Executive Summary
- This article describes our testing of Ivermectin bioequivalence.
Introduction
- A significant issue with the FDA is that they do not appropriately test manufacturing facilities; in particular, their testing is far worse in foreign manufacturing facilities. This has created a dual pricing market, where the IVM from the higher quality countries is very expensive — even though the item is generic.
- Then, inexpensive sources are of dubious bioequivalence.
- The case of IVM is why it is not as simple as a drug simply becoming a generic, and then the price becomes reasonable for a high-quality source.
The Problem With the FDA’s Lack of Testing and Bioequivalence Curves
The FDA does not test the outcomes of drugs in people but instead allows manufacturers to submit bioequivalence tests performed in labs. However, the standards for measuring bioequivalence are very low.
This is explained by the following quote from the book Bottle of Lies.
Patients getting switched from one generic to another might be on the low end one day; the high end the next. The FDA allowed drug companies to use different additional ingredients, known as excipients, that could be of lower quality.
Those differences could affect a drug’s bioavailability, the amount of drug potentially absorbed into the bloodstream.
And there is more to it — because the amount of API or active pharmaceutical ingredient can be reduced to save costs.
But there was another problem that really drew Graedon’s attention.
Generic drug companies submitted the results of patients’ blood tests in the form of bioequivalence curves. The graphs consisted o a vertical axis called Cmax, which mapped the maximum concentration of drugs in the blood, and a horizontal axis called Tmax, the time-to maximum concentration. The resulting curve looked like an upside-down U.
The FDA was using the highest point on that curve, peak drug concentration, to assess the rate of absorption into the blood. But peak drug concentration, the point at which the blood had absorbed the largest amount of drug, was a single number at one point in time. The FDA was using that point as a stand-in or “rate of absorption.” So long as the generic hit a similar peak o drug concentration in the blood as the brand name, it could be deemed bioequivalent, even the two curves reflecting the time to that peak looked totally different.
Two different curves indicated two entirely different experiences in the body, Graedon realized.
This perfectly illustrates that even when testing is done, the FDA has very low standards that make it easy for generic drug manufacturers to game.
The measurement of time to maximum concentration, the horizontal axis, was crucial or time-release drugs, which had not been widely available when the DA first cre-ated its bioequivalence standard in 1992. That standard had not been significantly updated since then. “The time to Tmax can vary all over the place and they don’t give a damn.”
Yes, the FDA does not place any type of priority of drug quality. Remember, the FDA does not, in a practical sense, work for the public or in the public interest — they work for pharmaceutical companies, but they happen to take in US taxpayer dollars and also getting directly paid by pharmaceutical companies — funding they are only allowed to use to approving drugs, not for any other purpose like say — adverse event reporting. However, the FDA cannot be transferred to Pfizer or Merck because it would not “send the right message.”
The Problem With Lab Testing
Many people have taken drug tests for recreational drug testing and see how quick, easy, and widely available they are and will often assume that the same type of kits are available for testing pharmaceuticals. There is a chasm between the ubiquitousness of illegal recreational drug testing and testing for APIs and impurities. The market for drug testing kits is very much organized around illegal recreational drug testing, and they have very convenient testing. The chemical profiles of those types of drugs are well-published and standardized, and because of the high volume of recreational drug testing, companies have created low-cost kits that are widely used. This is not the case for APIs and excipients (the other stuff in the pill).
In order to perform lab testing, one would need to get and be able to use one of a few types of spectrometry machines. This is not only a significant investment in terms of the machines, but they require specialized understanding to operate correctly. Some labs might do this type fo testing, but there are a few problems with this in that the business we would be able to offer them would be low. Recreational drug testing labs are used to low volume “consumer” walk-ins, but labs that test APIs are not set up like that.
Lab testing is the appropriate way to go for repetitive testing, but it is distinctly inferior to testing in animals or humans.
How We Tested
We have stepped in to address this issue by performing our independent testing but by doing actual animal testing. Technical lab tests are far less accurate than tests with real subjects. However, the problem is that many things that Ivermectin is helpful for are difficult and expensive to test. So we needed to find an outcome that was easy to observe and test. Luckily, this outcome is known and goes back to the origin of the drug.
Description of The Test
Over two months, we purchased and tested several products for their most easily observable and measurable item: effectiveness against parasites. As we cover in detail in articles for subscribers at this site, Ivermectin is effective against many things; however, parasites are the most measurable thing to test. As soon as the item is effective against parasites, its other benefits can be realized.
Why We Were Able to Test in a Reliable Fashion
The initial tests of Ivermectin were published, and we copied those tests. However, all of our tests were with well-priced generics.
Mites will often infect the interior of the large ears of rabbits — and rabbits, which is where we apply the mites, are easy to infect with mites, and it is straightforward to measure when the mites have been cleared from the rabbits. Mites are a common parasitic infection for rabbits in the wild. The testing is also humane as the mites are not very painful for the rabbits, mainly if the style is cleared quickly and the testing process can clear them. Rabbits in the wild that have mites will often result in skin damage to the ear as the mites burrow and reproduce. IVM works quickly as if the IVM is high quality; the mites are impacted rapidly by the IVM and will begin to die as their neurological system is affected by the IVM. Rabbits are treated with IVM, with a 200-400 mcg/kg dosage, SC, two or three treatments 10-21 days apart.
Where We Obtained the Testing Protocol
We followed this well-established protocol that we found reading the research into animal testing. IVM works the same way in humans as it does in animals. However, we tested human IVM on rabbits. Finally, if a less effective brand does not give the desired outcome, all rabbits are given the most effective brand at the end of the test. We currently have 6 of these testing rabbits, and they are great pets and test subjects, are well cared for, and have an open area where they forage in a controlled setting.
Performing Effective Comparison Testing
Because mite infection, growth, and elimination in rabbits are measurable, we were able to test the effectiveness of IVM between different manufactured items. This test is also “real world” as it is tested in animals with measurable outcomes.
Covering Testing Costs
Subscribers receive our most up-to-date testing. After weeks of discussions with a supplier to carry the IVM that passed our tests, they have just brought their website for those we recommend to them online.
Our Testing Frequency
So far, we have gone through three rounds of testing. Because we are using animals, we can’t test as frequently as if we used a specialized lab testing machine — however, we consider animal testing far more accurate than using a lab testing machine and comparing curves between the original Merck product and different generic versions of Ivermectin. We are unsure where our testing will go as we have already received several requests from companies to do testing they can use. But as for now, all of our testing has been done with animals. Also, because we don’t use a machine, we don’t have a specific bioequivalence percentage — of, say, this tested Ivermectin is “93%” of the original Merck product. Instead, we record the effect on the rabbits for how quickly the mites drop off. Our testing and the Ivermectin we selected for Summit Products to carry are roughly the same as those of the rabbits who were given Merck Ivermectin. At a certain point, it becomes difficult to distinguish the effect when it is close, as there are also variances between the individual animals and how the drug is processed. Just as with humans, not all rabbits have the same immune system.
One question we have received is whether it is possible for the manufacturer of the Ivermectin that Summit Products carries to change something, making the drug less effective. The answer is that it is possible. The only way to stop this would be to run a sample of each batch of the product received by Summit through a lab machine and then compare it to the last tested batch and Merck’s original product. We have never stated that we are doing this. Rather we are performing periodic testing. As per the request I mentioned, we have been asked to get into testing more, but I am not clear that we are interested in running a pharmaceutical testing lab that constantly tests new orders. That is a very different business than the one we are in.
A Question on Which Version of Ivermectin to Buy
I received this question on Ivermectin, which was used against cancer in studies.
All the studies I have read on ivermectin didn’t use your brand and yet it still worked.
This question assumes that the Ivermectin in any study versus cancer is the same as the Ivermectin that a person would purchase. It implies a level of standardization that does not exist. When one looks at studies on drugs, they typically use the original drug. So, in this case, it would be Merck’s Ivermectin.
They usually don’t state the drug version they use in the study, but that is typically what is done. Those who run the study do this to remove the issue of variance in the active pharmaceutical ingredient, and it is not only the API that is different between the original drug and a generic.
However, to duplicate the effect, buying Merck’s Ivermectin is expensive. The Ivermectin that most people purchase is made in India which has no bioequivalence or safety regulation. The FDA also does nothing to test drugs, particularly those manufactured outside the US. I cover this topic, which is very little know at a number of articles at the site, which you can see at the Drug Sourcing Article Index.
We tested a number of Indian versions of Ivermectin to arrive at the one we ended up partnering with Summit to carry, the one with the highest bioequivalence to the original Merck product.
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