USP〈1085〉GUIDELINES ON TESTS FOR ENDOTOXINS

▲INTRODUCTION

The first version of Bacterial Endotoxins Test 〈85〉 appeared in USP 20–NF 15 (1980). The chapter was subsequently harmonized with the Japanese Pharmacopoeia and European Pharmacopoeia, and the first harmonized chapter appeared in USP 25–NF 20 (2002). Since its first publication, the content has changed very little, but years of experience, increasing knowledge, and more complex parenteral formulations suggest that the basic methodologies described herein could benefit from additional supporting information. The purpose of this general information chapter is to provide additional background information and guidance for the performance and proper application of the compendial bacterial endotoxins tests.

BACKGROUND

Pyrogens, or fever-causing agents, are possible extrinsic contaminants in parenteral products. Many substances can cause fevers when injected, infused, implanted, or when they come in contact with the bloodstream or cerebrospinal fluid of mammals. The predominant and most potent pyrogenic contaminants in the manufacturing of parenteral drugs and medical devices are bacterial endotoxins. Endotoxins are integral with the outer cell membrane of Gram-negative bacteria (GNB). Endotoxins may retain their ability to elicit a pyrogenic response after cells die, so a sterile material may still contain endotoxin. Although some biologics, vaccines, and cell and gene therapies may, by their nature, elicit pyrogenic responses in patients, bacterial endotoxins, when present in parenteral products (including biological products) or medical devices, indicate the presence of GNB at some point during manufacture of the product.

Due to the potential quality and patient safety risks associated with the presence of endotoxins, testing of materials and components used in the process and the final product is required. All laboratories must demonstrate that the chosen bacterial endotoxins test (BET) methodology is suitable for a specific product or material tested according to the applicable BET test for interfering factors, also known as inhibition/enhancement testing or method verification, and consistent with Verification of Compendial Procedures 〈1226〉. This suitability testing will require the following prerequisites:

Calculation or assignment of an endotoxin specification or limit for the material under test and calculation of the maximum valid dilution (MVD). See Method Suitability.

Demonstration that the positive product control (PPC) can be recovered at a dilution of material that does not exceed the MVD as calculated in the applicable BET.

Once assay suitability has been demonstrated, the laboratory may perform routine testing according to the calculations and sample preparation conditions that were described in the suitability study. Changes to those conditions (e.g., the lysate and/or endotoxins source, product component(s), formulation, or changes in manufacturing) are subject to change control and may require that the laboratory repeat the suitability study. An alternative approach for verification within similar product matrices may be used where the worst-case (e.g., most inhibitory) item(s) is defined with appropriate technical rationale and verified as representative of other similar product matrices.

Source from USP and Please refer to USP for details:

https://online.uspnf.com/uspnf/document/2_GUID-CC17E1DF-5576-4A86-90EF-78ED081ECB76_30101_en-US?source=TOC

Polymer Vial for cell and gene therapies

RTU(ready to use) 2ml COP vial