Dietary supplement Current Good Manufacturing Practices (cGMPs), dictated in 21 CFR Part 111, have been in place for close to two decades. Even with the FDA efforts to ensure consistent manufacturing to established product specifications, industry confusion with the basic tenets of the regulation result in numerous FDA observations and warning letters.
The quality of the raw materials that are used in manufacturing a regulated final product marketed to consumers is one of the most critical aspects of GMPs. Ensuring the raw material quality begins with properly and effectively qualifying the raw material supplier.
In the dietary supplement cGMPs, as well as other regulated industries, supplier qualification is a requirement. However, there are many different approaches to supplier qualification, and the FDA does not outline specifics of what should be included in a supplier qualification program.
Getting Started The dietary supplement cGMPs require that companies qualify a supplier before relying on their certificate of analysis (CofA) results in lieu of testing (21 CFR 111.75). Note that identity testing of a dietary ingredient must always be conducted.
In order to properly qualify a supplier, a company should first establish a program and document it in a standard operating procedure (SOP). The program should outline the specific requirements to qualify a supplier, and the qualification steps that need to be performed prior to utilizing an ingredient they provide.
Additionally, all supplier qualification activities must be documented. It is highly recommended that the qualification requirements be commensurate with the supplier and ingredient risk. Therefore, a foundation in supplier qualification should be determining the risk level of the supplier and the ingredient.
Assessing Risk
The method for conducting a risk analysis should be summarized or referenced in the supplier qualification SOP. A checklist or risk assessment table is often useful.
Some example considerations when assessing the risk of a supplier are:
- Are they in a country with low regulatory oversight (higher risk) or a mature regulatory body (lower risk)?
- Have they been inspected by a regulatory body and what were the results? Frequent inspections with acceptable results would lower the risk of the supplier.
- How long have they been manufacturing the ingredient you want to procure? If they are a new manufacturer, they will be higher risk. Conversely, a manufacturer with extensive experience and expertise would be lower risk.
- If you have used the supplier previously, were the interactions positive (low risk), negative (high risk), or a mix of each?
Some example considerations when determining the risk of the ingredient are:
- How complex is the process to manufacture the ingredient? The more steps, reactions, processes etc., the higher the risk of the ingredient.
- Is the ingredient one that is associated with economic adulteration? Per the FDA, economic adulteration is when a manufacturer “intentionally leaves out, takes out, or substitutes a valuable ingredient or part of a food.” The FDA.gov website provides information on ingredients associated with economic adulteration, and these ingredients should be classified as higher risk.
- What is the compendial status of the ingredient? If it is a USP grade material it is likely lower risk as opposed to a novel ingredient with no compendia which may be higher risk.
- The volume of use of the raw material may also be used to assess risk. If it is a high-volume ingredient or associated with the brand name of the product, a higher risk may be assigned due to the high business risk.
The items listed above are some risk considerations when assigning a risk level to the ingredient and supplier but are not all encompassing. Once the combined risk is assigned, it can be used to determine what qualification requirements there will be for the supplier and potentially aid in determining a testing program for the ingredient. Utilizing risk-based principles allows companies to best allocate their resources while devoting more time to higher risk suppliers.
Selecting and Qualifying
The main tools used to select and qualify a supplier are a supplier technical review (including specifications, feasibility, capacity, etc.), questionnaire (or paper audit), an on-site audit, confirmatory CofA testing, and ongoing analysis of their qualification status. Technical documentation should be initially requested from the supplier in order to evaluate potential suppliers and determine their viability. The information requested should include a CofA and specifications and general regulatory, manufacturing, and facility information.
There are several valuable industry references that may be used as a guide to facilitate this initial communication between supplier and manufacturer, including the SIDI Protocol, which is a voluntary guideline developed jointly by dietary supplement trade organizations and industry representatives.
Once the appropriate potential suppliers are selected from the technical review, the questionnaire (or paper audit) is typically a good first step in the qualification process. The questionnaire needs to have detailed and preferably open-ended questions about their quality system, regulatory history, and any third-party certifications they may have. The questionnaire should be reviewed by someone who is qualified to ascertain if the answers are acceptable or need additional follow-up.
Completion of the questionnaire alone is not enough; the content is important. Answers from the questionnaire and technical review can be used to assign a risk level to the supplier and ingredient. In alignment with an established supplier program documented in a SOP, low and medium-low risk suppliers may not need an on-site audit. It is recommended that medium-high and high-risk suppliers receive an on-site audit.
If it is determined based on risk that an on-site audit is required, it should be performed by a qualified auditor. This can be someone within the qualifying organization or a third party, such as a consulting firm. The audit can be extremely valuable, not only in assessing the supplier’s quality system, but also in building a relationship with the supplier. The results of the audit should be used to determine the qualification status of the supplier. They may be approved, provisionally approved, or disqualified. Provisional approvals may be used if there are some gaps in the quality system, but the supplier has committed to resolve them. A provisionally approved supplier should receive an extra level of scrutiny during incoming material acceptance activities. This extra evaluation can be in the form of increased sampling or testing.
In the case of dietary supplements, it is a requirement that if the supplier’s CofA will be used in lieu of testing for strength, composition, purity, and/or contaminants, the reliability of the CofA must first be confirmed. This means that the supplier needs to be approved, and then the manufacturer using the material needs to conduct the same testing the supplier did for an established number of lots (minimum of three) in order to confirm the reliability of the CofA. If it is determined to be reliable, the results may be used in lieu of testing going forward, provided the CofA is periodically requalified.
This is typically accomplished by repeating the CofA testing every tenth lot or annually (whichever comes first). Note, for dietary ingredients, identity testing must always be performed by the manufacturer receiving the material. If any failures are obtained either during the periodic or initial qualification, full testing should be utilized until reliability can be re-established.
Qualification is Ongoing
One of the most important things to remember regarding supplier qualification is that it should be ongoing. Periodic routine reassessments are critical to ensure there have been no changes and that the supplier’s quality management system remains acceptable. Additionally, requalification may be necessary if poor performance is observed. Poor performance could be repeat failing results, late deliveries, inadequate communication, or new production run-ability issues. Frequency of requalification should be based on risk and defined in the supplier qualification SOP.
Ensuring the quality of finished products not only requires in-house quality control processes but also a robust supplier qualification process. Establishing a supplier qualification program is one of the most critical quality system activities for a manufacturer to reduce risks. The quality of the raw materials and the reliability of the supplier directly impact the quality of the finished product, which is necessary to protect both the public’s health and the reputation of the manufacturer.
References
U.S. FDA. (2007, June). Current Good Manufacturing Practice In Manufacturing, Packaging, Labeling, Or Holding Operations For Dietary Supplements.
Council for Responsible Nutrition. Standardized Information on Dietary Ingredients (SIDI) archives. [accessed July 1, 2025]