What are endotoxins? They're pieces of the outer coating of certain bacteria that can cause fever and shaking chills when injected. At high levels, they can cause shock, when blood pressure falls dangerously low. The bacteria don't have to be alive.
A pyrogen is a substance that causes fever; endotoxin is one type. Because endotoxin doesn't need living bacteria, a medicine can pass a sterility test and still contain something that makes a person sick.
What are endotoxins in official terms?
CDC puts it plainly: “Endotoxins are harmful substances produced by certain types of bacteria.”
Those bacteria are called Gram-negative bacteria, a group with an extra outer membrane. The material is lipopolysaccharide, or LPS: a molecule made from fat and sugar in that outer coating.
USP, the United States Pharmacopeia, publishes medicine-quality standards. Its General Chapter <85>, Bacterial Endotoxins Test, describes testing for this material.
Why sterility and endotoxin are different checks
Sterile means free of living germs, including bacteria and fungi. Sterilization is the process that removes or kills those germs. It doesn't automatically remove the bacterial material left behind, as Fennrich and colleagues' 2016 review explains.
| Check | The question it answers |
|---|---|
| Sterility | Can living germs grow from the tested samples? |
| Bacterial endotoxin | Is this bacterial material below the limit set for the product? |
| Chemical purity | What does the chemical analysis show about the sample's composition? |
A result in one row cannot stand in for the other two. The tests exist because living germs, bacterial debris and chemical composition are separate problems.
How this shows up in an NAD+ prescription
NAD+ is a molecule cells use in energy-related reactions. On October 30, 2024, FDA warned about food-grade NAD+ being used for intravenous products, meaning products given into a vein, without appropriate processing.
Reported reactions included “severe chills, shaking, vomiting and fatigue.” FDA described them as consistent with excessive endotoxin exposure. That wording identifies a possible explanation; it doesn't prove the cause of every reaction. The NAD+ regulatory guide follows that record.
As of October 29, 2026, the day this article was written, FDA's August 27, 2026 alert describes a similar ingredient problem involving glutathione, another substance made by the body. The glutathione injection illnesses involved compounded products made with an ingredient labeled for dietary supplements.
How bacterial endotoxin testing works
The familiar test uses LAL, short for Limulus amebocyte lysate, a test ingredient extracted from horseshoe crab blood. It reacts to endotoxin. Recombinant factor C, or rFC, is a lab-made version of one crab protein used to detect the same material.
Bolden and colleagues' 2020 review found comparable performance across studies comparing recombinant methods with traditional tests. Neither method measures every possible fever-causing substance.
USP's newer Chapter <86>, Bacterial Endotoxins Test Using Recombinant Reagents, adds methods using test ingredients made without crab blood. It became official in May 2025. Laboratories still need to show that the chosen method works with the material being tested.
As of October 29, 2026, the day this article was written, FDA's August 31, 2026 notice reports that FDA and other regulators jointly reviewed, and in June 2026 approved, one submission to switch several biological products from the horseshoe-crab test to a recombinant endotoxin test. It concerns changing the testing method, rather than removing the test.
The endotoxin limit for injections depends on the product
Results often use endotoxin units, or EU, a measure of how strongly endotoxin reacts in the test. EU is not a count of living bacteria.
The acceptable limit depends on how much medicine could be given and where it enters the body. A concentration per milliliter cannot tell that whole story. FDA's Pyrogen and Endotoxins Testing: Questions and Answers, Edition 2, dated March 2026, says the appropriate way to set a limit is to use the calculation methods in the USP or AAMI standards. Questions 7 and 8 explain why the particular product and process matter.
A test on the raw ingredient and a test on the finished medicine are two different results, and each should name the batch it describes.
What peptide testing needs to show
For a peptide such as BPC-157, a short chain of protein building blocks, an online purity badge leaves the contamination question unanswered. A certificate of analysis needs an identified batch, test method, result and acceptance limit. A vial labeled for laboratory use doesn't establish that those checks happened.
The wider gray-market peptide guide explains what a documented prescription and pharmacy relationship add.
Mistakes that leave injection quality unanswered
“A filter makes it safe.” Ordinary sterilizing filters can remove bacteria while leaving endotoxin behind. FDA's technical guide explains that distinction. Filtration alone cannot establish an unknown vial's suitability for injection.
“No living germs means no contamination.” In Ashraf and colleagues' 2024 Journal of Medical Internet Research test-purchase study, researchers ordered semaglutide from six illegal online pharmacies selling without a prescription; all three vials that arrived contained endotoxin, although none grew living germs. That's a small laboratory sample, not a failure rate for prescribed medications. Our counterfeit Ozempic guide covers the separate question of product authenticity.
“A prescription or approval statement replaces testing.” As of October 29, 2026, the day this article was written, HHS has filed a draft, non-binding policy (October 28, 2026) saying it “does not intend to take enforcement action” against pharmacies or physicians compounding six named peptides, including BPC-157, “when all of the following circumstances are present.” One of those ten conditions is a certificate of analysis for the peptide ingredient, and the policy's testing table lists a bacterial endotoxins test under USP <85> among the checks for injectable forms. The HHS peptide policy explainer covers the rest.
Compounded NAD+ and BPC-157 are not FDA-approved. Compounded semaglutide is different from an FDA-approved product: the formulation offered here is not FDA-approved. A licensed provider may still prescribe — that decision is between you and your doctor. Those facts and the preparation's quality records answer different questions.
Related terms and reactions worth reporting
USP <797> covers preparing sterile compounded medicines. A certificate of analysis reports specified laboratory results. Sterility concerns living germs. Endotoxin concerns one kind of fever-causing bacterial material.
Fever and rigors—intense, uncontrollable shaking—after an injection warrant prompt medical assessment. CDC's guidance identifies difficulty breathing, fainting and signs of shock as reasons for emergency care. Symptoms alone cannot establish what caused a reaction.
A passing result describes what the test could detect in the samples examined. It doesn't examine every container. Ingredient sourcing and preparation controls still matter alongside testing, as FDA's guidance explains.
A licensed U.S. compounding pharmacy can investigate the preparation and its batch records; the prescriber assesses the person's symptoms. Those records connect a prescription to the medicine dispensed and the ingredients used. They make a complaint traceable, even though a prescription cannot guarantee that contamination will never happen.
At Promise, a licensed provider reviews every request, and not everyone qualifies.
