0572 Rx Labeling Requirements SSA 2025 REV

UNITED STATES FOOD & DRUG ADMINISTRATION

Labeling Requirements for Prescription Drugs

OMB Control Number 0910-0572 - Revision

SUPPORTING STATEMENT – Part A: Justification

1. Circumstances Making the Collection of Information Necessary

This information collection helps the Food and Drug Administration (FDA, the agency) implement statutory and regulatory requirements that govern the labeling of prescription drugs. Respondents to the information collection are sponsors of product labeling subject to applicable requirements. We characterize the information collection activities as recordkeeping, consistent with 5 CFR 1320.3(m), noting that a recordkeeping requirement means a requirement to maintain specified records, including the requirement to retain, notify third parties, the Federal government, or the public regarding such records. FDA regulations in 21 CFR part 201 govern the statement of ingredients and declaration of net quantity of contents with regard to prescription drug product labeling. The regulations require that firms identify bulk or transport containers with the name of the product contained therein and that containers be accompanied by documentation that identifies the product as meeting applicable compendial standards. New drug product and biological product applicants must: (1) design and create prescription drug labeling containing “Highlights,” “Contents,” and “Full Prescribing Information;” (2) test the designed labeling (for example, to ensure that the designed labeling fits into carton-enclosed products); and (3) submit it to FDA for approval.

In addition to incorporating general labeling provisions in 21 CFR 201, subpart A, agency regulations in 21 CFR part 201, subpart B (21 CFR 201.50 through 201.58) set forth specific content and format requirements applicable to prescription drug (and/or insulin) labeling. The regulations also provide for requesting waiver from any labeling requirement,­­ and do not apply to biological products that are subject to the requirements of section 351 of the Public Health Service Act. Also included in the scope of activity is information collection provided for under 21 CFR § 201.25(d), requiring that manufacturers submit a written request for exemption from applicable bar code requirements, and for tasks provided for under 21 CFR 201.26 relating to exceptions or alternatives to the labeling requirements of the Strategic National Stockpile (SNS). Finally, consistent with statutory authority under the Consolidated Appropriations Act, 2017 (Pub. L. 115-31), medical gas containers must meet labeling requirements found in §§ 201.161 and 201.328, established by final rule in the Federal Register of June 18, 2024 (89 FR 51738).

Because product labeling information is a requisite element included in new drug application submissions, we issue topic-specific guidance documents consistent with our regulations in 21 CFR 314.445, 21 CFR 601.29 (guidance documents), and 21 CFR 10.115, intended to enhance respondents’ understanding of applicable requirements. The following guidance documents communicate relevant information regarding the scope of activity covered by the collection:

“Safety Labeling Changes--Implementation of Section 505(o)(4) of the Federal Food, Drug, and Cosmetic Act,” (July 2013). The guidance document includes instruction on communicating with FDA regarding labeling changes required under section 505(o)(4) (Section IV – Procedures) and is available for download from our website at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safety-labeling-changes-implementation-section-505o4-federal-food-drug-and-cosmetic-act.

“Guidance for Industry on Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims,” (March 2011). The guidance document is intended to help respondents with developing labeling for cardiovascular outcome claims for drugs that are indicated to treat hypertension. The guidance document is available for download from our website at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/hypertension-indication-drug-labeling-cardiovascular-outcome-claims.

We therefore request OMB approval for the information collection provisions found in 21 CFR part 201 pertaining to prescription drug labeling, and activity attributable to recommendations found in the referenced guidance documents, as discussed in this supporting statement.

2. Purpose and Use of the Information Collection

The labeling regulations discussed in this supporting statement are part of FDA’s strategic initiative to manage the risks of medical product use and reduce adverse events involving the products that we regulate. We intend for the regulations on the content and format of labeling to make it easier for health care practitioners to access, read, and use information in prescription drug labeling, thereby increasing the extent to which they rely on labeling to obtain information. We believe compliance with the regulations will enhance the safe and effective use of prescription drug products, and in turn, reduce the number of adverse reactions resulting from medication errors due to misunderstood or incorrectly applied drug information. The requirements are important to the success of other initiatives aimed at improving patient care and decreasing the likelihood of medication errors. For example, the DailyMed, a collaboration between FDA and the National Library of Medicine will be an innovative means of electronically disseminating up-to-date and comprehensive medication information to use in information systems that support patient care. The DailyMed makes current information about FDA-regulated products readily available to physicians, other health care practitioners, and patients. In addition, manufacturers can use the new format for prescription drug labeling with electronic prescribing systems under development.

3. Use of Improved Information Technology and Burden Reduction

Manufacturers submit drug product labeling to FDA for approval as part of a new drug application (NDA), an abbreviated new drug application (ANDA), a biologics license application (BLA), or a supplement to an application. Manufacturers electronically report these applications and associated submissions.

4. Efforts to Identify Duplication and Use of Similar Information

We are unaware of duplicative information collection, although we have established information collection in control no. 0910-0340 to account for burden attributable to over-the-counter labeling requirements. Additionally, labeling requirements are found in a number of FDA regulations.

5. Impact on Small Businesses or Other Small Entities

We do not believe the information collection imposes undue burden on small entities. Manufacturers provide labeling information to FDA as part of the review for drugs and biological products application review process.

6. Consequences of Collecting the Information Less Frequently

This information collection schedule is consistent with the statutory and regulatory requirements. There are no legal obstacles to reducing burden. Respondents initiate submission and include labeling information as part of product marketing applications.

7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5

No special circumstances apply to this collection of information.

8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the Agency

In accordance with 5 CFR 1320.8(d), we published a 60-day notice in the Federal Register of September 19, 2024 (89 FR 76853), requesting public comment on the proposed collection of information. Although two comments were received, they were not responsive to the four collection of information topics solicited. In accordance with 5 CFR 1320.5(a)(1)(vi), a 30-day notice is scheduled for publication in the Federal Register on February 3, 2025, having been inadvertently delayed due to unforeseen circumstances. Because the information collection activities cover a range of critical public health programs, we obtained OMB permission to submit the ICR in advance of this date. OMB has not waived publication requirements under 5 CFR 1320.5(a)(1)(iv).

9. Explanation of Any Payment or Gift to Respondents

We do not provide payments or gifts to respondents.

10. Assurance of Confidentiality Provided to Respondents

The Privacy Act of 1974

In preparing this supporting statement, we consulted our Privacy Office to ensure the appropriate identification and handling of the information FDA is collecting. We conclude that personally identifiable information (PII) is collected in the context of the subject individuals’ professional capacity and the FDA-related work performed for their employer (for example, the point of contact at a regulated entity). The PII is submitted using Form FDA 356h (Application to Market a New or Abbreviated New Drug for Human Use https://www.fda.gov/media/86080/download), and includes the name, work email address, work telephone numbers, work address, and work fax telephone number for the primary contact at a business. Other information FDA receives through Form 356h includes potentially identifying work information including job title, credentials, and the country of the contact.

The Freedom of Information Act (FOIA)

Under 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 to 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.

Confidentiality of the information submitted under these regulations is protected under 21 CFR 314.430, 21 CFR 601, and 21 CFR part 20. The unauthorized use or disclosure of trade secrets required in applications is specifically prohibited under section 301(j) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 331(j)).

11. Justification for Sensitive Questions

No questions of a sensitive nature are included in the information collection.

12. Estimates of Annualized Burden Hours and Cost

12a. Annualized Hourly Burden Estimate.

Tale 1.--Estimated Annual Recordkeeping Burden

Activity/21 CFR Section	No. of Respondents	No. of Responses per Respondent	Total Annual Responses	Average Burden per Response	Total Hours
Labeling requirements for prescription drugs; §§ 201.56 and 201.57	414	1.326	549	3,349	1,838,601
Labeling applicable to medical gas containers; §§ 201.161(b); 201.328	260	1,663	432,380	0.17 (10 mins.)	73,505
Exemption from barcode requirements § 201.25(d)	2	1	2	24	48
Safety labeling required under FFDCA sec. 505(o)(4), and rebuttal statement	36	1	36	6	216
Safety labeling changes; posting approved letter on applicable holder’s website	351	1	351	4	1,404
Exceptions or alternatives to labeling requirements for human drug product held by the SNS; § 201.26	1	1	1	32	32
Hypertension claims; recommend labeling considerations	5	1	5	18	90
Total			433,324		1,913,896

Based on our evaluation, we have retained the currently approved estimate that 414 applicants will prepare an average of 549 prescription drug labels annually, and assume it will require 3,349 hours to design, test, and submit to FDA as part of a new drug application or a biologics license application.

New medical gas containers must meet applicable requirements found in new 21 CFR parts 210, 211, as well as specific labeling requirements in § 201.328. We estimate 260 respondents will incur burden for the design, testing, production, and submission of labeling for new medical gas containers as established in § 201.328 and assume an average of 10 minutes (0.17) is required for these activities. However, FDA issued rulemaking (0910-AH96) applicable to compressed medical gases effective December 18, 2025, and will evaluate the impact of burden that may result upon implementation of the new requirements.

Based on our evaluation, few requests for exemption from barcode requirements are received and we have therefore made no changes to the currently approved estimate for this activity. Likewise, we have also retained the currently approved estimate for information collection activities associated with safety labeling requirements established in 505(o)(4) of the Act. Similarly, we retain the currently approved estimate for exceptions to labeling under § 201.26, however this activity was previously approved in OMB control number 0910-0614 and is a new element to the collection, adding 1 response and 32 hours annually.

Finally, we have combined activity elements associated with labeling recommendations regarding drugs products that include a hypertension indication as discussed in the applicable March 2011 guidance referenced above, reducing the overall estimate for this element by 4 hours annually.

12b. Annualized Cost Burden Estimate.

We assume an average pharmaceutical industry wage rate of $75.00 per hour to prepare and submit to FDA the required information. We multiplied $75.00 by the total burden hours above 1,912,106 and estimate a cost to respondents of $143,407,950.

13. Estimates of Other Total Annual Costs to Respondents/Recordkeepers or Capital Costs

There are no capital or operating and maintenance costs associated with the information collection.

13. Annualized Cost to the Federal Government

Compliance with requirements is reviewed on a product-by-product basis contemporaneously with the review of product application submissions. Assuming labeling costs reflect 15% of total administrative costs for product application submissions and using currently approved costs in 0910-0001 (new drug applications NDAs) and 0910-0338 (biologics licensing applications) for such costs, we estimate annual costs to the government for review of prescription drug labels to be $41,785,141.

13. Explanation for Program Changes or Adjustments

The information collection reflects nominal adjustments that include the addition of one response and 32 hours annually, and we have removed costs previously attributable to respondents publicly posting safety labeling changes which we believe is now usual and customary practice. At the same time, we have clarified the scope of activity announcing in our notice OMB approved-modifications since last review (changes approving the addition of recommendations found in guidance; burden associated with Strategic National Stockpile labeling; bar code exemptions; and hypertension claims) and invited public comment. Although no comments were received as discussed in Q-8, we characterized the renewal request as a revision.

13. Plans for Tabulation and Publication and Project Time Schedule

We do not intend to publish tabulated results of the information collection.

13. Reason(s) Display of OMB Expiration Date is Inappropriate

We will display the OMB expiration date as required by 5 CFR 1320.5.

13. Exceptions to Certification for Paperwork Reduction Act Submissions

No exceptions to the certification are associated with this information collection.