Editor’s note: This is part two of a two-part series about the obligations of own-label distributors. Read part one here.
It's not easy to develop and implement a quality management system (QMS) compliant with all applicable FDA regulations and statutory requirements—particularly current good manufacturing practices (cGMPs) dictated in 21 CFR 111, “Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements.”
To be successful, the system must be scientifically sound, efficient and practical; and it must always be unique to the own-label distributor to accommodate for its specific products, personnel, facilities, operations and contractual relationships.
That said, certain controlled processes and procedures must be incorporated into every successful own-label distributor QMS. The following summary highlights some of these necessary processes essential for current FDA compliance.
- The own-label distributor will have to establish finished product specifications for all dietary supplement products as dictated in 21 CFR 111.70(e) and (f). The own-label distributor also must have a written procedure to explain why meeting this specification will ensure the product meets the quality requirements of identity, purity, strength, composition, and limits of potential contaminants. This written procedural requirement is met by preparing a standard operating procedure (SOP) to describe the establishment of finished product specifications, along with an associated finished product specification template. Finished product specifications will then have to be established for each product using that template.
- The own-label distributor must then qualify the contract manufacturer to demonstrate it is ultimately responsible for ensuring the dietary supplement it places into commerce, or causes to be placed into commerce, is not adulterated under section 402(g) of the Federal Food, Drug and Cosmetic Act (FDCA) for failure to comply with dietary supplement cGMP requirements. This procedure will ensure the facility is registered as a food facility with FDA and that a U.S. agent has been assigned for communication with FDA when a foreign manufacturer is used. It will encompass the use of a contract manufacturer qualification questionnaire, or documentation audit, which will be verified in person with an onsite audit of the facility. The procedure will also outline the process of reviewing and approving the master manufacturing records (MMRs) prior to the production of any finished product, as well as a review of completed batch production records (BPRs) when product lots are manufactured via the use of a BPR checklist to ensure the MMR was exactly followed and all cGMP requirements have been met.
- The responsibilities of the quality unit (QU) must be designated in a written procedure to demonstrate quality personnel are fulfilling all of the numerous requirements in 21 CFR 111, and the group has the authority to reject materials and products as necessary. A quality unit responsibilities procedure must be prepared for this purpose.
- Only the QU can approve or reject each batch of finished dietary supplement product for release and distribution to the U.S. consumer. And, when the product is manufactured by a contract manufacturer for an own-label distributor, FDA expects this final decision to be made by the own-label distributor QU. A procedure must be developed and implemented that defines the own-label distributor product release process and documentation thereof.
- Another vital responsibility of the QU is to conduct a material review and make a disposition decision as required in 21 CFR 111.113(a). This must be done whenever:
- A material or product specification is not met.
- There is a deviation from an MMR.
- An unanticipated occurrence happens during manufacturing or an in-process control system. This includes any controlled process or SOP.
- An instrument calibration problem may have adversely impacted a batch.
- A dietary supplement being returned.
The decision must be made to either accept or reject the material or product as-is; but if rejected, it is possible to potentially rework the product such that it does meet all of the established specifications. This requires a controlled material review process documented on an associated material review form.
- Returned dietary supplements are subject to a material review, and thus must all be evaluated in accordance with a written procedure. The returns may be salvaged if it has been determined the quality of the product has not been impacted and still meets all of the pre-established finished product specifications. However, consideration must be given to the security and environmental conditions of the product while out of the control of the own-label distributor and/or distribution contractor. This decision is the responsibility of the own-label distributor.
- A complaint system documented in a written procedure must be in place to ensure all consumer complaints related to the quality of the dietary supplement product or that have an accusation of illness or injury due to product use are reviewed and investigated in accordance with 21 CFR 111, Subpart O – “Product Complaints.” In addition, any product complaints with allegations of a serious adverse event must be reported to FDA—per the Dietary Supplement and Nonprescription Drug Consumer Protection Act of 2006—within 15 business days.
- In the event a market withdrawal or recall is required for a dietary supplement product, it is imperative that the own-label distributor and contracting partners can quickly coordinate all necessary activities such that the own-label distributor can appropriately work with FDA. An annual mock recall should be performed in preparation, and a written procedure to govern the process is required.
- With all of the procedural requirements needed at the own-label distributor, a process must be in place to dictate the format, use and control of all documents and records. This is often referred to as the SOP on SOPs.
- A change control process must then be developed and implemented to ensure that revisions to any procedures or documents are tracked and monitored. This procedure can govern a variety of, if not all, own-label distributor company operations.
- In accordance with 21 CFR 111.12, each person engaged in manufacturing, packaging, labeling or holding, or in performing any quality control (QC) operations, must be qualified to do so with a combination of education, training and experience. A job description is therefore required for each job function, and an own-label distributor written procedure regarding personnel training is required. This training must also include cGMP training.
- It is highly recommended that a quality agreement be established between the own-label distributor and contract manufacturer to ensure all QU responsibilities required throughout 21 CFR 111 are assigned to at least one of the contracting parties or shared among them. This will include critical decisions such as product release and the potential review of manufacturing deviations or out-of-specification testing results. The quality agreement will also assign responsibility for the generation of data to support any expiration or best-by dates that will be placed on the product. Finally, the agreement will ensure each party will inform the other regarding FDA inspections and any resulting 483 list of observations, received warning letters, or other type of agency communication.
It bears repeating that indeed, FDA is inspecting dietary supplement own-label distributors and digging deep (frequently, very deep) into the cGMP QMS to ensure the own-label distributor QU meets its responsibility to distribute to the U.S. consumer only safe, quality products that are manufactured in compliance with all applicable laws.
Tara Lin Couch, Ph.D., owner of TLC Regulatory and Laboratory Consulting, is an analytical/organic chemist who also obtained a bachelor’s degree in mathematics. She has more than 35 years of diverse laboratory and regulatory experience in academic, field, contract and manufacturing environments. Couch is a sought-after expert on issues pertaining to quality control in pharmaceutical, dietary supplement, tobacco manufacturing and the cannabis industries. As a consultant, she assists with the development, improvement and implementation