Frequently Asked Questions: USP Verification Services
Dietary Supplements Verification Program
- What is the verification process?
- What does a USP Verification Program GMP review consist of?
- When is the USP verification mark granted to a dietary supplement product?
- Why does USP utilize its own laboratories to test products?
- Can consumers assume that a USP-verified supplement is safe?
- Can consumers assume that a USP-verified supplement is effective?
- Is the USP GMP audit a substitute for a regulatory audit?
- If my site is ISO certified, does this automatically lead to USP Verification?
- My company is frequently audited already. Why should we invite USP to audit us?
- What is the time cycle for GMP audits? Is the GMP audit unannounced?
- Will USP auditors help train and improve the skills of my staff to advance the quality of our internal audits?
- How can I tell my customers what USP verification means to them?
- How does USP protect participants' data?
- Would USP report an adverse situation to a regulatory body?
- How does USP determine the fee structure for verification?
- How is the fee paid to USP?
- What is the remedy structure of the USP Audit when a deficiency is identified?
- Who are USP auditors?
- If your auditor travels to my company and finds it is not prepared for an audit, what happens?
- If my company has global manufacturing sites, how will that be addressed?
- Who will collect the samples for surveillance studies?
- What is the time between signing the License Agreement and completion of the verification process?
- What is the procedure for getting another ingredient verified after a time lapse of, for example, 6 months since the first ingredient's verification?
- Will regulators from my country recognize the USP verification?
- If specifications are different from the USP–NF monograph, what is the course of action by USP?
Dietary Supplements Verification Program
USP's Dietary Supplement Verification Program is a multi-step process. It begins with a pre-audit review, which entails an initial assessment of the manufacturing company's quality system infrastructure. The program is designed to help ensure that critical elements of a manufacturing company's quality systems are in place prior to conducting extensive on-site facility audits, documentation review, and product testing. (See Verification Program process graphic.)
- When the USP verification program staff has determined that a manufacturing company's quality systems infrastructure is in place, an extensive on-site audit of the manufacturer's facility and operations is conducted. The audit covers all aspects of the manufacturing operation from receiving materials to shipping of the final product. The on-site facility audit helps ensure that the system controls and operation used to manufacture a product are functioning properly.
- Upon successful completion of the on-site facility audit, an extensive review of product quality control and manufacturing documentation is performed on specific lots of products. These documents need to demonstrate that a manufacturer is producing products according to their specifications, as per the Food Drug Administration (FDA) and USP manufacturing practices requirements. The review of these documents is designed to identify areas of improvement for all aspects of the manufacturing process that helps ensure that a quality product is consistently obtained.
- Once the manufacturer has met the requirements of the documentation review, the USP verification program staff sample a statistically determined number of the manufacturer's products and tests them to verify that they conform to the product’s specifications and ingredient quantitative label claims. This step primarily confirms the observations obtained from the on-site facility audit and review of product documentation. The USP verification program staff works closely with the manufacturer to resolve any issues that may arise during testing. Other testing programs merely report test results.
- If a dietary supplement manufacturer has reached this point in the program, they have met the requirements of the program, and the product under review is awarded the USP Verified Mark. Afterwards, to help ensure that the product continues to meet the requirements of the program, the program staff conducts market surveillance product testing, product documentation review, and manufacturing site facility audits, on an annual basis.
USP's Verification Program is designed to be the most rigorous program currently available. It was created to help dietary supplement manufacturers meet not only FDA current good manufacturing practices (cGMPs) codified in 21 CFR Part 111, but also USP <2750> Manufacturing Practices for Dietary Supplements. When manufacturers enter the program, they are required to submit extensive documentation about their manufacturing operations. The documentation provided by a manufacturer must demonstrate that they have the systems needed to produce quality dietary supplements. USP conducts a six (6) quality systems audit evaluating the manufacturer’s quality management, facilities and equipment, materials, production, packaging and labeling, and laboratory control systems. An on-site facility audit of the manufacturing operation is conducted to help ensure that the systems and controls needed to consistently manufacture quality dietary supplements are in place and are functioning properly.
Upon successfully meeting the requirements of the Dietary Supplement Verification Program, the manufacturer's product is awarded the use of the USP Verified Mark (the Mark). The manufacturer may display the Mark only on specific products that have met all of the requirements of the verification process.
Unlike pharmaceutical drugs with single active components, dietary supplements may contain several dietary ingredients, or might be botanical products that are extremely complex in chemical composition. Proper knowledge, skill, and experience are essential to ensure that accurate results are obtained. USP scientists have extensive experience in evaluating both drug and dietary supplement products. USP has multiple stages of test data review to provide added assurance that the test results and interpretations are accurate
USP's Verification Program addresses the issue of dietary supplement safety in several ways. The USP verification program staff, in consultation with USP's Dietary Supplement Expert Committee, evaluate each product's ingredient content. Those products that contain ingredients that have a known safety risk will not be accepted into the Verification Program. Determining the safety of dietary supplements is a broad undertaking, and includes assessment of drug interactions, contraindications, and side effects. USP's Verification Program only verifies that supplements contain the ingredients stated on the label, in the stated amounts, and that they meet acceptable limits for contaminants such as heavy metals, pesticides, dioxins, furans, PCBs, and microbes. The program also verifies that the products are manufactured using safe, sanitary, and well-controlled procedures. The Verification Program helps protect and inform consumers by providing them assurances that the products with the USP Verified Mark will not contain harmful levels of contaminants, toxic botanical species, or greater amounts of active/marker compounds than that indicated on the product specification and label.
USP's Verification Program will not accept a dietary supplement into its program if it does not have the proper performance characteristics (e.g. dissolution or disintegration). Products verified by USP are required to dissolve or disintegrate properly, meeting USP monograph requirements, thereby releasing the dietary ingredients and making them available to be absorbed the body. USP's Verification Program does not comprehensively address the issue of efficacy of a dietary supplement. The efficacy of dietary supplements is an issue best addressed by FDA.
The USP GMP audit is not a substitute for a regulatory audit, but it will help a participant to prepare for a regulatory audit. USP employs professional certified quality auditors, all of whom have many years of experience, to help ensure that your organization can meet the challenges of a rigorous regulatory audit.
ISO certification does not automatically lead to USP verification. There are significant differences between ISO certification and USP verification. USP verifies ingredient manufacturing practices that are specific to the site where the ingredient is manufactured, whereas ISO certifies the company's overall business processes. Also, ISO does not deal with individual products/ingredients, or with manufacturing practices that are specific to the ingredients and the site.
USP's GMP audit is a mandatory component of the comprehensive USP verification program. The program goes far beyond just a GMP facility audit to include also 1) review of product quality control and manufacturing documentation, 2) laboratory testing of 3 lots of product samples, and 3) post-verification monitoring and surveillance. USP's comprehensive approach assures participants and their customers that USP is thoroughly and objectively verifying the quality and consistency of the manufacturer’s products and processes, not just one or the other
USP verification program GMP audits typically last 3 days, but can be longer depending on the number of products submitted and the size of the manufacturing facility and operations. The participant will have prepared for the audit, by having submitted initial audit documentation for review by USP auditors. USP and the participant will agree to audit dates, at a time when the participant will be manufacturing the product(s) submitted for verification. USP will provide the participant with an agenda for the audit. USP conducts on-site facility GMP audits annually for ingredients. However, if USP has reason to be concerned about a situation or an event at the participant's manufacturing facility, USP reserves the right to conduct an unannounced audit at its sole discretion.
USP auditors will provide observations that the audited company should be able to use in order to improve its manufacturing quality systems. Training the participants' staff could be a considered a conflict of interest and thus is beyond the scope of the verification program. USP does provide Global Education and Training (GET) services that operate independently from the verification program that could be of benefit to verification program participants.
USP verification provides assurance that both the manufacturing process (i.e., good manufacturing practice) and product will be of consistent quality, based on the determination by an independent, scientific, ethical and credible third party organization. USP verification is evidenced by the use of the USP Verified DietarySupplement Mark on product labels.
USP protects participants' data with the utmost confidentiality. We are bound by United States law in the Document Non-Disclosure Agreement that we sign with each participant to do so. Furthermore, USP has nearly 200 years of independent experience in handling and protecting the confidentiality of companies' data through their submissions of information that are used for standards development.
If USP uncovered an imminently threatening deficiency regarding the safety of a product in the marketplace, USP would work with the participant's management to report these deficiencies to the appropriate regulatory authority in the interest of the public health. If the participant's management chose not to comply, as stated in the Dietary Supplement Verification Program Manual for Participants and in the License Agreement, USP would be compelled to report these deficiencies on behalf of the public health.
The fee structure is based on the actual costs associated with conducting the on-site facility GMP audit, and the anticipated costs associated with review of product manufacturing and quality control documentation, and laboratory testing of product samples for conformance to specifications.
The anticipated fee associated with review of product manufacturing and quality control documentation and also with laboratory testing of product samples is payable at the time the License Agreement is signed and work commences. This fee will be placed in account designated only for the participant and charges will be debited against it, as work is performed on the product. The participant will receive an invoice when verification work has been performed. The actual costs for conducting the on-site facility GMP audit will be invoiced after the audit report has been submitted to the participant.
Deficiencies noted during the audit will be described in writing in the form of a report and ranked by their severity. Manufacturers are required to address each deficiency with the goal of full compliance. All deficiencies must be addressed before the verification process can move forward to the next program step. Details on types of deficiencies can be obtained in the Dietary Supplement Verification Program Manual for Participants on the USP website.
USP auditors are highly competent professionals with years of second- and third-party auditing experience, as well as rigorous training with USP. USP uses its own staff as auditors and, when necessary, complements that staff with carefully selected contract auditors who serve as highly experienced independent consultants to USP. Contracted auditors serve USP under the same rules of confidentiality as USP’s full time staff.
USP will make every effort to ensure the participant is prepared for the cost and activities related to an audit before it is scheduled. This is supported by the requirement for pre-audit documentation which provides USP staff the opportunity to assess the level of preparedness and enables the participant to understand whether they are ready for the audit. If the USP staff believes that the participant is prepared for an audit, the USP staff will schedule the audit at a time convenient to both parties. If the participant is unprepared, USP will provide feedback to the participant regarding the deficiencies that need to be addressed.
USP is prepared to have its auditors travel to the locations where participant's manufacturing sites are located to conduct the GMP audit, recognizing that actual travel expenses are invoiced separately from the GMP audit fee. USP also has auditors located at its international sites in Shanghai, China and Hyderabad, India to help reduce travel expenses.
USP will request the participant's representative to collect and ship the samples of selected lots of the product(s) to USP's laboratory.
A highly prepared participant can expect to complete the verification process within 3 to 4 months after the License Agreement is signed. Although it can take a participant longer, USP will continue to work with participants to help them meet the program requirements, so that their products can become USP verified.
If the new product is manufactured using similar procedures as the first one with similar equipment at the same site, a second GMP facility audit might not be necessary. At the time of the next regularly scheduled audit, both products would be evaluated. If the manufacturing process and/or site is different, a second GMP facility audit would be necessary. In either case, documentation review and analytical testing of the new product would be required.
USP meets with selected regulatory agencies worldwide, on a continuing basis, to help them understand the value that USP verification brings to improving health care quality. Each regulatory agency will determine what recognition to give USP verification.
USP can verify the quality of a product using other compendial monographs (e.g., Ph.Eur., J.P., Ch.P.). If there is no USP–NF or other compendial monograph, USP will use the specification submitted by the participant to verify the quality of the product. USP will evaluate the adequacy of the specification to control the quality of the product and will perform laboratory testing of the product for conformance to the specification. Upon successful completion of the Dietary Supplement Verification Program, USP may encourage the participant to submit the specification and supporting documentation to USP for developing a draft monograph that would be published in Pharmaceutical Forum for public comment and eventual inclusion into the official USP–NF compendia.