Description
This guidance is intended to help stakeholders develop, maintain, and implement risk management plans (RMPs) to proactively assist in the prevention of human drug product and biological product shortages. RMPs can provide stakeholders with a framework to proactively identify, prioritize, and implement strategies to mitigate hazards that can cause a supply disruption. Such a supply disruption may lead to a drug shortage. Effective quality risk management can facilitate better, more informed decisions; can provide FDA with greater assurance that stakeholders understand and can manage the associated risks; and can potentially affect the extent and level of direct regulatory oversight. Based on recent publications and reports, the majority of drug shortages are associated with quality issues. This guidance describes a framework for stakeholders to consider when developing RMPs that aligns with principles stated in the International Council for Harmonisation (ICH) guidance for industry Q9 Quality Risk Management (June 2006). In addition, FDA also recommends risk factors to consider when developing the content of the RMPs.
Scope & Applicability
Product Classes
4Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
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
Products used in the event of a potential public health emergency
Drug product manufactured by only one entity for sale in the United States.
Stakeholders
7Entity responsible for submitting NDINs
Assess the suitability and competence of potential contractors before outsourcing operations or selecting material suppliers
Assess the suitability and competence of potential contractors before outsourcing operations
Non-traditional manufacturer producing devices designed by an OEM
Facilities referenced in 21 CFR 200.10(b)
Entity that determines materials and services necessary to produce a drug product; Entity responsible for developing the overarching RMP strategy.; Entity responsible for overarching strategy across multiple facilities.
Entities with detailed insight into specific segments of the supply chain; Entity that interprets broader risks within the context of a specific facility.
Regulatory Context
Attributes
3Stability data evaluation beyond the labeled date.
Identify the normal capacity and surge capacity of the facility
Identify the normal capacity and surge capacity of the facility
Identified Hazards
Hazards
5Event that may lead to a drug shortage
Equipment susceptibility to unauthorized access or software vulnerabilities.; equipment or systems used in manufacturing or distribution could be susceptible to cybersecurity threats
The primary risk being mitigated by the RMP.
CARES Act authorities aim to assess, prevent, and mitigate shortages; Risk the Agency efforts to reduce through data visibility
Rise in attacks on drug manufacturers affecting the drug supply chain
Related CFR Sections (10)
- 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 →
- 21CFR310.306§ 310.306 Notification of a permanent discontinuance or an interruption in manufacturing of marketed prescription drugs for human use without approved new drug applications.
(a) Applicability. Marketed prescription drug products that are not the subject of an approved new drug or abbreviated new drug application are subject to this section.Read full regulation →
- 21CFR207.1§ 207.1 What definitions and interpretations of terms apply to this part?
The definitions and interpretations of terms in sections 201 and 510 of the Federal Food, Drug, and Cosmetic Act apply to the terms used in this part, if not otherwise defined in this section. The following definitions apply to this part:Read full regulation →
- 21CFR600.3§ 600.3 Definitions.
As used in this subchapter:Read full regulation →
- 21CFR200.10§ 200.10 Contract facilities (including consulting laboratories) utilized as extramural facilities by pharmaceutical manufacturers.
(a) Section 704(a) of the Federal Food, Drug, and Cosmetic Act specifically authorizes inspection of consulting laboratories as well as any factory, warehouse, or establishment in which prescription drugs are manufactured, processed, packed, or held.Read full regulation →
- 21CFR3.2§ 3.2 Definitions.
For the purpose of this part:Read full regulation →
- 21CFR600.82§ 600.82 Notification of a permanent discontinuance or an interruption in manufacturing.
(a) Notification of a permanent discontinuance or an interruption in manufacturing.Read full regulation →
- 21CFR211.84§ 211.84 Testing and approval or rejection of components, drug product containers, and closures.
(a) Each lot of components, drug product containers, and closures shall be withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit.Read 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 →
Related Warning Letters (10)
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated/Misbranded
Royal Philips
- 2025-10-07
CGMP/QSR/Medical Devices/Adulterated
Technological Medical Advancements LLC
- 2025-08-19
CGMP/QSR/Medical Devices/Adulterated
Les Encres LLC
- 2025-08-05
CGMP/QSR/Medical Devices/Adulterated/Misbranded
Visgeneer, Inc
- 2025-07-29
CGMP/QSR/Medical Devices/Adulterated
Onkos Surgical, Inc.
- 2025-06-24
CGMP/QSR/Medical Devices/Adulterated
Aju Pharm Co., Ltd.
- 2025-05-21
CGMP/QSR/Medical Devices/Adulterated
Kabe Labortechnik GmbH
- 2025-05-20
CGMP/Finished Pharmaceuticals/Adulterated
NWL Netherlands Services B.V.
- 2025-05-20
CGMP/QSR/Medical Devices/Adulterated
NeuroSync, Inc.
- 2025-03-25
CGMP/Finished Pharmaceutical/API/Adulterated
Yangzhou Sion Commodity Co., Ltd.
See Also (8)
- Notifying FDA of a Discontinuance or Interruption in Manufacturing of Finished Products or Active Pharmaceutical Ingredients Under Section 506C of the FD&C Act (Status: Draft)
- Control of Nitrosamine Impurities in Human Drugs: Guidance for Industry (Status: Final)
- Submission of Quality Metrics Data Guidance for Industry (Status: Draft)
- Compounded Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act Guidance for Industry (Status: Final)
- Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry (Status: Final)
- Evaluation of Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act (Status: Final)
- Drug Master Files Guidance for Industry (Status: Draft)
- Chemistry, Manufacturing, and Controls Changes to an Approved Application: Certain Biological Products: Guidance for Industry (Status: Final)