82 FR 57996 - Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements and Commitments; Availability
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 82, Issue 235 (December 8, 2017)
Food and Drug Administration
Federal Register Volume 82, Issue 235 (December 8, 2017)
| Page Range | 57996-58003 | |
| FR Document | 2017-26470 |
[Federal Register Volume 82, Number 235 (Friday, December 8, 2017)] [Notices] [Pages 57996-58003] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2017-26470] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2016-N-3083] Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements and Commitments; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice of availability. ----------------------------------------------------------------------- SUMMARY: Under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), the Food and Drug Administration (FDA or Agency) is required to report annually in the Federal Register on the status of postmarketing requirements (PMRs) and postmarketing commitments (PMCs) required of, or agreed upon by, holders of approved drug and biological products. This notice is the Agency's report on the status of the studies and clinical trials that applicants have agreed to, or are required to, conduct. FOR FURTHER INFORMATION CONTACT: Cathryn C. Lee, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6484, Silver Spring, MD 20993-0002, 301- 796-0700; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911. SUPPLEMENTARY INFORMATION: I. Background A. Postmarketing Requirements and Commitments A PMR is a study or clinical trial that an applicant is required by statute or regulation to conduct postapproval. A PMC is a study or clinical trial that an applicant agrees in writing to conduct postapproval, but that is not required by statute or regulation. PMRs and PMCs can be issued upon approval of a drug \1\ or postapproval, if warranted. --------------------------------------------------------------------------- \1\ For the purposes of this notice, references to ``drugs'' or ``drug products'' include drugs approved under the FD&C Act and biological products licensed under the Public Health Service Act other than biological products that also meet the definition of a device in section 201(h) of the FD&C Act (21 U.S.C. 321(h)). --------------------------------------------------------------------------- FDA can require application holders to conduct postmarketing studies and clinical trials:To assess a known serious risk, assess signals of serious risk, or identify an unexpected serious risk related to the use of a drug product (section 505(o)(3) of the FD&C Act (21 U.S.C. 355(o)(3)), as added by the Food and Drug Administration Amendments Act of 2007 (FDAAA) (Pub. L. 110-85)). Under the Pediatric Research Equity Act (PREA) (Pub. L. 108-155), to study certain new drugs for pediatric populations, when these drugs are not adequately labeled for children. Under section 505B(a)(3) of the FD&C Act (21 U.S.C. 355c), the initiation of these studies may be deferred until required safety information from other studies in adults has first been submitted and reviewed. To verify and describe the predicted effect or other clinical benefit for drugs approved in accordance with the accelerated approval provisions in section 506(c)(2)(A) of the FD&C Act (21 [[Page 57997]] U.S.C. 356(c)(2)(A)) (21 CFR 314.510 and 21 CFR 601.41). For a drug that was approved on the basis of animal efficacy data because human efficacy trials are not ethical or feasible (21 CFR 314.610(b)(1) and 21 CFR 601.91(b)(1)). PMRs for drug products approved under the animal efficacy rule \2\ can be conducted only when the drug product is used for its indication and when an exigency (or event or need) arises. In the absence of a public health emergency, these studies or clinical trials will remain pending indefinitely. --------------------------------------------------------------------------- \2\ 21 CFR 314.600 for drugs; 21 CFR 601.90 for biological products. --------------------------------------------------------------------------- B. Reporting Requirements Under the regulations (21 CFR 314.81(b)(2)(vii) and 21 CFR 601.70), applicants of approved drugs are required to submit annually a report on the status of each clinical safety, clinical efficacy, clinical pharmacology, and nonclinical toxicology study or clinical trial either required by FDA or that they have committed to conduct, either at the time of approval or after approval of their new drug application (NDA), abbreviated new drug application (ANDA), or biologics license application (BLA). Applicants are required to report to FDA on these requirements and commitments made for NDAs and ANDAs under Sec. 314.81(b)(2)(viii). The status of PMCs concerning chemistry, manufacturing, and production controls and the status of other studies or clinical trials conducted on an applicant's own initiative are not required to be reported under Sec. Sec. 314.81(b)(2)(vii) and 601.70 and are not addressed in this report. Furthermore, section 505(o)(3)(E) of the FD&C Act requires that applicants report periodically on the status of each required study or clinical trial and each study or clinical trial ``otherwise undertaken . . . to investigate a safety issue. . . .'' An applicant must report on the progress of the PMR/PMC on the anniversary of the drug product's approval \3\ until the PMR/PMC is completed or terminated and FDA determines that the PMR/PMC has been fulfilled or that the PMR/PMC is either no longer feasible or would no longer provide useful information. The annual status report (ASR) must include a description of the PMR/PMC, a schedule for completing the PMR/PMC, and a characterization of the current status of the PMR/PMC. The report must also provide an explanation of the PMR/PMC status by describing briefly the progress of the PMR/PMC. A PMR/PMC schedule is expected to include the actual or projected dates for the following: (1) Submission of the final protocol to FDA; (2) completion of the study or clinical trial; and (3) submission of the final report to FDA. --------------------------------------------------------------------------- \3\ An applicant must submit an annual status report on the progress of each open PMR/PMC within 60 days of the anniversary date of United States approval of the original application or on an alternate reporting date that was granted by FDA in writing. Some applicants have requested and been granted by FDA alternate annual reporting dates to facilitate harmonized reporting across multiple applications. --------------------------------------------------------------------------- C. PMR/PMC Status Categories The status of the PMR/PMC must be described in the ASR according to the terms and definitions provided in Sec. Sec. 314.81 and 601.70. For its own reporting purposes, FDA has also established terms to describe when the conditions of the PMR/PMC have been met, and when it has been determined that a PMR/PMC is no longer necessary.\4\ The PMR/PMC status categories are summarized in the following list. As reflected in the definitions, the status of a PMR/PMC is generally determined based on the original schedule.\5\ --------------------------------------------------------------------------- \4\ See the guidance for industry entitled ``Reports on the Status of Postmarketing Study Commitments--Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997'' available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM080569.pdf. \5\ The definitions for the terms ``pending,'' ``ongoing,'' ``delayed,'' ``terminated,'' and ``submitted'' are adapted from Sec. Sec. 314.81 and 601.70; the definitions for the terms ``fulfilled'' and ``released'' are described in the guidance for industry entitled ``Reports on the Status of Postmarketing Study Commitments--Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997.'' --------------------------------------------------------------------------- Pending: The study or clinical trial has not been initiated (i.e., no subjects have been enrolled or animals dosed), but does not meet the criteria for delayed (i.e., the original projected date for initiation of subject accrual or initiation of animal dosing has not passed).\6\ --------------------------------------------------------------------------- \6\ It is important to note that PMRs/PMCs that are in pending status are not yet delayed; that is, per the milestones, the studies or clinical trials are indeed on schedule and are not expected to be underway yet. --------------------------------------------------------------------------- Ongoing: The study or clinical trial is proceeding according to or ahead of the original schedule. Delayed: The study or clinical trial is behind the original schedule.\7\ --------------------------------------------------------------------------- \7\ In some instances, an applicant may have justifiable reasons for delay of its PMR/PMC (see section I.D). --------------------------------------------------------------------------- Terminated: The study or clinical trial was ended before completion, but a final report has not been submitted to FDA. Submitted: The study or clinical trial has been completed or terminated, and a final report has been submitted to FDA. Fulfilled: The final report for the study or clinical trial was submitted to FDA and FDA notified the applicant that the requirement or commitment was fulfilled through written correspondence. Released: FDA has informed the applicant in writing that it is released from its obligation to conduct the study or clinical trial because the study or clinical trial is no longer feasible, would no longer provide useful information, or the underlying application has been formally withdrawn. In addition to the above statuses, PMRs/PMCs may also be characterized as open or closed. Open PMRs/PMCs comprise those that are pending, ongoing, delayed, submitted, or terminated; whereas closed \8\ PMRs/PMCs are either fulfilled or released. Open PMRs are also described by whether they are on- or off-schedule. On-schedule PMRs/ PMCs are those that are pending, ongoing, or submitted. Off-schedule PMRs/PMCs are those that have missed one of the milestone dates in the original schedule and are categorized as either delayed or terminated. --------------------------------------------------------------------------- \8\ Previous FDA reports on the status of PMRs/PMCs used the term ``completed'' to refer to PMRs/PMCs that are closed. --------------------------------------------------------------------------- D. Additional Requirements If an applicant fails to comply with the original schedule for completion of postmarketing studies or clinical trials required under section 505(o)(3) of the FD&C Act (i.e., under the FDAAA authorities), or fails to submit periodic reports on the status of the studies or clinical trials, the applicant is considered to be in violation of section 505(o)(3), unless it has demonstrated good cause for its noncompliance or other violation. Failure to meet an original milestone and, as a result, falling behind the original schedule is one type of noncompliance with a PMR issued under FDAAA. In these circumstances, the FDAAA PMR is considered delayed, with or without good cause. Section 505B(a)(3)(B) of the FD&C Act, as amended by the Food and Drug Administration Safety and Innovation Act, authorizes FDA to grant an extension of the deferred pediatric assessments that are required under PREA.\9\ On its own initiative or upon request, FDA may grant an extension of a pediatric assessment deferral, [[Page 57998]] provided that certain applicable PREA criteria for deferral are still met and the applicant submits certain materials in support of the extension.\10\ Applicants must submit requests for deferral extensions to FDA not less than 90 days before the date the deferral would otherwise expire. If FDA grants the extension of a pediatric study deferral, this new deferral date is considered the original due date of the PMR. Consequently, the status of PREA PMRs would be determined based on the new deferral date (and not the original PREA PMR schedule). --------------------------------------------------------------------------- \9\ This provision does not apply to PMRs required under other provisions, or to PMCs. \10\ See section 505B(a)(3)(B) of the FD&C Act. --------------------------------------------------------------------------- FDA may take enforcement action against applicants who are noncompliant with or otherwise fail to conduct studies and clinical trials required under FDA statutes and regulations (see, for example, sections 505(o)(1), 502(z), and 303(f)(4) of the FD&C Act (21 U.S.C. 355(o)(1), 352(z), and 333(f)(4))). II. Understanding FDA's Data on Postmarketing Studies and Clinical Trials A. FDA's Internal PMR/PMC Databases Databases containing information on PMRs/PMCs are maintained at the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). The information in these databases is periodically updated as new PMRs/PMCs are issued, upon FDA review of PMR/PMC ASRs or other PMR/PMC correspondence, upon receipt of final reports from completed studies and clinical trials, and after the final reports are reviewed and FDA determines that the PMR/PMC has been fulfilled, or when FDA determines that the PMR/PMC is either no longer feasible or would no longer provide useful information. Because applicants typically report on the status of their PMRs/PMCs annually, and because updating the status of PMRs/PMCs in FDA's databases involves FDA review of received information, there is an inherent lag in updating the data (that is, the data are not real time). FDA strives to maintain as accurate information as possible on the status of PMRs/ PMCs. Both CDER and CBER have established policies and procedures to help ensure that FDA's data on PMRs/PMCs are current and accurate. When identified, data discrepancies are addressed as expeditiously as possible and/or are corrected in later reports. B. Publicly Available PMR/PMC Data FDA also maintains an online searchable and downloadable database that contains information about PMRs/PMCs that is publicly reportable (i.e., for which applicants must report on the status of the study or clinical trial, as required under section 506B of the FD&C Act (21 U.S.C. 356b)). The data are a subset of all PMRs/PMCs and reflect only those postmarketing studies and clinical trials that, at the time of data retrieval, either had an open status or were closed within the past year. Information on PMRs/PMCs closed more than a year before the date the data are extracted (i.e., September 30, 2016) is not included on the public Web site. The FDA Web site is updated quarterly.\11\ The FDA Web site does not include information about PMCs concerning chemistry, manufacturing, and controls. It is FDA policy not to post information on the Web site until it has been verified and reviewed for suitability for public disclosure. --------------------------------------------------------------------------- \11\ https://www.accessdata.fda.gov/scripts/cder/pmc/index.cfm. --------------------------------------------------------------------------- III. About This Report This report is published to fulfill the annual reporting requirement under section 506B(c) of the FD&C Act. Information in this report covers any PMR/PMC that was made, in writing, at the time of approval or after approval of an application or a supplement to an application (see section I.A), and summarizes the status of PMRs/PMCs in fiscal year (FY) 2016 (i.e., as of September 30, 2016). Specifically, the report summarizes the status of all open PMRs/PMCs through the end of the fiscal year, and the status of only those PMRs/ PMCs that were closed in the fiscal year. If a requirement or commitment did not have a schedule, or an ASR was not received in the previous 12 months, the PMR/PMC is categorized according to the most recent information available to the Agency.\12\ --------------------------------------------------------------------------- \12\ Although the data included in this report do not include a summary of reports that applicants have failed to file by their due dates, the Agency notes that it may take appropriate regulatory action in the event reports are not filed on a timely basis. --------------------------------------------------------------------------- This report reflects combined data from CDER and CBER. Information summarized in the report includes the following: (1) The number of applicants with open PMRs/PMCs; \13\ (2) the number of open PMRs/PMCs; (3) the number of applications for which an ASR was expected but was not submitted within 60 days of the anniversary date of U.S. approval or an alternate reporting date that was granted by FDA; (4) FDA- verified status of open PMRs/PMCs reported in Sec. 314.81(b)(2)(vii) or Sec. 601.70 ASRs; (5) the status of closed PMRs/PMCs; and (6) the distribution of the status by fiscal year of establishment \14\ (FY2010 to FY2016) for PMRs and PMCs open at the end of FY2016, or those closed within FY2016. The tables in this report distinguish between PMRs and PMCs, PMRs/PMCs for NDAs and BLAs, and on-schedule and off-schedule PMRs/PMCs, according to the original schedule milestones. Additional information about PMRs/PMCs is provided on FDA's Web site at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/default.htm. --------------------------------------------------------------------------- \13\ At the end of FY2016, there were no PMRs/PMCs for ANDAs that met the reporting requirements under the Food and Drug Administration Modernization Act of 1997. Therefore, this report reflects information for NDAs and BLAs only. \14\ The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or requested (PMC) postmarketing study or clinical trial. --------------------------------------------------------------------------- Numbers published in this report cannot be compared with the numbers resulting from searches of the publicly accessible and downloadable database. This is because this report incorporates data for all PMRs/PMCs in FDA databases as of the end of the fiscal year, including PMRs/PMCs undergoing review for accuracy. The publicly accessible and downloadable database includes a subset of PMRs/PMCs, specifically those that, at the time of data retrieval, either had an open status or were closed within the past 12 months. In addition, the status information in this report is updated annually while the downloadable database is updated quarterly (i.e., in January, April, July, and October). IV. Summary of Information on PMR/PMC Status This report provides information on PMRs/PMCs as of September 30, 2016 (i.e., for FY2016). It is important to note that a comparison of the number of open and on-schedule or off-schedule PMRs/PMCs over time can be misleading because it does not take into account that the cohort of open PMRs/PMCs is not static from year to year. New PMRs/PMCs are continually being established for studies and clinical trials with varying start dates and durations; and other PMRs/PMCs are closed because they are either fulfilled or released. Also, ongoing PMRs/PMCs are carried forward into the subsequent fiscal year. Therefore, the number of on- and off-schedule PMRs/PMCs can vary from year to year, and a year-to-year [[Page 57999]] comparison of on- or off-schedule PMRs (e.g., to assess for a potential trend) is not appropriate. Finally, due to rounding, the percentages in the tables may not add up to 100 percent. A. Applicants With Open PMRs/PMCs An applicant may have multiple approved drug products, and an approved drug product may have multiple PMRs and/or PMCs. Table 1 shows that as of September 30, 2016, there were 285 unique applicants with open PMRs/PMCs under 890 unique NDAs and BLAs. There were 207 unique NDA applicants (and 734 associated applications) and 78 unique BLA applicants (and 156 associated applications) with open PMRs/PMCs. Table 1--Applicants and Applications (NDA/BLA) With Open Postmarketing Requirements and Commitments [Numbers as of September 30, 2016] ---------------------------------------------------------------------------------------------------------------- Total (NDA and NDA \1\ BLA \2\ BLA) ---------------------------------------------------------------------------------------------------------------- Number of unique applicants with open PMRs/PMCs............... 207 78 285 Number of applications with open PMRs/PMCs.................... 734 156 890 ---------------------------------------------------------------------------------------------------------------- \1\ As of September 30, 2016, there were only NDAs with associated PMRs/PMCs managed by CDER. \2\ Includes BLAs managed by both CDER and CBER. B. Annual Status Reports Received As previously mentioned, applicants must submit an ASR on the progress of each open PMR/PMC within 60 days of the anniversary date of United States approval of the original application or an alternate reporting date that was granted by FDA (Sec. Sec. 314.81 and 601.70).\15\ Table 2 shows that there were 764 NDAs and BLAs with an ASR due in FY2016 (622 NDAs and 142 BLAs).\16\ Of the 622 NDA ASRs due in that fiscal year, 66 percent (411/622) were received on time, 11 percent (66/622) were not received on time, and 23 percent (145/622) were not received during FY2016. Of the 142 BLA ASRs due, 72 percent (102/142) were received on time, 17 percent (24/142) were not received on time, and 11 percent (16/142) were not received during FY2016. --------------------------------------------------------------------------- \15\ Some applicants have requested and been granted by FDA alternate annual reporting dates to facilitate harmonized reporting across multiple applications. \16\ The number of ASRs that were expected is different from the total number of unique applications with open PMRs/PMCs because not all applications had an ASR due during FY2016. Applicants with PMRs/ PMCs associated with multiple applications may have submitted the ASR to only one of the applications. In addition, if all of the PMRs/PMCs for an application were established in the preceding fiscal year, or if all PMRs/PMCs for an application were closed before the ASR due date, submission of an ASR would not have been expected. Table 2--Annual Status Reports Received [Numbers as of September 30, 2016] \1\ ---------------------------------------------------------------------------------------------------------------- Received, on time Received, not on Expected but not \2\ Expected \3\ (% of time \4\ (% of received (% of expected) expected) expected) ---------------------------------------------------------------------------------------------------------------- NDA.................................... \5\ 622 411 (66%) 66 (11%) 145 (23%) BLA.................................... 142 102 (72%) 24 (17%) 16 (11%) ------------------------------------------------------------------------ Total.............................. 764 513 (67%) 90 (12%) 161 (21%) ---------------------------------------------------------------------------------------------------------------- \1\ Percentages may not total 100 due to rounding. \2\ ASR expected during fiscal year (within 60 days (before or after) of the anniversary of original approval date or alternate agreed-upon date). \3\ ASR was received within 60 days (before or after) of the anniversary of the original approval date or alternate agreed-upon date. \4\ ASR was received, but not within 60 days (before or after) of the anniversary of the original approval date or alternate agreed-upon date. \5\ The total number of NDA ASRs expected in FY2016 (622) increased compared to the number of ASRs expected in FY2015 (451). The increase is primarily due to the establishment of several FDAAA safety PMRs for which a serious safety issue applied to a class of drug products. In those cases, each applicant with a drug product (i.e., application) in the class was required to conduct the same postmarketing safety study or trial, and each applicant was required to submit an ASR for that PMR. As a consequence, multiple ASRs were expected during FY2016 for the same FDAAA safety PMR. C. Overview of On- and Off-Schedule Open PMRs/PMCs Table 3 shows that as of September 30, 2016, most open PMRs (84 percent for NDAs and 91 percent for BLAs) and most open PMCs (71 percent for NDAs and 83 percent for BLAs) were progressing on schedule. Table 3--Summary of On- and Off-Schedule Postmarketing Requirements and Commitments [Numbers as of September 30, 2016] \1\ -------------------------------------------------------------------------------------------------------------------------------------------------------- Open PMRs N = 1,323 Open PMCs N = 365 --------------------------------------------------------------------------------------------------- NDA (% of open NDA BLA (% of open BLA NDA (% of open NDA BLA (% of open BLA PMRs) PMRs) PMCs) PMCs) -------------------------------------------------------------------------------------------------------------------------------------------------------- On-schedule......................................... 882 (84%) 247 (91%) 123 (71%) 159 (83%) Off-schedule........................................ 169 (16%) 25 (9%) 51 (29%) 32 (17%) --------------------------------------------------------------------------------------------------- [[Page 58000]] Total........................................... 1,051 272 174 191 -------------------------------------------------------------------------------------------------------------------------------------------------------- \1\ Percentages may not total 100 due to rounding. D. Open and On-Schedule PMRs Table 4 shows that as of September 30, 2016, nearly half of the open NDA and BLA PMRs were pending (49 percent (517/1,051) and 45 percent (123/272), respectively). PREA PMRs and FDAAA PMRs comprised 55 percent (349/640) and 39 percent (249/640) of pending PMRs, respectively. The next largest category of open and on-schedule PMRs comprised those that were ongoing (29 percent (306/1,051) of NDA PMRs and 37 percent (100/272) of BLA PMRs). Table 4--Summary of Open and On-Schedule Postmarketing Requirements [Numbers as of September 30, 2016] \1\ -------------------------------------------------------------------------------------------------------------------------------------------------------- NDA N = 1,051 (% of open NDA PMRs) BLA N = 272 (% of open BLA PMRs) Reporting authority/PMR status ----------------------------------------------------------------------------------------------- Pending Ongoing Submitted Pending Ongoing Submitted -------------------------------------------------------------------------------------------------------------------------------------------------------- Accelerated approval.................................... 16 (2%) 19 (2%) 3 (<1%) 13 (5%) 10 (4%) 4 (1%) PREA \2\................................................ 300 (28%) 124 (12%) 14 (1%) 49 (18%) 29 (11%) 8 (3%) Animal efficacy \3\..................................... 4 (<1%) 0 1 (<1%) 9 (3%) 0 0 FDAAA safety............................................ 197 (19%) 163 (16%) 41 (4%) 52 (19%) 61 (22%) 12 (4%) ----------------------------------------------------------------------------------------------- Total............................................... 517 (49%) 306 (29%) 59 (6%) 123 (45%) 100 (37%) 24 (9%) -------------------------------------------------------------------------------------------------------------------------------------------------------- \1\ Percentages may not total 100 due to rounding. \2\ Many PREA studies have a pending status. PREA studies are usually deferred because the drug product is ready for approval in adults. Initiation of these studies may be deferred until additional safety information from other studies has first been submitted and reviewed before beginning the studies in pediatric populations. \3\ PMRs for drug products approved under the animal efficacy rule (21 CFR 314.600 for drugs; 21 CFR 601.90 for biological products) can be conducted only when the drug product is used for its indication and when an exigency (or event or need) arises. In the absence of a public health emergency, these studies or clinical trials will remain pending indefinitely. E. Open and Off-Schedule PMRs Table 5 provides additional information on the status of open and off-schedule PMRs (i.e., delayed and terminated). At the end of September 30, 2016, 16 percent (169/1,051) of the open NDA PMRs and 9 percent (25/272) of the open BLA PMRs were off schedule. Of the off- schedule NDA PMRs, 97 percent (164/169) were off schedule because they were delayed and the remaining 3 percent (5/169) were terminated. Similarly, 88 percent of the off-schedule BLA PMRs were delayed (22/ 25). In certain situations, the original PMR schedules were adjusted for unanticipated delays in the progress of the study or clinical trial (e.g., difficulties with subject enrollment in a clinical trial for a marketed drug or the need for additional time to analyze results). In this report, study or clinical trial status reflects the status in relation to the original \17\ study or clinical trial schedule regardless of whether FDA has acknowledged that additional time was required to complete the study or clinical trial. --------------------------------------------------------------------------- \17\ With the exception of PREA PMRs for which a deferral extension of the final report submission date has been granted. Table 5--Summary of Open and Off-Schedule Postmarketing Requirements [Numbers as of September 30, 2016] \1\ ---------------------------------------------------------------------------------------------------------------- NDA N = 1,051 (% of open NDA BLA N = 272 (% of open BLA PMRs) PMRs) Reporting authority/PMR status --------------------------------------------------------------- Delayed Terminated Delayed Terminated ---------------------------------------------------------------------------------------------------------------- Accelerated approval............................ 9 (1%) 1 (<1%) 1 (<1%) 0 PREA............................................ 84 (8%) 2 (<1%) 6 (2%) 2 (1%) Animal efficacy................................. 0 0 0 0 FDAAA safety.................................... 71 (7%) 2 (<1%) 15 (6%) 1 (<1%) --------------------------------------------------------------- [[Page 58001]] Total....................................... 164 (16%) 5 (<1%) 22 (8%) 3 (1%) ---------------------------------------------------------------------------------------------------------------- \1\ Percentages may not total 100 due to rounding. F. Open On-Schedule and Off-Schedule PMCs Table 6 provides the status of open on-schedule and off-schedule PMCs. As of September 30, 2016, most open, on-schedule NDA PMCs were pending (36 percent; 62/174) and most open, on-schedule BLA PMCs were ongoing (43 percent; 83/191). Fewer open NDA and BLA PMCs were considered off schedule (29 percent (51/174) and 17 percent (32/191), respectively). The majority of off-schedule NDA and BLA PMCs were delayed according to the original schedule milestones. Table 6--Summary of Open Postmarketing Commitments [Numbers as of September 30, 2016] \1\ ------------------------------------------------------------------------ NDA N = 174 (% BLA N = 191 (% open PMCs) open PMCs) ------------------------------------------------------------------------ On-Schedule: Pending..................... 62 (36%) 52 (27%) Ongoing..................... 40 (23%) 83 (43%) Submitted................... 21 (12%) 24 (13%) --------------------------------------- Total................... 123 (71%) 159 (83%) ------------------------------------------------------------------------ Off-Schedule: Delayed..................... 50 (29%) 30 (16%) Terminated.................. 1 (1%) 2 (1%) --------------------------------------- Total................... 51 (29%) 32 (17%) ------------------------------------------------------------------------ \1\ Percentages may not total 100 due to rounding. G. Closed PMRs and PMCs Table 7 provides details about PMRs and PMCs that were closed (fulfilled or released) within FY2016. The majority of closed PMRs were fulfilled (72 percent of NDA PMRs and 82 percent of BLA PMRs) at the end of FY2016. Similarly, the majority of closed PMCs were fulfilled at the end of FY2016. Table 7--Summary of Closed \1\ Postmarketing Requirements and Commitments [Numbers as of September 30, 2016] \2\ ------------------------------------------------------------------------ NDA BLA ------------------------------------------------------------------------ Postmarketing Requirements Closed PMRs (% of Total Closed PMRs).... N = 174 N = 33 Requirement met (fulfilled)......... 126 (72%) 27 (82%) Requirement not met (released and 19 (11%) 4 (12%) new revised requirement issued).... Requirement no longer feasible or 29 (17%) 2 (6%) drug product withdrawn (released).. Postmarketing Commitments Closed PMCs (% of Total Closed PMCs).... N= 54 N=28 Requirement met (fulfilled)......... 44 (82%) 23 (82%) Requirement not met (released and 1 (2%) 1 (4%) new revised requirement issued).... Requirement no longer feasible or 9 (17%) 4 (14%) drug product withdrawn (released).. ------------------------------------------------------------------------ \1\ The table shows data for those PMRs/PMCs that were closed (fulfilled or released) within FY2016. Therefore, data for PMRs/PMCs that were closed in prior fiscal years are not included. \2\ Percentages may not total 100 due to rounding. [[Page 58002]] H. Distribution of the Statuses of PMRs and PMCs Tables 8 and 9 show the distribution of the statuses of PMRs/PMCs as of September 30, 2016, presented by the years that the PMRs/PMCs were established \18\ (FY2010 to FY2016).\19\ \20\ Note that the data shown for closed (fulfilled or released) PMRs/PMCs are for all PMRs/ PMCs that were closed as of FY2016. Therefore, data for PMRs/PMCs that were closed in prior fiscal years are included. --------------------------------------------------------------------------- \18\ The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or requested (PMC) postmarketing study or clinical trial. \19\ Tables 8 and 9 include data for only the past 7 fiscal years. Data on the distribution of statuses for PMRs/PMCs established in FY2009 and as of FY2015 are presented in the FY2015 status of postmarketing requirements and commitments report (81 FR 85573) (https://www.federalregister.gov/d/2016-28442). \20\ The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA's databases as of September 30, 2016. Because of data corrections and improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/ PMCs established in each fiscal year are different from those reported in the prior fiscal year's (FY2015) Federal Register report. --------------------------------------------------------------------------- Based on the data shown in table 8, an average of 261 PMRs were established each year since FY2010.\21\ Most PMRs that were established in the earlier years were either fulfilled or released. For example, as of September 30, 2016, 54 percent (122/224) of the PMRs that were established in FY2010 were fulfilled, and 12 percent (27/224) were released. The majority of PMRs that were established in more recent years were either pending (i.e., not yet underway) or ongoing (i.e., still in progress and on schedule). For example, as of September 30, 2016, 86 percent (232/269) of the PMRs established in FY2016 were pending, and 8 percent (22/269) were ongoing. Overall, of the PMRs that were pending as of September 30, 2016, 83 percent (510/614) were created within the past 3 years (FY2014, FY2015, and FY2016). Finally, table 8 shows that, on average, 7 percent (137/1,829) of the PMRs established since FY2010 were delayed as of September 30, 2016. --------------------------------------------------------------------------- \21\ The number of PMRs issued at any particular period is determined by a variety of factors including but not necessarily limited to: (1) The number of NDAs approved in that period; (2) whether additional efficacy or clinical benefit issues were evaluated; (3) if any drug-associated serious risk(s) had been identified; and (4) whether or not FDA determines that a postmarketing study or clinical trial is necessary to further assess risk(s) or efficacy issues. Table 8--Summary of Status of Postmarketing Requirements Established \1\ Between FY2010 and FY2016 \2\ [Numbers as of September 30, 2016] \3\ -------------------------------------------------------------------------------------------------------------------------------------------------------- Fiscal year of PMR establishment PMR status as of FY2016 (% of total PMRs in each ------------------------------------------------------------------------------------------ establishment year) 2010 2011 2012 2013 2014 2015 2016 -------------------------------------------------------------------------------------------------------------------------------------------------------- Pending...................................................... 8 (4%) 16 (6%) 24 (11%) 56 (20%) 114 (39%) 164 (58%) 232 (86%) Ongoing...................................................... 26 (12%) 49 (19%) 52 (24%) 69 (25%) 80 (27%) 52 (18%) 22 (8%) Submitted.................................................... 15 (7%) 7 (3%) 9 (4%) 8 (3%) 12 (4%) 16 (6%) 2 (1%) Delayed...................................................... 26 (12%) 18 (7%) 25 (11%) 30 (11%) 25 (9%) 13 (4%) 0 Terminated................................................... 0 2 (<1%) 1 (<1%) 0 0 1 (<1%) 0 Released..................................................... 27 (12%) 59 (23%) 30 (14%) 33 (12%) 14 (5%) 5 (2%) 4 (2%) Fulfilled.................................................... 122 (54%) 110 (42%) 79 (36%) 82 (29%) 48 (16%) 33 (12%) 9 (3%) ------------------------------------------------------------------------------------------ Total \4\................................................ 224 261 220 278 293 284 269 -------------------------------------------------------------------------------------------------------------------------------------------------------- \1\ The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or -requested (PMC) postmarketing study or clinical trial. \2\ The table shows data for PMRs that were closed (fulfilled or released) as of FY2016. Therefore, data for PMRs that were closed in prior fiscal years are included. \3\ Percentages may not total 100 due to rounding. \4\ The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA's databases as of September 30, 2016. Because of data corrections and improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/PMCs established in each fiscal year are different from those reported in the prior fiscal year's (FY2015) Federal Register report. Table 9 provides an overview of PMCs in a similar format as table 8 for PMRs. The results for PMCs are similar to those for PMRs as described above and in table 8. Table 9--Summary of Status of Postmarketing Commitments Established \1\ Between FY2010 and FY2016 \2\ [Numbers as of September 30, 2016] \3\ -------------------------------------------------------------------------------------------------------------------------------------------------------- Fiscal year of PMC establishment PMR status as of FY2016 (% of total PMCs in each ------------------------------------------------------------------------------------------ establishment year) 2010 2011 2012 2013 2014 2015 2016 -------------------------------------------------------------------------------------------------------------------------------------------------------- Pending...................................................... 1 (1%) 3 (4%) 0 3 (7%) 8 (14%) 25 (40%) 48 (80%) Ongoing...................................................... 11 (12%) 17 (21%) 11 (27%) 16 (35%) 19 (34%) 18 (28%) 4 (7%) Submitted.................................................... 8 (9%) 1 (1%) 2 (5%) 3 (7%) 7 (13%) 1 (2%) 2 (3%) Delayed...................................................... 13 (14%) 5 (6%) 4 (10%) 3 (7%) 0 5 (8%) 0 Terminated................................................... 0 0 0 0 0 0 0 Released..................................................... 10 (11%) 12 (15%) 1 (2%) 1 (2%) 0 1 (2%) 0 Fulfilled.................................................... 51 (54%) 42 (53%) 23 (56%) 20 (43%) 22 (39%) 13 (21%) 6 (10%) ------------------------------------------------------------------------------------------ Total \4\................................................ 94 80 41 46 56 63 60 -------------------------------------------------------------------------------------------------------------------------------------------------------- \1\ The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or requested (PMC) postmarketing study or clinical trial. [[Page 58003]] \2\ The table shows data for PMCs that were closed (fulfilled or released) as of FY2016. Therefore, data for PMCs that were closed in prior fiscal years are included. \3\ Percentages may not total 100 due to rounding. \4\ The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA's databases as of September 30, 2016. Because of data corrections, as well as improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/PMCs established in each fiscal year are different from those reported in the prior fiscal year's (FY2015) Federal Register report. Dated: December 4, 2017. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2017-26470 Filed 12-7-17; 8:45 am] BILLING CODE 4164-01-P
![57996 Federal Register / Vol. 82, No. 235 / Friday, December 8, 2017 / Notices
Sciences Authority), and the United document, please see https:// commitments (PMCs) required of, or
States (U.S. FDA). The World Health www.fda.gov/MedicalDevices/ agreed upon by, holders of approved
Organization and the Asia-Pacific InternationalPrograms/IMDRF/ drug and biological products. This
Economic Cooperation Life Sciences default.htm. notice is the Agency’s report on the
Innovation Forum Regulatory status of the studies and clinical trials
II. Significance of Guidance
Harmonization Steering Committee are that applicants have agreed to, or are
IMDRF Official Observers. The Asian This guidance is being issued required to, conduct.
Harmonization Working Party and the consistent with FDA’s good guidance
FOR FURTHER INFORMATION CONTACT:
Pan American Health Organization are practices regulation (21 CFR 10.115).
Cathryn C. Lee, Center for Drug
IMDRF Affiliate Organizations. The guidance represents the current
thinking of FDA on ‘‘Software as a Evaluation and Research, Food and
The IMDRF Management Committee Drug Administration, 10903 New
(IMDRF MC) chartered the SaMD Medical Device (SaMD): Clinical
Evaluation.’’ It does not establish any Hampshire Ave., Bldg. 22, Rm. 6484,
Working Group (WG) to develop a
rights for any person and is not binding Silver Spring, MD 20993–0002, 301–
regulatory framework for SaMD and to
on FDA or the public. You can use an 796–0700; or Stephen Ripley, Center for
develop converged principles for global
alternative approach if it satisfies the Biologics Evaluation and Research,
regulators to adopt in their respective
requirements of the applicable statutes Food and Drug Administration, 10903
jurisdictions. The SaMD WG includes
and regulations. This guidance is not New Hampshire Ave., Bldg. 71, Rm.
representatives from the IMDRF
subject to Executive Order 12866. 7301, Silver Spring, MD 20993–0002,
members, industry, academia, and other
240–402–7911.
key stakeholders as well as regional III. Electronic Access
harmonization initiatives from around SUPPLEMENTARY INFORMATION:
the world. Persons interested in obtaining a copy
of the guidance may do so by I. Background
The IMDRF SaMD WG considered
comments received on the draft downloading an electronic copy from A. Postmarketing Requirements and
guidance that was announced in the the Internet. A search capability for all Commitments
Federal Register of October 14, 2016 (81 Center for Devices and Radiological
A PMR is a study or clinical trial that
FR 71105). The SaMD WG also Health guidance documents is available
an applicant is required by statute or
considered public comments received at https://www.fda.gov/MedicalDevices/
regulation to conduct postapproval. A
by other regulators and from other DeviceRegulationandGuidance/
PMC is a study or clinical trial that an
global stakeholders. The final IMDRF/ GuidanceDocuments/default.htm. This
applicant agrees in writing to conduct
SaMD WG/N41 document, ‘‘Software as guidance document is also available at
postapproval, but that is not required by
a Medical Device (SaMD): Clinical https://www.regulations.gov. Persons
statute or regulation. PMRs and PMCs
Evaluation,’’ submitted to IMDRF MC unable to download an electronic copy
can be issued upon approval of a drug 1
was revised appropriately in response to of ‘‘Software as a Medical Device
or postapproval, if warranted.
all of the comments. The IMDRF MC in (SaMD): Clinical Evaluation’’ may send
Ottawa, Canada, at the 12th meeting an email request to CDRH-Guidance@ FDA can require application holders
held from September 19 to 21, 2017, fda.hhs.gov to receive an electronic to conduct postmarketing studies and
unanimously approved the document copy of the document. Please use the clinical trials:
entitled ‘‘Software as a Medical Device document number 16039 to identify the • To assess a known serious risk,
(SaMD): Clinical Evaluation.’’ This final guidance you are requesting. assess signals of serious risk, or identify
IMDRF/SaMD WG/N41 document is an unexpected serious risk related to the
Dated: December 4, 2017. use of a drug product (section 505(o)(3)
available for regulatory implementation Leslie Kux,
according to the regulatory process in of the FD&C Act (21 U.S.C. 355(o)(3)), as
Associate Commissioner for Policy. added by the Food and Drug
each jurisdiction.
This guidance adopts the [FR Doc. 2017–26441 Filed 12–7–17; 8:45 am] Administration Amendments Act of
internationally converged principles BILLING CODE 4164–01–P 2007 (FDAAA) (Pub. L. 110–85)).
agreed upon by the IMDRF. FDA • Under the Pediatric Research Equity
adoption of these principles provides Act (PREA) (Pub. L. 108–155), to study
FDA with an initial framework when DEPARTMENT OF HEALTH AND certain new drugs for pediatric
further developing the Agency’s specific HUMAN SERVICES populations, when these drugs are not
regulatory approaches and expectations adequately labeled for children. Under
Food and Drug Administration
for regulatory oversight. This guidance section 505B(a)(3) of the FD&C Act (21
does not provide recommendations for [Docket No. FDA–2016–N–3083] U.S.C. 355c), the initiation of these
FDA Staff and Industry to apply to studies may be deferred until required
specific regulatory situations, nor does Report on the Performance of Drug safety information from other studies in
it modify current regulatory and Biologics Firms in Conducting adults has first been submitted and
expectations, including those for Postmarketing Requirements and reviewed.
regulatory submissions, at this time. Commitments; Availability • To verify and describe the predicted
FDA intends to consider the principles AGENCY: Food and Drug Administration, effect or other clinical benefit for drugs
of this guidance in the development of HHS. approved in accordance with the
regulatory approaches for SaMD and ACTION: Notice of availability. accelerated approval provisions in
digital health technologies. In
sradovich on DSK3GMQ082PROD with NOTICES
section 506(c)(2)(A) of the FD&C Act (21
developing regulatory approaches based SUMMARY: Under the Federal Food,
on the principles of this guidance, the Drug, and Cosmetic Act (the FD&C Act), 1 For the purposes of this notice, references to
Agency intends to follow a public the Food and Drug Administration (FDA ‘‘drugs’’ or ‘‘drug products’’ include drugs approved
process, including providing or Agency) is required to report under the FD&C Act and biological products
licensed under the Public Health Service Act other
opportunities for public input. For more annually in the Federal Register on the than biological products that also meet the
information on FDA adoption of IMDRF status of postmarketing requirements definition of a device in section 201(h) of the FD&C
documents as an FDA guidance (PMRs) and postmarketing Act (21 U.S.C. 321(h)).
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comparison of on- or off-schedule PMRs A. Applicants With Open PMRs/PMCs there were 285 unique applicants with
(e.g., to assess for a potential trend) is open PMRs/PMCs under 890 unique
not appropriate. Finally, due to An applicant may have multiple NDAs and BLAs. There were 207 unique
rounding, the percentages in the tables approved drug products, and an NDA applicants (and 734 associated
may not add up to 100 percent. approved drug product may have applications) and 78 unique BLA
multiple PMRs and/or PMCs. Table 1 applicants (and 156 associated
shows that as of September 30, 2016, applications) with open PMRs/PMCs.
TABLE 1—APPLICANTS AND APPLICATIONS (NDA/BLA) WITH OPEN POSTMARKETING REQUIREMENTS AND COMMITMENTS
[Numbers as of September 30, 2016]
Total
NDA 1 BLA 2 (NDA and BLA)
Number of unique applicants with open PMRs/PMCs ............................................................ 207 78 285
Number of applications with open PMRs/PMCs ..................................................................... 734 156 890
1 As of September 30, 2016, there were only NDAs with associated PMRs/PMCs managed by CDER.
2 Includes BLAs managed by both CDER and CBER.
B. Annual Status Reports Received granted by FDA (§§ 314.81 and received on time, and 23 percent (145/
As previously mentioned, applicants 601.70).15 Table 2 shows that there were 622) were not received during FY2016.
must submit an ASR on the progress of 764 NDAs and BLAs with an ASR due Of the 142 BLA ASRs due, 72 percent
each open PMR/PMC within 60 days of in FY2016 (622 NDAs and 142 BLAs).16 (102/142) were received on time, 17
the anniversary date of United States Of the 622 NDA ASRs due in that fiscal percent (24/142) were not received on
approval of the original application or year, 66 percent (411/622) were received time, and 11 percent (16/142) were not
an alternate reporting date that was on time, 11 percent (66/622) were not received during FY2016.
TABLE 2—ANNUAL STATUS REPORTS RECEIVED
[Numbers as of September 30, 2016] 1
Received, Received, Expected but
2 Expected on time 3 not on time 4 not received
(% of expected) (% of expected) (% of expected)
NDA ............... 5 622 411 (66%) 66 (11%) 145 (23%)
BLA ................ 142 102 (72%) 24 (17%) 16 (11%)
Total ........ 764 513 (67%) 90 (12%) 161 (21%)
1 Percentages may not total 100 due to rounding.
2 ASR expected during fiscal year (within 60 days (before or after) of the anniversary of original approval date or alternate agreed-upon date).
3 ASR was received within 60 days (before or after) of the anniversary of the original approval date or alternate agreed-upon date.
4 ASR was received, but not within 60 days (before or after) of the anniversary of the original approval date or alternate agreed-upon date.
5 The total number of NDA ASRs expected in FY2016 (622) increased compared to the number of ASRs expected in FY2015 (451). The in-
crease is primarily due to the establishment of several FDAAA safety PMRs for which a serious safety issue applied to a class of drug products.
In those cases, each applicant with a drug product (i.e., application) in the class was required to conduct the same postmarketing safety study or
trial, and each applicant was required to submit an ASR for that PMR. As a consequence, multiple ASRs were expected during FY2016 for the
same FDAAA safety PMR.
C. Overview of On- and Off-Schedule Table 3 shows that as of September most open PMCs (71 percent for NDAs
Open PMRs/PMCs 30, 2016, most open PMRs (84 percent and 83 percent for BLAs) were
for NDAs and 91 percent for BLAs) and progressing on schedule.
TABLE 3—SUMMARY OF ON- AND OFF-SCHEDULE POSTMARKETING REQUIREMENTS AND COMMITMENTS
[Numbers as of September 30, 2016] 1
Open PMRs Open PMCs
N = 1,323 N = 365
NDA BLA NDA BLA
(% of open NDA PMRs) (% of open BLA PMRs) (% of open NDA PMCs) (% of open BLA PMCs)
On-schedule ..................................... 882 (84%) 247 (91%) 123 (71%) 159 (83%)
Off-schedule ..................................... 169 (16%) 25 (9%) 51 (29%) 32 (17%)
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15 Some applicants have requested and been applications with open PMRs/PMCs because not all established in the preceding fiscal year, or if all
granted by FDA alternate annual reporting dates to applications had an ASR due during FY2016. PMRs/PMCs for an application were closed before
facilitate harmonized reporting across multiple Applicants with PMRs/PMCs associated with the ASR due date, submission of an ASR would not
applications. multiple applications may have submitted the ASR have been expected.
16 The number of ASRs that were expected is to only one of the applications. In addition, if all
different from the total number of unique of the PMRs/PMCs for an application were
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TABLE 3—SUMMARY OF ON- AND OFF-SCHEDULE POSTMARKETING REQUIREMENTS AND COMMITMENTS—Continued
[Numbers as of September 30, 2016] 1
Open PMRs Open PMCs
N = 1,323 N = 365
NDA BLA NDA BLA
(% of open NDA PMRs) (% of open BLA PMRs) (% of open NDA PMCs) (% of open BLA PMCs)
Total .......................................... 1,051 272 174 191
1 Percentages may not total 100 due to rounding.
D. Open and On-Schedule PMRs percent (517/1,051) and 45 percent next largest category of open and on-
(123/272), respectively). PREA PMRs schedule PMRs comprised those that
Table 4 shows that as of September and FDAAA PMRs comprised 55 were ongoing (29 percent (306/1,051) of
30, 2016, nearly half of the open NDA percent (349/640) and 39 percent (249/ NDA PMRs and 37 percent (100/272) of
and BLA PMRs were pending (49 640) of pending PMRs, respectively. The BLA PMRs).
TABLE 4—SUMMARY OF OPEN AND ON-SCHEDULE POSTMARKETING REQUIREMENTS
[Numbers as of September 30, 2016] 1
NDA BLA
N = 1,051 N = 272
Reporting authority/PMR status (% of open NDA PMRs) (% of open BLA PMRs)
Pending Ongoing Submitted Pending Ongoing Submitted
Accelerated approval ............................... 16 (2%) 19 (2%) 3 (<1%) 13 (5%) 10 (4%) 4 (1%)
PREA 2 ..................................................... 300 (28%) 124 (12%) 14 (1%) 49 (18%) 29 (11%) 8 (3%)
Animal efficacy 3 ....................................... 4 (<1%) 0 1 (<1%) 9 (3%) 0 0
FDAAA safety .......................................... 197 (19%) 163 (16%) 41 (4%) 52 (19%) 61 (22%) 12 (4%)
Total .................................................. 517 (49%) 306 (29%) 59 (6%) 123 (45%) 100 (37%) 24 (9%)
1 Percentages may not total 100 due to rounding.
2 Many PREA studies have a pending status. PREA studies are usually deferred because the drug product is ready for approval in adults. Initi-
ation of these studies may be deferred until additional safety information from other studies has first been submitted and reviewed before begin-
ning the studies in pediatric populations.
3 PMRs for drug products approved under the animal efficacy rule (21 CFR 314.600 for drugs; 21 CFR 601.90 for biological products) can be
conducted only when the drug product is used for its indication and when an exigency (or event or need) arises. In the absence of a public
health emergency, these studies or clinical trials will remain pending indefinitely.
E. Open and Off-Schedule PMRs PMRs, 97 percent (164/169) were off difficulties with subject enrollment in a
schedule because they were delayed and clinical trial for a marketed drug or the
Table 5 provides additional the remaining 3 percent (5/169) were need for additional time to analyze
information on the status of open and terminated. Similarly, 88 percent of the results). In this report, study or clinical
off-schedule PMRs (i.e., delayed and off-schedule BLA PMRs were delayed trial status reflects the status in relation
terminated). At the end of September (22/25). to the original 17 study or clinical trial
30, 2016, 16 percent (169/1,051) of the In certain situations, the original PMR schedule regardless of whether FDA has
open NDA PMRs and 9 percent (25/272) schedules were adjusted for acknowledged that additional time was
of the open BLA PMRs were off unanticipated delays in the progress of required to complete the study or
schedule. Of the off-schedule NDA the study or clinical trial (e.g., clinical trial.
TABLE 5—SUMMARY OF OPEN AND OFF-SCHEDULE POSTMARKETING REQUIREMENTS
[Numbers as of September 30, 2016] 1
NDA BLA
N = 1,051 N = 272
Reporting authority/PMR status (% of open NDA PMRs) (% of open BLA PMRs)
Delayed Terminated Delayed Terminated
Accelerated approval ....................................................................................... 9 (1%) 1 (<1%) 1 (<1%) 0
PREA ............................................................................................................... 84 (8%) 2 (<1%) 6 (2%) 2 (1%)
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Animal efficacy ................................................................................................. 0 0 0 0
FDAAA safety .................................................................................................. 71 (7%) 2 (<1%) 15 (6%) 1 (<1%)
17 With the exception of PREA PMRs for which
a deferral extension of the final report submission
date has been granted.
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TABLE 5—SUMMARY OF OPEN AND OFF-SCHEDULE POSTMARKETING REQUIREMENTS—Continued
[Numbers as of September 30, 2016] 1
NDA BLA
N = 1,051 N = 272
Reporting authority/PMR status (% of open NDA PMRs) (% of open BLA PMRs)
Delayed Terminated Delayed Terminated
Total .......................................................................................................... 164 (16%) 5 (<1%) 22 (8%) 3 (1%)
1 Percentages may not total 100 due to rounding.
F. Open On-Schedule and Off-Schedule schedule NDA PMCs were pending (36 schedule (29 percent (51/174) and 17
PMCs percent; 62/174) and most open, on- percent (32/191), respectively). The
Table 6 provides the status of open schedule BLA PMCs were ongoing (43 majority of off-schedule NDA and BLA
on-schedule and off-schedule PMCs. As percent; 83/191). Fewer open NDA and PMCs were delayed according to the
of September 30, 2016, most open, on- BLA PMCs were considered off original schedule milestones.
TABLE 6—SUMMARY OF OPEN POSTMARKETING COMMITMENTS
[Numbers as of September 30, 2016] 1
NDA BLA
N = 174 N = 191
(% open PMCs) (% open PMCs)
On-Schedule:
Pending ............................................................................................................................................. 62 (36%) 52 (27%)
Ongoing ............................................................................................................................................ 40 (23%) 83 (43%)
Submitted .......................................................................................................................................... 21 (12%) 24 (13%)
Total ........................................................................................................................................... 123 (71%) 159 (83%)
Off-Schedule:
Delayed ............................................................................................................................................. 50 (29%) 30 (16%)
Terminated ........................................................................................................................................ 1 (1%) 2 (1%)
Total ........................................................................................................................................... 51 (29%) 32 (17%)
1 Percentages may not total 100 due to rounding.
G. Closed PMRs and PMCs released) within FY2016. The majority BLA PMRs) at the end of FY2016.
Table 7 provides details about PMRs of closed PMRs were fulfilled (72 Similarly, the majority of closed PMCs
and PMCs that were closed (fulfilled or percent of NDA PMRs and 82 percent of were fulfilled at the end of FY2016.
TABLE 7—SUMMARY OF CLOSED 1 POSTMARKETING REQUIREMENTS AND COMMITMENTS
[Numbers as of September 30, 2016] 2
NDA BLA
Postmarketing Requirements
Closed PMRs (% of Total Closed PMRs) ............................................................................................................... N = 174 N = 33
Requirement met (fulfilled) ............................................................................................................................... 126 (72%) 27 (82%)
Requirement not met (released and new revised requirement issued) ........................................................... 19 (11%) 4 (12%)
Requirement no longer feasible or drug product withdrawn (released) .......................................................... 29 (17%) 2 (6%)
Postmarketing Commitments
Closed PMCs (% of Total Closed PMCs) ............................................................................................................... N= 54 N=28
Requirement met (fulfilled) ............................................................................................................................... 44 (82%) 23 (82%)
Requirement not met (released and new revised requirement issued) ........................................................... 1 (2%) 1 (4%)
Requirement no longer feasible or drug product withdrawn (released) .......................................................... 9 (17%) 4 (14%)
1 The table shows data for those PMRs/PMCs that were closed (fulfilled or released) within FY2016. Therefore, data for PMRs/PMCs that were
closed in prior fiscal years are not included.
2 Percentages may not total 100 due to rounding.
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H. Distribution of the Statuses of PMRs Based on the data shown in table 8, progress and on schedule). For example,
and PMCs an average of 261 PMRs were as of September 30, 2016, 86 percent
Tables 8 and 9 show the distribution established each year since FY2010.21 (232/269) of the PMRs established in
of the statuses of PMRs/PMCs as of Most PMRs that were established in the FY2016 were pending, and 8 percent
September 30, 2016, presented by the earlier years were either fulfilled or (22/269) were ongoing. Overall, of the
years that the PMRs/PMCs were released. For example, as of September PMRs that were pending as of
established 18 (FY2010 to FY2016).19 20 30, 2016, 54 percent (122/224) of the September 30, 2016, 83 percent (510/
Note that the data shown for closed PMRs that were established in FY2010 614) were created within the past 3
(fulfilled or released) PMRs/PMCs are were fulfilled, and 12 percent (27/224) years (FY2014, FY2015, and FY2016).
for all PMRs/PMCs that were closed as were released. The majority of PMRs Finally, table 8 shows that, on average,
of FY2016. Therefore, data for PMRs/ that were established in more recent 7 percent (137/1,829) of the PMRs
PMCs that were closed in prior fiscal years were either pending (i.e., not yet established since FY2010 were delayed
years are included. underway) or ongoing (i.e., still in as of September 30, 2016.
TABLE 8—SUMMARY OF STATUS OF POSTMARKETING REQUIREMENTS ESTABLISHED 1 BETWEEN FY2010 AND FY2016 2
[Numbers as of September 30, 2016] 3
Fiscal year of PMR establishment
PMR status as of FY2016 (% of total
PMRs in each establishment year) 2010 2011 2012 2013 2014 2015 2016
Pending .................................................... 8 (4%) 16 (6%) 24 (11%) 56 (20%) 114 (39%) 164 (58%) 232 (86%)
Ongoing .................................................... 26 (12%) 49 (19%) 52 (24%) 69 (25%) 80 (27%) 52 (18%) 22 (8%)
Submitted ................................................. 15 (7%) 7 (3%) 9 (4%) 8 (3%) 12 (4%) 16 (6%) 2 (1%)
Delayed .................................................... 26 (12%) 18 (7%) 25 (11%) 30 (11%) 25 (9%) 13 (4%) 0
Terminated ............................................... 0 2 (<1%) 1 (<1%) 0 0 1 (<1%) 0
Released .................................................. 27 (12%) 59 (23%) 30 (14%) 33 (12%) 14 (5%) 5 (2%) 4 (2%)
Fulfilled ..................................................... 122 (54%) 110 (42%) 79 (36%) 82 (29%) 48 (16%) 33 (12%) 9 (3%)
Total 4 ................................................ 224 261 220 278 293 284 269
1 The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or -re-
quested (PMC) postmarketing study or clinical trial.
2 The table shows data for PMRs that were closed (fulfilled or released) as of FY2016. Therefore, data for PMRs that were closed in prior fiscal
years are included.
3 Percentages may not total 100 due to rounding.
4 The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA’s databases as of September 30, 2016.
Because of data corrections and improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/PMCs es-
tablished in each fiscal year are different from those reported in the prior fiscal year’s (FY2015) Federal Register report.
Table 9 provides an overview of PMCs for PMRs as described above and in
in a similar format as table 8 for PMRs. table 8.
The results for PMCs are similar to those
TABLE 9—SUMMARY OF STATUS OF POSTMARKETING COMMITMENTS ESTABLISHED 1 BETWEEN FY2010 AND FY2016 2
[Numbers as of September 30, 2016] 3
Fiscal year of PMC establishment
PMR status as of FY2016 (% of total
PMCs in each establishment year) 2010 2011 2012 2013 2014 2015 2016
Pending .................................................... 1 (1%) 3 (4%) 0 3 (7%) 8 (14%) 25 (40%) 48 (80%)
Ongoing .................................................... 11 (12%) 17 (21%) 11 (27%) 16 (35%) 19 (34%) 18 (28%) 4 (7%)
Submitted ................................................. 8 (9%) 1 (1%) 2 (5%) 3 (7%) 7 (13%) 1 (2%) 2 (3%)
Delayed .................................................... 13 (14%) 5 (6%) 4 (10%) 3 (7%) 0 5 (8%) 0
Terminated ............................................... 0 0 0 0 0 0 0
Released .................................................. 10 (11%) 12 (15%) 1 (2%) 1 (2%) 0 1 (2%) 0
Fulfilled ..................................................... 51 (54%) 42 (53%) 23 (56%) 20 (43%) 22 (39%) 13 (21%) 6 (10%)
Total 4 ................................................ 94 80 41 46 56 63 60
1 The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or requested
(PMC) postmarketing study or clinical trial.
18 The establishment date is the date of the formal report (81 FR 85573) (https:// 21 The number of PMRs issued at any particular
sradovich on DSK3GMQ082PROD with NOTICES
FDA communication to the applicant that included www.federalregister.gov/d/2016-28442). period is determined by a variety of factors
the final FDA-required (PMR) or requested (PMC) 20 The total number of PMRs/PMCs established in including but not necessarily limited to: (1) The
postmarketing study or clinical trial. FY2010 through FY2016 reflects the data in FDA’s number of NDAs approved in that period; (2)
19 Tables 8 and 9 include data for only the past databases as of September 30, 2016. Because of data whether additional efficacy or clinical benefit
corrections and improvements in ascertaining the issues were evaluated; (3) if any drug-associated
7 fiscal years. Data on the distribution of statuses
PMR/PMC establishment date, some of the total serious risk(s) had been identified; and (4) whether
for PMRs/PMCs established in FY2009 and as of numbers of PMRs/PMCs established in each fiscal or not FDA determines that a postmarketing study
FY2015 are presented in the FY2015 status of year are different from those reported in the prior or clinical trial is necessary to further assess risk(s)
postmarketing requirements and commitments fiscal year’s (FY2015) Federal Register report. or efficacy issues.
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![Federal Register / Vol. 82, No. 235 / Friday, December 8, 2017 / Notices 58003
2 The table shows data for PMCs that were closed (fulfilled or released) as of FY2016. Therefore, data for PMCs that were closed in prior fiscal
years are included.
3 Percentages may not total 100 due to rounding.
4 The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA’s databases as of September 30, 2016.
Because of data corrections, as well as improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/
PMCs established in each fiscal year are different from those reported in the prior fiscal year’s (FY2015) Federal Register report.
Dated: December 4, 2017. on or before April 16, 2018. The https:// Received comments, those filed in a
Leslie Kux, www.regulations.gov electronic filing timely manner (see ADDRESSES), will be
Associate Commissioner for Policy. system will accept comments until placed in the docket and, except for
[FR Doc. 2017–26470 Filed 12–7–17; 8:45 am] midnight Eastern Time at the end of those submitted as ‘‘Confidential
BILLING CODE 4164–01–P April 16, 2018. Comments received by Submissions,’’ publicly viewable at
mail/hand delivery/courier (for written/ https://www.regulations.gov or at the
paper submissions) will be considered Dockets Management Staff between 9
DEPARTMENT OF HEALTH AND timely if they are postmarked or the a.m. and 4 p.m., Monday through
HUMAN SERVICES delivery service acceptance receipt is on Friday.
or before that date. • Confidential Submissions—To
Food and Drug Administration submit a comment with confidential
Electronic Submissions
[Docket No. FDA–2017–N–6607] information that you do not wish to be
Submit electronic comments in the made publicly available, submit your
Oncology Center of Excellence following way: comments only as a written/paper
Listening Session; Public Meeting; • Federal eRulemaking Portal: submission. You should submit two
Request for Comments https://www.regulations.gov. Follow the copies total. One copy will include the
instructions for submitting comments. information you claim to be confidential
AGENCY: Food and Drug Administration, Comments submitted electronically, with a heading or cover note that states
HHS. including attachments, to https:// ‘‘THIS DOCUMENT CONTAINS
ACTION: Notice of public meeting; www.regulations.gov will be posted to CONFIDENTIAL INFORMATION.’’ The
request for comments. the docket unchanged. Because your Agency will review this copy, including
comment will be made public, you are the claimed confidential information, in
SUMMARY: The Food and Drug solely responsible for ensuring that your
Administration (FDA, the Agency, or its consideration of comments. The
comment does not include any second copy, which will have the
we) is announcing the following public confidential information that you or a
meeting entitled ‘‘Oncology Center of claimed confidential information
third party may not wish to be posted, redacted/blacked out, will be available
Excellence (OCE): Listening Session.’’ such as medical information, your or
The purpose of the public meeting and for public viewing and posted on
anyone else’s Social Security number, or https://www.regulations.gov. Submit
the docket for comments is for confidential business information, such
stakeholders to provide both copies to the Dockets Management
as a manufacturing process. Please note Staff. If you do not wish your name and
recommendations to the Agency that if you include your name, contact
regarding FDA’s OCE. Specifically, the contact information to be made publicly
information, or other information that available, you can provide this
Agency solicits comments regarding identifies you in the body of your
what stakeholders desire of the OCE in information on the cover sheet and not
comments, that information will be in the body of your comments and you
terms of structure, function, regulatory posted on https://www.regulations.gov.
purview, and activity. must identify this information as
• If you want to submit a comment ‘‘confidential.’’ Any information marked
DATES: The public meeting will be held with confidential information that you
on Thursday, March 15, 2018, from 9 as ‘‘confidential’’ will not be disclosed
do not wish to be made available to the except in accordance with 21 CFR 10.20
a.m. to 12 noon. Submit either public, submit the comment as a
electronic on written comments on this and other applicable disclosure law. For
written/paper submission and in the more information about FDA’s posting
public meeting by April 16, 2018. See manner detailed (see ‘‘Written/Paper
the SUPPLEMENTARY INFORMATION section of comments to public dockets, see 80
Submissions’’ and ‘‘Instructions’’). FR 56469, September 18, 2015, or access
for registration date and information.
Written/Paper Submissions the information at: https://www.gpo.gov/
ADDRESSES: The public meeting will be
fdsys/pkg/FR-2015-09-18/pdf/2015-
held at the FDA White Oak Campus, Submit written/paper submissions as
23389.pdf.
10903 New Hampshire Ave., Bldg. 31 follows:
Conference Center, the Great Room (Rm. • Mail/Hand delivery/Courier (for Docket: For access to the docket to
1503), Silver Spring, MD 20993–0002. written/paper submissions): Dockets read background documents or the
Entrance for the public meeting Management Staff (HFA–305), Food and electronic and written/paper comments
participants (non-FDA employees) is Drug Administration, 5630 Fishers received, go to https://www.regulations.
through Building 1 where routine Lane, Rm. 1061, Rockville, MD 20852. gov and insert the docket number, found
security check procedures will be • For written/paper comments in brackets in the heading of this
performed. For parking and security submitted to the Dockets Management document, into the ‘‘Search’’ box and
information, please refer to https:// Staff, FDA will post your comment, as follow the prompts and/or go to the
well as any attachments, except for Dockets Management Staff, 5630 Fishers
sradovich on DSK3GMQ082PROD with NOTICES
www.fda.gov/AboutFDA/
WorkingatFDA/BuildingsandFacilities/ information submitted, marked and Lane, Rm. 1061, Rockville, MD 20852.
WhiteOakCampusInformation/ identified, as confidential, if submitted FOR FURTHER INFORMATION CONTACT:
ucm241740.htm. as detailed in ‘‘Instructions.’’ Tamy Kim, Oncology Center of
You may submit comments as Instructions: All submissions received Excellence, Office of the Commissioner,
follows. Please note that late, untimely must include the Docket No. FDA– Food and Drug Administration, 10903
filed comments will not be considered. 2017–N–6607 for ‘‘Oncology Center of New Hampshire Ave., Bldg. 22, Rm.
Electronic comments must be submitted Excellence (OCE): Listening Session.’’ 2206, Silver Spring, MD 20993–0002,
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Document Created: 2017-12-08 01:43:49
Document Modified: 2017-12-08 01:43:49
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice of availability. | |
| Contact | Cathryn C. Lee, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6484, Silver Spring, MD 20993-0002, 301- 796-0700; or Stephen Ripley, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911. | |
| FR Citation | 82 FR 57996 |
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