Thread by @PriyankaPulla

A thread on why the rule pushing doctors to write only chemical names of drugs, and not brand names, is a bad idea. (1)

Let's first understand the regulatory system for new drugs the world over. First step: A company develops a new antibiotic, say XYZ, to treat respiratory infections (2)

How is this antibiotic approved? The company is required to do a randomised controlled trial, in which they compare drug XYZ with a control drug. Some sick people get XYZ, while other sick people will get an older antibiotic (3)

If XYZ now cures more people than the older antibiotic, or an equal proportion of people as the older antibiotic (simplifying this immensely), then the country's regulator approves XYZ for use in the country for the respiratory infection (4)

Now, let's say the company had a patent on XYZ for ten years. After 10 years, five more companies want to make XYZ too. In other words, they want to make generic XYZ (5)

These generic manufacturers do not have to do randomised control trials showing that generic XYZ is as effective as innovator XYZ (6)

Instead, the US FDA created a simpler system for them, under the 1984 Hatch Waxman act, to allow generics to come into the market quickly. (7)

Under this act, the 5 generics cos merely need to show bio-equivalence to innovator drug. In other words, they don't need to show generic XYZ cures respiratory infection. They need to show that blood levels of generic XYZ in patients is same as blood levels of innovator XYZ (8)

The principle behind this is: if generic XYZ is chemically equivalent to innovator XYZ (has the same active ingredient, same dissolution rate, similar levels of impurities etc etc), and if it can achieve same blood level as innovator XYZ, it will cure respiratory infection (9)

So, now the generic XYZ maker can avoid costly clinical RCTs showing efficacy against disease. Bio-equivalence (BE ) studies are cheaper. And yet, patients can get the generic drug, for cheaper, and with same efficacy. So, it's a win-win for all (10)

Now, let's see what India did. First, our Indian Pharmacopoeia (which sets standards for *chemical equivalence*) took its own route, separate from US Pharmacopoeia. We decided that we don't need dissolution testing to prove chemical equivalence (11)

So, many drugs didn't need dissolution tests at all. Impurity tests are also laxer. In other words, a generic maker can make XYZ, which they claim is chemically equivalent to innovator, but is isn't chemically equivalent, because it won't dissolve like innovator XYZ does(12)

In other words, Indian law and Indian government are not ensuring chemical equivalence of generic drugs in the Indian Pharmacopoeia. I wrote a 68 page report on it here. Check it out: (13)thakur-foundation.org/project-impact…

Now, let's come to bio-equivalence studies. Our brilliant government, in all their wisdom (and blind kowtowing to the pharma industry) did NOT EVEN REQUIRE bio-equivalence studies for generic drugs until the year 2017 (14)

Until then, CDSCO asked for BE studies only for the first XYZ licensed in India, and any other generics licensed in the next 4 years. After that, companies could make whatever the f*** they wanted, as long as it was chemically equivalent (15)

Now, go back up in my thread, and look at how the criteria for chemical equivalence is already compromised. So, CDSCO and government then did away with BE studies OVER AND ABOVE compromised chemical equivalence criteria (16)

All this was done in the name of cheap medicine, and encouraged by patient-activist groups, who I believe, didn't bother to understand the science (sorry to say) (17)

Today, we have around 60 itraconazole brands in India (maybe even more - 60 is what I counted from online sales websites), all of which follow different standards of chemical equivalence. Some follow US Pharmacopoeia, some follow British, some follow Indian, some follow NONE (18)

The vast majority of these drugs haven't undergone bio-equivalence studies. This is an absolute horror. Ask any doctor who prescribes itraconazole regularly, and they will tell you that J&J's drug is vastly superior (and it's been pushed out of Indian market) (19)

This horrific situation was known to doctors for ages (sadly, not to patients). Just this year, PGIMER published a study measuring innovator itraconazole vs generic, and found major differences (20)onlinelibrary.wiley.com/doi/abs/10.111…

Itraconazole is just the tip of the ice-berg. This can happen to any drug under India's lousy drug regulatory regime. The government knows this (21)

And yet, instead of fixing India's regulatory regime, and retrospectively fixing the MASSIVE problem of lack of chemical and bio-equivalence between generic and innovator drugs, the government gets away with pushing stupid mandates forcing chemical names to be written (22)

So, now, if a doctor knows through experience that some brands work better than others (because of chemical and bio-equivalence), they can't write the name of the brand (23)

Meanwhile, the government is doing absolutely nothing to ensure all generics are the same as innovator drugs, because patients simply don't know, and are being taken for a ride. Please educate yourself. (End) (24/24)