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How to Audit and Qualify Manufacturers, Service Providers for cGMP Compliance

<p>Creating simple, efficient and cost-effective ways to pre-select potential contract manufacturing partners prior to engaging in a formal contract is crucial to both the quality of the final product and the success of the partnership.</p>

In hundreds of inspections carried out by FDA since 2009—based on inspection observations released by FDA, many dietary supplement contract manufacturers have been found to be deficient in basic areas of cGMPs (current good manufacturing practices). So it is important for distributors who outsource their manufacturing activities to ensure their suppliers are compliant with the cGMPs and other applicable regulations. Creating simple, efficient and cost-effective ways to pre-select potential contract manufacturing partners prior to engaging in a formal contract is crucial to both the quality of the final product and the success of the partnership. Due diligence at the early stages of engagement increases the chances that the final firm selected will be compatible with the own-label distributor’s business needs and the requirements for cGMP compliance.

Qualification of contract manufacturers and other service providers can be summarized as a three step process:

1. Evaluate the firm’s regulatory history, documentation, processes and quality control systems

2. Define a quality agreement that allocates regulatory responsibilities

3. Qualify the manufactured product by independent verification and inspection

Most own-label distributors have limited resources, and visiting every candidate may not be practical. Prior to planning in-person audits, distributors should conserve time and travel budgets by utilizing internet searches and document reviews to eliminate obviously non-compliant manufacturers early in the selection process. More than 700 dietary supplement inspections have resulted in FDA Form-483 observations for failure to maintain batch records that meet the minimum cGMP requirements. A thorough review of the firm’s regulatory history, followed by a desk-based audit of process documents for cGMP compliance, may yield vital information about the overall quality of manufacturing operations. Assessment of master manufacturing records (MMRs) and batch production records (BPRs), together with standard operating procedures (SOPs), can help to verify that the manufacturer complies with the relevant cGMPs. Prior inspection observations and details on recalls, if any, can be obtained at FDA’s website ( or through Freedom of Information requests. Financial records, advertising, and mergers or acquisitions of the company may also provide valuable insights. Re-branding and changes of ownership are common in the supplement industry—social media and press releases will often reveal pertinent details regarding a company’s history and compliance record.

Identification and mitigation of risk factors is essential in deciding what level of scrutiny to apply to a firm. Whether an in-person visit is warranted at the early stages of negotiation often depends on the complexity of the specific operations—compare the potential hazards involved in formulation and blending with those for packaging and labeling, for example. Third-party certifications may be acceptable in lieu of an audit, but the certifier must be well-established and the certification must cover the actual services provided. A quality systems questionnaire filled out by the quality control (QC) unit can be a useful part of the assessment, but does not substitute for an in-person visit or independent audit. If a potential business partner resists requests to visit its facility or review process documents, remind the company that hosting audits is a necessary part of the transparency required in a regulated industry.

A comprehensive quality agreement describing how the firms will work together, with a focus on the identified risk items, is not required by regulation, but is highly recommended. The quality agreement should cover, in sufficient detail, exactly which party is responsible for following each section of the applicable regulations. Who will formulate? Who will check labels for legal compliance? Who is responsible for final product testing? Who keeps reserve samples? How will returns and complaints be handled? Make sure the quality agreement includes the right to conduct on-site audits at the manufacturer or supplier, and requires authorization for all deviations from the formula or MMR, especially those that might affect labeling.

Recent FDA warning letters have indicated own-label distributors must be aware of how cGMP-related activities are being carried out on their behalf. The agency also expects the distributor to employ qualified personnel who can approve and release (or reject) finished products for distribution. Product specifications must be established to ensure the product received from the contract manufacturer is adequately identified, consistent with the purchase order, and correctly labeled. Written procedures are required for any QC operations performed by the distributor on finished dietary supplements, which may include supplier qualification, handling returns and complaints, distribution, warehousing, material reviews and disposition decisions on items not meeting specifications.

After a partner is selected, and even when final product is routinely tested by the manufacturer or its contract laboratory, own-label distributors should verify the finished product consistently meets specifications. Periodic qualification of the manufacturer’s certificate of analysis (CoA) using an independent third-party analytical laboratory is advisable, although not specifically required by regulations. Analyze initial batches, then a subset of batches thereafter on a rotational basis, to confirm that the CoA provided is accurate and batch-representative. Ensure all label claims are met, and check that the contract manufacturer’s standards do not deteriorate over time. Consider auditing the analytical laboratories where testing is performed. Pilot batches may be warranted for high-risk products containing numerous or unusual ingredients—or when processing is complex—to ensure the proposed formulation meets specifications.

Finally, once the working relationship is established, make regular visits to observe operations, preferably when the actual product is being manufactured. Routinely monitor for FDA inspections or other regulatory actions, and encourage the contract manufacturer to share details, including the corrective actions taken, of inspection findings that may affect products already shipped or any future batches.

In summary, to find success in a contract manufacturing partnership:

• pre-audit potential partners based on evidence of compliance;

• create a quality agreement to allocate cGMP responsibilities;

• establish product specifications and QC oversight of manufacturing and distribution operations;

• visit contract manufacturers to observe product being manufactured; and

• inspect (and periodically test) finished batches to confirm specifications are consistently met.

Marian Boardley is an independent consultant who manages projects for dietary supplement manufacturers and distributors. She helps clients in the food, drug and dietary supplement industries to implement compliance with dietary supplement, food and other current good manufacturing practices (cGMP's). She regularly trains staff to be ready for FDA inspections and also writes documentation for quality control, laboratory and manufacturing operations.

Looking for more information on GMP Compliance?

Marian Boardley will speak on “How to Audit and Qualify Suppliers for cGMP Compliance" as part of the GMP Workshop at SupplySide West. The three-hour workshop will take place on Friday, Oct. 9, at Mandalay Bay in Las Vegas. Visit for the complete agenda and to get registered.

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