Long thread 👇
One of the biggest issues with our drug supply in India is that there is a high probability that what we purchase at the chemist shop/local pharmacy has never been proven to be therapeutically effective. Want to know why? Read on 1/n
One of the biggest issues with our drug supply in India is that there is a high probability that what we purchase at the chemist shop/local pharmacy has never been proven to be therapeutically effective. Want to know why? Read on 1/n
2/n How do you know if a particular drug is actually therapeutically effective against a disease target? Well, it has to go through a series of gates, checkpoints, where it is tested to see if it is therapeutically effective against a particular disease.
3/n For example, there has been a lot of discussion recently about HCQs to treat COVID-19. If you recall, it was first reported that the drug was effective against the virus in-vitro, meaning when tested in a lab, in a petri-dish, the drug killed the virus. We were all excited.
4/n Then what happened? The @WHO designed a study (the Solidarity Trial) to test whether it actually works when given to patients. We found out it does not. The point here is that unless you test it in a clinical study in patients affected by the disease you want to treat,
5/n you cannot say if a drug actually works even if it shows some activity in the lab. PS: Not getting into the prophylaxis issue for now.
Now, how do you know if a Generic drug works? Remember, Generic drugs are supposed to be “identical” copies of innovator drugs that
Now, how do you know if a Generic drug works? Remember, Generic drugs are supposed to be “identical” copies of innovator drugs that
6/n undergo extensive testing for safety and efficacy in clinical studies (like the Solidarity Trial). Identical in this context means it has the same “active ingredient”. Globally accepted regulations allow drug mfgs to substitute different excipients when making a generic drug.
7/n An excipient is a chemical substance that helps “formulate” the drug. For example, in order to make a tablet or a capsule, you may need to add what is called a “binder”, a chemical substance that “binds” the active ingredient and allows it to take the form of a tablet.
8/n Likewise, you may add a sweetener to make the liquid syrup easier to give to children. These excipients have an impact on how the drug works. 6.The way you prove that a generic formulation works “identically” to an innovator drug is by conducting what is called
9/n a bioequivalence study (BE study). These are small scale studies, in healthy volunteers (unlike patients affected by the disease you want to treat) and is of a short duration (usually weeks unlike a clinical study which can run into years). Therefore, they are much
10/n less expensive to conduct. Unlike a clinical trial, the goal of a BE study is to make sure that the drug is “available” in the blood stream of the patient in sufficient quantity for a sufficient amount of time. Remember, we are not testing whether the drug works;
11/n whether it has an acceptable benefit/risk ratio when we do a BE study. We are only interested in making sure that when someone takes that capsule or tablet, enough of the “active ingredient” makes it into the bloodstream. Simply put the drug needs to be able to dissolve and
12/n permeate its way into the bloodstream. The assumption we make here is that if the generic drug formulation “releases” an equivalent amount of active ingredient into the blood stream (become bioavailable), then the active drug will act much like it did when it was tested
13/n in a clinical study. If this dissolution profile does not match the innovator drug, the generic formulation cannot be a substitute for the innovator drug. Bioequivalence testing is a critical quality testing parameter for generic drugs. It ensures that generic drugs have
14/n the same bioavailability as the innovator drug and therefore act in a therapeutically effective manner. Here is the catch:
India did not make BE studies compulsory for all drugs until 2017 and even then, introduced major exceptions by allowing for a 'biowaiver'.
India did not make BE studies compulsory for all drugs until 2017 and even then, introduced major exceptions by allowing for a 'biowaiver'.
15/n So many of the drugs that were approved for marketing prior to 2017 never had to prove that they were bioavailable. Remember excipients? Those can vary widely among all the generic drugs we have on the market.
Remember all those US FDA warning letters for mfg plants?
Remember all those US FDA warning letters for mfg plants?
16/n Those were for not following what are called Good Manufacturing Practices when making the drug. This basically means that the confidence that the US FDA has in the product made in the facility cited that their drug would comply with US standards was low.
17/n If a drug is not properly formulated, it does not become bioavailable in the way it ought to be, which means, it wont be as therapeutically effective as it is supposed to be.
A biowaiver is a request to the regulator @CDSCO_INDIA_INF to allow these companies to market
A biowaiver is a request to the regulator @CDSCO_INDIA_INF to allow these companies to market
18/n their products without proving that they are bioequivalent. This allows for companies to use laboratory data instead of data from healthy human volunteers to get an approval from the regulator to market their drug.
Biowaivers are an evolving area that need to be judged
Biowaivers are an evolving area that need to be judged
19/n on a case-by-case basis. The 2017 rules simply granted a blanket waiver for certain categories which is unacceptable.
Regulations governing BE studies for drugs which are called Narrow Therapeutic Index drugs are very complex. Most CNS drugs, hormone regulation drugs,
Regulations governing BE studies for drugs which are called Narrow Therapeutic Index drugs are very complex. Most CNS drugs, hormone regulation drugs,
20/n drugs that prevent organ transplant rejection etc fall within this category. Here is a good published paper which explains why granting such waivers to these class of drugs is not a good idea: dineshthakur.com/wp-content/upl…
In India, we have a unique problem that exists nowhere
In India, we have a unique problem that exists nowhere
21/n else in the world. Our drug supply is littered with hundreds of what are called Fixed Dose Combination drugs, which The Kakote Committee had called irrational. Remember the SC judgement which set aside the ban on these irrational combinations: fopeindia.in/themes/img/new…
22/n No one knows on what basis were these irrational combinations approved in the first place.
15.We sent one more petition on behalf of CASEM to the Ministry of Health on the issue of bioequivalence testing.
15.We sent one more petition on behalf of CASEM to the Ministry of Health on the issue of bioequivalence testing.
23/n A summary of the petition can be accessed on this blog post: casemindia.org/a-petition-to-…
There are several issues including transparency, reference products, NTI drugs etc. that we tackle in our petition. It is a complicated issue but a crucial one to guarantee quality of
There are several issues including transparency, reference products, NTI drugs etc. that we tackle in our petition. It is a complicated issue but a crucial one to guarantee quality of
24/n our drug supply.
The entire petition can be accessed over here: casemindia.org/wp-content/upl…. Please do read the petition and let us know if you need any thoughts/comments.
We need more public support to force change to improve the quality of our drug supply.
The entire petition can be accessed over here: casemindia.org/wp-content/upl…. Please do read the petition and let us know if you need any thoughts/comments.
We need more public support to force change to improve the quality of our drug supply.
