Vaccines, Blood & Biologics

SOPP 8413: Postmarketing Requirement/Commitment Related Submissions - Administrative Handling, Review, and CBER Reporting

Version #6

Effective Date: January 12, 2015

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  1. Purpose

    This Standard Operating Policy and Procedure (SOPP) serves as a guide for Center for Biologics Evaluation and Research (CBER) staff to administratively process, review submissions and report on postmarketing requirements (PMRs) and postmarketing commitments (PMCs) received in CBER for Biological License Applications (BLAs) and New Drug Applications (NDAs).

  2. Scope
    1. This SOPP applies to all PMRs and PMCs for licensed biologics (including devices approved under a BLA) and drugs regulated by CBER. See Appendix A: Table 1: Requirements for the Categories of PMRs/PMCs for additional information.
    2. This SOPP does not apply to PMCs for Premarket Device Applications (PMAs) or to postmarketing studies conducted on an applicant’s own initiative (i.e. voluntary studies).
    3. This SOPP does not discuss policy and procedures for PMR/PMC development or data entry into RMS-BLA. These topics are described in SOPP 8415: Procedures for Developing Postmarketing Requirements and Commitments.
    4. This SOPP does not address the processing for safety-related good cause issues or deferral extension for deferred pediatric studies required under the Pediatric Research Equity Act (PREA) and updated in Section 505B of Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012. Processing of safety-related good cause issues are described in JA 860.04.01: Good Cause Data Entry Procedures and deferral extension requests are described JA 860.08: Instructions for Processing Deferral Extension Requests from the Applicant for Pediatric Postmarketing Requirements (PMR).
  3. Background
    1. PMRs/PMCs are generally studies or clinical trials that are conducted by the applicant after FDA has approved or licensed a product for marketing. These studies or clinical trials can be either required by regulation or statute (PMR) or agreed upon, in writing, between FDA and the applicant (PMC).
    2. Congress addressed concerns by FDA and patient/consumer groups about the timely completion of agreed-upon PMC studies by applicants in the FDA Modernization Act of 1997 (FDAMA). Section 130 of FDAMA added section 506B to the Food, Drug and Cosmetic (FD&C) Act.
      1. Section 506B, Reports of Postmarketing Studies, requires applicants that have agreed to conduct a postmarketing study to submit annual reports to the Agency on the status of the PMC until the applicant is notified in writing that the commitment has been fulfilled or that they have been released from the commitment.
      2. FDA issued guidance for industry in February 2006 to complement the final rule: FDA Guidance for Industry Reports on the Status of Postmarketing Study Commitments – Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997. This guidance describes in detail the content, format and timing of the annual report required by section 506B of the FD&C Act and the reporting of other postmarketing studies not subject to section 506B.
      3. In implementing Section 506B, CBER and the Center for Drug Evaluation and Research (CDER) revised 21 CFR 314.81(b)(2)(vii) (NDA annual report), 21 CFR 601.28 (biologics licensing, annual reports of postmarketing pediatric studies); and 21 CFR 601.70 (annual progress reports of postmarketing studies for biologics.)
      4. The requirements for annual reporting under 21 CFR 601.70 are limited to PMCs that concern clinical safety, clinical efficacy, clinical pharmacology and non-clinical toxicology.
    3. Section 901 of Food and Drug Administration Amendments Act (FDAAA) created section 505(o) of the FD&C Act, which authorizes the FDA to require postmarketing studies or clinical trials at the time of approval or after approval if the FDA becomes aware of “new safety information.”
      1. FDAAA section 505(o)(3)(B) states that the FDA has the authority to require certain postmarketing safety studies or clinical trials, and to require applicants to submit a milestone schedule for completing each study or clinical trial.
      2. In addition, FDA has the authority to enforce these requirements for postmarketing studies and clinical trials under FDAAA Section 505(o)(3)(E)(ii). Violations include the applicant’s failure to comply with the timetable, periodic report submissions, and other requirements of section 505(o)(3)(E)(ii) unless the applicant demonstrates good cause for the noncompliance or violation. The FDA will determine what constitutes good cause.
    4. PMRs and 506B PMCs are reported in the Federal Register and on the Agency’s Web site. FDA reports on the compliance of applicants with regard to PMR/PMC submissions as required by the FD&C Act. The applicant and FDA reporting requirements are detailed in FDA guidance for industry FDA Guidance for Industry Reports on the Status of Postmarketing Study Commitments – Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997.
  4. Definitions
    1. 506B-Reportable Postmarketing Commitment (506B PMC) – Postmarketing studies or clinical trials concerning clinical safety, clinical efficacy, clinical pharmacology, or nonclinical toxicology that applicants have agreed upon in writing to conduct. Note: Section 130 of FDAMA amended the FD&C Act by adding section 506B, Reports of Postmarketing Studies, which requires applicants to report on these PMCs in their annual reports. Types of 506B PMC studies include:
      1. Clinical Efficacy – Human studies intended to further characterize the effectiveness or optimal use of a product.
      2. Clinical Pharmacology – Human studies to further determine the effects of the product on the body including pharmacokinetics (what happens to the product while in the body), pharmacodynamics (the effects of the product, as pertaining to a subject’s biochemistry and physiology), toxicity, and drug interaction.
      3. Clinical Safety – Human studies intended to gather additional information on the safety of a product, e.g. at different dosage levels. These include immunogenicity studies intended to further define an immune response elicited by the introduction of an antigen (e.g., protein.)
      4. Non-Clinical Toxicology – Non-human studies (e.g., animal studies, in vivo animal models) to further characterize carcinogenicity, teratogenicity, reproductive toxicology, biopharmaceutic and pharmacokinetic properties of a product.
    2. Clinical Trial – Any prospective investigation in which an applicant or investigator determines the method of assigning the investigational product or other interventions to one or more human subjects.
    3. Non-506B, Reportable, Postmarketing Commitments (non-506B PMC) – Any study to assess drug or biologic product quality that was not required for approval, e.g. CMC/Stability studies; yet, the review committee felt was necessary to provide complete quality information. A non-506B PMC is agreed upon, in writing, by the applicant and FDA. Note: Studies may include manufacturing, stability, and other studies that do not have a safety endpoint. Non-506B PMC studies are not subject to 506B reporting requirements, although for NDAs, 21 CFR 314.81(b)(2)(viii) requires an applicant to advise the FDA on the status of non-506B PMCs in a separate section of the NDA annual report.
    4. PMR/PMC- Related Submission – A formal applicant submission intended to address an established PMR or PMC. Note: See Appendix A: Table 2:Identification of a PMR/PMC Related Submission to an IND, BLA or NDA for additional information.
    5. PMR/PMC Annual Report Review Form (PARRF) – Form used by CBER to review the PMR/PMC Annual Reports for 505(o) and 506B reportable PMRs/PMCs.
    6. PMR/PMC Schedule Milestones – The specific study dates for completing activities related to conducting a PMR/PMC.
    7. Postmarketing Commitment (PMC) – Any study or clinical trial that an applicant has agreed upon, in writing, to conduct after approval or licensing of a marketing application or supplement that is not a PMR.
    8. Postmarketing Requirement (PMR) – Any study or clinical trial that an applicant is required to conduct post-approval of a marketing application or a supplement. Note: Applicants may be subject to legal penalties for not conducting PMRs.
    9. Study – Any investigation other than a clinical trial, such as an investigation in humans (e.g., an observational epidemiologic study), an animal study, or a laboratory experiment.
    10. Voluntary Postmarketing Study or Trial – A study or clinical trial conducted on an applicant’s own initiative without a request by FDA. Note: Voluntary studies or clinical trials are not required or agreed upon postmarketing commitments. Voluntary studies/clinical trials are not subject to 506B reporting requirements, although for NDAs, 21 CFR 314.81(b)(2)(viii) requires the applicant advise the FDA on the status of voluntary studies/clinical trials in a separate section of the NDA annual report.
  5. Policy
    1. CBER will:
      1. Track PMR- and PMC-related submissions to ensure closure of the PMR or PMC;
      2. Track PMRs, 506B PMCs, and non-506B PMCs in the Regulatory Management System – Biologics License Application (RMS-BLA);
      3. Accurately and promptly process PMR- and PMC-related submissions upon receipt;
      4. Track and monitor PMR- and PMC-related submissions while under review; Use the RMS-BLA Data Entry for Postmarketing Requirements/Commitments and Related Submissions document for detailed instructions on entering and updating RMS-BLA.
      5. Review PMR- and PMC-related submissions according to the following time-frames:
        1. Protocols – CBER will conduct a timely review of all PMR/PMC protocols submitted by the applicant. CBER will provide detailed feedback to the applicant on noted deficiencies and suggested revisions if there are concerns with the submitted protocol design. Protocols do not have specific review time-frames.
        2. Annual Reports – If CBER does not agree with an applicant’s categorization of the status and/or explanation of status of the PMR/PMC, CBER will contact the applicant for resolution.
          1. PMR/PMC Annual Report – used for BLA annual reports (21 CFR 601.70) for reportable PMRs/PMCs: Reviewed on a 3 month time-frame.
          2. Changes to an Application/PMC Annual Report (AR) – used for NDA annual reports (21 CFR 314.81(b)(2)(vii)) including reportable PMRs/PMCs: Reviewed on a 3 month time-frame.
        3. Final Reports – CBER will review a Final Report submitted as a supplemental application according to established review times for supplements (e.g., for Prescription Drug User Fee Act (PDUFA) products). A Final Report submitted without a supplemental filing will generally be reviewed within one year of receipt. In either case, CBER will notify the applicant in writing of CBER’s determination with regard to the status of the PMC, i.e., fulfillment or release
          1. Final Study Report – PMR/PMC Submission/Final Study Report: Reviewed on a 12 month time-frame;
          2. Final Study Report – BLA/NDA Supplement:
            1. Standard Efficacy: Reviewed on a 10 month time-frame.
            2. Priority Efficacy: Reviewed on a 6 month time-frame.
            3. Prior Approval: Reviewed on 4 month (user fee products) or 6 months (non-user fee products) time-frame.
            4. Changes Being Effected (CBE) or 30-Day CBE: Reviewed on a 6 month time-frame.
        4. PREA Deferral Extension Requested: Reviewed on a 45 day time-frame
        5. Other types of PMR/PMC Submissions, such as those to INDs, status updates, and product correspondence do not have specific review time-frames
      6. Notify the Office of Compliance and Biologics Quality (OCBQ) of an applicant’s failure to comply with the requirements of section 505(o)(3)(E)(ii) e.g., milestone schedule for completion, and periodic report submissions.
      7. Receive 506B annual reports (BLA/NDA) each year within 60 days of the anniversary of the approval or licensure of the drug or biologic, until the applicant is notified, in writing, that CBER agrees that all of the PMRs or 506B PMCs have been fulfilled or released.
    2. Submissions related to PMRs/PMCs may be made to an Investigational New Drug Application (IND) or BLA/NDA, depending on the type of PMR/PMC submission. If a PMR/PMC submission is submitted to an IND, a letter that includes the cross-reference to the IND must be sent to the BLA/NDA and categorized appropriately (e.g., PMC Submission – Final Study Report).
    3. Applicants are required to submit their annual reports to the Agency within 60 days of the anniversary of U.S. product approvals. Further, Section 506B requires the Agency to publish annually in the Federal Register information on the compliance of the applicants with this reporting requirement.
    4. Schedule for Completion of PMR Safety Studies under FDAAA Required Studies (505(o)) is a set of milestone dates by which CBER measures progress of studies and clinical trials and compliance with requirements. FDAAA does not include provisions to amend or change milestone dates for purposes of reporting as required under 21 CFR 314.81(b)(2)(vii)(a)(8) and 21 CFR 601.70(b)(8). Therefore, status reporting under these regulations will remain based on the original schedule.
    5. Section 506B of the FD&C Act describes the different PMR/PMC status types which an applicant is required to use in their annual report. (See Final Rule, “Postmarketing Studies for Approved Human Drugs and Licensed Biological Products; Status Reports,” 65 FR 64607 (October 30, 2000) for status definitions):
      1. Open Status Types:
        1. Pending
        2. Ongoing
        3. Delayed
        4. Terminated
        5. Submitted
      2. Closed Status Types:
        1. Fulfilled
        2. Released
  6. Responsibilities
    1. Associate Director for Review Management (ADRM) – ensures that the PMR/PMC tracking and review process steps are implemented consistently and in a timely manner across CBER; supports changes to the PMR/PMC tracking and review process; ensures that adequate resources are allocated to develop and maintain RMS-BLA with optimal tracking and reporting functionality.
    2. CBER’s Document Control Center (DCC) – receives and processes all PMR/PMC – related submissions; logs all PMR/PMC-related submissions into the Document Accountability and Tracking System (DATS) and processes the submission according to usual procedures for that type of submission. DCC also routes the submission to the review division with product responsibility and maintains the record copy files for PMR/PMC-related submissions.
    3. Lead Reviewer – conducts primary review of 506B Annual Reports, documents review on the PMR/PMC Annual Report Review Form (PARRF), compiles comments from other reviewers and finalizes the PARRF.
    4. Office Director/ Division Director and/or Branch Chief – ensures staff are aware of and adheres to the procedures for tracking and reviewing PMR/PMC related submissions; identifies product or clinical review committee member(s) for each PMR/PMC related submission; participates in discussions and decisions determining whether a PMR or PMC is fulfilled or released; ensures that review goals for PMR/PMC submissions are met; and ensures that quarterly status reports are accurate and complete.
    5. Office PMR/PMC Coordinator – responsible for entering, tracking, and updating the PMR/PMC tracking system; provides input and acts as a resource for policy issues related to PMR/PMC tracking and closure; ensures that the data in the PMR/PMC tracking system are accurate and complete; actively monitors and provides support to RPMs/Review Committee Members; drafts and issues “PMC-Annual Report Request” letter for past due annual reports; monitors due dates to ensure that review(s) of the submission are performed and documented within established time-frames (if any); and uses the RMS-BLA Data Entry for Postmarketing Requirements/Commitments and Related Submissions for detailed instructions on entering and updating RMS-BLA.
    6. Product Office Branch/Lab Chief – ensures staff are aware of and adhere to the procedures for tracking and reviewing PMR/PMC related submissions, and provides information and support to the Office PMR/PMC Coordinator.
    7. Regulatory Project Manager (RPM) – responsible for managing the review based on the PMR/PMC submission; informs the Office PMR/PMC Coordinators of pending PMRs or PMCs submissions, correspondence, etc.; and uses the RMS-BLA Data Entry for Postmarketing Requirements/Commitments and Related Submissions for detailed instructions on entering and updating RMS-BLA.
    8. Regulatory Information Management Staff (RIMS) – ensures that all necessary tracking elements, reports and functionality for PMR/PMCs are available in RMS-BLA; makes PMR/PMC reports available (e.g., missing data, status, etc.) to all appropriate parties; and prepares the PMR and 506B PMC data for annual Federal Register notice and quarterly for posting on the Agency’s Web site.
    9. Review Committee Member – conducts a technical, scientific, or clinical review of the submission within the stated review time-frames; consults with appropriate Branch/Lab Chief and Office/Division Directors to determine whether a PMR/PMC should be fulfilled or released; and documents review in a review memo.
  7. Procedures

    Sections A-D below provide general steps to be followed for processing PMR/PMC-related submissions. Section E provides specific steps for how to process, review, and close different types of PMR/PMC-related submissions.

    1. Process, Receipt and Route a PMR/PMC-Related Submissions
      1. Receive and process submissions according to either SOPP 8110: Submission of Paper Regulatory Applications to CBER or DCC Procedure Guide #22 Procedure for Processing, Routing and Storing Electronic Submissions [DCC]
      2. Inform the Office PMR/PMC Coordinator once a submission is determined to contain information associated with a PMR or a PMC. Note: See the “Reviewers” tab within RMS-BLA to identify the responsible review division and the Office PMR/PMC Coordinator [RPM]
      3. Enter the receipt of the submission into RMS-BLA [RPM]
        1. Ensure all necessary information regarding the PMR/PMC-related submission is accurately and promptly entered into RMS-BLA
      4. Update the appropriate PMR/PMC in RMS-BLA upon receipt of a Final Study Report (FSR) or a supplement containing a PMR/PMC FSR [Office PMR/PMC Coordinator]
      5. Request reviewer assignments from division directors or branch chiefs, as appropriate [RPM]

        Note: If the submission pertains to an epidemiologic study (e.g., observational study, registry, or survey), contact the OBE Division Director and OBE-RPM for review assignments

      6. Determine Review Committee Members for the submission and inform the RPM [Division Director, OBE Division Director or OBE-RPM]
      7. Enter Review Committee Members into RMS-BLA, route the submission, and notify the Office PMR/PMC Coordinator [RPM]
    2. Review of submission
      1. Request consult as needed with other FDA centers or CBER review office(s) and/or divisions according to SOPP 8001.5: Intercenter Consultative/ Collaborative Review Process and SOPP 8001.1: Interoffice Consultative Review Procedures [Review Committee Member]
      2. Ensure that the submission is complete. If the submission is incomplete, inform the RPM indicating the missing information [Review Committee Member]
      3. Contact the applicant to submit an amendment containing the missing information [RPM]
      4. Notify and route the amendment to appropriate review committee members when received [RPM]
      5. Perform review within documented review time frames, see Section V.A.5 above for time frames. For submissions without agreed-upon time frames, coordinate agreed-upon time frame for completing the review of PMR/PMC-related submission [Review Committee Member, RPM]
      6. Ensure that the appropriate division(s) and/or office(s) have been consulted for evaluation and review, and that the recommendations have been addressed and/or incorporated into the review [Branch/ Lab Chief]
    3. Finalize the review of the PMR/PMC related submission
      1. Send any content-related questions or deficiencies, except for protocol related negotiations, to the BLA/NDA RPM for communication to the applicant [Review Committee Member]
      2. Ensure that the submission is complete. If the submission is incomplete, inform the RPM [Review Committee Member]
      3. Issue an information request as needed to facilitate the review per SOPP 8401.1: Issuance of and Review of Responses to Information Request Communications and Discipline Review Letters to Pending Submissions and send a courtesy copy to appropriate review personnel when any such correspondence is sent [RPM]
      4. Notify and route the amendment to appropriate review committee members when received [RPM]
      5. Participate in discussions and decisions to determine final resolution of the submission; such as, consider whether the submission would fulfill a PMR/PMC [Branch/ Lab Chief, Office Director/Division Director]
      6. Provide RPM and Office PMR/PMC Coordinator with an update on the status of the review when asked [Review Committee Member]
      7. Document all reviews in writing, incorporate any consultant’s recommendations into the review memo and include any letter ready comments [Review Committee Member]
      8. Perform secondary reviews [Branch/ Lab Chief]
      9. Inform the RPM and Office PMR/PMC Coordinator of completed reviews [Review Committee Member]
      10. Return the submission to DCC (See DCC Procedure Guide #8: Procedure For Filing Final Action Packages Containing Paper FDA Correspondence For Marketing Applications - Including Multiple Products or DCC Procedure Guide #23: Procedure for Filing Final Action Packages Containing Electronic FDA Communication for Marketing Applications) [Review Committee Member, RPM]
    4. Close the submission
      1. Issue PMR/PMC tracking-related correspondence to the applicant in a timely manner using the appropriate Review Letter Templates located on CBER’s Intranet Web page [RPM]
      2. Forward the complete action package, including the applicant’s PMR/PMC related submissions and all CBER reviews, forms and correspondence to DCC following DCC Procedure Guide #8: Procedure For Filing Final Action Packages Containing Paper FDA Correspondence For Marketing Applications - Including Multiple Products or DCC Procedure Guide #23: Procedure for Filing Final Action Packages Containing Electronic FDA Communication for Marketing Applications [RPM]
      3. Include the Office PMR/PMC Coordinator, the CBER/Regulatory Information Management Staff (RIMS) and consulting offices and divisions that have joint committee responsibility for evaluation of the PMR/PMC-related submissions in the distribution list of key correspondence for the PMR/PMC [RPM]
      4. Update RMS-BLA, as appropriate [Office PMR/PMC Coordinator]
    5. Submission Specific Processing Details
      1. PMR/PMC Study Protocol
        1. Ensure that the cross-reference letter is submitted to the BLA/NDA and the protocol is submitted to the IND [RPM]
        2. Close the cross-reference letter submission and notify the Office PMR/PMC Coordinator [RPM]
        3. Evaluate the study protocol and its ability to meet the objectives of the PMR/PMC. Define the milestone schedule when the notification letter contained a schedule based on a reference to the protocol agreement date. An example is “Protocol submitted: within 6 months after approval.” [Review Committee Member, Branch/Lab Chief]
        4. Coordinate with the Review Committee Member concerning review issues for a PMR/PMC Study Protocol; send PMR/PMC content-related correspondence (e.g., protocol deficiencies) to the applicant with a courtesy copy to appropriate review personnel [RPM]
        5. Issue the “PMC - Study Schedule Notification Letter” when the milestone schedule is developed with reference to the protocol agreement date and notify the Office PMR/PMC Coordinator [RPM]
        6. Ensure that RMS-BLA contains the IND number and any defined milestone schedule dates [Office PMR/PMC Coordinator]
      2. 506B Annual Reports (also known as 601.7 Annual Reports)
        1. Generate the PARRF for 506B annual reports. Note: Refer to JA 860.03: Instructions for Completing the PMR/PMC Annual Report Review Form (PARRF) for instructions on how to generate and complete the PARRF [Lead Reviewer]
          1. Generate and finalize the PARRF when the 506B annual report contains a PMR/PMC requested by the product office or when there are PMRs/PMCs requested by the product office and OBE. [Product Office Lead Reviewer]
            1. Review the status of PMR/PMCs requested by OBE and provide the required information to complete the PARRF for these PMRs/PMCs to the Product Office Lead Reviewer [OBE Lead Reviewer]
            2. Incorporate OBE’s information onto the PARRF [Product Office Lead Reviewer]
            3. Sign the PARRF [Product Office Lead Reviewer, Branch/Lab Chief]
          2. Generate and finalize the PARRF when the 506B annual report only contains PMR/PMC requested by OBE. [OBE Lead Reviewer]
            1. Sign the PARRF [OBE Lead Reviewer, Branch/Lab Chief]
        2. Ensure that the annual report contains updates on all open PMRs and PMCs. Refer to Appendix B: Reviewer considerations for 506B Annual Reports for details on the information expected in the annual report and consider the following: [Lead Reviewer]
          1. Determine whether the information on the study status and the explanation of status provided by the applicant are appropriate
          2. Ensure that the study is proceeding in accordance with the original schedule
          3. Summarize the explanation of status provided by the applicant onto the PARRF. The explanation of status is used to update RMS-BLA and may be posted on the Agency Web site
          4. Ensure that any discrepancies or questions identified during your review are addressed. Provide the RPM with letter ready comments
        3. Notify the RPM if the annual report is incomplete [Review Committee Member]
        4. Issue the “PMC-Incomplete Annual Report Letter” to the applicant and notify the Office PMR/PMC Coordinator [RPM]
          1. If the amendment is not received before the review due date:
            1. Document the incomplete information on the PARRF, finalize and forward the PARRF to the RPM and Office PMR/PMC Coordinator [Review Committee Member]
            2. Update the submission type and contact the applicant to resubmit the PMR/PMC – Annual Report in its entirety [RPM]
          2. If the amendment is received before the review due date,
            1. Contact RIMS to extend the review due date by 90 days [RPM]
            2. Confirm that amendment was received prior to the due date then extend the review due date [RIMS]
        5. Finalize the PARRF within the time frame identified in Section V.A.5 above, incorporate any consultant’s recommendations and notify the RPM and Office PMR/PMC Coordinator when the PARRF is finalized [Lead Reviewer]
        6. Update RMS-BLA with the status and the explanation of status for each PMR/PMC referenced in the completed PARRF [Office PMR/PMC Coordinator]
      3. PMR/PMC Submission/Final Study Report:
        1. Determine whether the final study report is complete, and document the rationale and whether the applicant has fulfilled the commitment in the review memo(s). Discuss issues with the branch chief, division director, applicant and/or other Review Committee Members (OBE and other offices), as appropriate [Review Committee Member]
        2. Notify the RPM of inadequate or incomplete Final Study Reports (FSRs) [Review Committee Member]
        3. Issue the “PMC-Final Study Report Not Accepted” letter to the applicant, if appropriate [RPM]
          1. For inadequate FSRs, request that the “PMC Submission / Final Study Report” be re-issued in its entirety and notify the Office PMR/PMC Coordinator [RPM]
          2. For FSRs missing some information, request that the information be provided in an amendment and notify the Office PMR/PMC Coordinator [RPM]
          3. If complete information is not received before the action due date:
            1. Document the incomplete information in a review memo, finalize and forward the review memo to the RPM and Office PMR/PMC Coordinator [Review Committee Member]
            2. Close the submission; contact the applicant to resubmit the “PMC Submission /Final Study Report” in its entirety [RPM]
            3. Contact RIMS to return the status of the appropriate PMR/PMC to its previous status or, if the original projected completion date is past, update the status to “delayed” [Office PMR/PMC Coordinator]
          4. If completing information is submitted before the action due date:
            1. Contact RIMS to extend the review due date by one (1) year [RPM]
            2. Confirm that amendment was received prior to due date then extend the review due date [RIMS]
        4. Complete the review of a final study report within the timeframes defined in V.A.5 and document in your review memo any missing information not received by the action due date [Review Committee Member]
        5. Incorporate any consultant’s recommendations into the review memo, finalize the review memo and inform the RPM to initiate final action on the commitment (e.g., issue letter to applicant) [Review Committee Member]
        6. Issue “PMC-Fulfilled” letter to the applicant; notify the Office PMR/PMC Coordinator to update RMS-BLA [RPM]
        7. Update RMS-BLA [Office PMR/PMC Coordinator]
      4. Submissions in response to non-506B PMC
        1. Assess whether the commitment is still required, needed or feasible; document rationale for considering the non-506B PMC released in a review memo [Review Committee Member]
        2. Assess if the non-506B PMC is fulfilled; document rationale for considering the non-506B PMC fulfilled in a review memo and incorporate any consultant’s recommendations into the review memo [Review Committee Member]
        3. Finalize the review memo and notify the RPM to initiate final action on the commitment (e.g., issue letter to applicant) [Review Committee Member]
        4. Issue the “PMC-Fulfilled” or “PMC-Released” letter to the applicant and notify the Office PMR/PMC Coordinator [RPM]
        5. Update RMS-BLA [Office PMR/PMC Coordinator]
      5. PMR/PMC Submission: Status Update

        An applicant may submit a Status Update to submit the protocol cross-reference letter, request a release from a PMR/PMC, to submit an annual status update for non-506B PMC agreed upon under a BLA or supplement, a Good Cause request, or a Deferral Extension Request.

        1. Review and finalize a review memo and notify the RPM of the status of the submission [Review Committee Member]
        2. Issue a “PMC – Release” letter, if appropriate, to release a PMR/PMC [RPM]
          1. If appropriate to replace the PMR/PMC with a new PMR/PMC, create and issue the new PMR/PMC following SOPP 8415: Procedures for Developing Postmarketing Requirements and Commitments [Review Committee Members]
        3. Close the submission and notify the Office PMR/PMC Coordinator [RPM]
        4. Update RMS-BLA [Office PMR/PMC Coordinator]
    6. Monitor RMS-BLA
      1. Check the quality of the data in RMS-BLA and resolve any discrepancies with the RPM/Review Committee Members [Office PMR/PMC Coordinator]
      2. Work with the Office PMR/PMC Coordinator to update RMS-BLA to ensure the quality of the data [RPM]
      3. Respond to requests concerning discrepancy issues [Office PMR/PMC Coordinator]
      4. Post a monthly report on all 505(o) and 506B PMRs/PMCs on the CBER Intranet Web page [RIMS]
      5. Provide PMR/PMC information for the public as mandated (e.g., annual Federal Register report, Agency’s Web site) [RIMS]
      6. Conduct an annual review of outstanding PMRs/PMCs [Office PMR/PMC Coordinator]
        1. Review PMR and PMC last annual report receipt date at least quarterly. If the annual report is late, use the “PMC-Annual Report Request” letter template, located on CBER’s Intranet Web page, draft the request letter and send to the RPM Branch Chief for approval. Generate a second level STN according to SOPP 8416: CBER Initiated Second Level STNs [Office PMR/PMC Coordinator]
        2. Receive draft Annual Report Request letters; coordinate with the Office PMR/PMC Coordinator to finalize the letter [RPM Branch Chief]
        3. Review, approve and serve as signatory authority for the Annual Report Request letters [RPM Branch Chief]
        4. Ensure that RMS-BLA is updated appropriately [Office PMR/PMC Coordinator]
    7. Reports
      1. Agency Web Page Report:
        1. Draft the PMR/PMC Status Report for the Web page at least two weeks before the Web Report is due. Send report to the Office PMR/PMC Coordinator for verification [RIMS]
        2. Reconcile issues identified on the “draft” Web Report, at the end of each quarter, and ensure all PMRs/PMCs are updated RMS-BLA [Office PMR/PMC Coordinator]
        3. Review and provide corrected reports to RIMS within 10 working days of receipt of report [RPM, Office Director]
        4. Provide the Office of Communication, Outreach, and Development (OCOD) with the Web Report to perform a Freedom of Information Act (FOIA) review [RIMS]
        5. Review the Web Report for privilege and confidential information. Send final report to RIMS [OCOD]
        6. Send final report to CDER’s Office of Strategic Programs by the last day of January, April, July, and October. The report will contain the required data for posting on the Agency’s Web site [RIMS]
      2. Federal Register Report:
        1. Generate, annually, a CBER summary - PMR/PMC report for the Federal Register notice [RIMS]
        2. Send the finalized CBER summary report to the designated Agency unit for drafting the Federal Register notice [RIMS]
        3. Review the draft Federal Register notice and ensure its accuracy with regard to CBER data [RIMS]
      3. FDAAA Section 921 Mandate
        1. On an annual basis, RIMS is to review the backlog of CBER’s PMRs/PMCs and report to Congress each year on the activity.
  8. Appendices
    1. Appendix A: Tables to Support SOPP 8413
      1. Table 1: Requirements for the Categories of PMRs/PMCs
      2. Table 2: Identification of a PMR/PMC Related Submission to an IND, BLA or NDA
    2. Appendix B: Review Committee Member Considerations for 506B Annual Reports
  9. References
    1. References below are located on CBER’s Intranet Web page unless otherwise noted
      1. Document Control Center Procedures
        1. DCC Procedure Guide #8: Procedure For Filing Final Action Packages Containing Paper FDA Correspondence For Marketing Applications - Including Multiple Products or
        2. DCC Procedure Guide #22 Procedure for Processing, Routing and Storing Electronic Submissions
        3. DCC Procedure Guide #23: Procedure for Filing Final Action Packages Containing Electronic FDA Communication for Marketing Applications
      2. Regulatory Job Aids
        1. JA 833.03: Instructions for Administratively Closing A Submission in RMS-BLA when a Written Review is not Necessary
        2. JA 860.01 Differences in Tracking and Reporting on Non-506B Postmarketing Commitments
        3. JA 860.03 Instructions for Completing the PMR/PMC Annual Report Review Form (PARRF)
        4. JA 860.04.01: Good Cause Data Entry Procedures
        5. JA 860.08: Instructions for Processing Deferral Extension Requests from the Applicant for Pediatric Postmarketing Requirements (PMR)
      3. Regulatory Reference
        1. R 860.03: Definitions for PMR/PMC Status Types
      4. RMS-BLA Related Documents
        1. RMS-BLA Data Dictionary for End Users available in the Resources Web Page under the Help menu in RMS-BLA
        2. RMS-BLA Data Entry for Postmarketing Requirements/Commitments and Related Submissions: available in RMS-BLA under the PMR/PMC information screen by clicking on the “Data Entry Guide” button
        3. PMR/PMC Annual Report Review Form (PARRF): available in RMS-BLA under the Communication Templates icon
    2. Web links to the references below can be found in the list following the history table:
      1. Statues and Regulations
        1. CFR – Code of Federal Regulations Title 21
        2. Federal Food, Drug, and Cosmetic Act (FD&C Act)
        3. FDA Modernization Act of 1997 (FDAMA)
        4. Food and Drug Administration Amendments Act (FDAAA) of 2007
        5. Food and Drug Administration Safety and Innovation Act (FDASIA) of 2012
        6. Pediatric Research Equity Act (PREA) of 2007
        7. Final Rule, “Postmarketing Studies for Approved Human Drugs and Licensed Biological Products; Status Reports,” 65 FR 64607 (October 30, 2000)
      2. Guidance Documents
        1. FDA Guidance for Industry: Postmarketing Studies and Clinical Trials – Implementation of Section 505(o) of the Federal Food, Drug, and Cosmetic Act
        2. FDA Guidance for Industry Reports on the Status of Postmarketing Study Commitments – Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997
        3. Guidance for Review Staff and Industry: Good Review Management Principles and Practices for PDUFA Products
      3. Internet Web sites
        1. Postmarketing Study Commitments Public Web site
      4. Standard Operating Policies and Procedures
        1. SOPP 8001.1: Interoffice Consultative Review Procedures
        2. SOPP 8001.5: Intercenter Consultative/ Collaborative Review Process
        3. SOPP 8110: Submission of Paper Regulatory Applications to CBER
        4. SOPP 8401.1: Issuance of and Review of Responses to Information Request Communications and Discipline Review Letters to Pending Submissions
        5. SOPP 8401.7: Action Package for Posting
        6. SOPP 8415: Procedures for Developing Postmarketing Requirements and Commitments
        7. SOPP 8416: CBER Initiated Second Level STNs
  10. History

Written/ Revised

Approved Date

Version Number

Comment

Menzies/RMCC Working Group

December 19, 2014

6

Updated to move initial data entry from RIMS to Office PMR/PMC Coordinators.

O’Leary/RIMS

August 2, 2010

5

Updated procedures to include findings from BAH study and to implement PMR/PMC Tracking Coordinator role

O'Leary/RIMS

January 28, 2008

4

Reference and form were updated to reflect database changes

Eastep/RIMS

April 13, 2007

3

Updated procedures and clarifications of previous version

Eastep/RIMS

August 21, 2006

2

Revisions to reflect changes in reporting procedures

Eastep/RMCC

January 16, 2001

1

Original version

 

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