. 2025 May 29;60(9):1209–1217. doi: 10.1038/s41409-025-02637-8

Table 2.

Comparison of the two endotoxin testing methods.

Method	Advantages	Limitations
LAL	- Widely used method. - Three variants available (Gel-clot, Chromogenic, Turbidimetric), providing flexibility based on needs. - The chromogenic method is more sensitive than the gel-clot method and allows for more precise quantification. - The turbidimetric method is faster, making it useful for high-throughput testing.	- The gel-clot method is less sensitive and may lack precision in complex matrices such as cell-based products. - Cellular components or excipients may interfere with the test by masking the presence of endotoxins or disrupting the lysate-endotoxin reaction.
rFC	- Avoids the use of horseshoe crabs, making it more ethical and sustainable. - Offers performance comparable to the LAL test. - Recognized by some regulatory agencies as a valid method for endotoxin detection.	- No specific disadvantages have been mentioned in sources, but as an alternative to the LAL test, it may face similar challenges regarding matrix interference in complex products.

Method

Advantages

Limitations

LAL

- Widely used method.

- Three variants available (Gel-clot, Chromogenic, Turbidimetric), providing flexibility based on needs.

- The chromogenic method is more sensitive than the gel-clot method and allows for more precise quantification.

- The turbidimetric method is faster, making it useful for high-throughput testing.

- The gel-clot method is less sensitive and may lack precision in complex matrices such as cell-based products.

- Cellular components or excipients may interfere with the test by masking the presence of endotoxins or disrupting the lysate-endotoxin reaction.

rFC

- Avoids the use of horseshoe crabs, making it more ethical and sustainable.

- Offers performance comparable to the LAL test. - Recognized by some regulatory agencies as a valid method for endotoxin detection.

- No specific disadvantages have been mentioned in sources, but as an alternative to the LAL test, it may face similar challenges regarding matrix interference in complex products.

Abbreviations: LAL Limulus Amebocyte Lysate; rFC Recombinant Factor C.