[Federal Register Volume 84, Number 29 (Tuesday, February 12, 2019)] [Notices] [Pages 3462-3467] From the Federal Register Online via the Government Publishing Office [www.gpo.gov] [FR Doc No: 2019-01962] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2014-N-1721] Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Investigational New Drug Applications AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: 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. DATES: Fax written comments on the collection of information by March 14, 2019. ADDRESSES: 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: 202-395-7285, or emailed to [email protected]. All comments should be identified with the OMB control number 0910-0014. Also include the FDA docket number found [[Page 3463]] in brackets in the heading of this document. FOR FURTHER INFORMATION CONTACT: JonnaLynn Capezzuto, Office of Operations, Food and Drug Administration, Three White Flint North, 10A- 12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-3794, [email protected]. SUPPLEMENTARY 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 Application--21 CFR Part 312 OMB Control Number 0910-0014-Extension This information collection supports FDA regulations in 21 CFR part 312 covering Investigational New Drugs. Part 312 implements provisions of section 505(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(i)) requiring FDA 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 ensure drug products marketed in the United States are shown to be safe and effective, properly manufactured, and properly labeled for their intended uses. Section 505(a) of the FD&C 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 investigational new drug application (IND) regulations under part 312 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. The regulations also include recordkeeping requirements pertaining to the disposition of drugs, records pertaining to individual case histories, and certain other documentation verifying the fulfillment of responsibilities by clinical investigators. Submissions are reviewed by medical officers and other Agency scientific reviewers assigned responsibility for overseeing a specific study. The details 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 monitor the clinical investigation of the safety and effectiveness of unapproved new drugs and biological products, including 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; and (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 as required under the IND regulations, FDA cannot authorize or monitor the clinical investigations that must be conducted before authorizing the sale and general use of new drugs. These reports enable FDA to monitor a study's progress, to ensure the safety of subjects, to ensure 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. To assist respondents with certain reporting requirements under part 312, we have developed two forms: Form FDA 1571 entitled, ``Investigational New Drug Application (IND)'' and Form FDA 1572 entitled, ``Statement of Investigator.'' Anyone who intends to conduct a clinical investigation must submit Form FDA 1571 as instructed. The reporting elements include: (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 is executed and submitted by the IND sponsor before an investigator may participate in an investigation. It includes background information on the investigator as well as the investigation, and a general outline of the planned investigation and study protocol. In the Federal Register of October 4, 2018 (83 FR 50102) FDA published a 60-day notice requesting public comment on the proposed collection of information. We received one comment. The comment did not pertain to the regulations or estimates provided in the 60-day notice requesting that OMB extend its approval for the information collection in these regulations. Rather, the comment discussed issues that pertained to Docket No. FDA-2010-D-0503 for the ``Guidance for Clinical Investigators, Sponsors, and Institutional Review Boards (IRBs): Investigational New Drug Applications (INDs)--Determining Whether Human Research Studies Can Be Conducted Without an IND.'' Accordingly, we have submitted the comment to Docket No. FDA-2010-D-0503. FDA estimates the burden of this collection of information as follows: Table 1--Estimated Annual Reporting Burden for Human Drugs (CDER) \1\ ---------------------------------------------------------------------------------------------------------------- Number of 21 CFR section Number of responses per Total annual Average burden Total hours respondents respondent responses per response ---------------------------------------------------------------------------------------------------------------- Sec. 312.2(e); Requests for 400 1 400 24 9,600 FDA advice on the applicability of part 312 to a planned clinical investigation......... Sec. 312.8; Requests to charge 74 1.23 91 48 4,368 for an investigational drug.... Sec. 312.10; Requests to waive 86 1.84 158 24 3,792 a requirement in part 312...... [[Page 3464]] Sec. 312.23(a) through (f); 2,187 1.7 3,718 1,600 5,948,800 IND content and format (including Form FDA 1571)...... Sec. 312.30(a) through (e); 4,418 5.52 24,387 284 6,925,908 Protocol amendments............ Sec. 312.31(b); Information 6,691 3.32 22,214 100 2,221,400 amendments..................... Sec. 312.32(c) and (d); IND 867 15.78 13,681 32 437,792 safety reports................. Sec. 312.33(a) through (f); 3,376 2.86 9,655 360 3,475,800 IND annual reports............. Sec. 312.38(b) and (c); 930 1.61 1,497 28 41,916 Notifications of withdrawal of an IND......................... Sec. 312.42; Sponsor requests 198 1.38 273 284 77,532 that a clinical hold be removed, including sponsor submission of a complete response to the issues identified in the clinical hold order.......................... Sec. 312.44(c) and (d); 12 1.16 14 16 224 Sponsor responses to FDA when IND is terminated.............. Sec. 312.45(a) and (b); 231 1.84 425 12 5,100 Sponsor requests for or responses to an inactive status determination of an IND by FDA. Sec. 312.47; Meetings, 122 1.51 184 160 29,440 including ``End-of-Phase 2'' meetings and ``Pre-NDA'' meetings....................... Sec. 312.54(a); Sponsor 15 2.4 36 48 1,728 submissions to FDA concerning investigations involving an exception from informed consent under Sec. 50.24............. Sec. 312.54(b); Sponsor 2 1 2 48 96 notifications to FDA and others concerning an IRB determination that it cannot approve research because it does not meet the criteria in the exception from informed consent in Sec. 50.24(a)....................... Sec. 312.56(b), (c), and (d); 6,100 7 42,700 80 3,416,000 Sponsor notifications to FDA and others resulting from: (1) The sponsor's monitoring of all clinical investigations and determining that an investigator is not in compliance with the investigation agreements; (2) the sponsor's review and evaluation of the evidence relating to the safety and effectiveness of the investigational drug; and (3) the sponsor's determination that the investigational drug presents an unreasonable and significant risk to subjects... Sec. 312.58(a); Sponsor's 73 1 73 8 584 submissions of clinical investigation records to FDA on request during FDA inspections. Sec. 312.70; During the 4 1 4 40 160 disqualification process of a clinical investigator by FDA, the number of investigator responses or requests to FDA following FDA's notification to an investigator of its failure to comply with investigation requirements................... Sec. 312.110(b)(4) and (b)(5); 11 26.28 289 75 21,675 Written certifications and written statements submitted to FDA relating to the export of an investigational drug........ Sec. 312.120(b); Submissions 1,414 8.62 12,189 32 390,048 to FDA of ``supporting information'' related to the use of foreign clinical studies not conducted under an IND..... Sec. 312.120(c); Waiver 35 2.34 82 24 1,968 requests submitted to FDA related to the use of foreign clinical studies not conducted under an IND................... Sec. 312.130; Requests for 3 1 3 8 24 disclosable information in an IND and for investigations involving an exception from informed consent under Sec. 50.24.......................... Sec. Sec. 312.310(b) and 935 2.77 2,590 8 20,720 312.305(b); Submissions related to expanded access and treatment of an individual patient........................ Sec. 312.310(d); Submissions 480 2.15 1,032 16 16,512 related to emergency use of an investigational new drug....... Sec. Sec. 312.315(c) and 118 2.52 297 120 35,640 312.305(b); Submissions related to expanded access and treatment of an intermediate- size patient population........ Sec. 312.320(b); Submissions 10 12.9 129 300 38,700 related to a treatment IND or treatment protocol............. ------------------------------------------------------------------------------- Total....................... .............. .............. .............. .............. 23,125,527 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. [[Page 3465]] Table 2--Estimated Annual Recordkeeping Burden for Human Drugs (CDER) \1\ ---------------------------------------------------------------------------------------------------------------- Number of Average burden 21 CFR section Number of records per Total annual per Total hours recordkeepers recordkeeper records recordkeeping ---------------------------------------------------------------------------------------------------------------- Sec. 312.52(a); Sponsor 1,300 1 1,300 2 2,600 records for the transfer of obligations to a contract research organization.......... Sec. 312.57; Sponsor 13,000 1 13,000 100 1,300,000 recordkeeping showing the receipt, shipment, or other disposition of the investigational drug and any financial interests............ Sec. 312.62(a); Investigator 13,000 1 13,000 40 520,000 recordkeeping of the disposition of drugs........... Sec. 312.62(b); Investigator 13,000 1 13,000 40 520,000 recordkeeping of case histories of individuals................. Sec. 312.160(a)(3); Records 547 1.43 782 * 0.50 391 pertaining to the shipment of drugs for investigational use in laboratory research animals or in vitro tests.............. Sec. 312.160(c); Shipper 547 1.43 782 * 0.50 391 records of alternative disposition of unused drugs.... ------------------------------------------------------------------------------- Total....................... .............. .............. .............. .............. 2,343,382 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. * 30 minutes. Table 3--Estimated Annual Third-Party Disclosure Burden for Human Drugs (CDER) \1\ ---------------------------------------------------------------------------------------------------------------- Number of 21 CFR section Number of disclosures Total annual Average burden Total hours respondents per respondent disclosures per disclosure ---------------------------------------------------------------------------------------------------------------- Sec. 312.53(c); Investigator 1,732 7.94 13,752 80 1,100,160 reports submitted to the sponsor, including Form FDA 1572, curriculum vitae, clinical protocol, and financial disclosure........... Sec. 312.55(a); Investigator 995 4 3,980 48 191,040 brochures submitted by the sponsor to each investigator... Sec. 312.55(b); Sponsor 995 4 3,980 48 191,040 reports to investigators on new observations, especially adverse reactions and safe use. Sec. 312.64; Investigator 13,000 1 13,000 24 312,000 reports to the sponsor, including progress reports, safety reports, final reports, and financial disclosure reports........................ ------------------------------------------------------------------------------- Total....................... .............. .............. .............. .............. 1,794,240 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. Table 4--Estimated Annual Reporting Burden for Biologics (CBER) \1\ ---------------------------------------------------------------------------------------------------------------- Number of 21 CFR section Number of responses per Total annual Average burden Total hours respondents respondent responses per response ---------------------------------------------------------------------------------------------------------------- Sec. 312.2(e); Requests for 217 1.18 256 24 6,144 FDA advice on the applicability of part 312 to a planned clinical investigation......... Sec. 312.8; Requests to charge 20 1.50 30 48 1,440 for an investigational drug.... Sec. 312.10;Requests to waive 2 1 2 24 48 a requirement in part 312...... Sec. 312.23(a) through (f); 335 1.35 452 1,600 723,200 IND content and format......... Sec. 312.30(a) through (e); 694 5.84 4,053 284 1,151,052 Protocol amendments............ Sec. 312.31 (b); Information 77 2.43 187 100 18,700 amendments..................... Sec. 312.32(c) and (d); IND 161 8.83 1,422 32 45,504 Safety reports................. Sec. 312.33(a) through (f); 745 2.14 1,594 360 573,840 IND Annual reports............. Sec. 312.38(b) and (c); 134 1.69 226 28 6,328 Notifications of withdrawal of an IND......................... Sec. 312.42; Sponsor requests 67 1.30 87 284 24,708 that a clinical hold be removed, including sponsor submission of a complete response to the issues identified in the clinical hold order.......................... Sec. 312.44(c) and (d); 34 1.15 39 16 624 Sponsor responses to FDA when IND is terminated.............. Sec. 312.45(a) and (b); 55 1.38 76 12 912 Sponsor requests for or responses to an inactive status determination of an IND by FDA. Sec. 312.47; Meetings, 88 1.75 154 160 24,640 including ``End-of-Phase 2'' meetings and ``Pre-NDA'' meetings....................... Sec. 312.53(c); Investigator 453 6.33 2,867 80 229,360 reports submitted to the sponsor, including Form FDA 1572, curriculum vitae, clinical protocol, and financial disclosure........... [[Page 3466]] Sec. 312.54(a); Sponsor 1 1 1 48 48 submissions to FDA concerning investigations involving an exception from informed consent under Sec. 50.24............. Sec. 312.54(b); Sponsor 1 1 1 48 48 notifications to FDA and others concerning an IRB determination that it cannot approve research because it does not meet the criteria in the exception from informed consent in Sec. 50.24(a)....................... Sec. 312.55(a); Number of 239 1.91 456 48 21,888 investigator brochures submitted by the sponsor to each investigator.............. Sec. 312.55(b); Number of 243 4.95 1,203 48 57,744 sponsor reports to investigators on new observations, especially adverse reactions and safe use. Sec. 312.56(b), (c), and (d); 108 2.21 239 80 19,120 Sponsor notifications to FDA and others resulting from: (1) The sponsor's monitoring of all clinical investigations and determining that an investigator is not in compliance with the investigation agreements; (2) the sponsor's review and evaluation of the evidence relating to the safety and effectiveness of the investigational drug; and (3) the sponsor's determination that the investigational drug presents an unreasonable and significant risk to subjects... Sec. 312.58(a); Number of 7 1 7 8 56 sponsor's submissions of clinical investigation records to FDA on request during FDA inspections.................... Sec. 312.64; Number of 2,728 3.82 10,421 24 250,104 investigator reports to the sponsor, including progress reports, safety reports, final reports, and financial disclosure reports............. Sec. 312.70; During the 5 1 5 40 200 disqualification process of a clinical investigator by FDA, the number of investigator responses or requests to FDA following FDA's notification to an investigator of its failure to comply with investigation requirements................... Sec. 312.110(b)(4) and (b)(5); 18 1 18 75 1,350 Number of written certifications and written statements submitted to FDA relating to the export of an investigational drug........... Sec. 312.120(b); Number of 280 9.82 2,750 32 88,000 submissions to FDA of ``supporting information'' related to the use of foreign clinical studies not conducted under an IND................... Sec. 312.120(c); Number of 7 2.29 16 24 384 waiver requests submitted to FDA related to the use of foreign clinical studies not conducted under an IND......... Sec. 312.130; Number of 350 1.34 469 8 3,752 requests for disclosable information in an IND and for investigations involving an exception from informed consent under Sec. 50.24............. Sec. 312.310(b) and 78 1.08 84 8 672 312.305(b); Number of submissions related to expanded access and treatment of an individual patient............. Sec. 312.310(d);Number of 76 2.76 210 16 3,360 submissions related to emergency use of an investigational new drug....... Sec. 312.315(c) and 9 1 9 120 1,080 312.305(b); Number of submissions related to expanded access and treatment of an intermediate-size patient population..................... Sec. 312.320(b); Number of 1 1 1 300 300 submissions related to a treatment IND or treatment protocol....................... ------------------------------------------------------------------------------- Total....................... .............. .............. .............. .............. 3,254,606 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. Table 5--Estimated Annual Recordkeeping Burden for Biologics (CBER) \1\ ---------------------------------------------------------------------------------------------------------------- Number of Average burden 21 CFR section Number of records per Total annual per Total hours recordkeepers recordkeeper records recordkeeping ---------------------------------------------------------------------------------------------------------------- Sec. 312.52(a); Sponsor 75 1.40 105 2 210 records for the transfer of obligations to a contract research organization.......... Sec. 312.57; Sponsor 335 2.70 904 100 90,400 recordkeeping showing the receipt, shipment, or other disposition of the investigational drug, and any financial interests............ [[Page 3467]] Sec. 312.62(a); Investigator 453 1 453 40 18,120 recordkeeping of the disposition of drugs........... Sec. 312.62(b); Investigator 453 1 453 40 18,120 recordkeeping of case histories of individuals................. Sec. 312.160(a)(3); Records 111 1.40 155 * 0.5 78 pertaining to the shipment of drugs for investigational use in laboratory research animals or in vitro tests.............. Sec. 312.160(c); Shipper 111 1.40 155 * 0.5 78 records of alternative disposition of unused drugs.... ------------------------------------------------------------------------------- Total....................... .............. .............. .............. .............. 127,006 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. * 30 minutes. Because we have received an increased number of IND submissions since the last OMB approval of the information collection, we have increased our estimate of the associated burden accordingly. Dated: February 6, 2019. Lowell J. Schiller, Acting Associate Commissioner for Policy. [FR Doc. 2019-01962 Filed 2-11-19; 8:45 am] BILLING CODE 4164-01-P