USP Verification Services FAQs

Dietary Supplements Verification Program

  1. What is the verification process?

    USP's Verification Program is a multi-step process. It begins with a pre-audit review, which entails an initial assessment of the company's quality system infrastructure. The program is designed to ensure that critical elements of a company's manufacturing systems are in place prior to conducting extensive site audits, documentation review, and product testing. (See Verification Program process graphic)

    • When the Verification Program's staff has determined that a company's manufacturing infrastructure is in place, an extensive on-site audit of the manufacturer's facility and manufacturing operations is conducted. The audit covers all aspects of the manufacturing operation from receiving materials to shipping of the final product. The on-site audit goes a step further than most programs by ensuring that the system controls and operation used to manufacture a product are functioning properly.
    • Upon successful completion of the on-site audit, an extensive review of quality control and manufacturing documentation is performed on specific lots of products. These documents demonstrate that a manufacturer is producing products according to their specifications, as per USP manufacturing practices. The review of these documents is designed to identify areas of improvement for all aspects of the manufacturing process that ensures that a quality product is obtained.
    • Once the manufacturer has met the requirements of the documentation review, the program's staff tests a statistically determined number of the manufacturer's products against specifications and ingredient label claim. This step primarily confirms the observations obtained from the on-site audit and review of product documentation. The program's staff works closely with the manufacturer to resolve any issues that may arise during testing. Other 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 verification mark. To 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 audits, on a continual 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 USP's manufacturing practices for dietary supplements, and proposed FDA good manufacturing practices (GMPs). 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 quality assurance (QA) systems needed to produce quality dietary supplements. USP evaluates the QA systems, which consist of 15 different program elements that address matters such as employee training, document management, equipment calibration and maintenance, manufacturing and laboratory control procedures, and product shelf life evaluation. An on-site audit of the manufacturing operation is conducted to ensure that the QA systems are functioning properly.

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

    Upon successfully meeting the requirements of the verification process, the manufacturer's product is awarded the use of the USP verification 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 program's staff, in consultation with USP's Dietary Supplement Information Expert Committee, evaluate each product's ingredient content. Those products that contain ingredients that the committee finds to have a safety risk will not be accepted into the Verification Program. The Verification Program, however, does not comprehensively address this broad issue. No single program or organization could be expected to completely address the issue of safety. Determining the safety of dietary supplements is a broad undertaking, and includes assessment of drug interactions, contraindications, and side effects. USP's Verification Program does ensure 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 ensures 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 verification mark will not contain harmful levels of contaminants, toxic botanical species, or greater amounts of active/marker compounds than that indicated on the 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 certified by USP will be required to dissolve or disintegrate properly, meeting USP monograph requirements, thereby releasing the nutrients to dissolve and making them available to the body. USP's Verification Program does not comprehensively address the issue of efficacy of a dietary supplement. The efficacy of dietary supplements can vary between consumers. There is not a single or simple way to completely characterize efficacy of a dietary supplement. Studies of dietary supplement efficacy require governmental, financial, educational, and industrial resources, likely on an international level, to thoroughly address the issue.

Dietary Ingredient Verification Program

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

    After a company has spoken with our product team and has decided to enroll in the dietary supplement ingredient verification program (DS IVP):

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

    Dietary supplement ingredient manufacturers are audited against the stringent requirements of the International Conference on Harmonisation ICH Q7 Guideline: Good Manufacturing Practices Guide for Active Pharmaceutical Ingredients.

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

    Contact Dr. John Atwater, Director, USP Verification Programs, at jba@usp.org or +1-301-816-8529.

  4. Is your audit a substitute for a regulatory audit?

    The USP audit is not a substitute for a regulatory audit, but it will prepare a participant for the strictest of regulatory audits. USP employs world-class professional auditors, all of whom have many years of experience, to help ensure that your organization can meet the challenges of the most rigorous regulatory scrutiny.

  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 many differences between the 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 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 audit is a mandatory component of a comprehensive verification program. The program goes far beyond just an audit to include also 1) document review, 2) laboratory testing and 3) post-verification monitoring and surveillance. USP's comprehensive approach assures participants that USP is thoroughly and objectively verifying the quality of their ingredients and processes, not just one or the other.

  7. What guidance is used to determine cGMP compliance?

    Dietary supplement ingredient manufacturers are audited against the stringent requirements of the International Conference on Harmonisation ICH Q7 Guideline: Good Manufacturing Practices Guide for Active Pharmaceutical Ingredients.

  8. What is the time cycle for these audits? Is the audit a surprise?

    USP will visit a site for approximately 3-5 days for the initial audit with 3 days being the target. The participant will have already prepared for the audit by completing pre-audit steps with USP. USP and the participant will collaborate on an audit date window, during which the participant will be manufacturing the ingredient. USP will inform the participant of the schedule and agenda for the audit. 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.

  9. Will USP Verification replace the DMF?

    No, the DMF-type of information is a critical portion of the document review associated with the verification program.

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

    Our auditors will offer observations that the audited company should be able to use in order to improve manufacturing quality. Training the participants' staff is beyond the scope of this program.

  11. How can I tell my customers what USP Verification means to them?

    The USP verification assures that the consistency of quality in process (good manufacturing practice) and ingredient has been verified by an independent, ethical, and credible third party, as evidenced by the use of the USP Verified Ingredient Mark on product/ingredient labels and certificate of analyses.

  12. How does USP protect participants' data?

    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 an imminently threatening deficiency were exposed regarding an ingredient that is used in an ingredient 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 programs' Manual for Participants and 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 anticipated and actual costs associated with review of manufacturing and quality control documents, laboratory testing, and performance of the GMP audit.

  15. How is the fee paid to USP?

    The fee is payable at the time the License Agreement is signed and work commences. The fee will be placed in account designated only for the participant and charges will be debited against it. The participant will receive a monthly statement of account.

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

    The life cycle of the license agreement is for three-years. Re-verification follows the exact process as the initial verification, and a well-prepared company following best practices could expect to move through 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 normally 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, as long as the derivative ingredient was manufactured using similar equipment and on the same site. These derivative ingredients are subject to the same performance standards and testing as the parent ingredient. If other ingredients are manufactured at the same site, it may be possible to perform an extended audit and cover all of these ingredients at the same time, which might reduce the cost of the audit.

  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 grouped by their severity. Manufacturers are required to address each deficiency with the goal of full compliance to the ICH Q7 Good Manufacturing Practices Guide. All deficiencies must be fully addressed before the verification process may move to the next program step. Details on types of deficiencies can be viewed in the program's participants manual (865KB).

  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 our own staff as auditors and, when necessary, complements that staff with carefully selected contract auditors who serve as highly experienced independent consultants to USP. Our contracted auditors serve USP under the same rules of confidentiality as our employed 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 my company has manufacturing sites in a third country, how will that be addressed?

    USP is prepared to have their auditors travel to the locations where participant's manufacturing sites are located, recognizing that actual travel expenses are billed separately from the verification fee.

  22. If my company purchases small quantities of ingredients from another company that purchases the bulk amount, how will that be handled?

    If a participant is purchasing small amounts of ingredients from another company the additional company might have to be audited as part of the process. Factors that play into this decision include review of the participant's vendor qualification program and the nature and intended use of the ingredient purchased.

  23. If my company makes different grades (food, cosmetic, drug) of the same ingredient, how will this affect the audit process?

    The USP Verification Programs cover a broad range of ingredients used in human health care, such as drug substances, dietary ingredients, and excipients. These programs differ from each other with respect to the Good Manufacturing Practices (GMP) requirements. The most stringent GMP requirement will be used in the case of multiple uses of the same ingredient.

  24. Who will collect the samples for surveillance studies?

    USP may request the participant's representative to collect and ship the samples of selected lots of the ingredient(s) to USP's laboratory. Alternatively, the USP auditor may collect the samples during the audit and/or the post-verification surveillance period.

  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 6-8 months after the License Agreement is signed.

  26. What is the procedure for getting another ingredient verified after a time lapse of, for example, 6 months since the initial 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 audit might not be necessary. At the time of the next regularly scheduled audit, both ingredients will be evaluated. In either case, document review and analytical testing will be required for the new ingredient.

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

    USP is meeting with selected regulatory agencies worldwide 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?

    Where there is no USP–NF monograph, then USP will use the specification submitted by the participant for the laboratory testing. Part of this testing will include a determination of the adequacy of the specification. Upon successful completion of the Dietary Supplement Ingredient Verification Program, the participant may be asked for permission to use the submitted information in developing a draft monograph that will be published in Pharmaceutical Forum for public comment and eventual inclusion into the official compendia.

Pharmaceutical Ingredient Verification Program

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

    After a customer has spoken with our Product Team and decided to enroll an API or excipient:

      1. Execute License Agreement with USP.
      2. Participant submits pre-audit documentation for facility systems and operations review by USP.
      3. Participant submits lot histories and randomly selected samples as well as the quality control (QC) and manufacturing documentation for the randomly selected product lots.
      4. USP coordinates analytical testing, conducts review of QC and manufacturing documentation, and conducts On-Site Audit.
      5. USP prepares Summary Report of Findings.
      USP either issues a USP Certificate of Standards Compliance or notifies the Participant in writing about any outstanding deficiencies that must be corrected.

    At each step, USP will notify the Participant of any observations or deficiencies that may preclude successful completion of the Program. The Program is a partnership where both USP and the Participant must follow time lines and specified steps. The most efficient verification occurs when these timelines are optimized.

  2. What is acceptance criteria?

    The ICH Q6A guideline Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances defines "Specification" as a list of tests, reference to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described. "Conformance to specification" means that the drug substance or drug product when tested according to the listed analytical procedures will meet the listed acceptance criteria.

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

    Contact V. Srini Srinivasan, Executive Vice President, Global Science and Standards & Chief Science Officer, at vs@usp.org or by telephone at +1-301-816-8334.

  4. Is your audit a substitute for a regulatory audit?

    The USP audit is not a substitute for a regulatory audit, but it will prepare a Participant for the strictest of regulatory audits. USP hires world-class professional auditors, all of whom have many years of experience, to help ensure that your organization can meet the challenges of the most rigorous regulatory scrutiny.

  5. Why will we still have an FDA audit?

    An ANDA filing with the USFDA may be facilitated for an ingredient that has successfully completed all of the requirements of the PIVP and that has "USP Verified" on the label. The rationale for this is the fact that we will have audited the site using the same guideline that FDA will use and we will have reviewed the same chemistry, manufacturing, and control data that will be submitted to FDA for FDA's review. Since we will have examined many of the same issues as the FDA will examine, the FDA audit should find few deficiencies (there will always be some because the auditor is a different person) and the document review by FDA should be easier as we will have identified any major problem areas during our review. However, there will still be an FDA audit and review.

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

    ISO certification does not automatically lead to USP verification. There are many differences between the ISO certification and USP Pharmaceutical Ingredient Verification Program. USP verifies ingredient manufacturing practices that are specific to the site where the ingredient is manufactured, whereas ISO certifies the Company's overall processes. Also, ISO does not deal with individual products/ingredients, or with manufacturing practices that are specific to ingredients and the site.

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

    USP's audit is a mandatory component of a comprehensive verification program. The program goes far beyond just an audit to also include 1) document review, 2) laboratory testing and 3) post-verification monitoring and surveillance. USP's comprehensive approach assures our customers that we are thoroughly and objectively verifying the quality of their ingredients and processes, not just one or the other. On the audit itself, the USP audits for drug substances and excipients are meant to be the most rigorous and independent of audits based upon ICH Q7 Guideline — Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients and the IPEC/PQG Guide for Pharmaceutical Excipients.

  8. What guidance is used to determine cGMP?

    The ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients is used for drug substances while the IPEC/PQG Guide for Pharmaceutical Excipients is used for excipients.

  9. What is the time cycle for these audits? Is the audit a surprise?

    USP will visit a site for approximately 3-5 days for the first year's audit with 3 days being the target. The Participant will have already prepared for it, by completing pre-audit steps with USP. A Participant will have the opportunity to submit several timeframes during which the Participant will be manufacturing the ingredient and USP can visit. USP will inform the Participant of the general timing for the audit and offer an agenda. However, in certain situations, if USP has reason to be concerned about a situation or event at the Participant's manufacturing facility, USP reserves the right to conduct an unannounced audit at its sole discretion.

  10. Will USP Verification replace the DMF?

    No, the DMF-type of information is a critical portion of the document review associated with the verification program.

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

    Our auditors will offer observations that the audited company should be able to use in order to improve manufacturing quality. Training the Participants' staff is beyond the scope of this program.

  11. How can I tell my customers what USP Verification means to them?

    The USP verification assures that the consistency of quality in process (good manufacturing practice) and product has been verified by an independent, ethical, and credible third party - USP; and that USP has issued a Certificate of Standards Compliance.

  12. How does USP protect customer data?

    USP protects customer data with the utmost confidentiality. We are bound by United States law in the License Agreement that we sign with each client to do so, further, USP has nearly 200 years of independent experience in handling and protecting the confidentiality of customer data through their submissions of information that are used for standards development.

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

    If an imminently threatening deficiency were exposed regarding an ingredient that is used in an approved product, 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 management chose not to comply, and as stated in our Programs Manual for Participants and 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 anticipated and actual costs associated with review of manufacturing and quality control documents, laboratory testing, and performance of the GMP audit.

  15. How is the fee paid to USP?

    The fee is payable at the time the License Agreement is signed and work commences. The fee will be placed in an account designated only for the Participant and charges will be debited against it. The Participant will receive a monthly statement of account.

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

    The life cycle of the License Agreement is for three years. Re-verification follows the exact process as the initial verification and a well-prepared company, following best practices may expect to move through 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 normally ingredient specific, however, if a parent ingredient is verified, derivative ingredients (e.g.; esters, salts,) may be covered without an additional GMP audit, as long as the derivative ingredient was manufactured using similar equipment and on the same site. These derivative ingredients are subject to the same performance standards and testing as the parent ingredient. If other ingredients are manufactured at the same site, it may be possible to perform an extended audit and cover all of these ingredients at the same time which may reduce the cost of the audit.

  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 grouped by their severity. Manufacturers are required to address each deficiency with the goal of full compliance to the ICH Q7 Guidance. All deficiencies must all be fully addressed before the verification process may move to the next program step. Details on types of deficiencies can be viewed in our Participants Manual.

  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 our own staff as auditors and, when necessary, complements that staff with carefully selected contract auditors who serve as highly experienced independent consultants to USP. Our contracted auditors serve USP under the same rules of confidentiality as our employed 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 insure 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 our staff the opportunity to assess the level of preparedness and enables the Participant to understand whether they are ready for an audit. If the USP staff believes that the Participant is prepared for an audit, the USP staff will coordinate a time convenient to both parties. If the Participant is unprepared, USP will not come for the audit and will provide feedback to the Participant regarding the deficiencies that need to be addressed.

  21. If my company has manufacturing sites in a third country, how will that be addressed?

    USP is prepared to have their auditors travel to the location(s) where a Participant's manufacturing site is or are located, recognizing that actual travel expenses are billed separately from the Verification Fee.

  22. If my company purchases small quantities of ingredients from another company that purchases the bulk amount, how will that be handled?

    If a Participant is purchasing small amounts of ingredients from another company the additional company might have to be audited as part of the process. Factors that play into this decision include review of the participant's vendor qualification program and the nature and intended use of the ingredient purchased.

  23. If my company makes different grades (food, cosmetic, drug) of the same ingredient, how will this affect the audit process?

    The USP Verification Programs cover a broad range of ingredients used in human health care such as drug substances, dietary ingredients used in dietary supplements, and excipients. These Programs differ from each other in respect to the Good Manufacturing Process (GMP).

  24. Who will collect the samples for surveillance studies?

    USP may request that the Participant's representative ship the identified samples to USP's laboratory. Alternatively the USP auditor, when on site for audits, may pick up randomly selected samples of the ingredient(s) from the lots identified by USP for testing during the post-verification period documentation review or during the GMP audit as necessitated by circumstances.

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

    A highly prepared participant can expect to receive the Certificate of Standards Compliance within 6-8 months after the License Agreement is signed.

  26. What is the procedure for getting another ingredient verified after a time lapse of, for example, 6 months since the initial 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 audit may not be necessary. At the time of the next regular audit, both ingredients will be considered. However, document review and analytical testing will be required.

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

    USP is meeting with selected regulatory agencies worldwide to help them understand the value that USP verification brings to improving drug quality. Each regulatory agency will determine what recognition to give USP verification.

  28. Does USP partner or collaborate with EDQM?

    USP is interested in partnering with EDQM but has not yet reached an agreement. The competent authorities in the European Union will accept third party audits; it is incumbent upon the Participant to work with authorities for acceptance of third party reviews.

  29. How does the program help to market products in Europe and elsewhere?

    The competent authorities of the European Union will be accepting third party audits as part of the review of marketing applications. The audit performed by USP should be accepted under these conditions. USP–NF monographs are recognized and accepted by many regulatory authorities in countries around the world.

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

    Where there is no USP–NF monograph, then USP will use the specification submitted by the Participant for the laboratory testing. Part of this testing will include a determination of the adequacy of the specification. Upon successful completion of the Pharmaceutical Ingredient Verification Program, the participant may be asked for permission to use the submitted information in developing a draft monograph that will be published in Pharmaceutical Forum for public comment and eventual inclusion into the compendia.