Description
This guidance is intended to help positron emission tomography (PET) drug producers better understand FDA’s thinking concerning compliance with the current good manufacturing practice (CGMP) regulations. The guidance addresses resources, procedures, and documentation for all PET drug production facilities, academic and commercial. In some cases, the guidance provides practical examples of methods or procedures that PET drug production facilities can use to comply with the CGMP requirements.
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
1Guidance focuses on oversight of positron emission tomography drugs; Positron Emission Tomography drugs subject to specific ANDA policies; Regulatory scenarios for PET NDA and ANDA submissions
Stakeholders
6Entities responsible for compliance with CGMP regulations.
reviews laboratory testing and batch records for release
Person whose actions may cause a product to be deemed adulterated
outsourced operation provider
Individuals with access to label storage or signing certificates
committee that approves human research using radioactive drugs
Regulatory Context
Regulatory Activities
4New Drug Application
Regulatory pathway for terminal sterilization without sterility testing
Abbreviated New Drug Application
Investigational New Drug submissions
Document Types
10Standardized records for manufacturing processes; must be prepared, dated, and signed to assure uniformity
Records of written and oral complaints
Records maintained to facilitate location of recalled products
Reporting category for minor changes like removing a color additive
Records documenting the manufacturing of a batch
Created for each new batch to document production and testing
Electronic workflow requiring validation
Document indicating analytical results of testing; record relied on to control L. monocytogenes in ingredients; document provided for a food prior to or upon receipt of the food; COA documentation
Reviewed for accuracy and completeness before final release.
Records documenting the production of a specific batch; must be prepared for each batch of medical gas produced
Attributes
5Requirements for staff involved in PET drug production.
Should be approximately 95% to minimize artifactual results.
Required record element for investigational product management.
Requirement for devices provided sterile or non-sterile
Labeling status for incoming materials before release
Technical Details
Substances
6The final product form requiring specific microbiological controls.
used for final rinses in depyrogenation by washing
Active ingredient in the proposed generic and RLD
Example of a PET drug where finished-product testing ensures correct components; Example of a PET drug where identity is established during finished-product testing; every batch undergoes full finished-product testing (e.g., FDG F 18); example of PET drug where kryptofix may be a specific impurity
examples of such components include but are not limited to the active moiety (API)
Wipe with an appropriate disinfectant such as sterile 70 percent isopropyl alcohol.
Testing Methods
10Testing used to justify leveraging data across products
Quality control testing performed prior to final labeling
PQIT is a noncritical test performed in addition to specification tests
Methods that can distinguish degradation products and impurities
Used to verify that the measurement system and analytical operations are fit for purpose.
Gas Chromatography used for impurities or assay.
High-Performance Liquid Chromatography used for impurities or assay.
validated filter integrity test
Integrity testing of membrane filters should always be performed postfiltration
Failure to conduct media fills that closely simulate aseptic production operations
Processes
8implied manufacturing process under QS regulation
End-user sterilization validation
Required for parenteral interventions and biopsies.
Sterilization and depyrogenation validation; Changes in vial sterilization or depyrogenation method
Microbiological control process for PET drugs; Part of the synthesis and purification of PET drugs; drug is considered to be nonsterile until it is passed through a sterilizing grade filter
Required for contaminated equipment and media before disposal
Primary process described in the guideline; Core activity described in the guidance; General process for evaluating product quality over time; Formal stability studies to assess adjuvant stability; Evaluation of attributes at all storage conditions; The process of evaluating product quality over time under specified conditions.; Evaluation of product quality over time
Sterilization method for drug products
Clinical Concepts
1Increased risk when daily wear lenses are worn overnight
Identified Hazards
Hazards
6Environmental factors affecting biological products
radiation-related stability concern for PET drugs
risk in transfer lines and resin columns
risk in multidose drug products
Risk addressed by pyrogenicity testing
automated liquid handling systems can pose a risk of contamination within or between test runs
Standards & References
External Standards
10Validation of Compendial Procedures
Automated Radiochemical Synthesis Apparatus
Endotoxin should be assessed following USP <85> Bacterial Endotoxins Test.
Sterility testing may be performed in accordance with USP <71>.
Radiopharmaceuticals for Positron Emission Tomography — Compounding
United States Pharmacopeia standard for Injections.
Bacterial endotoxins testing standard; Endotoxin limits for subcutaneous administration
Sterility Tests
Validation of Compendial Procedures
United States Pharmacopeia standards for compendial drug substances; confirming conformance to the application-approved specification and USP
Specifications
3limits for solid state form and particle size; Tightening acceptance criteria; Numerical limits or ranges for tests
Review of complaints to determine if product met specifications
The minimum percentage of yield requiring investigation if not met.
ICH References (1)
Text on Validation of Analytical Procedures
Related CFR Sections (17)
- 21CFR212.110§ 212.110 How must I maintain records of my production of PET drugs?
(a) Record availability. Records must be maintained at the PET drug production facility or another location that is reasonably accessible to responsible officials of the production facility and to employees of FDA designated to perform inspections.Read full regulation →
- 21CFR212.100§ 212.100 What do I do if I receive a complaint about a PET drug product produced at my facility?
(a) Written complaint procedures. You must develop and follow written procedures for the receipt and handling of all complaints concerning the quality or purity of, or possible adverse reactions to, a PET drug product.Read full regulation →
- 21CFR212.90§ 212.90 What actions must I take to control the distribution of PET drug products?
(a) Written distribution procedures. You must establish, maintain, and follow written procedures for the control of distribution of PET drug products shipped from the PET drug production facility to ensure that the method of shipping chosen will not adversely affect the identity, purity, or quality Read full regulation →
- 21CFR212.80§ 212.80 What are the requirements associated with labeling and packaging PET drug products?
(a) A PET drug product must be suitably labeled and packaged to protect the product from alteration, contamination, and damage during the established conditions of shipping, distribution, handling, and use.Read full regulation →
- 21CFR212.71§ 212.71 What actions must I take if a batch of PET drug product does not conform to specifications?
(a) Rejection of nonconforming product. You must reject a batch of a PET drug product that does not conform to specifications. You must have and follow procedures to identify and segregate the product to avoid mix-ups. You must have and follow procedures to investigate the cause(s) of the nonconformRead full regulation →
- 21CFR212.70§ 212.70 What controls and acceptance criteria must I have for my finished PET drug products?
(a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity, and, if appropriate, sterility and pyrogens.Read full regulation →
- 21CFR314.50§ 314.50 Content and format of an NDA.
NDAs and supplements to approved NDAs are required to be submitted in the form and contain the information, as appropriate for the particular submission, required under this section. Three copies of the NDA are required: An archival copy, a review copy, and a field copy. An NDA for a new chemical enRead full regulation →
- 21CFR212.61§ 212.61 What must I do to ensure the stability of my PET drug products through expiry?
(a) Stability testing program. You must establish, follow, and maintain a written testing program to assess the stability characteristics of your PET drug products. The test methods must be reliable, meaningful, and specific. The samples tested for stability must be representative of the lot or batcRead full regulation →
- 21CFR212.60§ 212.60 What requirements apply to the laboratories where I test components, in-process materials, and finished PET drug products?
(a) Testing procedures. Each laboratory used to conduct testing of components, in-process materials, and finished PET drug products must have and follow written procedures for the conduct of each test and for the documentation of the results.Read full regulation →
- 21CFR314.70§ 314.70 Supplements and other changes to an approved NDA.
(a) Changes to an approved NDA.Read full regulation →
- 21CFR212.50§ 212.50 What production and process controls must I have?
You must have adequate production and process controls to ensure the consistent production of a PET drug that meets the applicable standards of identity, strength, quality, and purity.Read full regulation →
- 21CFR212.40§ 212.40 How must I control the components I use to produce PET drugs and the containers and closures I package them in?
(a) Written procedures. You must establish, maintain, and follow written procedures describing the receipt, login, identification, storage, handling, testing, and acceptance and/or rejection of components and drug product containers and closures. The procedures must be adequate to ensure that the coRead full regulation →
- 21CFR212.5§ 212.5 To what drugs do the regulations in this part apply?
(a) Application solely to PET drugs. The regulations in this part apply only to the production, quality assurance, holding, and distribution of PET drugs. Any human drug that does not meet the definition of a PET drug must be manufactured in accordance with the current good manufacturing practice reRead full regulation →
- 21CFR212.10§ 212.10 What personnel and resources must I have?
You must have a sufficient number of personnel with the necessary education, background, training, and experience to perform their assigned functions. You must have adequate resources, including facilities and equipment, to enable your personnel to perform their functions.Read full regulation →
- 21CFR212.20§ 212.20 What activities must I perform to ensure drug quality?
(a) Production operations. You must oversee production operations to ensure that each PET drug meets the requirements of the act as to safety and has the identity and strength, and meets the quality and purity characteristics, that it is supposed to have.Read full regulation →
- 21CFR361.1§ 361.1 Radioactive drugs for certain research uses.
(a) Radioactive drugs (as defined in § 310.3(n) of this chapter ) are generally recognized as safe and effective when administered, under the conditions set forth in paragraph (b) of this section, to human research subjects during the course of a research project intended to obtain basic informationRead full regulation →
- 21CFR212.30§ 212.30 What requirements must my facilities and equipment meet?
(a) Facilities. You must provide adequate facilities to ensure the orderly handling of materials and equipment, the prevention of mix-ups, and the prevention of contamination of equipment or product by substances, personnel, or environmental conditions that could reasonably be expected to have an adRead full regulation →
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 2026-02-24
CGMP/Finished Pharmaceuticals/Adulterated
AQ USA Inc., d.b.a Ross Healthcare Inc.
- 2026-02-24
Compounding Pharmacy/Adulterated Drug Products
MedisourceRx
- 2026-02-24
CGMP/Finished Pharmaceuticals/Adulterated
A. Nelson & Co. Ltd.
- 2026-02-17
CGMP/Finished Pharmaceuticals/Adulterated
Cosmetic Manufacturers Pty Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
Related Warning Letters (10)
- 2026-02-24
CGMP/Finished Pharmaceuticals/Adulterated
AQ USA Inc., d.b.a Ross Healthcare Inc.
- 2026-02-24
Compounding Pharmacy/Adulterated Drug Products
MedisourceRx
- 2026-02-24
CGMP/Finished Pharmaceuticals/Adulterated
A. Nelson & Co. Ltd.
- 2026-02-17
CGMP/Finished Pharmaceuticals/Adulterated
Cosmetic Manufacturers Pty Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
SV Labs Corporation
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Guangdong Renhe Guozhuang Biotechnology Co., Ltd.
- 2025-12-23
CGMP/Finished Pharmaceuticals/Adulterated
Medinatura New Mexico, Inc.
- 2025-12-16
CGMP/Positron Emission Tomography (PET) Drugs/Adulterated
3D Imaging Drug Design and Development LLC
- 2025-12-16
CGMP/Finished Pharmaceuticals/Adulterated
Sklar Personal Care Inc.
- 2025-12-16
CGMP/Deviations/Biologics License Application (BLA)
Microvascular Tissue, Inc.
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Current Good Manufacturing Practice for Phase 1 Investigational Drugs: Guidance for Industry (Status: Final)
- PET Drugs--Current Good Manufacturing Practice (CGMP); Small Entity Compliance Guide (Status: Final)
- PET Drug Applications - Content and Format for NDAs and ANDAs_2011 (Status: Final)
- Media Fills for Validation of Aseptic Preparations for Positron Emission Tomography (Status: Final)
- Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs (Status: Final)
- FDA Oversight of PET Drug Products -- Questions and Answers (Status: Final)
- Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance (Status: Final)
- Data Integrity and Compliance With Drug CGMP: Questions and Answers: Guidance for Industry (Status: Final)