[Federal Register Volume 64, Number 155 (Thursday, August 12, 1999)] [Notices] [Pages 44019-44023] From the Federal Register Online via the Government Publishing Office [www.gpo.gov] [FR Doc No: 99-20846] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. 99N-1010] Agency Information Collection Activities; Submission for OMB Review; Comment Request; Investigational New Drug Regulations AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA) is announcing that the proposed collection of information listed below has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995 (the PRA). DATES: Submit written comments on the collection of information by September 13, 1999. ADDRESSES: Submit written comments on the collection of information to the Office of Information and Regulatory Affairs, OMB, New Executive Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: Wendy Taylor, Desk Officer for FDA. FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Information Resources Management (HFA-250), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-1482. SUPPLEMENTARY INFORMATION: In compliance with section 3507 of the PRA (44 U.S.C. 3507), FDA has submitted the following proposed collection of information to OMB for review and clearance. Investigational New Drug (IND) Regulations--21 CFR Part 312 (OMB Control Number 0910-0014)-- Renewal FDA is requesting OMB approval for the reporting and recordkeeping requirements contained in FDA's regulation ``Investigational New Drug Application'' part 312 (21 CFR part 312). This regulation implements provisions of section 505(i) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 355(i)) to issue regulations under which the clinical investigation of the safety and effectiveness of unapproved new drugs and biological products can be conducted. FDA is charged with implementing statutory requirements that drug products marketed in the United States be shown to be safe and effective, properly manufactured, and properly labeled for their intended uses. Section 505(a) of the act provides that a new drug may not be introduced or delivered for introduction into interstate commerce in the United States unless FDA has previously approved a new drug application (NDA). FDA approves an NDA only if the sponsor of the application first demonstrates that the drug is safe and effective for the conditions prescribed, recommended, or suggested in the product's labeling. Proof must consist, in part, of adequate and well-controlled studies, including studies in humans, that are conducted by qualified experts. The IND regulations establish reporting requirements that include an initial application as well as amendments to that application, reports on significant revisions of clinical investigation plans, and information on a drug's safety or effectiveness. In addition, the sponsor is required to give FDA an annual summary of the previous year's clinical experience. Submissions are reviewed by medical officers and other agency scientific reviewers assigned responsibility for overseeing the specific study. The IND regulations also contain recordkeeping requirements that pertain to the responsibilities of sponsors and investigators. The detail and complexity of these requirements are dictated by the [[Page 44020]] scientific procedures and human subject safeguards that must be followed in the clinical tests of investigational new drugs. The IND information collection requirements provide the means by which FDA can: (1) Monitor the safety of ongoing clinical investigations; (2) determine whether the clinical testing of a drug should be authorized; (3) ensure production of reliable data on the metabolism and pharmacological action of the drug in humans; (4) obtain timely information on adverse reactions to the drug; (5) obtain information on side effects associated with increasing doses; (6) obtain information on the drug's effectiveness; (7) ensure the design of well-controlled, scientifically valid studies; (8) obtain other information pertinent to determining whether clinical testing should be continued and information related to the protection of human subjects. Without the information provided by industry in response to the IND regulations, FDA cannot authorize or monitor the clinical investigations which must be conducted prior to authorizing the sale and general use of new drugs. These reports enable FDA to monitor a study's progress, to assure subject safety, to assure that a study will be conducted ethically, and to increase the likelihood that the sponsor will conduct studies that will be useful in determining whether the drug should be marketed and available for use in medical practice. There are two forms that are required under part 312: Form FDA- 1571-- ``Investigational New Drug Application.''A person who intends to conduct a clinical investigation submits this form to FDA. It includes: (1) A cover sheet containing background information on the sponsor and investigator, (2) a table of contents, (3) an introductory statement and general investigational plan, (4) an investigator's brochure describing the drug substance, (5) a protocol for each planned study, (6) chemistry, manufacturing, and control information for each investigation, (7) pharmacology and toxicology information for each investigation, and (8) previous human experience with the investigational drug. Form FDA-1572-- ``Investigator Statement.'' Before permitting an investigator to begin participation in an investigation, the sponsor must obtain and record this form. It includes background information on the investigator and the investigation, and a general outline of the planned investigation and the study protocol. FDA is requesting OMB approval for the following reporting and recordkeeping requirements in part 312: Table 1.--Reporting Requirements ------------------------------------------------------------------------ 21 CFR Section Explanations ------------------------------------------------------------------------ 312.7(d)............................ Applications for permission to sell an investigational new drugs. 312.10(a)........................... Applications for waiver of requirements under part 312. Only emergency requests are estimated under this section; other requests are included under Secs. 312.23 and 312.31. 312.20(c)........................... Applications for investigations involving an exception from informed consent under Sec. 50.24 (21 CFR 50.24). Estimates for this requirement are included under Sec. 312.23. 312.23.............................. IND's (content and format). 312.23(a)(1)........................ Cover sheet FDA-1571. 312.23(a)(2)........................ Table of contents. 312.23(a)(3)........................ Investigational plan for each planned study. 312.23(a)(5)........................ Investigator's brochure. 312.23(a)(6)........................ Protocols--Phase 1, 2, and 3. 312.23(a)(7)........................ Chemistry, manufacturing, and control information. 312.23(a)(7)(iv)(a), (b), and (c)... A description of the drug substance, a list of all components, and any placebo used. 312.23(a)(7)(iv)(d)................. Labeling--copies of labels and labeling to be provided each investigator. 312.23(a)(7)(iv)(e)................. Environmental impact analysis regarding drug manufacturing and use. 312.23(a)(8)........................ Pharmacological and toxicology information. 312.23(a)(9)........................ Previous human experience with the investigational drug. 312.23(a)(10)....................... Additional information. 312.23(a)(11)....................... Relevant information. 312.23(f)........................... Identification of exception from informed consent. 312.30.............................. Protocol amendments. 312.30(a)........................... New protocol. 312.30(b)........................... Change in protocol. 312.30(c)........................... New investigator. 312.30(d)........................... Content and format. 312.30(e)........................... Frequency. 312.31.............................. Information amendments. 312.31(b)........................... Content and format. .................................. Chemistry, toxicology, or technical information. 312.32.............................. Safety reports. 312.32(c)(1)........................ Written reports to FDA and to investigators. 312.32(c)(2)........................ Telephone reports to FDA for fatal or life-threatening experience. 312.32(c)(3)........................ Format or frequency. 312.32(d)........................... Followup submissions. 312.33.............................. Annual reports. 312.33(a)........................... Individual study information. 312.33(b)........................... Summary information. 312.33(b)(1)........................ Adverse experiences. 312.33(b)(2)......................... Safety report summary. 312.33(b)(3)......................... List of fatalities and causes of death. 312.33(b)(4)......................... List of discontinuing subjects. [[Page 44021]] 312.33(b)(5)......................... Drug action. 312.33(b)(6)......................... Preclinical studies and findings. 312.33(b)(7)......................... Significant changes. 312.33(c)........................... Next year general investigational plan. 312.33(d)........................... Brochure revision. 312.33(e)........................... Phase I protocol modifications. 312.33(f)........................... Foreign marketing developments. 312.35.............................. Treatment use of investigational new drugs. 312.35(a)........................... Treatment protocol submitted by IND sponsor. 312.35(b)........................... Treatment IND submitted by licensed practitioner. 312.36.............................. Requests for emergency use of an investigational new drugs. 312.38(b) and (c)................... Notification of withdrawal of an IND. 312.44(c) and (d)................... Opportunity for sponsor response to FDA when IND is terminated. 312.45(a) and (b)................... Sponsor request for or response to inactive status determination of an IND. 312.47(b)........................... ``End-of-Phase 2'' meetings and ``Pre-NDA'' meetings. 312.53(c)........................... Investigator information. Investigator report (Form FDA- 1572) and narrative; Investigator's background information; Phase 1 outline of planned investigation; and Phase 2 outline of study protocol; financial disclosure information. 312.54(a) and (b)................... Sponsor submissions concerning investigations involving an exception from informed consent under Sec. 50.24. 312.55(b)........................... Sponsor reports to investigators on new observations, especially adverse reactions and safe use. Only ``new observations'' are estimated under this section; investigator brochures are included under Sec. 312.23. 312.56(b), (c), and (d)............. Sponsor monitoring of all clinical investigations, investigators, and drug safety; notification to FDA. 312.58(a)........................... Sponsor's submission of records to FDA on request. 312.64.............................. Investigator reports to the sponsor. 312.64(a)........................... Progress reports. 312.64(b)........................... Safety reports. 312.64(c)........................... Final reports. 312.64(d)........................... Financial disclosure reports. 312.66.............................. Investigator reports to Institutional Review Board. Estimates for this requirement are included under Sec. 312.53. 312.70.............................. Investigator disqualification; opportunity to respond to FDA. Estimates for this requirement are not included in the estimates for part 312. 312.83.............................. Sponsor submission of treatment protocol. Estimates for this requirement are included under Secs. 312.34 and 312.35. 312.85.............................. Sponsors conducting phase 4 studies. Estimates for these postmarketing studies are not included in the estimates for part 312. 312.110(b).......................... Request to export an investigational drug. 312.120(b) and (c)(2)............... Sponsor's submission to FDA for use of foreign clinical study to support an IND. 312.120(c)(3)....................... Sponsor's report to FDA on findings of independent review committee on foreign clinical study. 312.130(d).......................... Request for disclosable information for investigations involving an exception from informed consent under Sec. 50.24. ------------------------------------------------------------------------ Table 2.--Recordkeeping Requirements ------------------------------------------------------------------------ 21 CFR Section Explanations ------------------------------------------------------------------------ 312.52(a)........................... Transfer of obligations to a contract research organization. 312.57(a) and (b)................... Sponsor recordkeeping. 312.59.............................. Sponsor recordkeeping of disposition of unused supply of drugs. Estimates for this requirement are included under Sec. 312.57. 312.62(a)........................... Investigator recordkeeping of disposition of drugs. 312.62(b)........................... Investigator recordkeeping of case histories of individuals. 312.160(a).......................... Records maintenance--shipment of drugs for investigational use in laboratory research animals or in vitro tests. 312.160(c).......................... Shipper records of alternative disposition of unused drugs. ------------------------------------------------------------------------ In the Federal Register of May 6, 1999 (64 FR 24402), the agency requested comments on the proposed collections of information. No comments were received. [[Page 44022]] Table 3.--Estimated Annual Reporting Burden for Human Drugs\1\ ---------------------------------------------------------------------------------------------------------------- No. of No. of Responses Total Annual Hours per 21 CFR Section Respondents Per Responses Response Total Hours Respondent ---------------------------------------------------------------------------------------------------------------- 312.7(d) 7 1 7 24 168 312.10(a) 0 0 0 0 0 312.23(a) and (f) 1,601 1.25 1,996 1,600 3,193,600 312.30(a) through (e) 918 14.85 13,629 284 3,870,636 312.31(b) 760 8.87 6,738 100 673,800 312.32(c) and (d) 459 14.33 6,576 32 210,432 312.33(a) through (f) 1,841 2.35 4,318 350 1,511,300 312.35(a) and (b) 1 1 1 300 300 312.36 643 1.2 720 16 11,520 312.38(b) 621 1.24 773 28 21,644 312.38(c) 621 1.24 773 160 123,680 312.44(c) and (d) 710 1.10 780 16 12,480 312.45(a) and (b) 294 1.32 389 12 4,668 312.47(b) 252 1 252 160 40,320 312.53(c) 4,500 1 4,500 80 360,000 312.54(a) and (b) 4 1 4 48 192 312.55(b) 4,500 1 4,500 48 216,000 312.56(b), (c), and (d) 5 1 5 80 400 312.58(a) 337 1 337 8 2,696 312.64(a) through (d) 8,200 1 8,200 24 196,800 312.110(b) 150 2 303 75 22,725 312.120(b) and (c)(2) 100 2 200 168 33,600 312(c)(3) 100 2 200 40 8,000 312.130(d) 4 1 4 8 32 Total Reporting Burden 10,514,993 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. Table 4.--Estimated Annual Recordkeeping Burden for Human Drugs\1\ ---------------------------------------------------------------------------------------------------------------- Annual 21 CFR Section No. of Frequency per Total Annual Hours per Total Hours Recordkeepers Recordkeeping Records Recordkeeper ---------------------------------------------------------------------------------------------------------------- 312.52(a) 360 1 360 2 720 312.57(a) and (b) 4,000 2.05 8,200 100 400,000 312.62(a) 8,200 1 8,200 40 328,000 312.62(b) 8,200 12.2 100,000 40 328,000 312.160(a) 3,400 7.35 25,000 30 min 1,700 312.160(c) 3,400 2.35 8,000 30 min 1,700 Total Recordkeeping 1,060,120 Burden Human Drugs Total Burden 11,575,113 Hours ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. Table 5.--Estimated Annual Reporting Burden for Biologics\1\ ---------------------------------------------------------------------------------------------------------------- No. of 21 CFR Section No. of Responses Total Annual Hours per Total Hours Respondents Per Response Responses Response ---------------------------------------------------------------------------------------------------------------- 312.7(d) 9 1.3 12 24 288 312.10(a) 1 1 1 40 40 312.23(a) and (f) and 312.120(b), 278 1.8 492 1,600 787,200 (c)(2), and (c)(3) 312.30(a) and (e) 975 6.5 6,411 284 1,820,724 312.31(b) 975 9.2 9,005 100 900,500 312.32(c) and (d) and 312.56(c) 602 6.7 4,034 32 129,088 312.33(a) and (f) and 312.56(c) 1,253 1.6 1,989 350 696,150 312.35(a) and (b) 1 1 1 300 300 312.36 22 5.5 122 16 1,952 312.38(b) 128 1.7 212 28 5,936 312.38(c) 128 1.7 212 160 33,920 312.44(c) and (d) 55 1.9 107 16 1,712 312.45(a) and (b) 74 1.4 105 12 1,260 312.47(b) 150 1.8 274 160 43,840 312.53(c) 672 6.6 4,421 80 353,680 312.54(a) and (b) 4 1 4 48 192 312.55(b) 374 6.1 2,288 48 109,824 312.56(b) and (d) 12 1.6 20 80 1,600 312.58(a) 10 1 10 8 80 312.64(a) and (d) 5,014 1 5,014 24 120,336 [[Page 44023]] 312.110(b) 10 1.3 13 75 975 312.130(d) 1 1 1 0.5 0.5 Total Reporting Burden 5,009,597.5 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. Table 6.--Estimated Annual Recordkeeping Burden for Biologics\1\ ---------------------------------------------------------------------------------------------------------------- Annual 21 CFR Section No. of Frequency per Total Annual Hours per Total Hours Recordkeepers Recordkeeping Records Recordkeeper ---------------------------------------------------------------------------------------------------------------- 312.52(a) 27 2.5 67 5 135 312.57(a) and (b) 1,253 2 2,506 100 125,300 312.62(a) 5,014 1 5,014 40 200,560 312.62(b) 8,200 12.2 100,000 40 328,000 312.160(a) 3,400 7.35 25,000 30 min 1,700 312.160(c) 320 1 320 0.5 160 Total Biologics 655,855 Recordkeeping Hours Total Biologics Burden 5,665,452.5 Hours Total Human Drugs Burden 11,575,113 Hours Total Combined Burdens 17,240,565.5 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. Dated: August 6, 1999 William K. Hubbard, Senior Associate Commissioner for Policy, Planning, and Legislation. [FR Doc. 99-20846 Filed 8-11-99; 8:45 am] BILLING CODE 4160-01-F
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Agency Information Collection Activities; Submission for OMB Review; Comment Request; Investigational New Drug Regulations
The Food and Drug Administration (FDA) is announcing that the proposed collection of information listed below has been submitted to the Office of Management and Budget (OMB) for...
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“Agency Information Collection Activities; Submission for OMB Review; Comment Request; Investigational New Drug Regulations,” thefederalregister.org (August 12, 1999), https://thefederalregister.org/documents/99-20846/agency-information-collection-activities-submission-for-omb-review-comment-request-investigational-new-drug-regulations.