Food and Drug Administration, HHS.
Notice of availability.
Under the Food and Drug Administration Modernization Act of 1997 (Modernization Act), the Food and Drug Administration (FDA) is required to report annually in the
Meg Pease-Fye, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 4156, Silver Spring, MD 20993–0002, 301–796–0700; or Stephen Ripley, Center for Biologics Evaluation and Research (HFM–17), Food and Drug Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852, 301–827–6210.
Section 130(a) of the Modernization Act (Pub. L. 105–115) amended the Federal Food, Drug, and Cosmetic Act (the FD&C Act) by adding a new provision requiring reports of certain postmarketing studies, including clinical trials, for human drug and biological products (section 506B of the FD&C Act (21 U.S.C. 356b)). Section 506B of the FD&C Act provides FDA with additional authority to monitor the progress of a postmarketing study or clinical trial that an applicant has been required to, or has agreed to, conduct by requiring the applicant to submit a report annually providing information on the status of the postmarketing study/clinical trial. This report must also include reasons, if any, for failure to complete the study/clinical trial. These studies and clinical trials are intended to further define the safety, efficacy, or optimal use of a product, and therefore play a vital role in fully characterizing the product.
Under the Modernization Act, commitments to conduct postmarketing studies or clinical trials included both studies/clinical trials that applicants agreed to conduct, as well as studies/clinical trials that applicants were required to conduct under FDA regulations.
On September 27, 2007, the President signed Public Law 110–85, the Food and Drug Administration Amendments Act of 2007 (FDAAA). Section 901, in Title IX of FDAAA, created a new section 505(o) of the FD&C Act authorizing FDA to require certain studies and clinical trials for human drug and biological products approved under section 505 of the FD&C Act or section 351 of the Public Health Service Act. Under FDAAA, FDA has been given additional authority to require applicants to conduct and report on 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 product. This new authority became effective on March 25, 2008. FDA may now take enforcement action against applicants who fail to conduct studies and clinical trials required under FDAAA, as well as studies and clinical trials required under FDA regulations (see 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))).
Although regulations implementing the Modernization Act postmarketing authorities use the term “postmarketing commitment” to refer to both required
On October 30, 2000 (65 FR 64607), FDA published a final rule implementing section 130 of the Modernization Act. This rule modified the annual report requirements for new drug applications (NDAs) and abbreviated new drug applications (ANDAs) by revising § 314.81(b)(2)(vii) (21 CFR 314.81(b)(2)(vii)). The rule also created a new annual reporting requirement for biologics license applications (BLAs) by establishing § 601.70 (21 CFR 601.70). The rule described the content and format of the annual progress report, and clarified the scope of the reporting requirement and the timing for submission of the annual progress reports. The rule became effective on April 30, 2001. The regulations apply only to human drug and biological products approved under NDAs, ANDAs, and BLAs. They do not apply to animal drugs or to biological products regulated under the medical device authorities.
The reporting requirements under §§ 314.81(b)(2)(vii) and 601.70 apply to PMRs and PMCs made on or before the enactment of the Modernization Act (November 21, 1997), as well as those made after that date. Therefore, studies and clinical trials required under FDAAA are covered by the reporting requirements in these regulations.
Sections 314.81(b)(2)(vii) and 601.70 require applicants of approved drug and biological products to submit annually a report on the status of each clinical safety, clinical efficacy, clinical pharmacology, and nonclinical toxicology study/clinical trial either required by FDA or that they have committed to conduct, either at the time of approval or after approval of their NDA, ANDA, or BLA. The status of PMCs concerning chemistry, manufacturing, and production controls and the status of other studies/clinical trials conducted on an applicant's own initiative are not required to be reported under §§ 314.81(b)(2)(vii) and 601.70 and are not addressed in this report. It should be noted, however, that applicants are required to report to FDA on these commitments made for NDAs and ANDAs under § 314.81(b)(2)(viii). Furthermore, section 505(o)(3)(E) of the FD&C Act, as amended by FDAAA, requires that applicants report periodically on the status of each required study/clinical trial and each study/clinical trial “otherwise undertaken * * * to investigate a safety issue * * *.”
According to the regulations, once a PMR has been required, or a PMC has been agreed upon, an applicant must report on the progress of the PMR/PMC on the anniversary of the product's approval 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 progress report 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/clinical trial, and (3) submission of the final report to FDA. The status of the PMR/PMC must be described in the annual report according to the following definitions:
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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).
This report, published to fulfill the annual reporting requirement under the Modernization Act, summarizes the status of PMRs and PMCs as of September 30, 2011. If a requirement or commitment did not have a schedule, or a postmarketing progress report was not received in the previous 12 months, the PMR/PMC is categorized according to the most recent information available to the Agency.
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, including PMRs required under FDAAA (section 505(o)(3) of the FD&C Act), PMRs required under FDA regulations (e.g., PMRs required to demonstrate clinical benefit of a product following accelerated approval (see footnote 1 of this document)), and PMCs agreed to by the applicant.
Information summarized in this report includes the following: (1) The number of applicants with open (uncompleted) PMRs/PMCs, (2) the number of open PMRs/PMCs, (3) the status of open PMRs/PMCs as reported in § 314.81(b)(2)(vii) or § 601.70 annual reports, (4) the status of concluded PMRs/PMCs as determined by FDA, and (5) the number of applications with open PMRs/PMCs for which applicants did not submit an annual report within 60 days of the anniversary date of U.S. approval.
Additional information about PMRs/PMCs submitted by applicants to CDER and CBER is provided on FDA's Web site at
Many applicants have more than one approved product and for many products there is more than one PMR or PMC. Specifically, there were 175 unique applicants with 198 NDAs/ANDAs that had open PMRs/PMCs. There were 72 unique applicants with 99 BLAs that had open PMRs/PMCs.
Annual status reports are required to be submitted for each open PMR/PMC within 60 days of the anniversary date of U.S. approval of the original application. In fiscal year 2011 (FY11), 21 percent (43/208) of NDA/ANDA and 41 percent (41/99) of BLA annual status reports were not submitted within 60 days of the anniversary date of U.S. approval of the original application. Of the annual status reports due but not submitted on time, 100 percent of the NDA/ANDA and 56 percent (23/41) of the BLA reports were submitted before the close of FY11 (September 30, 2011).
Most PMRs are progressing on schedule (87 percent for NDAs/ANDAs; 88 percent for BLAs). Most PMCs are also progressing on schedule (80 percent for NDAs/ANDAs; 75 percent for BLAs). Most of the PMCs that are currently listed in the database were developed before the postmarketing requirements section of FDAAA took effect.
This report provides six separate summary tables. The tables in this document distinguish between PMRs and PMCs and between on-schedule and off-schedule PMRs and PMCs according to the original schedule milestones. On-schedule PMRs/PMCs are categorized as pending, ongoing, or submitted. Off-schedule PMRs/PMCs that have missed one of the original milestone dates are categorized as delayed or terminated. The tables include data as of September 30, 2011.
Table 1 of this document provides an overall summary of the data on all PMRs and PMCs. Tables 2 and 3 of this document provide detail on PMRs. Table 2 of this document provides additional detail on the status of on-schedule PMRs.
Table 1 of this document shows that most PMRs (87 percent for NDAs/ANDAs and 88 percent for BLAs) and most PMCs (80 percent for NDAs/ANDAs and 75 percent for BLAs) are on schedule. Overall, of the PMRs that are pending (
Table 3 of this document provides additional detail on the status of off-schedule PMRs. The majority of off-schedule PMRs (which account for 13 percent of the total for NDAs/ANDAs and 12 percent for BLAs) are delayed according to the original schedule milestones (98 percent (83/85) for NDAs/ANDAs; 95 percent (20/21) for BLAs). In certain situations, the original schedules may have been adjusted for unanticipated delays in the progress of the study/clinical trial (
Tables 4 and 5 of this document provide additional detail on the status of PMCs. Table 4 of this document provides additional detail on the status of on-schedule PMCs. Pending PMCs comprise 48 percent (141/295) of the on-schedule NDA/ANDA PMCs and 39 percent (81/209) of the on-schedule BLA PMCs.
Table 5 of this document provides additional details on the status of off-schedule PMCs. The majority of off-schedule PMCs (which account for 20 percent for NDAs/ANDAs and 25 percent for BLAs) are delayed according to the original schedule milestones (93 percent (69/74) for NDAs/ANDAs; 97 percent (69/71) for BLAs). As noted previously in this document, this report reflects the original due dates for study/clinical trial results and does not reflect discussions between the Agency and the sponsor regarding studies/clinical trials that may require more time for completion.
Table 6 of this document provides details about PMRs and PMCs that were concluded in the previous year. The majority of concluded PMRs and PMCs were fulfilled (70 percent of NDA/ANDA PMRs and 84 percent of BLA PMRs; 85 percent of NDA/ANDA PMCs and 80 percent of BLA PMCs).