Description
This guidance provides recommendations for biological product, drug, and device firms on FDA’s current thinking concerning the testing recommendations and acceptance criteria in the United States Pharmacopeia (USP) Chapter Bacterial Endotoxins Test, USP Chapter Transfusion and Infusion Assemblies and Similar Medical Devices, and the Association for the Advancement of Medical Instrumentation (AAMI) ST72:2002/R2010, Bacterial Endotoxins—Test Methodologies, Routine Monitoring, and Alternatives to Batch Testing (AAMI ST72). These three documents describe the fundamental principles of the gel clot, photometric, and kinetic test methods, and recommend that appropriate components and finished products be tested for the presence of pyrogens and endotoxins.
Scope & Applicability
Product Classes
4Medical devices intended for human use; Approved or cleared medical devices
Determining endotoxins limits for products targeting multiple species.
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
Generally recommended for Enhanced Documentation; Regulatory classification mentioned for implantable sensors and HPV tests; Mentioned in the context of an in vitro nucleic acid test for CMV DNA.
Regulatory Context
Attributes
1The dilution of a sample at which the endotoxins limit would be detected.
Identified Hazards
Hazards
2A substance that induces a febrile reaction in a patient.
Pyrogenic substances monitored in cleaning studies
Related CFR Sections (6)
- 21CFR514.1§ 514.1 Applications.
(a) Applications to be filed under section 512(b) of the act shall be submitted in the form and contain the information described in paragraph (b) of this section, as appropriate to support the particular submission. If any part of the application is in a foreign language, an accurate and complete ERead full regulation →
- 21CFR211.160§ 211.160 General requirements.
(a) The establishment of any specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, shall be drafted Read 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 →
- 21CFR814.39§ 814.39 PMA supplements.
(a) After FDA's approval of a PMA, an applicant shall submit a PMA supplement for review and approval by FDA before making a change affecting the safety or effectiveness of the device for which the applicant has an approved PMA, unless the change is of a type for which FDA, under paragraph (e) of thRead 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 →
- 21CFR610.13§ 610.13 Purity.
Products shall be free of extraneous material except that which is unavoidable in the manufacturing process described in the approved biologics license application. In addition, products shall be tested as provided in paragraphs (a) and (b) of this section.Read full regulation →
Related Warning Letters (10)
- 2025-12-09
CGMP/QSR/Medical Devices/Adulterated
Envoy Medical Inc.
- 2025-11-25
CGMP/QSR/Medical Devices/Adulterated
Hong Qiangxing Shenzhen Electronics Limited
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated
Contec Medical Systems Co., Ltd.
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated/Misbranded
Royal Philips
- 2025-10-28
CGMP/QSR/Medical Devices/Adulterated/Misbranded
Qianjiang Kingphar Medical Material Co Ltd.
- 2025-10-21
CGMP/QSR/Medical Devices/Adulterated
LEVO AG
- 2025-10-07
CGMP/QSR/Medical Devices/Adulterated
Technological Medical Advancements LLC
- 2025-09-23
Medical Device/Adulterated/Misbranded/Lacks PMA and/or 510(k)
The Richline Group, Inc.
- 2025-09-16
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA) Adulterated Device
SeniorLife Technologies, Inc.
- 2025-08-26
CGMP/QSR/Medical Devices/Adulterated
Miach Orthopaedics
See Also (8)
- CPG Sec. 460.600 Content Uniformity Testing of Tablets and Capsules (Status: Final)
- Guidance for Industry: Pyrogen and Endotoxins Testing: Questions and Answers (Status: Final)
- Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products: Guidance for Industry (Status: Final)
- BLA for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System: Guidance for Industry (Status: Final)
- Submission of Quality Metrics Data Guidance for Industry (Status: Draft)
- Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act Guidance for Industry: Draft Guidance for Industry (Status: Draft)
- Expiration Dating of Unit-Dose Repackaged Solid Oral Dosage Form Drug Products: Guidance for Industry (Status: Final)
- Development and Submission of Near Infrared Analytical Procedures (Status: Final)