Supporting Statement A

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BIOLOGICS LICENSE APPLICATIONS – 
PROCEDURES & REQUIREMENTS

OMB Control No. 0910-0338  - Extension

SUPPORTING STATEMENT Part A – Justification:

    1. Circumstances Making the Collection of Information Necessary
This information collection helps support implementation of statutory and regulatory requirements under the Public Health Service Act (PHS) and the Federal Food, Drug, and Cosmetic Act (FD&C Act) that govern biologics product licensing.  The Food and Drug Administration (FDA) has promulgated regulations in 21 CFR parts 600-680 setting forth applicable standards and procedures that include associated reporting, recordkeeping, and -disclosure requirements.  Respondents to the information collection are persons or entities who engage in manufacture of biologics products.  We provide information on our website at https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/biologics-license-applications-bla-process-cber regarding biologics license applications (BLAs), including available agency resources.
Regulations in 21 CFR part 600, subparts A through C (21 CFR 600-600.21), and regulations in 21 CFR 601, subpart A (21 CFR 601.2 – 21 CFR 601.9) cover general provisions and prescribe requisite content and format elements for applications.  Regulations in 21 CFR part 601, subpart C (21 CFR 601.12 – 21 CFR 601.29) pertain to BLA changes; the electronic submission of information; the suspension, revocation, and reissuance of BLAs; and also provide for the availability of guidance documents by FDA to assist respondents in complying with applicable requirements (21 CFR 601.29).  Regulations in 21 CFR 601, subparts D and E, respectively, establish requirements applicable to diagnostic radiopharmaceuticals and for the accelerated approval of biological products for serious or life-threatening illnesses.  The confidentiality of information submitted to FDA is covered in 21 CFR 601, subpart F (601.50-601.51).  Finally, the regulations also provide for the approval of biological products when human efficacy studies are not ethical or feasible (21 CFR 601, subpart H).  Finally, regulations in 21 CFR parts 610-680 establish both general and specific standards applicable to all biological products.  The information collection also includes labeling provisions pertaining to exceptions or alternatives to the labeling of products in the Strategic National Stockpile (SNS), established in 21 CFR 610.28.
We include the following instruments, which are also approved for use in other information collections (OMB control nos. 0910-0001 (applications to market a new drug) and 0910-0014 (investigational drugs):

Forms.
    • Form FDA 356h, Application to Market a New or Abbreviated New Drug or Biologic for Human Use  
    • Form FDA 2252, Transmittal of Annual Report for Drugs and Biologics for Human Use;
    • Form FDA 2253, Transmittal of Advertisements and Promotional Labeling for Drugs and Biologics for Human Use; and
    • Form FDA 3674, Certificate of Compliance Under 42 U.S.C. 282(j)(5)(B), with Requirements of ClinicalTrials.gov Data Bank.
    • Form FDA 3988 entitled, “Transmittal of PMR/PMC Submissions for Drugs and Biological Products”; and 
    • Form FDA 3989 entitled, “PMR/PMC Annual Status Report for Drugs and Biological Products.”  
Section 506B of the FD&C Act (21 U.S.C. 356b), and implementing regulations in 21 CFR parts 314.81, 312.20 and 601.70, provide for the submission of postmarket study reports (PMRs), requiring sponsors of approved drugs and biological products to report to FDA annually on the progress of their postmarketing study commitments (PMCs), including reports on required studies, clinical trials, and agreed upon commitments.  Under section 506B(b) and (c), FDA is required to track these PMCs and report on them annually in the Federal Register.  The forms are also intended for use in OMB control nos. 0910-0001 and 0910-0014.
Cover Sheets
	As provided for under 21 CFR part 601.2(a), we utilize cover sheets, so denoted for purposes of identifying specific content information within a given application.
Guidance Documents

Agency regulations in 21 CFR 601.29 complement our Good Guidance Practice regulations in 21 CFR 10.115 by providing for the issuance of guidance documents to assist respondents with applicable requirements in 21 CFR part 601.  We have issued the following guidance documents to assist respondents with activities covered by the information collection:

    • 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 in order to facilitate product development and manufacturing flexibility.  The guidance document 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 but incorporate reporting and recordkeeping provisions that are part of usual and customary business practices.

    • The guidance document entitled, “Voluntary Consensus Standards Recognition Program for Regenerative Medicine Therapies” (October 2023), describes a standards recognition program for regenerative medicine therapies (SRP-RMT) designed to identify and recognize Voluntary Consensus Standards (VCS) to facilitate the development and assessment of regenerative medicine therapy (RMT) products when such standards are appropriate.  The guidance document also explains that any interested party may request recognition of a VCS.  The guidance document is available for download from our website at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/voluntary-consensus-standards-recognition-program-regenerative-medicine-therapies. 

We therefore request OMB approval of the information collections associated with BLAs, including the referenced agency forms and the associated guidance, as discussed in this supporting statement.
    2. Purpose and Use of the Information Collection 
The information collection helps fulfill FDA’s mandate to promote and protect the public health.  Biological product sponsors and biological products not in compliance with applicable requirements may be subject to enforcement action by the agency.

    3. Use of Improved Information Technology and Burden Reduction

We have developed and continue to maintain the FDA-Electronic Submissions Gateway (ESG) for accepting electronic regulatory submissions, including BLAs and associated information. The FDA ESG is a highly scalable, easily available, high performance and secure exchange point for FDA and its partners to transact a variety of documents and submissions over industry-standard protocols.    The FDA ESG enables the secure submission of premarket and postmarket regulatory information for review, functioning as a single point of entry for receiving and processing all electronic submissions in a highly secure environment.  The FDA ESG complies with secure Hypertext Transfer Protocol (HTTP) messaging standards and uses digital certificates for secure communication.  The electronic submission process encompasses the receipt, acknowledgment of receipt (to the sender), routing and notification (to a receiving Center or Office) of the delivery of an electronic submission.

We are not aware of any other improved technology to reduce the burden. We have issued agency guidance regarding technical specifications applicable to certain submissions, consistent with our Good Guidance Practice regulations in 21 CFR 10.115, which provides for public comment at any time.  Also, agency regulations pertaining to electronic records and electronic signatures are found in 21 CFR part 11, with corresponding information collection activities approved in OMB control no. 0910-0303.

    4. Efforts to Identify Duplication and Use of Similar Information 
We are unaware of duplicative information collection.  We acknowledge that general provisions of 21 CFR part 600 may have applicability in other currently approved information collections noting, for example, that information collection pertaining to records and postmarket reporting for biologic products is currently approved in control no. 0910-0308; information collection pertaining to adverse event reporting generally and FDA’s MedWatch Program (consumer reporting) is currently approved in control no. 0910-0291; information collection pertaining to postmarket adverse drug experience reporting is approved in control no. 0910-0230 (postmarket adverse drug experience reporting); and potentially other approved collections established for information collection associated with the adverse experience of any FDA-regulated product.
    5. Impact on Small Businesses or Other Small Entities
We do not believe the information collection imposes undue burden on small entities.
    6. Consequences of Collecting the Information Less Frequently
The information collection schedule is consistent with statutory and regulatory requirements. There are no technical or legal obstacles to reducing the burden.
    7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
An applicant may be required to submit to FDA proprietary trade secret or other confidential information when submitting a license application, change to an approved application, or an annual report. FDA protects confidential information received from manufacturers to the extent permitted by law. In addition, certain changes to an approved application are required to be submitted each time a change is made. This information is necessary for FDA to ensure that the proposed changes do not have an adverse effect on the strength, quality, purity, or potency as they may relate to the safety and effectiveness of a product.
    8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the Agency
In accordance with 5 CFR 1320.8(d), FDA published a 60-day notice for public comment in the Federal Register of July 6, 2026 (91 FR 41406).  No comments were received.

    9. Explanation of Any Payment or Gift to Respondents
There are no incentives, payments or gifts associated with this information collection.
    10. Assurance of Confidentiality Provided to Respondents
The Privacy Act of 1974 

In preparing this supporting statement, we consulted our Privacy Office to ensure appropriate identification and handling of information collected.  Although this ICR collects personally identifiable information (PII), it is collected in the context of the subject individuals’ professional capacity and the FDA-related work performed for their employer (e.g., point of contact at a regulated entity).  The PII is collected using the Electronic Submission Gateway through which users must establish and maintain a username and password.  We have determined, however, that although PII is collected, the collection is not subject to the Privacy Act of 1974 and the particular notice and other requirements of the Privacy Act do not apply.  Specifically, FDA does not use name or any other personal identifier to retrieve records from the information collected.  Through appropriate form and webpage design, FDA limited submission fields and minimized the PII collected to protect the privacy of the individuals.

The Freedom of Information Act

Under the Freedom of Information Act (FOIA) (5 U.S.C. 552), the public has broad access to government documents. However, FOIA provides certain exemptions from mandatory public disclosure of government records (5 U.S.C. 552(b)(1-9)).  FDA will make the fullest possible disclosure of records to the public, consistent with the rights of individuals to privacy, the property rights of persons in trade and confidential commercial or financial information.

    11. Justification for Sensitive Questions
The collection of information does not involve sensitive questions.
    12. Estimates of Annualized Burden Hours and Cost
Description of Respondents:  Respondents to the information collection are licensed manufacturers of biological products.  Based on agency data, we estimate there are 371 respondents to the information collection.

12a.  Annualized Hour Burden Estimate
Table 1.--Estimated Annual Reporting Burden1
21 CFR Subchapter F:  Biologics or Other Authority; Information Collection Activity
Form FDA No.
No. of Respondents
No. of Responses per Respondent
Total Annual Responses
Average Burden per Response
Total Hours2
Parts 601 (§§ 601.2-601.95); applications and supplements, including applicable labeling standards in part 610 (610.15, 610.65) and requests for samples
356h
371
177.40
65,814
~12.35
812,607
601.12; Changes to an approved application
356h
170
27.888
4,741
10
47,410
Guidance documents issued in accordance with 601.29:
    • Cooperative Manufacturing Agreements
    • Voluntary Consensus Standard Programs
NA
9
1
9
3
27
610.15(d); Request for exceptions or alternatives to the regulation for constituent materials
NA
1
1
1
1
1
Part 680 (§§ 680.1-680.3); additional standards
NA
10
1
10
2
20
Section 402(j)(5)(B) of the PHS Act (42 U.S.C.); Certification to accompany biological product applications
3674
371
1
371
0.28
(17 minutes)
105
TOTAL

371

70,946

860,170
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.

Noting that 5 CFR 1320.3(m) defines a recordkeeping requirement to include the reporting to the Federal government regarding such records, we have characterized the submission tasks reflected in Table 1 as reporting burden, assuming that respondents retain records in support of the respective submissions.  

Table 2.--Estimated Annual Third-Party Disclosure Burden1
21 CFR Section; Activity
No. of Respondents
No. of Disclosures per Respondent
Total Annual Disclosures
Average Burden per Disclosure
Total Hours2
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.  

Based on our experience with the information collection, we account for disclosures under 21 CFR 601.6(a) distinctly, as reflected above in Table 2.  Again, FDA assumes that respondents subject to regulatory requirements in 21 CFR 601.6 will retain corresponding records.

12b.  Annualized Cost Burden Estimate


We assume wage rates for a regulatory affairs specialist ($58/hour), who would be responsible for filling out the form, and preparing an application, supplement, postmarketing report, or other similar submission; and a medical director ($96/hour), who would be responsible for preparing notification to FDA of discontinuance of a product.

    13. Estimates of Other Total Annual Costs to Respondents/Recordkeepers or Capital Costs 
There are no capital costs or operating and maintenance costs associated with this collection of information.
14.  Annualized Cost to the Federal Government

Assuming the allocation of 145 full-time equivalents (FTEs) to administration of the information collection and an average annual salary per FTE of $143,658 to include benefits but no overhead costs, we calculate the cost to the Federal government as follows:

Activity
Number of FTEs
Average Annual Reviewer Salary
Total Cost
Application/Supplement Review
103
$143,658
$14,796,774
License Processing
36
$143,658
$5,171,688
Advertisement/Promotional Labeling
5
$143,658
$718,290
Review Postmarketing Report
1
$143,658
$143,658
TOTAL
145

$20,830,410.

    15. Explanation for Program Changes or Adjustments
There have been no program changes to the information collection.  At the same time, burden previously captured in control no. 0910-0206 regarding the collection of samples and now incorporated into IC elements # 1 (Applications and supplements, including labeling and requests for samples) and # 5 (Part 680; additional standards) together with nominal fluctuations in submission activity over the past three years shows a decrease of 2,168 responses and an increase of 29,133 burden hours annually.
    16. Plans for Tabulation and Publication and Project Time Schedule
The information collected will not be published or tabulated.
    17. Reason(s) Display of OMB Expiration Date is Inappropriate
Display of the OMB expiration date is appropriate.
    18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.