Guidance for Industry: Pyrogen and Endotoxins Testing: Questions and Answers

Description

1. How do I establish a sampling plan for in-process testing and finished product release?2. When is retesting appropriate?3. Is sample storage and handling important?4. Can finished product samples for analysis of bacterial endotoxins be pooled into a composite sample prior to analysis?5. May a firm use alternative assays to those in the USP for a compendial article?6. What is the best process for transitioning from one alternate bacterial endotoxins test (BET) method to another?7. What happened to the endotoxins limit table in Appendix E of the 1987 Guidance?8. How can Quality by Design concepts support endotoxins limits?9. When is the USP Chapter <151> Pyrogenicity Test (the rabbit pyrogen test) appropriate?10. How would an appropriate endotoxins limit be determined for a veterinary product that targets multiple species?11. What are the endotoxins limits for medical devices?12. What is the FDA’s expectation for regular screening of therapeutic drug products?13. Are control standard endotoxins still acceptable for use in running BETs?

Scope & Applicability

Regulatory Context

• 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 →

• 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 →

• 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 →

• CGMP/QSR/Medical Devices/Adulterated

  Aju Pharm Co., Ltd.

  2025-06-24

• CGMP/QSR/Medical Devices/Adulterated

  Rolence Ent. Inc.

  2024-11-08

• CGMP/QSR/Medical Devices/Adulterated

  Optikem International, Inc.

  2024-09-10

• CGMP/QSR/Medical Devices/Adulterated

  Deymed Diagnostic s.r.o.

  2024-01-09

• Medical Device/Adulterated/Misbranded/Lacks PMA and/or 510(k)

  North American Diagnostics, LLC

  2023-04-18

• CGMP/QSR/Medical Devices/Adulterated

  Global Medical Production Co Ltd

  2021-12-21

• CGMP/QSR/Medical Devices/Adulterated

  Magnolia Medical Technologies, Inc.

  2021-10-19

• CGMP/Finished Pharmaceuticals/Adulterated

  Absara Cosmetics S.A.P.I DE C.V.

  2021-02-23

• CGMP/Finished Pharmaceuticals/Adulterated

  Clientele, Inc.

  2020-12-29

• CGMP/QSR/Medical Devices/Adulterated

  Unetixs Vascular, Inc.

  2020-02-25

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