The “Deemed to be a License” Provision of the BPCI Act: Questions and Answers : Guidance for Industry | Guideline Explorer

postmarketing reportingControl Strategy

Description

This guidance is intended to provide answers to common questions about FDA’s implementation of the “transition” provision of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) under which an application for a biological product approved under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355) as of March 23, 2020, will be deemed to be a license for the biological product under section 351 of the Public Health Service Act (PHS Act) (42 U.S.C. 262) on March 23, 2020 (the transition date). This guidance also describes FDA’s compliance policy for the labeling of biological products that are the subject of deemed biologics license applications (BLAs). This guidance is intended to facilitate planning for the transition date and provide further clarity regarding the Agency’s implementation of this statutory provision.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

Biological Product

Regulated under section 351(i) of the PHS Act; Virus, therapeutic serum, toxin, vaccine, or protein applicable to prevention or treatment; Alternative regulation category for products meeting device definition

Protein

Included in the definition of biological product; Alpha amino acid polymer greater than 40 amino acids in size

Biosimilar Product

biological products shown to be biosimilar to a reference product

Interchangeable

Biological product shown to be interchangeable with a reference product

Biosimilar

Biological product shown to be highly similar to an FDA-licensed reference product; Biological product demonstrated to be highly similar to a reference product

Interchangeable product

A biosimilar that may be substituted for the reference product

Stakeholders

Prescribing health care provider

Role involved in substitution of interchangeable products

BLA holder

Entity expected to have control over manufacturing for biological products

Manufacturer

Entity responsible for submitting NDINs

application holder

Entity seeking to use the alternative reporting process.; entity responsible for seeking alternative reporting processes

Regulatory Context

Regulatory Activities

BLA

Biologics License Application

CBE-0 Supplement

Changes Being Effected supplement for identical labeling changes; Changes-being-effected supplement required within 15 days of an SLC order

505(b)(2) pathway

Regulatory pathway for drug applications that rely on data not developed by the applicant

Prior Approval Supplement

Major changes requiring FDA approval before implementation

505(b)(2)

Regulatory pathway for drug applications relying on existing data

505(j)

Drugs submitted for approval under the FD&C Act

351(k)

Biosimilar regulatory pathway

351(k) application

application for a proposed biosimilar product; Pathway for biosimilar licensure; submission of data derived from comparator products in support of a 351(k) application

NDA

New Drug Application

351(a) BLA

Original biologics license application pathway

Document Types

Orange Book

Approved Drug Products With Therapeutic Equivalence Evaluations

Annual Report

Reporting category for minor changes like removing a color additive

Biological Product Deviation Report

Reporting mechanism for manufacturing problems under PHS Act

Field Alert Report

Report required if distributed products exceed safety limits for DEG or EG.

Container Label

dosage terminology on the container label and carton labeling should be consistent

Carton Labeling

Required to state maximum level of aluminum

Purple Book

Lists of Licensed Biological Products

Labeling

Cybersecurity information should be included in device labeling

prescribing information

With the exception of the prescribing information and Medication Guide.

Attributes

Transition Date

March 23, 2020; March 23, 2020, when NDAs are deemed to be BLAs

Established Name

Naming format required for other products in the combination regimen.

License Number

U.S. license number assigned to the BLA holder

Proper Name

Naming format for biological products in the combination regimen.

Safety, purity, and potency

Standards for demonstrating biosimilarity

Technical Details

Substances

Peptide

Amino acid polymer composed of 40 or fewer amino acids

Preservative

Exception excipient for parenteral, ophthalmic, or otic use.

Testing Methods

Potency Assay

Analytical procedures used to measure product potency; replacing or changing a validated potency assay

Stability Data

Documentation of stability data for drug products; Accelerated and long-term stability testing

Processes

Chemical Synthesis

Manufacturing process for synthetic APIs

Manufacturing Process Validation

Evidentiary source used in conjunction with AI models.

Lot Release

FDA review and release of product lots

pre-license inspections

Inspections conducted before a license is granted

Clinical Concepts

adverse drug experiences

reporting suspected adverse events

Standards & References

Specifications

chemistry, manufacturing, and controls

CMC requirements for biological products

Sterility

general BLA requirement for biological products

Purity

Drug product purity should be carefully evaluated early in product development.

Potency

Specific ability or capacity of the product to effect a given result

ICH References (1)

ICH Q5E

Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process

View on FDA.gov Download PDF

Related CFR Sections (19)

21CFR610.60§ 610.60 Container label.
(a) Full label. The following items shall appear on the label affixed to each container of a product capable of bearing a full label:Read full regulation →
21CFR208.20§ 208.20 Content and format of a Medication Guide.
(a) A Medication Guide shall meet all of the following conditions:Read full regulation →
21CFR201.80§ 201.80 Specific requirements on content and format of labeling for human prescription drug and biological products; older drugs not described in § 201.56(b)(1) .
Each section heading listed in § 201.56(d) , if not omitted under § 201.56(d)(3) , shall contain the following information in the following order:Read full regulation →
21CFR201.57§ 201.57 Specific requirements on content and format of labeling for human prescription drug and biological products described in § 201.56(b)(1) .
The requirements in this section apply only to prescription drug products described in § 201.56(b)(1) and must be implemented according to the schedule specified in § 201.56(c) , except for the requirement in paragraph (c)(18) of this section to reprint any FDA-approved patient labeling at the end oRead full regulation →
21CFR201.56§ 201.56 Requirements on content and format of labeling for human prescription drug and biological products.
(a) General requirements. Prescription drug labeling described in § 201.100(d) must meet the following general requirements:Read full regulation →
21CFR610.64§ 610.64 Name and address of distributor.
The name and address of the distributor of a product may appear on the label provided that the name, address, and license number of the manufacturer also appears on the label and the name of the distributor is qualified by one of the following phrases: “Manufactured for _____”, “Distributed by _____Read full regulation →
21CFR201.1§ 201.1 Drugs; name and place of business of manufacturer, packer, or distributor.
(a) A drug or drug product (as defined in § 320.1 of this chapter ) in finished package form is misbranded under section 502 (a) and (b)(1) of the act if its label does not bear conspicuously the name and place of business of the manufacturer, packer, or distributor. This paragraph does not apply toRead full regulation →
21CFR314.70§ 314.70 Supplements and other changes to an approved NDA.
(a) Changes to an approved NDA.Read full regulation →
21CFR601.12§ 601.12 Changes to an approved application.
(a) General.Read full regulation →
21CFR601.2§ 601.2 Applications for biologics licenses; procedures for filing.
(a) General. To obtain a biologics license under section 351 of the Public Health Service Act for any biological product, the manufacturer shall submit an application to the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing aRead full regulation →
21CFR600.14§ 600.14 Reporting of biological product deviations by licensed manufacturers.
(a) Who must report under this section?Read full regulation →
21CFR600.90§ 600.90 Waivers.
(a) An applicant may ask the Food and Drug Administration to waive under this section any requirement that applies to the applicant under §§ 600.80 and 600.81 . A waiver request under this section is required to be submitted with supporting documentation. The waiver request is required to contain onRead full regulation →
21CFR314.81§ 314.81 Other postmarketing reports.
(a) Applicability. Each applicant shall make the reports for each of its approved applications and abbreviated applications required under this section and section 505(k) of the act.Read full regulation →
21CFR600.81§ 600.81 Distribution reports.
(a) Reporting requirements. The applicant must submit to the Center for Biologics Evaluation and Research or the Center for Drug Evaluation and Research, information about the quantity of the product distributed under the biologics license, including the quantity distributed to distributors. The intRead full regulation →
21CFR610.2§ 610.2 Requests for samples and protocols; official release.
(a) Licensed biological products regulated by CBER. Samples of any lot of any licensed product together with the protocols showing results of applicable tests, may at any time be required to be sent to the Director, Center for Biologics Evaluation and Research (see mailing addresses in § 600.2(c) ofRead full regulation →
21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
21CFR207.57§ 207.57 What information must registrants submit when updating listing information and when?
Registrants must review and update listing information at a minimum, as follows:Read full regulation →
21CFR314.105§ 314.105 Approval of an NDA and an ANDA.
(a) FDA will approve an NDA and send the applicant an approval letter if none of the reasons in § 314.125 for refusing to approve the NDA applies. FDA will issue a tentative approval letter if an NDA otherwise meets the requirements for approval under the Federal Food, Drug, and Cosmetic Act, but caRead full regulation →
21CFR610.61§ 610.61 Package label.
The following items shall appear on the label affixed to each package containing a product:Read full regulation →

Enforcement Impact

Deficiencies cited in Warning Letters referencing the same regulations

Misbranded drug

False or misleading claims concerning the compounder

False or misleading risk presentation

Failure to submit under Form FDA-2253

Failure to submit promotional materials

Introduction of misbranded drugs into interstate commerce

Omission of material facts

Introduction of misbranded products into interstate commerce

False or misleading promotional communication

False or misleading claims about efficacy and risks

Recent Cases

Related Warning Letters (10)

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

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