by Vince Paternoster

Even with years of awareness concerning the requirements established by the Part 111 cGMP (current good manufacturing practice) rule for dietary supplement products, companies are being cited for serious regulatory compliance deficiencies as FDA conducts inspections of the more than 1,000 dietary supplement companies in the United States. While FDA may be lenient for first-time offenders with minor problems, more warning letters are being issued. Of major concern is the worst-case scenario of not being in compliance with the cGMP rule can cause the products to be deemed adulterated by FDA.

A company is subject to the dietary supplement cGMP rule when it manufactures, packages, labels, holds or distributes a dietary supplement product. Companies with manufacturing operations tend to be more complaint with the cGMP rule; however, a large number of dietary supplement companies, referred to as own-label distributors can be less knowledgeable of their direct regulatory compliance requirements and their obligations regarding their contract manufacturers' operations. Own-label distributors are companies that have their products contract manufactured. Additionally, a company that holds and distributes any dietary supplement product needs to comply with the parts of the regulations concerning their operations and confirm its contract manufacturer is in compliance, too. As such, there are some specific questions own-label distributors should ask to ensure they are distributing cGMP compliant dietary supplements.

Raw Material Sourcing

1. Are the raw materials and packaging components acceptable for use?

Make sure the raw materials come from suppliers that can be qualified under the Part 111 regulation. This will involve conducting audits and testing of suppliers raw materials as applicable. Problems in this area can cause ongoing supply interruptions or possible product adulteration. Do not use unstable raw materials since this could affect product shelf life. Conduct an adequate evaluation of dietary ingredients and technical ingredients, including scientifically valid identity testing. Plant- and animal-sourced ingredients often require extra attention to ensure they meet purity and potency specifications and are free from contamination. Regarding Prop 65 contaminants, some ingredients can be more problematic then others and require additional testing.

All packaging components should be suitable to protect the product from tampering and for the storage conditions the product will be subject to, while being inert to the product itself. Packaging materials that come in contact with the product need to be free of filth and potential contaminants. Verify companies supplying packaging materials that are in direct contact with the finished dietary supplement are knowledgeable about the 21 CFR regulations that apply to those components.

Labeling Concerns

2. Will the labels cause the product to be misbranded or possibly recalled?

Labels and labeling issues cause more regulatory and legal action against products than all other cGMP matters. Ensure product labels have been reviewed by an expert in labeling regulations and laws that impact supplements. Labeling regulations are quite extensive, with primary label regulations for dietary supplements found at 21 CFR 101.36. However, additional labeling regulations for conventional foods also apply, principally found in 21 CFR 101 and elsewhere.

Claims and claims substantiation and having submitted to FDA the required 30 day notification are areas to focus on during establishment inspections. When using FDA-approved health claims, confirm the wording follows what is required for the specific nutrient; its worthwhile to be familiar with the general requirements for health claims found at 21 CFR 101.14. Labeling issues include the required format, layout, font size/type and information.

Here are some points to consider when reviewing the labeling:

Inspection Preparation

3. Is my company ready for an FDA cGMP inspection?

During an FDA inspection, the area of focus for Part 111 cGMP compliance can be quite extensive, typically taking a few to several days. This will include a thorough inspection of the facility, operations, components, quality control (QC), written procedures, documentation/record keeping, etc. The inspection also includes an intensive series of questions that detail each subpart of the cGMP rule. Of particular importance is whether all employees have completed cGMP training. Such a program should include a general overview of Part 111, and subparts and sections related to appropriate operations, including inspecting and approving suppliers.

Don't wait to implement a compliance program until FDA conducts an inspection. Too often companies put off cGMP compliance until an FDA inspection, which can lead to enforcement actions and being thrust into a costly panic mode to catch-up on Part 111 compliance activities. Do have a contract manufacturing agreement that clearly delineates the Part 111 compliance obligations. In general, Own Label Distributors are responsible for the operations they are directly involved with, but should also conduct audits to confirm their contract manufacturers cGMP compliance.

Don't put off conducting onsite inspections of contract manufacturing facilities, and have written records to prove to FDA inspectors this was undertaken on a regular basis. Do check to determine whether the contract manufacturer has been inspected by FDA for Part 111 CGMP compliance. Proof of FDA compliance can be indicated in Establishment Inspection Reports, and cGMP certifications issued by the state of business operations.

Don't ignore the importance of written procedures, documentation and record keeping obligations. Do have written procedures required for your operations, and make sure the contract manufacturer has them as well. Part 111 requires establishing and following a number of written procedures, as specified in the various subparts of the rule, for example:

Don't forget the documentation/record keeping. Documentation/records required by the Part 111 rule are quite extensive. Which of the following examples concerns your operations or your suppliers operations related to dietary supplement manufacturing, packaging, holding and distributing?

Becoming cGMP compliant can be overwhelming for companies new to the regulatory world, and have not yet been through an FDA inspection. Working with a contract manufacturer and consultants with cGMP compliance experience, in addition to hiring qualified personnel, is vital for passing FDA inspections and avoiding warning letters and enforcement actions that can disrupt business operations and may lead to incurring avoidable liabilities.  

Vince Paternoster is the president of NutriSport Pharmacal , a custom contract developer, manufacturer and packager of all types of dietary supplements, with experience in developing and manufacturing a variety of controlled-release dietary supplement tablets and capsules. Contact NSP at (888)703-3300, (973)209-7200 or [email protected].