3 ms·

>While several companies have come up with synthetic alternatives for detecting the presence of endotoxins in vaccines, medicine, and medical instruments, LAL i

>While several companies have come up with synthetic alternatives for detecting the presence of endotoxins in vaccines, medicine, and medical instruments, LAL is still the only test that has received FDA approval. I wish they would have elaborated on this. Are the alternatives known to be inferior at this time, or are they promising, but stuck in the long, complicated approval process?

hammock 9y ago
The common sense answer is that an alternative which was inferior would never be developed to the point of submission for FDA approval, as it would not be viable to take to market.
- logicallee 9y ago
  But the article says the crab blood costs $14,000 per quart - if something works "well enough" and can be made synthetically, certainly it could be used in some cases due to the cost alone. For example, consider if there is a simple case where the test is not administered at all today in some cases, due to the cost. (Use your imagination.) In that case "good enough" to quickly administer for a quick read, might well be a very low threshold indeed! Who says "good enough to administer" must be "the best level in existence"?
  - digitalzombie 9y ago
    > "well enough" This is the medical field. There is no well enough. Even modeling for cancer detection we do 95% and medical device they do 99% confidence interval IIRC. And with model, we choose sensitivity over specificity. We rather accidentally diagnosed them with cancer over accidentally say they don't have cancer when they do. Also FDA might have a bar what well enough is, and it could high enough that other companies cannot pass it.
    - logicallee 9y ago
      What makes you think I thought "good enough" means 55% or 60% efficient, or whatever you object to? Good enough might mean 99% of the time. You said it yourself! >Even modeling for cancer detection we do 95% and medical device they do 99% confidence interval IIRC So, in these applications, 95% and 99% respectively is the meaning of good enough. So to put these in crab terms: maybe the crabs do it at 99.99% (3.89 sigma) and the synthetic they want to push through is only 99%, only 2.5 sigma. So I am saying 99% can be good enough in some contexts - just as you've said. Especially if it costs thousands to do it a la crab. It doesn't have to be better than the crabs' blood to be good enough.
sndean 9y ago
AFAIK, they're inferior. But a different, better avenue to avoid using the LAL test is to simply not have endotoxin present in the first place [0]. If at least vaccines and medicines can be produced in strains without LAL-positive LPS, that should lower the test's usage significantly. [0] https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-015-0241-5 https://microbialcellfactories.biomedcentral.com/articles/10...
ajryan 9y ago
I was a software developer at a company that produces LAL-based endotoxin tests. The best alternative[0] is an enzyme produced recombinantly in insect cells. It triggers an enzymatic reaction similar to LAL's (but more complicated). It is effective for testing most of the same products as LAL, and it has been accepted as an "alternative method" by the FDA and European Pharmacopeia. That means it can be used but with more extensive, expensive validation testing. There are some products it's not compatible with, and there is a small set of products that are more easily tested with the alternative enzyme. Also interesting that the article doesn't mention the standard before the LAL method was discovered: rabbits were injected with the test material and monitored for developing a fever. [0](http://www.lonza.com/products-services/pharma-biotech/endotoxin-detection/endotoxin-detection-assays/recombinant-factor-c-assay.aspx http://www.lonza.com/products-services/pharma-biotech/endoto...)

hammock 9y ago

The common sense answer is that an alternative which was inferior would never be developed to the point of submission for FDA approval, as it would not be viable to take to market.

logicallee 9y ago
But the article says the crab blood costs $14,000 per quart - if something works "well enough" and can be made synthetically, certainly it could be used in some cases due to the cost alone. For example, consider if there is a simple case where the test is not administered at all today in some cases, due to the cost. (Use your imagination.) In that case "good enough" to quickly administer for a quick read, might well be a very low threshold indeed! Who says "good enough to administer" must be "the best level in existence"?
- digitalzombie 9y ago
  > "well enough" This is the medical field. There is no well enough. Even modeling for cancer detection we do 95% and medical device they do 99% confidence interval IIRC. And with model, we choose sensitivity over specificity. We rather accidentally diagnosed them with cancer over accidentally say they don't have cancer when they do. Also FDA might have a bar what well enough is, and it could high enough that other companies cannot pass it.
  - logicallee 9y ago
    What makes you think I thought "good enough" means 55% or 60% efficient, or whatever you object to? Good enough might mean 99% of the time. You said it yourself! >Even modeling for cancer detection we do 95% and medical device they do 99% confidence interval IIRC So, in these applications, 95% and 99% respectively is the meaning of good enough. So to put these in crab terms: maybe the crabs do it at 99.99% (3.89 sigma) and the synthetic they want to push through is only 99%, only 2.5 sigma. So I am saying 99% can be good enough in some contexts - just as you've said. Especially if it costs thousands to do it a la crab. It doesn't have to be better than the crabs' blood to be good enough.

sndean 9y ago

AFAIK, they're inferior. But a different, better avenue to avoid using the LAL test is to simply not have endotoxin present in the first place [0]. If at least vaccines and medicines can be produced in strains without LAL-positive LPS, that should lower the test's usage significantly. [0] https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-015-0241-5 https://microbialcellfactories.biomedcentral.com/articles/10...

ajryan 9y ago

I was a software developer at a company that produces LAL-based endotoxin tests. The best alternative[0] is an enzyme produced recombinantly in insect cells. It triggers an enzymatic reaction similar to LAL's (but more complicated). It is effective for testing most of the same products as LAL, and it has been accepted as an "alternative method" by the FDA and European Pharmacopeia. That means it can be used but with more extensive, expensive validation testing. There are some products it's not compatible with, and there is a small set of products that are more easily tested with the alternative enzyme. Also interesting that the article doesn't mention the standard before the LAL method was discovered: rabbits were injected with the test material and monitored for developing a fever. [0](http://www.lonza.com/products-services/pharma-biotech/endotoxin-detection/endotoxin-detection-assays/recombinant-factor-c-assay.aspx http://www.lonza.com/products-services/pharma-biotech/endoto...)