2022-23728. Agency Information Collection Activities; Proposed Collection; Comment Request; Biologics License Applications Procedures and Requirements

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA or 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 the collection of information associated with biologics license application (BLA) procedures and requirements.

DATES:

Either electronic or written comments on the collection of information must be submitted by January 3, 2023.

ADDRESSES:

You may submit comments as follows. Please note that late, untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of January 3, 2023. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are received 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-2022-N-2440 for “Biologics License Applications Procedures and Requirements.” 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, 240-402-7500.

• 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 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.govinfo.gov/​content/​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, 240-402-7500.

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, [e-mail].

SUPPLEMENTARY INFORMATION:

Under the PRA (44 U.S.C. 3501-3521), 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.

Biologics License Applications Procedures and Requirements

OMB Control Number 0910-0338—Extension

This information collection supports Agency regulations and recommendations found in associated guidance pertaining to BLA procedures and requirements. A BLA is a request for permission to introduce, or deliver for introduction, a biological product into interstate commerce (601.2 (21 CFR 601.2)). BLAs are regulated under parts 600 through 680 (21 CFR parts 600 through 680). A BLA is submitted by any legal person or entity who is engaged in manufacture or an applicant for a license who takes responsibility for compliance with product and establishment standards. Interested persons may visit https://www.fda.gov/​vaccines-blood-biologics/​development-approval-process-cber/​biologics-license-applications-bla-process-cber for additional information, including available Agency resources.

Regulations in part 601 set forth applicable procedures for the submission of license application information, including content and format elements. The regulations also explain requirements for suspension, revocation, and reissuance of BLAs and communicate procedures for requesting a hearing. Additionally, the information collection includes the submission of manufacturing change information governed by section 506A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356a), as well as postmarketing reports for approved human drugs and licensed biological products governed by section 506B of the FD&C Act (21 U.S.C. 356b). Finally, regulations in parts 610 through 680 establish both general and specific biological product standards.

To implement these provisions, we have developed the following collection instruments:

1. Forms

Form FDA 356h, Application to Market a New or Abbreviated New Drug or Biologic for Human Use, provides a uniform format for submitting BLAs. Form FDA 356h is a fillable PDF form that may be submitted through our Electronic Submission Gateway (ESG), for which respondents must create and maintain a user account. Utilizing Form FDA 356h helps to ensure that an application is complete and contains all the necessary information, so that delays due to lack of information may be avoided. In addition, the form provides key information to FDA for efficient handling and distribution to the appropriate staff for review. We have recently made minor updates to Form FDA 356h resulting from the October 3, 2022, reauthorization of the Prescription Drug User Fee Act (PDUFA). In this collection we account for BLAs submitted using Form FDA 356h.

Form FDA 2252, Transmittal of Annual Report for Drugs and Biologics for Human Use, is used by an applicant of a licensed biological product to submit annual reports required by § 601.70(b) (21 CFR 601.70(b)). Form FDA 2252 is also a fillable PDF form and approved in OMB control number 0910-0001; however, in this information collection we account for submissions pertaining to biological products.

Form FDA 2253, Transmittal of Advertisements and Promotional Labeling for Drugs and Biologics for Human Use, was developed for use by respondents to transmit specimens of advertisements and promotional labeling ( e.g., circulars, package labels, container labels, etc.), as well as labeling changes. The submission of this information is required by 601.12 (21 CFR 601.12) for biological products and by 21 CFR 314.81 for drug products. Form FDA 2253 is a fillable PDF form and is approved for use in OMB control number 0910-0001; however, in this information collection we account for submissions pertaining to biological products.

Form FDA 3674, Certificate of Compliance Under 42 U.S.C. 282(j)(5)(B), with Requirements of ClinicalTrials.gov Data Bank, was developed for use by respondents to certify submissions as required by section 402(j)(5)(B) of the PHS Act and is submitted through our ESG. Form FDA 3674 is a fillable PDF form and is approved for use in OMB control number 0910-0616; however, in this information collection we account for submissions pertaining to biological products.

2. Cover Sheets

As provided for under part 601.2(a), we also utilize cover sheets, so denoted for purposes of identifying specific content information within a given application.

3. Guidance Documents

The guidance document “Cooperative Manufacturing Arrangements for Licensed Biologics,” (November 2008), available at https://www.fda.gov/​regulatory-information/​search-fda-guidance-documents/​cooperative-manufacturing-arrangements-licensed-biologics, discusses strategies for meeting an increased need for flexible manufacturing arrangements. Since cooperative manufacturing arrangements can take a considerable amount of time to develop, the guidance is intended to be useful for planning purposes in the early phases of product development. Many companies that perform only limited aspects of manufacturing processes are interested in sharing or contracting parts of manufacturing to facilitate product development and manufacturing flexibility. The guidance discusses recommended communication between licensed manufacturers and contract manufacturers regarding changes to production and facilities, results of tests and investigations regarding the product, types of products manufactured in the contract facility, and standard operating procedures. We believe that the information collection provisions in the guidance do not create a new burden for respondents. We believe the reporting and recordkeeping provisions are part of usual and customary business practices.

All Agency guidance documents issued are consistent with our good guidance practice regulations in 21 CFR 10.115, which provide for public comment at any time. We maintain a searchable database of our guidance documents at https://www.fda.gov/​regulatory-information/​search-fda-guidance-documents.

Respondents to this collection of information are licensed manufacturers of biological products. Based on the number of 2021 fiscal year application submissions, we estimate there are 371 such respondents. The total annual responses are based on the number of submissions ( i.e., license applications, labeling and other supplements, protocols, advertising and promotional labeling, notifications) for a particular product received annually by FDA. The hours per response are based on informal communications with industry and our experience with the information collection.

We estimate the burden of this collection of information as follows:

Table 1—Estimated Annual Reporting Burden ¹

21 CFR section or other citation; activity	Form FDA No.	Number of respondents	Number of responses per respondent	Total annual responses	Average burden per response	Total hours 2
601.2(a) and 610.60 through 610.65; Application for biologics license (includes labeling)	356h	51	1.078	55	860	47,300
601.5(a); Requirement to notify FDA of intention to discontinue manufacture of a product or all products	NA	17	1.0589	18	0.33 (20 minutes)	6
601.6(a); Requirement to provide FDA with copy of notification to selling agents and distributors upon suspension of its license	NA	1	1	1	0.33 (20 minutes)	1
601.12(a)(5); Requirement to inform FDA of changes to an approved application	NA	327	10.263	3,356	1	3,356
601.12(b)(1), (b)(3), and (e); Requirement to inform FDA of changes to an approved application	356h	195	5.795	1,130	80	90,400
601.12(c)(1) and (3); Requirement to inform FDA of changes to an approved application	356h	153	4.6536	712	50	35,600
601.12(c)(5); Requirement to inform FDA of changes to an approved application	356h	73	2.740	200	50	10,000
601.12(d)(1), (d)(3), and (f)(3); Requirement to inform FDA of changes to an approved application	356h	279	3.398	948	24	22,752
601.12(f)(1); Requirement to inform FDA of changes to an approved application	2253	64	2.75	176	40	7,040
601.12(f)(2); Requirement to inform FDA of changes to an approved application	2253	66	1.758	116	20	2,320
601.12(f)(4) and 601.45; Requirement to inform FDA of changes to an approved application	2253	173	340.416	58,892	10	588,920
601.27(b); Request for deferred submission of some or all safety and effectiveness assessments	NA	9	1.778	16	24	384
601.27(c); Request for full or partial waiver of safety and effectiveness assessments	NA	8	1	8	8	64
601.70(b) and (d), and 601.28; Annual progress reports of postmarketing studies	2252	101	1.84	186	24	4,464
610.15(d); Request for exceptions or alternatives to the regulation for constituent materials	NA	1	1	1	1	1
680.1(c); Requirement to annually update a license file with the list of source materials and the suppliers of the materials	NA	9	1	9	2	18
680.1(b)(3)(iv); Requirement to notify FDA when certain diseases are detected in source materials	NA	1	1	1	2	2
601.12; Amendments/Resubmissions	356h	170	27.888	4741	20	94,820
Section 402(j)(5)(B) of the PHS Act; Certification to accompany biological product applications	3674	1,291	1	1,291	0.28 (17 minutes)	358
Total						907,806
1  There are no capital costs or operating and maintenance costs associated with this collection of information.
2  The numbers in this column have been rounded to the nearest whole number.

Table 2—Estimated Annual Third-Party Disclosure Burden ¹

21 CFR section; activity	Number of respondents	Number of disclosures per respondent	Total annual disclosures	Average burden per disclosure	Total hours 2
601.6(a); Requirement to notify selling agents and distributors upon suspension of license	1	20	20	0.33 (20 minutes)	7
1  There are no capital costs or operating and maintenance costs associated with this collection of information.
2  The number in this column has been rounded to the nearest whole number.

Our estimated burden for the information collection reflects an overall increase of 467,907 hours and a corresponding increase in responses. We attribute part of this adjustment in the total hours to an increase in the number of submissions that we have received under 601.12(b)(1) and (3), (e), and (f)(4), and 601.45 over the last few years, which accounts for an increase of 467,549 hours. An additional increase of 358 hours is associated with certifications on Form FDA 3674.

Dated: October 27, 2022.

Lauren K. Roth,

Associate Commissioner for Policy.