USP Verification Services FAQs

Dietary Supplements Verification Program

  1. What is the verification process?

    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 ensures 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.
  2. What does a USP Verification Program GMP review consist of?

    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.

  3. When is the USP verification mark granted to a dietary supplement product?

    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.

  4. Why does USP utilize its own laboratories to test products?

    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.

  5. Can consumers assume that a USP-verified supplement is safe?

    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.

  6. Can consumers assume that a USP-verified supplement is effective?

    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.

Dietary Ingredient Verification Program

  1. What are the steps involved in obtaining USP verification?

    After a company has submitted an application form (available on the USP website) and has spoken with the USP verification program staff to receive a price estimate for verification work and has decided to enroll in the USP Dietary Ingredient Verification Program (DIVP):

    1. Participant executes License Agreement with USP.
    2. Participant submits initial audit documentation for the facility’s manufacturing operations and quality systems for review by USP auditors.
    3. Participant submits lot histories for submitted dietary ingredients from which USP randomly selects ingredient lots for evaluation.
    4. Participant submits samples and the quality control (QC) and manufacturing documentation for the randomly selected ingredient lots.
    5. USP performs the on-site facility GMP audit, conducts analytical testing of ingredient samples, and reviews the QC and manufacturing documentation for the selected ingredient lots. USP notifies the participant of any observations or deficiencies that may preclude successful completion of the program requirements.
    6. Participant takes appropriate corrective action on the observations or deficiencies cited by USP.
    7. USP prepares summary report of findings and the corrective and preventative action taken by the participant
    8. Upon successful completion of the program requirements, USP grants the participant the right to use the USP Dietary Ingredient Verified Mark on the labels and certificate of analysis of the USP verified dietary ingredient.
  2. What is acceptance criteria?

    USP audits dietary ingredient manufacturers for compliance to the stringent requirements of the International Conference on Harmonization ICH Q7 Good Manufacturing Practices Guide for Active Pharmaceutical Ingredients.

  3. How can we apply for the qualification and verification program?

    Submit an application form (available on the USP website), and contact Dr. John Atwater, Senior Director, USP Verification Programs, at jba@usp.org or +1-301-816-8529 for questions about program requirements and estimated costs and timing.

  4. Is the USP GMP audit a substitute for a regulatory audit?

    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..

  5. If my site is ISO certified, does this automatically lead to USP Verification?

    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.

  6. My company is frequently audited already. Why should we invite USP to audit us?

    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 ingredient quality control and manufacturing documentation, 2) laboratory testing of 3 lots of ingredient 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 ingredients and processes, not just one or the other

  7. What is the time cycle for GMP audits? Is the GMP audit unannounced?

    USP verification program GMP audits typically last 3 days, but can be longer depending on the number of ingredients 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 ingredient(s) submitted for verification. USP will provide the participant with an agenda for the audit. USP conducts on-site facility GMP audits triennially 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.

  8. Will USP verification replace the Drug Master File (DMF)?

    No. However, USP review of the type of information reported in a DMF is an important step of the verification process. USP encourages product information to be submitted in the format of the ICH Common Technical Document (CTD), Module 3: Quality, so as to eliminate the need to reformat the information for submission to regulatory authorities, and to facilitate the review process.

  9. Will USP auditors help train and improve the skills of my staff to advance the quality of our internal audits?

    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.

  10. How can I tell my customers what USP verification means to them?

    USP verification provides assurance that both the manufacturing process (i.e., good manufacturing practice) and ingredient 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 Dietary Ingredient Mark on bulk labels and certificate of analyses of finished ingredients..

  11. How does USP protect participants' data?

    USP has nearly 200 years of independent experience in maintaining and protecting the confidentiality of data obtained from companies through the USP standards-setting process.

  12. Would USP report an adverse situation to a regulatory body?

    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.

  13. Would USP report an adverse situation to a regulatory body?

    If USP uncovered an imminently threatening deficiency regarding the safety of an ingredient that is used in 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 Ingredient Verification Program Manual for Participants and in the License Agreement, USP would be compelled to report these deficiencies on behalf of the public health.

  14. How does USP determine the fee structure for verification?

    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 ingredient manufacturing and quality control documentation, and laboratory testing of ingredient samples for conformance to specifications.

  15. How is the fee paid to USP?

    The anticipated fee associated with review of ingredient manufacturing and quality control documentation and also with laboratory testing of ingredient 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 ingredient. 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.

  16. What is the re-verification process and what does it cost?

    The life cycle of the License Agreement is three years. Re-verification follows the same exact process as the initial verification, and a well-prepared company following best practices could expect to complete re-verification with ease.

  17. Will the GMP audit be ingredient specific or manufacturing site specific or ingredient cluster specific? Does this affect my pricing?

    GMP audits are typically ingredient specific, however, if a parent ingredient is verified, derivative ingredients (e.g. d-alpha-Tocopherol Acetate from d-alpha Tocopherol) may be covered without an additional GMP audit, so long as the derivative ingredient was manufactured using similar equipment and at the same site. These derivative ingredients are subject to the same performance standards and testing as the parent ingredient. If other ingredients different from the parent ingredient are manufactured at the same site, it is possible for USP to perform an extended audit to cover all of these ingredients at the same time, which will help to reduce the cost of performing multiple audits.

  18. What is the remedy structure of the USP Audit when a deficiency is identified?

    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 to the ICH Q7 Good Manufacturing Practice Guide. 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 Ingredient Verification Program Manual for Participants on the USP website.

  19. Who are USP auditors?

    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.

  20. If your auditor travels to my company and finds it is not prepared for an audit, what happens?

    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.

  21. If your auditor travels to my company and finds it is not prepared for an audit, what happens?

    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 participants to submit initial audit documentation which provides USP staff the opportunity to assess the participant’s level of preparedness for the audit 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 acceptable to both parties. If the participant is unprepared, USP will provide feedback to the participant regarding the deficiencies that need to be addressed.

  22. If my company has global manufacturing sites, how will that 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.

  23. Who will collect the samples for surveillance studies?

    During the initial and triennial GMP audits, the USP auditor may observe the collection of the samples by the participant’s staff. At other times, USP may request the participant's representative to collect and ship the samples of selected lots of the ingredient(s) to USP's laboratory.

  24. Who will collect the samples for surveillance studies?

    During the initial and triennial GMP audits, the USP auditor may observe the collection of the samples by the participant’s staff. At other times, USP may request the participant's representative to collect and ship the samples of selected lots of the ingredient(s) to USP's laboratory.

  25. What is the time between signing the License Agreement and completion of the verification process?

    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 ingredients can become USP verified.

  26. What is the procedure for getting another ingredient verified after a time lapse of, for example, 6 months since the first ingredient's verification?

    If the new ingredient 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 ingredients 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 ingredient would be required.

  27. Will regulators from my country recognize the USP verification?

    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.

  28. If specifications are different from the USP–NF monograph, what is the course of action by USP?

    USP can verify the quality of an ingredient 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 ingredient. USP will evaluate the adequacy of the specification to control the quality of the ingredient and will perform laboratory testing of the ingredient for conformance to the specification. Upon successful completion of the Dietary Ingredient 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.