 21 CFR Part 111 from the standpoint of manufacturing and control operations.
Despite this, warning letters are consistently issued by FDA to both dietary supplement manufacturers and dietary supplement own-label distributors for lack of basic GMP compliance over the past 10 years since the requirements have been in place. While citations encompass nearly all subparts of the regulation, the most common relate to failure to:
- Establish adequate specifications for finished products and dietary ingredients;
- Maintain master manufacturing records (MMRs) and batch production records;
- Identify responsibilities of the quality unit and management in written procedures; and
- Conduct investigations of complaints and returned products.
Contract manufacturers must not only comply with GMP regulations, but must also ensure the products they manufacture do not contain any new dietary ingredients (NDIs) in the formulation; and if they provide a finished, labeled product, they must ensure the labels do not include any unapproved claims, which can cause the product to be an unapproved new drug. Such unapproved new drugs cannot be legally marketed without prior approval from FDA. Warning letters on these topics make statements such as, “Your product contains a new dietary ingredient and is deemed adulterated under section 402(f) of the Act (The Food, Drug and Cosmetic Act),” and “Your products are not generally recognized as safe and effective for the referenced used and, therefore, the products are ‘new drugs’ under section 201(p) of the Act.”
An additional challenge for the contract manufacturer is they do not have control over what their customers do with the products or how they label them. For example, if the contract manufacturer provides products to customers unlabeled, they, of course, will not be responsible for the final product label. When the contract manufacturer does label the product, then both the contract manufacturer and the own-label distributor have responsibility for the label content.
Own Label Distributors
FDA has made it clear in numerous warning letters; contract manufacturers are not the only ones responsible for GMP, ingredient and label compliance. Own-label distributors routinely receive warning letters stating, “Your firm introduced or delivers, or causes the introduction or delivery, of dietary supplements into interstate commerce for distribution to consumers. As such, your firm has an overarching and ultimate responsibility to ensure that all phases of the production of that product are in compliance with dietary supplement cGMP requirements.” Other observations of non-compliance with 21 CFR Part 111 are also issued in warning letters, and these were discussed in an INSIDER article written by Dean R. Cirotta, president of EAS Consulting Group, in the April 2013 Digital Magazine “Regulatory Roundup.”
What this practically means is the own-label distributor must have a program to “qualify” all their contract manufacturers and this includes on-site audits of those facilities to confirm their products are manufactured in compliance with the 21 CFR Part 111 requirements. However, prior to this, most own-label distributors obtain a completed questionnaire from prospective contract manufacturers to gather basic background information about the company and their controls, records and testing systems. If the information seems reasonable, then they will proceed with the on-site audit. Own-label distributors that do not have the expertise to perform the audits themselves must have them done by consultants.
To avoid these types of FDA enforcement actions, the own-label distributor can:
- Employ staff that are knowledgeable about the 21 CFR Part 111 requirements;
- Have a well-qualified director of the quality unit;
- Continually train staff on 21 CFR Part 111, and other statutory requirements;
- Conduct frequent internal audits with staff as well as outside expert consultants;
- If it receives an FDA 483 list of observations during an FDA inspection, respond quickly and completely. Obtain outside expert consultant assistance, if necessary, to ensure the response is adequate; and
- Establish a quality agreement with the contract manufacturer. Such agreements will make it clear who is responsible for all aspects of compliance with FDA laws and regulations. When these suggestions are followed, the likelihood of regulatory problems is significantly decreased.
Robert Fish, independent advisor for quality and compliance, joined EAS Consulting Group LLC in November 2006 after 10 years consulting for FDA regulated industries. He spent 33 years with FDA, the last 6 years of that service as Director, Division of Field Investigations (DFI). He was responsible for general policy and guidance for the agency’s domestic and international investigation activities.