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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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

Version #5

Effective Date: August 25, 2010


  1. Purpose

    1. The purpose of this document is to describe the policies and procedures for the Center for Biologics Evaluation and Research (CBER) staff for administrative handling and regulatory review of annual status reports, final study reports, and other submissions to the CBER for Biological License Applications (BLAs) and New Drug Applications (NDAs) related to postmarketing commitments (PMCs) and postmarketing requirements (PMRs).
    2. The procedures outlined in this SOPP apply to all reportable 506B PMRs/PMCs for drugs and licensed biologics and to non-506B commitments (e.g., CMC commitments, stability studies), but not to postmarketing studies conducted on an applicant’s own initiative (elective studies). The differences in managing non-506B postmarketing commitments are outlined in the regulatory job aid JA 860.01 Differences in Tracking and Reporting on Non-506B Postmarketing Commitments posted on CBER’s Intranet Web page. These procedures also apply to safety studies and clinical trials required under the Food and Drug Administration Amendments Act (FDAAA) of 2007.
    3. This SOPP does not discuss policy and procedures for PMR/PMC development. That topic is described in SOPP 8415: Procedures for Developing Postmarketing Requirements and Commitments.
  2. Scope

    The procedures detailed in this document apply to all PMRs/PMCs for licensed biologics (including licensed devices) and drugs regulated by CBER. They do not apply to PMCs for Premarket Device Applications (PMAs).
     
  3. Background

    1. PMRs/PMCs are generally studies or clinical trials that are to be conducted by the applicant after FDA has approved a product for marketing/licensing. These studies or clinical trials can be either required by regulation or statute (Postmarketing Requirements) or agreed-upon between FDA and the applicant (Postmarketing Commitments) (see “Definitions” Section).
    2. In the FDA Modernization Act of 1997 (FDAMA), Congress attempted to address concerns by FDA and patient/consumer groups about the timely completion of agreed upon PMC studies by drug and biologic manufacturers. FDAMA section 130 added section 506B to the Food, Drug and Cosmetic Act (the Act). Section 506B, Reports of Postmarketing Studies, which requires applicants that have agreed to conduct a postmarketing study to submit annual status reports to the Agency on the study’s status until they are notified in writing that the commitment has been fulfilled or that they have been released from the commitment. Applicants are required to submit their annual status reports to FDA within 60 days of the anniversary of U.S. product approvals. Further, Section 506B requires FDA to publish annually in the Federal Register information on the compliance of the applicants with this reporting requirement. FDA issued guidance for industry in February 2006 to complement the final rule. This guidance, titled Reports on the Status of Postmarketing Study Commitments - Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997, describes in detail the content, format, and timing of the PMR/PMC reports required by section 506B of the Act.
    3. In implementing Section 506B, CBER and the Center for Drug Evaluation and Research (CDER) developed revisions to 21 CFR 314.81(b)(2)(vii) (NDA annual reporting requirements) and 21 CFR 601.28 (annual reports of postmarketing pediatric studies for biologics); and a new regulation (21 CFR 601.70) for annual progress reports of postmarketing studies for biologics. [Note that the requirements for postmarketing pediatric study reporting under the Pediatric Research Equity Act (PREA) reauthorization by FDAAA have superseded the 601.28 requirements.]
    4. Section 506B does not apply to animal drugs or biologics meeting the definition of a device under the Act. Further, the requirements for reporting under 21 CFR 601.70 are limited to postmarketing commitments that concern a biologic’s clinical safety, clinical efficacy, clinical pharmacology, and non-clinical toxicology.
    5. Section 901 of FDAAA gives CBER and CDER the authority to require certain postmarketing safety studies/clinical trials, and requires applicants to submit a timetable for completion of each study/clinical trial.
    6.  The applicant is required to periodically report on each study/clinical trial required or otherwise undertaken by the applicant to investigate a safety issue.
    7. The new amendments to the Act give the FDA authority to enforce the Section 505(o)(3)(E)(ii) requirements for postmarketing studies and clinical trials. 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. A responsible person may not introduce or deliver into interstate commerce the drug involved, if the applicant is in violation of these requirements. In addition, violations of the requirements for postmarketing studies and clinical trials may result in misbranding charges and civil penalties.
       
  4. Definitions

    1. PMR/PMC Tracking Coordinator – The person assigned responsibility for ensuring PMRs/PMCs associated with an Office, Division or Branch have been verified for accuracy, including the current status, and that expected activities (e.g., applicant submissions and CBER review) are completed in a timely fashion. The PMR/PMC Tracking Coordinator may be assigned primary responsibility for communicating with the applicant regarding the PMR/PMC process after approval. Because this role or some of the responsibilities could be assigned to one or more Consumer Safety Technicians (CSTs), Consumer Safety Officers (CSOs), or Regulatory Project Managers (RPMs) in each organizational unit, these responsibilities are combined in this SOPP under “Tracking Coordinator” to make it easier to follow the process.
    2. Postmarketing Commitment (PMC) – Any written, agreed upon commitment made by an applicant before or after FDA has granted approval to market a product or approval of a supplement to conduct a postmarketing study or studies, or to otherwise gather and submit additional information about product safety, efficacy, or use; or to further evaluate chemistry or manufacturing issues.
    3. Postmarketing Requirement (PMR) – Any study or clinical trial that an applicant is required to conduct post-approval of a marketing application or a supplement. Applicants may be subject to legal penalties for not conducting PMRs. Studies or clinical trials may be required under the following conditions:

      • Accelerated approval clinical benefit studies (21 CFR 314.510 and 601.41)
      • Deferred pediatric studies (21 CFR 14.55(b) and 601.27(b))
      • Animal Efficacy Rule Clinical Efficacy and Safety Studies (21 CFR 314.610(b)(1) and 601.91(b)(1))
      • Safety studies – FDAAA Required Studies ((505(o)): FDA is authorized to require these studies or clinical trials at the time of approval or after approval, if CBER is aware of new safety information
       
    4. Reportable (506B) Postmarketing Studies – Applicants must submit annual status reports for all PMRs and PMCs for clinical safety, clinical efficacy, clinical pharmacology, and non-clinical toxicology studies that are documented in the approval letter or any other letter to the applicant under 506B of the Act and 21 CFR 601.70 (314.81(b)(2) for NDAs). PMRs must also be reported under 506B (all references to 506B reportable postmarketing studies in this document include 505(o) PMRs). All other postmarketing commitments are “non-506B,” i.e., non-reportable under 601.70 or 314.81(b) (2).
    5. Postmarketing Requirement/Commitment Related Submission – A formal applicant submission intended to address an established PMR/PMC.
      1. The submission may be made to an Investigational New Drug Application (IND) or BLA/NDA, depending on the type of PMR/PMC submission. However, if submitted to an IND, a cross reference letter of the submission must be sent to the BLA/NDA and categorized appropriately (e.g., PMC Submission/Final Study Report).
      2. The following are types of PMR/PMC related submissions that can be submitted:

        • PMR/PMC Protocol
        • PMR/PMC Correspondence/Status Update
        • Annual Status Report
        • Final Study Report (FSR)
        • Supplemental application submitted to address a PMR/PMC
    6. PMR/PMC Schedule Milestones – The specific study schedule dates for completing activities related to conducting a PMR/PMC. Note that these milestones were originally established for 506B PMCs under FDAMA. Although FDAAA has a reporting timetable for PMRs, these PMC milestones are also applicable to PMRs.
      1. The applicant must report a PMR’s/PMC’s status in each annual status report according to the original study schedule that was established for the PMR/PMC. These dates should be captured and updated as necessary in the PMR/PMC section of CBER’s regulatory database, and may include:

        • Final protocol submission date
        • Study/trial completion date or a date in relation to another milestone listed above (e.g., X months after final protocol submission)
        • Projected final report due date or a date in relation to the actual completion date (e.g., within X months from completion) 
    7. Timetable for Completion of PMR Safety Studies – FDAAA Required Studies (505(o)):
      1. For each study:

        • A report of the status of the study, including whether any difficulties in completing the study have been encountered
         
      2. For each clinical trial: 

        • A report of the status of the trial, including whether any difficulties in completing the study have been encountered
        • The number of participants enrolled
        • The expected completion date
        • Registration information with respect to the requirements under section 402(j)
    8. PMR/PMC Status Types – 506B of the Act requires that applicants report on the status of open PMR/PMCs annually using the following categories (see the regulatory job aid JA 860.02 Definitions for PMR/PMC Status Types):
      1. Open Status Types:

        • Pending
        • Ongoing
        • Delayed
        • Terminated
        • Submitted
         
      2. Closed Status Types:

        • Fulfilled
        • Released
         
    9. Elective (Applicant Initiated) Postmarketing Study – A study initiated by an applicant without a request by FDA. Elective studies are not required or agreed upon postmarketing commitments, and generally are not tracked in CBER’s regulatory databases.
  5. Policy

    CBER will:
    1. Track PMR/PMC-related submissions prior to and after receipt from applicants;
    2. Accurately and promptly process PMR/PMC-related submissions received;
    3. Track and monitor PMR/PMC-related submissions while under review;
    4. Review PMR/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.
      2. Annual Status Reports – CBER will review annual status reports within three months of receipt. 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. After verification of the information submitted in annual status reports by the reviewer, the CBER regulatory database will be updated with the correct status and/or explanation of status as supported by the review memo and information provided by the applicant in the annual status report.
      3. Final Reports – A Final Report submitted as a supplemental application will be reviewed 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.
         
    5. Update PMR/PMC statuses in CBER’s regulatory database in a timely manner; and
    6. Report on the compliance of applicants with regard to PMR/PMC submissions as required by the Federal Food, Drug, and Cosmetic Act (the Act). Applicant and CBER reporting requirements are detailed in FDA guidance for industry (see References).
    7. 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., timetable for completion, periodic report submissions.

      Elective studies, i.e., those that are not required or agreed upon, are not commitments and are not covered by this SOPP; such studies are generally not tracked in the regulatory databases or reported on. Although all non-elective PMCs are tracked in CBER's regulatory databases, only the 506B (601.70 reportable) PMRs/PMCs are required to be reported in the Federal Register and on the Web site.

                               Table 1. Requirements for the Categories of PMRs/PMCs
      PMR/PMC
      Categories
      Types   
      Covered
      under
      this
      SOPP?
      Tracked
       in RMS-
      BLA or
      BLT
      Annual
      Report
      required
      under
      601.70
      or 314.81?
      Reportable
      by FDA
      under
      505(o)/
      506B?
      Required
      Studies/Clinical
      Trials
      Accelerated
      Approval (21CFR
      314.510 Subpart H
      and 601.41 Subpart E)
      YesYesYesYes
      Deferred Pediatric
      (21 CFR 314.55(b) and 601.27(b))
      YesYesYesYes
      Animal Efficacy
      (21 CFR 314.610(b)(1) and 601.91(b)(1))
      YesYesYesYes
      FDAAA Safety (Section 901)YesYesYesYes
      Agreed Upon Studies/Clinical
      Trials
      Clinical Safety,
      Clinical Efficacy, Clinical
      Pharmacology, and Non-Clinical Pharmacology (Section 130
      FDAMA, 506B of
      FD&C Act)
      YesYesYesYes
      ALL other Agreed Upon StudiesCMC, Stability, etc.YesYesNo*No
      Elective StudiesN/ANoNoNo*No
      * NDA regulations require that all PMRs/PMCs be reported on in the 314.81 annual report, including non-506B PMCs and elective studies. 601.70 does not require reporting of non-506B studies for biologics. Although elective NDA postmarketing studies are reported on, they are not tracked in CBER's databases. 
       
  6. Responsibilities 

    [Note: Since the responsibilities and procedures for tracking the submissions varies in the offices between RPMs, CSOs, and CSTs, these procedures refer to the role and functions of the “Tracking Coordinator” rather than the positions of the people performing those functions. For the offices where the RPMs/CSTs/CSOs are splitting the Tracking Coordinator functions, all who have any of the functions should be kept abreast at the appropriate points in the process.] The PMR/PMC tracking and communication process flow is illustrated in Appendix A.
    1. Overall Responsibilities
      1. Associate Director for Review Management
        1. Ensure that the PMR/PMC tracking and review process steps are implemented consistently and in a timely manner across the organization
        2. Support changes to the PMR/PMC tracking and review process that will improve the quality and timeliness of status updates and submission review
        3. Ensure that adequate resources are allocated to develop and maintain a PMR/PMC database with optimal tracking and reporting functionality
        4. Provide a forum (e.g., as an agenda item at a standing meeting) for Review Management to share updates on PMR/PMC status as well as tracking or review process issues/changes
           
      2. Office Directors/Division Directors and/or Branch Chief
        1. Ensure staff are aware of and adhere to standardized policies for PMR/PMC tracking and review
        2. Identify a product or clinical reviewer for each PMR/PMC related submission
        3. Participate in discussions and decisions pertaining to determination of PMR/PMC fulfillment or release
        4. Ensure that review goals for PMR/PMC submissions are met
        5. Identify a forum for reporting and review of PMR/PMC status at least quarterly
           
      3. Product Office Branch/Lab Chief
        1. Provide information and support to the Tracking Coordinator as needed
        2. Ensure staff adhere to standardized policies for PMR/PMC tracking and review
           
      4. Reviewer
        1. Conduct a technical, scientific, or clinical review of the submission within the stated review timelines in consultation with appropriate Branch/Lab Chief and Office/Division Directors
        2. Determine whether a PMR/PMC has been fulfilled or should be released
        3. Ensure that all PMR/PMCs are still feasible and required/needed, with appropriate input/managerial oversight by Branch/Lab Chief and Office/Division Director to validate the assessment.
      5. Tracking Coordinator
        1. Facilitate compliance with responsibilities outlined in SOPP 8415: Procedures for Developing Postmarketing Requirements and Commitments by ensuring staff are aware of CBER policies and procedures
        2. Ensure that the data in the regulatory databases are quality checked (e.g., ensure accuracy for incoming PMR/PMC document submission codes, current status, schedule milestones, explanation of status)
        3. Actively monitor and provide support for PMR/PMC-related submissions and annual status reports to RPMs/Reviewers on a regularly scheduled basis
        4. Provide PMR/PMC status updates to appropriate review personnel when prompted/necessary
        5. Monitor due dates and ensure that the review(s) of the submission is performed within established timeframes (if any) and documented
      6. Regulatory Information Management Staff (RIMS)

        1. Ensure that all necessary tracking elements, reports and functionality for the PMR/PMC are available in the PMR/PMC tracking system
        2. Provide training to staff across all offices/divisions to ensure that all roles and responsibilities are understood and met
        3. Provide input and act as a resource for policy issues related to PMR/PMC development, tracking, and review
        4. Conduct periodic process audits to determine compliance with the defined policies and procedures, and provide audit results to Associate Director for Review Management for any necessary follow up
           
      7. Document Control Center
        1. Receive and process all PMR/PMC-related submissions
        2. Log all PMR/PMC-related submissions into the DATS system and process it according to usual procedures for that type of submission: BLA PMR/PMC Submission or Annual Report/PMR-PMC, NDA-PMC or NDA-Annual Report, BLA/NDA supplement, or amendment to an IND.
        3. Route the submission to the Applications Division with product responsibility and then further route copies to assigned reviewers upon receipt of routing instructions
        4. Maintain files for PMR/PMC related submissions by STN, NDA number or IND number, as appropriate.
  7. Procedures
    1. Procedures for Initial Data Entry of PMR/PMC

      1. When a BLA/NDA application or supplement is approved and the approval letter contains required or agreed upon PMRs/PMCs, or when any other letter establishes any PMR/PMC, CBER RIMS must receive notification or a copy of the letter. RIMS will enter the relevant information into the PMR/PMC Tracking system. NDA PMRs/PMCs are not entered into BLT, but maintained manually; since the BLT system has limited fields for capturing PMR/PMC-related submissions, the comments fields should be used to describe any PMR/PMC for the NDA.
      2. Ideally, there should only be one study or trial per PMR/PMC, and the letter to the applicant describing the required or agreed upon PMRs/PMCs should so list them, and they should be entered into RMS-BLA as individual PMRs/PMCs.
      3. See the RMS-BLA Data Entry for Postmarketing Requirements/Commitments and Related Submissions document for detailed instructions on entering PMR/PMC information and updates in the licensing system.

         
    2. Postmarketing Requirement/ Postmarketing Commitment Related Submissions

            1. Table 2. A PMR/PMC related submission may be made to an IND/BLA/NDA as follows:
      PMCRS
      Type
      IND
      (BIMS/BIRAMS)
      BLA
      (RMS-BLA)
      NDA
      (BLT)*
      PMR/PMC
      Protocol
      AmendmentPMC
      Submission/Correspondence
       - Status Update
      NDA - PMC
      (PMC Protocol)
      PMR/PMC
      Annual
      Report
      (505(o) &
      506B only)
      Annual Report**Annual Report/PMC Annual ReportNDA - Annual Report
      (PMC Annual Report)
      Status
      Update (non-
      506B)
      AmendmentPMC
      Submission/Correspondence
       - Status Update
      NDA - PMC
       (Status Update)
      Final Study
      Report
      Amendment**Supplement or
      PMR/PMC
      Submission/Final Study
      Report
      Supplement or
      NDA - PMC
      (Final Study Report)
      All Other
      PMR/PMC
      Submissions
      AmendmentPMR/PMC Submission/
      Correspondence - Status
      Update
      NDA - PMC
      (PMC
      Submission/ Correspondence)
      * BLT has limited submission types for PMR/PMC related submissions.  The submissions should be entered as stated above and enter specific details in the comments field (e.g., PMC protocol; Final Study Report). 
      **PMR/PMC annual reports and final study reports must be submitted to the BLA or NDA.  They may be submitted to the IND, but if they are, a submission must also be sent to the BLA or NDA referencing the IND submission.
       
    3. Administrative Handling and Review of PMR/PMC-Related Submissions

      1. The timeframes for reviewing PMR/PMC-related submissions, including administrative handling by the entire process team, are as follows:
        1. Annual Report – PMR/PMC Annual Report: 3 months;
        2. Final Study Report – PMR/PMC Submission/Final Study Report: 12 months;
        3. Final Study Report – BLA/NDA Supplement:

          1. Standard Efficacy: 10 months  
          2. Priority Efficacy: 6 months  
          3. Prior Approval: 4 months (user fee products); 6 months (non-user fee)  
          4. Changes Being Effected (CBE) or 30-Day CBE: 6 months.
      2. Other types of PMR/PMC Submissions, such as those to INDs, status updates, and correspondence do not have specific review timeframes.

         

    4. Procedures for Processing PMR/PMC-Related Submissions:
      1. Tracking Coordinator

                General

        1. Conduct an initial administrative review as appropriate for the type of submission
        2. Ensure all necessary information regarding the PMR/PMC-related submission is accurately and promptly entered into the regulatory database, e.g., enter as a second level STN in RMS-BLA as appropriate; if necessary, update the submission with the appropriate document submission code; for FSR submissions and supplements that contain a PMR/PMC FSR, update the status of the applicable PMR/PMC to “Submitted."
        3. In consultation with the Branch Chief, determine who should review the submission and request routing from DCC. If the submission pertains to an epidemiologic study (observational study, registry, or survey), two copies should be routed to OBE; one copy to the appropriate Division of Epidemiology Branch Chief (TBSB or VSB) and one copy to the Division of Biostatistics
        4. Ensure all reviewer names are documented in the regulatory database and submissions are routed/distributed to appropriate staff for each PMR/PMC-related submission and annual status report
        5. Notify appropriate staff that the PMR/PMC-related submission was received by CBER and to which reviewer(s) the submission is distributed
        6. Serve as the primary point of contact for communications with the applicant related to the PMR/PMC
        7. Coordinate with RPMs/Reviewers as needed to capture status and reconcile the current status of PMRs/PMCs for all approved products in the office, division, or branch

          1. Track PMR/PMC-related submissions for all approved products (e.g., using simple tracking sheet or PMC database report) in the office, division, or branch

             
        8. Assure through all steps of the process that the regulatory database is updated, whether the submission is made to a BLA, NDA, or IND
        9. Conduct discussions with applicants to encourage compliance with PMRs/PMCs as required

          Annual Status Reports

           
        10. Contact the applicant to amend the submission if it is a 601.70 Annual Report – PMR/PMC Annual Report and:
          1. not all of the outstanding 505(o) or 506B PMRs/PMCs have been addressed
          2. non-506B or other notifications have been included with the 601.70 report (they must be submitted separately)
          3. the Form FDA 2252 and 3674 has not been submitted
          4. the applicant has failed to provide the schedule with original projected completion dates

             
        11. Notify appropriate review personnel when annual status reports are incomplete
        12. Generate a PMR/PMC Annual Report Review Form (PARRF) for 601.70 submissions and send it to the reviewer to complete
        13. If the annual status report is incomplete, ensure the completing information comes in as an amendment
        14. If completing information is submitted before the review due date, the amendment may extend the due date by 90 days; contact RIMS to extend review clock
        15. If complete information is not received before the due date, ensure the reviewer finalizes the PARRF and document that the information is not complete; the Tracking Coordinator should close the submission and contact the applicant to resubmit the PMR/PMC – AR in its entirety
        16. Ensure that applicant-reported statuses are verified by the reviewer (on the PARRF for such submissions), and the verification is entered in the appropriate database

          PMC Submission/ Final Study Report (PMR/PMC-FSR)

           
        17. Ensure PMR/PMC-FSR is complete
        18. If incomplete, contact the sponsor to submit completing information
        19. Notify appropriate review personnel when FSR is incomplete
        20. If incomplete, ensure the completing information comes in as an amendment
        21. If completing information is submitted before the review due date, the amendment may extend the due date by one (1) year; contact RIMS to extend review clock
        22. If complete information is not received before the due date, ensure the reviewer documents that the information is not complete and close the submission; contact the applicant to resubmit the PMC Submission/Final Study Report in its entirety
           
    5. Review of PMR/PMC Related-Submissions and Verification of Status
      1. Reviewer
        1. Document the PMR/PMC-related submission review in memorandum format (or using the PARRF for 601.70 submissions), including determinations and recommendations for any necessary actions (e.g., letter to applicant)
        2. Provide appropriate communication of deficiencies and status updates as needed to the RPM and/or the Tracking Coordinator
        3. If the PMR/PMC is no longer required/needed or feasible, document the reason in a review and forward to the Tracking Coordinator to prepare a release letter to applicant
        4. Work with the Tracking Coordinator to coordinate an agreed-upon timeline for completing the review of PMR/PMC-related submission
        5. Consult as needed with other CBER review office(s) and/or divisions according to SOPP 8001.1: Interoffice Consultative Review Procedures and SOPP 8001.5: Intercenter Consultative/Collaborative Review Process; incorporate the recommendations into the review and/or final fulfillment recommendation
        6. PMR/PMC Study Protocol:

          1. Evaluate the study protocol and its ability to meet the objectives of the PMR/PMC 
          2. Work with the RPM concerning any issues that require discussion with the applicant
          3. Inform the Tracking Coordinator when the protocol has been agreed upon and other PMR/PMC-related submission dates that were dependent on that agreement date
             
        7. PMR/PMC Annual Status Reports:
          1. Ensure that all outstanding 505(o) PMRs and 506B PMCs are addressed if the submission is an Annual Report – PMR/PMC Annual Report
          2. Determine that the information on the study status and the status summary provided by the applicant are appropriate to the extent that can be determined by the submission, including whether the study is proceeding in accordance with the original schedule; resolve any discrepancies or questions by contacting the applicant; provides the RPM or Tracking Coordinator as soon as possible with any resulting data corrections or changes for the regulatory database(s)
          3. If the applicant does not amend the submission in the agreed upon time, document that the information is not complete and forward your review to either the RPM, Tracking Coordinator, or other office designee
          4. Complete the PARRF for such submissions within three (3) months of the receipt date and returns it to the RPM or Tracking Coordinator to update RMS-BLA. Please refer to regulatory job aid JA 860.03 Instructions for Completing the PMR/PMC Annual Report Review Form (PARRF).

             
        8. PMR/PMC Submission/Final Study Report:

          1. If the final report is being reviewed, determine whether the applicant has fulfilled the commitment and contact the RPM, Tracking Coordinator, or other office designee to initiate final action on the commitment, e.g., written notification to the applicant. Discuss issues with the branch chief, division director, applicant and/or other reviewers as appropriate
          2. The review of a final study report should be completed within 12 months from the date of receipt or according to the PDUFA timelines, when applicable
          3. If the final report submission is not a complete submission and the completing amendment is not received before the due date, you should document that the information is not complete and forward your review to either the RPM, Tracking Coordinator, or other office designee

             
        9. Provide RPM or Tracking Coordinator with an update on the review status when prompted
        10. Send any content-related questions or deficiencies, except for protocol related negotiations, to the Tracking Coordinator to communicate to the applicant
        11. Document all reviews in writing, with any comments, questions or requests for additional information for the applicant
        12. Following specific office procedures, obtain necessary clearances, assure that the RPM or Tracking Coordinator receives the review, and return the submission and review to DCC either directly or through the division coordinator or RPM

           
      2. Branch/ Lab Chief
        1. Ensure that PMR/PMC study/clinical trial protocols are evaluated for their ability to meet the objective(s) of the commitment
        2. 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
        3. Participate in discussions and decisions pertaining to determination of PMR/PMC fulfillment or release
        4. Conduct secondary reviews, as needed
           
      3. Office Director/ Division Director
        1. Participate in discussions and decisions pertaining to determination of PMR/PMC fulfillment or release
        2. Ensure that review goals for PMR/PMC submissions are met
        3. Identify a forum for reporting and review of PMR/PMC status at least quarterly
           
      4. Tracking Coordinator
        1. Work with the reviewer concerning review issues for a PMR/PMC Study Protocol and send PMR/PMC content-related correspondence (e.g., protocol deficiencies) to the applicant and courtesy copy appropriate review personnel when any such letter is sent
        2. Work with the Review Team to coordinate an agreed-upon timeline for the review of PMR/PMC-related submissions within the stated review timelines.
        3. If a supplemental application is submitted in response to a PMR/PMC and upon review meets the objective of the PMR/PMC, include notification of fulfillment in the action letter or ensure that a separate fulfillment letter is sent
        4. Issue PMR/PMC tracking-related correspondence to the applicant using the appropriate letter templates located on CBER’s Intranet Web page.
        5. Issue a letter in a timely manner, not to exceed 30 days, when a reviewer has completed a determination of fulfillment for PMR/PMCs or when the division has concluded that the applicant may be released from the commitment
        6. Include the RPM, the CBER/Regulatory Information Management Staff (RIMS) and consulting offices and divisions that have joint/team responsibility for evaluation of the PMR/PMC-related submissions in the distribution list of key correspondence for the PMR/PMC
    6. Update Status of PMR/PMC in the PMR/PMC Tracking System and File Completion Package
      1. Tracking Coordinator
        1. Forward the completion package, including the applicant’s PMR/PMC related submissions and all CBER reviews, forms, and correspondence to DCC following the appropriate DCC Procedures Guides
        2. Update appropriate PMRs/PMCs upon receipt of submissions, if applicable
        3. Update PMRs/PMCs based on action letters and/or reviews
        4. Process the PMR/PMC annual status report verification form and update appropriate PMRs/PMCs in the PMR/PMC Tracking system
        5. For PMRs/PMCs where the protocol has been agreed upon and other PMR/PMC related submission dates were dependent on that agreement date, update the PMR/PMC Tracking system with the specific dates in the “Original Projected Completion Date” screen

           
      2. Regulatory Information Management Staff (RIMS)
        1. Quality check the data in the PMR/PMC Tracking system related to the PMR/PMC and resolve any discrepancies with the appropriate Tracking Coordinator, RPM or office information specialist
    7. Postmarketing Requirement/Commitment Reports
      1. Tracking Coordinator
        1. Respond to requests from RIMS to reconcile any discrepancies identified
        2. At the end of each quarter, reconcile issues identified on the “draft” Web Report and ensure all PMRs/PMCs are updated in the PMR/PMC Tracking system
        3. Conduct an annual review of the backlog of outstanding PMRs/PMCs

           
      2. RIMS
        1. Ensure that the PMR/PMC Tracking system is populated and updated according to the current operating procedures
        2. Post a monthly report on all 505(o) and 506B PMRs/PMCs on the CBER website
        3. Provide status reports from the PMR/PMC database to the Center Director, Associate Director for Review Management and Office/Division Director on a quarterly basis
        4. Provide PMR/PMC information for the public as mandated (e.g., annual Federal Register report, public Website)
        5. Web Site Report:
          1. At the end of each quarter, the review offices assure that all information on PMRs/PMCs is updated in the regulatory databases; this process is completed by a date announced by RIMS each quarter.
          2. RIMS will check the data in the system and reconcile any discrepancies with the review office
          3. RIMS will draft the PMR/PMC Status Report update for the Web site, which includes any manual entries necessary for BLAs/NDAs, and, at least two weeks before the Web report is due, sends it to the application review offices for verification; the offices are asked to respond within 10 working days.
          4. Consult with the Office of Communication, Outreach, and Development (OCOD) concerning PMR/PMC releasability issues
          5. Once all data corrections have been made, RIMS sends the required data for the Web site report electronically for posting on the CBER Web site; this is done by the last day of the first month of the quarter.
             
        6. Federal Register Report:
          1. Annually, RIMS generates a summary PMR/PMC report for the Federal Register. The information for this report is derived from the quarterly Web site report data.
          2. The reports are based on the same procedures for checking and clearance, and have the same timeframes.
          3. The finalized report is sent to the designated Agency unit for drafting the Federal Register notice.
          4. RIMS assures the accuracy of the draft Federal Register notice with regard to CBER data.
             
        7. FDAAA Section 921 Mandate
          1. Generate annually a summary of PMRs/PMCs that have been revised or released
          2. RIMS checks the system for PMRs/PMCs without a completion date and works with the RPM/Tracking Coordinator to resolve the missing original schedule
  8. Appendix

     

    1. Appendix A: Process Flows for PMR/PMC Tracking, Communicating, and Reviewing
  9. References
    1. References below are located on CBER’s Intranet Web Page unless otherwise noted
      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
      4. Regulatory Job Aid: JA 860.01 Differences in Tracking and Reporting on Non-506B Postmarketing Commitments
      5. Regulatory Job Aid: JA 860.02 Definitions for PMR/PMC Status Types
      6. Regulatory Job Aid: JA 860.03 Instructions for Completing the PMR/PMC Annual Report Review Form (PARRF)

         

    2. Web Links to the references below can be found in the list following the History Table
      1. Food and Drug Administration Amendments Act of 2007
      2. Federal Food, Drug, and Cosmetic Act, Section 506B
      3. 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. FDA Guidance for Industry: Postmarketing Studies and Clinical Trials – Implementation of Section 505(o) of the Federal Food, Drug, and Cosmetic Act
      5. Postmarketing Study Commitments Public Website
      6. SOPP 8415: Procedures for Developing Postmarketing Requirements and Commitments
      7. Final Rule, “Postmarketing Studies for Approved Human Drugs and Licensed Biological Products; Status Reports,” 65 FR 64607 (October 30, 2000)
      8. 21 CFR 314.81(b)(2), Other Postmarketing Reports (for NDAs)
      9. 21 CFR 601.70, Annual Progress Reports of Postmarketing Studies
  10. History

    Written/RevisedApprovedApproval DateVersion NumberComment
    O'Leary/RIMSRobert A. Yetter, PhDAugust 2, 20105Updated procedures to include findings from BAH study and to implement PMR/PMC Tracking Coordinator role
    O'Leary/RIMSRobert A. Yetter, PhDJanuary 28, 20084Reference and form were updated to reflect database changes
    Eastep/RIMSRobert A. Yetter, PhDApril 13, 20073Updated procedures and clarifications of previous version
    Eastep/RIMSRobert A. Yetter, PhDAugust 21, 20062Revisions to reflect changes in reporting procedures
    Eastep/RMCCRobert A. Yetter, PhDJanuary 16, 20011Original version