Skip to Content


Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Investigational New Drug Regulations

Document Details

Information about this document as published in the Federal Register.

Published Document

This document has been published in the Federal Register. Use the PDF linked in the document sidebar for the official electronic format.

Start Preamble


Food and Drug Administration, HHS.




The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.


Fax written comments on the collection of information by June 8, 2009.


To ensure that comments on the information collection are received, OMB recommends that written comments be faxed to the Office of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, FAX: 202-395-6974, or e-mailed to All comments should be identified with the OMB control number 0910-0014. Also include the FDA docket number found in brackets in the heading of this document.

Start Further Info


Elizabeth Berbakos, Office of Information Management (HFA-710), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-796-3792.Start Printed Page 21691

End Further Info End Preamble Start Supplemental Information


In compliance with 44 U.S.C. 3507, FDA has submitted the following proposed collection of information to OMB for review and clearance.

Investigational New Drug Regulations—OMB Control Number 0910-0014—Extension

FDA is requesting OMB approval for the reporting and recordkeeping requirements contained in the FDA regulations “Investigational New Drug Application” in part 312 (21 CFR part 312). Part 312 implements provisions of section 505(i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)) (the act) 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 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 do the following: (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 the following information: (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.

The second form is 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 and Recordkeeping Requirements in 21 CFR Part 312

21 CFR SectionRequirements
312.7(d)Applications for permission to sell an investigational new drug
312.8Charging for investigational drugs under an IND
312.10Applications for waiver of requirements under part 312; as indicated in § 312.10(a), estimates for this requirement are included under §§ 312.23 and 312.31. In addition, separate requests under § 312.10 are estimated in table 2 of this document.
312.20(c)Applications for investigations involving an exception from informed consent under § 50.24 (21 CFR 50.24); estimates for this requirement are included under § 312.23.
312.23INDs (content and format)
(a)(1)Cover sheet FDA-1571
(a)(2)Table of contents
(a)(3)Investigational plan for each planned study
(a)(5)Investigator's brochure
(a)(6)Protocols—Phases 1, 2, and 3
(a)(7)Chemistry, manufacturing, and control information
(a)(7)(iv)(a), (b), and (c)A description of the drug substance, a list of all components, and any placebo used
Start Printed Page 21692
(a)(7)(iv)(d)Labeling: Copies of labels and labeling to be provided each investigator
(a)(7)(iv)(e)Environmental impact analysis regarding drug manufacturing and use
(a)(8)Pharmacological and toxicology information
(a)(9)Previous human experience with the investigational drug
(a)(10)Additional information
(a)(11)Relevant information
(f)Identification of exception from informed consent
312.30Protocol amendments
(a)New protocol
(b)Change in protocol
(c)New investigator
(d)Content and format
312.31Information amendments
(b)Content and format Chemistry, toxicology, or technical information
312.32Safety reports
(c)(1)Written reports to FDA and to investigators
(c)(2)Telephone reports to FDA for fatal or life-threatening experience
(c)(3)Format or frequency
(d)Followup submissions
312.33Annual reports
(a)Individual study information
(b)Summary information
(b)(1)Adverse experiences
(b)(2)Safety report summary
(b)(3)List of fatalities and causes of death
(b)(4)List of discontinuing subjects
(b)(5)Drug action
(b)(6)Preclinical studies and findings
(b)(7)Significant changes
(c)Next year general investigational plan
(d)Brochure revision
(e)Phase I protocol modifications
(f)Foreign marketing developments
312.35Treatment use of investigational new drugs
(a)Treatment protocol submitted by IND sponsor
(b)Treatment IND submitted by licensed practitioner
312.36Requests for emergency use of an investigational new drug
312.38(b) and (c)Notification of withdrawal of an IND
312.42(e)Sponsor requests that a clinical hold be removed and submits a complete response to the issues identified in the clinical hold order
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
312.54(a) and (b)Sponsor submissions concerning investigations involving an exception from informed consent under § 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 § 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
312.64Investigator reports to the sponsor
Start Printed Page 21693
(a)Progress reports
(b)Safety reports
(c)Final reports
312.66Investigator reports to Institutional Review Board; estimates for this requirement are included under § 312.53
312.70(a)Investigator disqualification; opportunity to respond to FDA
312.83Sponsor submission of treatment protocol; estimates for this requirement are included under §§ 312.34 and 312.35
312.85Sponsors conducting Phase 4 studies; estimates for this requirement are included under § 312.23 in 0910-0014, and §§ 314.50, 314.70, and 314.81 in 0910-0001
312.110(b)Request to export an investigational drug
312.120Submissions related to foreign clinical studies not conducted under an IND
312.130(d)Request for disclosable information for investigations involving an exception from informed consent under § 50.24
21 CFR SectionRequirements
312.52(a)Transfer of obligations to a contract research organization
312.57Sponsor recordkeeping
312.59Sponsor recordkeeping of disposition of unused supply of drugs; estimates for this requirement are included under § 312.57
312.62(a)Investigator recordkeeping of disposition of drugs
312.62(b)Investigator recordkeeping of case histories of individuals
312.120(d)Recordkeeping requirements for submissions related to foreign clinical studies not conducted under an IND; estimates for this requirement are included under § 312.57
312.160(a)(3)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 February 11, 2009 (74 FR 6889), FDA published a 60-day notice requesting public comment on the information collection provisions. No comments were received.

In tables 2 and 3 of this document, the estimates for “No. of Respondents,” “No. of Responses per Respondent,” and “Total Annual Responses” were obtained from the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) reports and data management systems for submissions received in 2007 and from other sources familiar with the number of submissions received under 21 CFR part 312. The estimates for “Hours per Response” were made by CDER and CBER individuals familiar with the burden associated with these reports and from estimates received from the pharmaceutical industry.

FDA estimates the burden of this collection of information as follows:

Table 2.—Estimated Annual Reporting Burden for Human Drugs and Biologics (CDER)1

21 CFR SectionNo. of RespondentsNo. of Responses per RespondentTotal Annual ResponsesHours per ResponseTotal Hours
312.23(a) through (f)2,4961.263,1561,6005,049,600
312.30(a) through (e)2,0308.9118,0792845,134,436
Start Printed Page 21694
312.32(c) and (d)98523.0622,71332726,816
312.33(a) through (f)2,5642.345,9943602,157,840
312.35(a) and (b)91.11103003,000
312.38(b) and (c)6541.348742824,472
312.44(c) and (d)1591.13179162,864
312.45(a) and (b)2541.43362124,344
312.54(a) and (b)1114848
312.56(b) ,(c), and (d)18118801,440
1 There are no capital and startup, or operation, maintenance, and purchase costs associated with the collection of information requirements.
2 Section 312.120 includes the burden estimate for both CDER and CBER.

Table 3.—Estimated Annual Recordkeeping Burden for Human Drugs and Biologics (CDER)1

21 CFR SectionNo. of RecordkeepersNo. of Records per RecordkeeperTotal Annual RecordsHours per RecordTotal Hours
1 There are no capital and startup, or operation, maintenance, and purchase costs associated with the collection of information requirements.

Table 4.—Estimated Annual Reporting Burden for Biologics (CBER)1

21 CFR SectionNo. of RespondentsNo. of Responses per RespondentTotal Annual ResponsesHours per ResponsesTotal Hours
312.23(a) through (f)21681.52561,600409,600
312.30(a) through (e)3726.42,369284672,796
Start Printed Page 21695
312.32(c) and (d)17514.62,5633282,016
312.33(a) through (f)5122.31,168360420,480
312.35(a) and (b)111300300
312.38(b) and (c)811.5120283,360
312.44(c) and (d)341.13916624
312.45(a) and (b)411.45912708
312.54(a) and (b)1114848
312.56(b), (c), and (d)101.616801,280
1 There are no capital and startup, or operation, maintenance, and purchase costs associated with the collection of information requirements.
2 The reporting requirement for § 312.10 is included in the estimates for §§ 312.23 and 312.31.

Table 5.—Estimated Annual Recordkeeping Burden for Biologics (CBER)1

21 CFR SectionNo. of RecordkeepersAnnual Frequency per RecordkeepingTotal Annual RecordsHours per RecordTotal Hours
1 There are no capital and startup, or operation, maintenance, and purchase costs associated with the collection of information requirements.
Start Printed Page 21696

Table 6.—Totals for Estimated Annual Reporting and Recordkeeping Burdens for CDER and CBER

Reporting Burden130,190,510
Start Signature

Dated: May 1, 2009.

Jeffrey Shuren,

Associate Commissioner for Policy and Planning.

End Signature End Supplemental Information

[FR Doc. E9-10730 Filed 5-7-09; 8:45 am]