| Page Range | 50102-50107 | |
| FR Document | 2018-21610 |
[Federal Register Volume 83, Number 193 (Thursday, October 4, 2018)] [Notices] [Pages 50102-50107] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-21610] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2014-N-1721] Agency Information Collection Activities; Proposed Collection; Comment Request; Investigational New Drug Applications AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is announcing an opportunity for public comment on the proposed collection of certain information by the Agency. Under the Paperwork Reduction Act of 1995 (PRA), Federal Agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, and to allow 60 days for public comment in response to the notice. This notice solicits comments on regulations under which the clinical investigation of the safety and effectiveness of unapproved new drugs and biological products can be conducted. DATES: Submit either electronic or written comments on the collection of information by December 3, 2018. ADDRESSES: You may submit comments as follows. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before December 3, 2018. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of December 3, 2018. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date. Electronic Submissions Submit electronic comments in the following way:Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov. If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ``Written/Paper Submissions'' and ``Instructions''). Written/Paper Submissions Submit written/paper submissions as follows: Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ``Instructions.'' Instructions: All submissions received must include the Docket No. FDA-2014-N-1721 for ``Agency Information Collection Activities; Proposed Collection; Comment Request; Investigational New Drug Applications.'' Received comments, those filed in a timely manner (see ADDRESSES), will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday. Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this [[Page 50103]] information on the cover sheet and not in the body of your comments and you must identify this information as ``confidential.'' Any information marked as ``confidential'' will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.thefederalregister.org/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations, Food and Drug Administration, Three White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-5733, [email protected]. SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal Agencies must obtain approval from the Office of Management and Budget (OMB) for each collection of information they conduct or sponsor. ``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or requirements that members of the public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 60-day notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing notice of the proposed collection of information set forth in this document. With respect to the following collection of information, FDA invites comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA's functions, including whether the information will have practical utility; (2) the accuracy of FDA's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology. 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)) 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 (21 U.S.C. 355(a)) 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 21 CFR 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 [[Page 50104]] investigation. It includes background information on the investigator as well as the investigation, and a general outline of the planned investigation and study protocol. Below, we estimate the burden of the information collection as reported by FDA's Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) 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...... 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............. ------------------------------------------------------------------------------- [[Page 50105]] Total....................... .............. .............. .............. .............. 23,125,527 ---------------------------------------------------------------------------------------------------------------- \1\ There are no capital costs or operating and maintenance costs associated with this collection of information. 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 ---------------------------------------------------------------------------------------------------------------- 312.2(e) Requests for FDA advice 217 1.18 256 24 6,144 on the applicability of part 312 to a planned clinical investigation.................. 312.8 Requests to charge for an 20 1.50 30 48 1,440 investigational drug........... 312.10 Requests to waive a 2 1 2 24 48 requirement in part 312........ 312.23(a) through (f) IND 335 1.35 452 1,600 723,200 content and format............. 312.30(a) through (e) Protocol 694 5.84 4,053 284 1,151,052 amendments..................... 312.31(b) Information amendments 77 2.43 187 100 18,700 312.32(c) and (d) IND Safety 161 8.83 1,422 32 45,504 reports........................ 312.33(a) through (f) IND Annual 745 2.14 1,594 360 573,840 reports........................ 312.38(b) and (c) Notifications 134 1.69 226 28 6,328 of withdrawal of an IND........ [[Page 50106]] 312.42 Sponsor requests that a 67 1.30 87 284 24,708 clinical hold be removed, including sponsor submission of a complete response to the issues identified in the clinical hold order............ 312.44(c) and (d) Sponsor 34 1.15 39 16 624 responses to FDA when IND is terminated..................... 312.45(a) and (b) Sponsor 55 1.38 76 12 912 requests for or responses to an inactive status determination of an IND by FDA............... 312.47 Meetings, including ``End- 88 1.75 154 160 24,640 of-Phase 2'' meetings and ``Pre- NDA'' meetings................. 312.53(c) Investigator reports 453 6.33 2,867 80 229,360 submitted to the sponsor, including Form FDA-1572, curriculum vitae, clinical protocol, and financial disclosure..................... 312.54(a) Sponsor submissions to 1 1 1 48 48 FDA concerning investigations involving an exception from informed consent under 21 CFR 50.24.......................... 312.54(b) Sponsor notifications 1 1 1 48 48 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 50.24(a)............ 312.55(a) Number of investigator 239 1.91 456 48 21,888 brochures submitted by the sponsor to each investigator... 312.55(b) Number of sponsor 243 4.95 1,203 48 57,744 reports to investigators on new observations, especially adverse reactions and safe use. 312.56(b), (c), and (d) Sponsor 108 2.21 239 80 19,120 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... 312.58(a) Number of sponsor's 7 1 7 8 56 submissions of clinical investigation records to FDA on request during FDA inspections. 312.64 Number of investigator 2,728 3.82 10,421 24 250,104 reports to the sponsor, including progress reports, safety reports, final reports, and financial disclosure reports........................ 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................... 312.110(b)(4) and (b)(5) Number 18 1 18 75 1,350 of written certifications and written statements submitted to FDA relating to the export of an investigational drug........ 312.120(b) Number of submissions 280 9.82 2,750 32 88,000 to FDA of ``supporting information'' related to the use of foreign clinical studies not conducted under an IND..... 312.120(c) Number of waiver 7 2.29 16 24 384 requests submitted to FDA related to the use of foreign clinical studies not conducted under an IND................... 312.130 Number of requests for 350 1.34 469 8 3,752 disclosable information in an IND and for investigations involving an exception from informed consent under Sec. 50.24.......................... 312.310(b) and 312.305(b) Number 78 1.08 84 8 672 of submissions related to expanded access and treatment of an individual patient....... 312.310(d) Number of submissions 76 2.76 210 16 3,360 related to emergency use of an investigational new drug....... 312.315(c) and 312.305(b) Number 9 1 9 120 1,080 of submissions related to expanded access and treatment of an intermediate-size patient population..................... 312.320(b) Number of submissions 1 1 1 300 300 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. [[Page 50107]] 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 ---------------------------------------------------------------------------------------------------------------- 312.52(a) Sponsor records for 75 1.40 105 2 210 the transfer of obligations to a contract research organization................... 312.57 Sponsor recordkeeping 335 2.70 904 100 90,400 showing the receipt, shipment, or other disposition of the investigational drug, and any financial interests............ 312.62(a) Investigator 453 1 453 40 18,120 recordkeeping of the disposition of drugs........... 312.62(b) Investigator 453 1 453 40 18,120 recordkeeping of case histories of individuals................. 312.160(a)(3) Records pertaining 111 1.40 155 * 0.5 78 to the shipment of drugs for investigational use in laboratory research animals or in vitro tests................. 312.160(c) Shipper records of 111 1.40 155 * 0.5 78 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: September 28, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-21610 Filed 10-3-18; 8:45 am] BILLING CODE 4164-01-P
| 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. | |
| Dates | Submit either electronic or written comments on the collection of information by December 3, 2018. | |
| Contact | Domini Bean, Office of Operations, Food and Drug Administration, Three White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-5733, [email protected] | |
| FR Citation | 83 FR 50102 |