In the US to market a generic you need to show that it’s the same as an existing approved product currently on the market.

To avoid genetics being produced companies withdraw products where patent coverage has expired. They then release a new product which is substantially the same and has no or minor benefits, but is covered by patents.

Because the old product is no longer on the market, the FDA will not approve a generic. Even though the exact same product /was/ on the market.

This seems like a weird interaction between patents and the FDA rules which wouldn’t occur in the same way elsewhere (seems like the FDA rules kind of suck to me at first glance).

There’s more information in the lawsuit here:

https://casefilingsalert.com/wp-content/uploads/2022/08/GSK-...

On a related note, you don't need to show that it's actually the same, just that it's close enough. And that doesn't always work out for the best. An easy example being anticonvulsants. My younger brother died from an epileptic seizure and post-death examination determined the active ingredient of the anticonvulsant he was taking wasn't present in his blood. He had just been switched from brand-name to generic. Come to find out that this is/was a known issue that the FDA hadn't figured out how to solve. The generics aren't made using the same process and the end result isn't identical to the real drug.

This isn't the case, it doesn't need to still be on the market.

However if the approved product was produced with chemicals that are now banned (or the approved drug itself was banned) - then you _can't_ make a generic because you would have to use a banned chemical to do it.

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Similar shenanigans to prevent generics include slightly modifying existing generics like ketamine for example, before getting it approved for depression treatment. You cannot patent ketamine for depression, so you can slightly modify it and patent that instead.

That's not a requirement to get a generic approved.

As long as a molecule has been approved before (through a New Drug Application), all follow-on drugs get approved through an ANDA (Abbreviated New Drug Application).

The real reason why inhalers are so hard to make generics for is that it's not just a drug - it's a delivery system, which is way more technologically complex than just producing a bunch of a chemical and putting it in pills.

Generic companies aren't interested in the investment. Having a factory make a ton of drug is cheap for the most part. You can put it in pills can cost a few cents per pill.

Investing in a new inhaler device is a major investment. Kind of similar to how generic injectable drugs is not as attractive - the investment is much higher.

Because of the complexities of producing drug-device combinations like inhalers, the Food and Drug Administration employs a special set of regulatory requirements when approving generic inhalers.

Specifically, when a brand-name manufacturer lists a patent for a product with the Food and Drug Administration (FDA), the FDA is prohibited from approving the generic version of that product until the patent protection expires or is challenged and overturned.

If someone wants to make a generic, not only does the drug patent need to expire, but also the device patent.

But nothing stops a company from developing their own device. The issue is that it won't be a generic - it will be a new inhaler.

That's expensive to do.

But there are shenanigans that can happen there. IIRC, to get a new generic approved, you have to demonstrate it's the same as the existing generics, which requires a supply of that drug. Years ago I read a company (it might have been one of Martin Shkreli's) that played a trick with that:

1. they manufactured a generic drug,

2. put extreme restrictions on its supply chain so no competitor could get ahold of enough of their product to do the equivalency testing, and

3. jacked up the price to an extreme degree.

We went from "let's put this stuff into every household item, and release it into the atmosphere by the billions of tons" to "nothing must ever contain CFCs ever again, including critical medical products that use only insignificant amounts".

Similar mistakes were made with asbestos and dental amalgam, where the panicked removal often released more contaminants than would have been during the item's entire lifetime otherwise, and the substitute materials were later found to have their own problems.

There's a big lesson in this for future regulatory action regarding environmental issues.

I used to love removing those little lead pellets from curtain weight ropes. It wouldn't have crossed my mind to so much as wash my hands afterwards. I've seen children chewing on fishing lead, and nobody seemed to even be aware there's a risk involved.

I mean, people used to ADD LEAD TO THEIR WINE(!!!) by the grams to give it that "heavy sweetness". Still, it took centuries for the population at large to notice that this might be a problem.

> Nah, that's not how any of it works, you can stop fearmongering. Even if so, it's not lead but a material composed with lead atoms, just like how lead is used now in many alloys without danger. I don't understand the low key fearmongering.

Nah, that's not fearmongering. That is plain reasoning within the context of a valid concerned discussion of lead.

Previous uses of lead, historically incorrectly assumed to be (using your words) "without danger", have been phased out for a long time (e.g. lead additives for car gasoline), or are being actively replaced (e.g. lead-based water pipes in homes). https://www.epa.gov/lead/learn-about-lead

LK-99, the possible superconductor implied in adastra22's lead apatite comment, is 74 percent lead by mass.

Due to lead's negative environmental and health impacts ( https://echa.europa.eu/hot-topics/lead ) it is regulated e.g. by REACH ( https://en.wikipedia.org/wiki/Registration,_Evaluation,_Auth... ) and the Toxic Substances Control Act of 1976 ( https://en.wikipedia.org/wiki/Toxic_Substances_Control_Act_o... ).

I up the ante: imagine lead-based superconductor technology becomes a mass market reality, and therefore lead would be used in everyday appliances such as electrical cables, floating toys etc.

Nobody wants bulk masses of lead landing in trash uncontrollably.

If your only concern is the lead landing in trash uncontrollably, you can solve it by just controlling the trash (we mostly do that already).

Lead has been phased out because of direct contamination and environment contamination. A chemically stable superconductor tape won't be a problem for either of those.

The manufacturing process will probably be much more of a problem, but again, it's a matter of solving that problem.

And it isn't a hole, it is needed for anti-knock. Most General Aviation (GA) Planes really do run on very basic carb systems (with magnetos!) and believe me, the Air Fuel (AF) mixture is a big deal when you are at 10,000 feet or so, especially when it is warm.

When it's cold it's easier to fly, and also less lead is needed AFAIK.

> There were a few exceptions for "essential uses" where no acceptable substitutes were initially found (for example, in the past metered dose inhalers commonly used to treat asthma and chronic obstructive pulmonary disease were exempt) or Halon fire suppression systems used in submarines and aircraft (but not in general industry).

You write "and the substitute materials were later found to have their own problems."

Could you be more specific? I mean, there's no wonder material that has no problems. I don't think you mean that trivial observation, so do you mean the substitutes overall were more harmful than asbestos, across the full product cycle from mining to disposal?

And, does "the panicked removal" mean to include the use of unlicensed workers not following legal requirements for removal? As I recall, predatory contractors did take advantage of the situation, but then what's the lesson - that we need more government oversight of all building contract work?

The scare is that amalgamated filings contained mercury. The thing is that they were bonded with silver which made them safe.

The thing is that some dentists are often removing them, to replace with other filings. The process exposes patient to mercury and the alternative filings often don't last as long as the amalgamated one.

Even limiting it to dental amalgam, p-e-w says there is a lesson for future regulatory action. What is that lesson?

I don't recall the government ever said amalgam fillings should be removed, and the FDA now certainly says to leave them in: https://www.fda.gov/medical-devices/dental-devices/dental-am...

https://en.wikipedia.org/wiki/Dental_amalgam_controversy makes it seem like much of the controversy came from people "using pseudoscience to scare patients into more lucrative treatment options", not the government. The major new regulations in the US seems to be installing filters at the dentists' to keep mercury waste out of the public sewer system.

I therefore don't see the lesson from regulating CFCs, nor from asbestos, nor from dental amalgam.

https://www.bbc.com/future/article/20220321-what-happened-to...

We have sadly not applied the same ideas to asbestos. We definitely need to. And to many other terrible materials that poison us and our environment all the time (like PFAS).

This was not a mistake. It was a humanity saving decision. It's the blueprint to save us from the climate catastrophe.

That's one lesson. Another lesson is that when powerful people take such celebrated "decisive" action, less powerful people get trampled underfoot, in this case through potentially crippling medical costs.

> This was not a mistake. It was a humanity saving decision.

The phasing out of CFCs was not a mistake. The way it was implemented, however, contained many mistakes, some of which have negatively impacted many lives, as illustrated by the top-level comment.

The problem isn't that CFC got removed. The problem is that a new patent got granted for an insignificant change. Why that change happened in the first place doesn't matter.

They caused massive damage to the planet. And they continue to do so, the CFCs they emitted will be in the atmosphere for decades.

https://downloads.hindawi.com/journals/crj/1998/137198.pdf In 1991 metered inhalers were responsible for 1% of all CFCs. Since then production has gone down 30-fold https://i0.wp.com/research.csiro.au/acc/wp-content/uploads/s...

Had we done nothing, CFCs from inhalers would be something like 1/3rd of total emissions right now (simply because of the drop). But it's far worse. The world population is much higher now, and healthcare is much more accessible around the world. India, China, the Philippines, many countries with hundreds of millions of people can now prescribe them; they were never included in any 1991 numbers because their healthcare systems weren't that well developed back then. If you factor all of those people in, the majority of CFCs would be emitted by inhalers.

CFCs and Inhalers are a significant problem. No one deserves to get skin cancer because of CFCs.

You should blame manufacturers and the insane patent system, not the scientists working hard to keep the planet from dying.

I really think we are looking at a case of "corruption harms people" and not one of "unintended side effects should be looked upon".

Removing asbestos causes its own problems and if not done correctly can cause more damage than just leaving it alone. Obviously we should never use asbestos as building material again, and when we run across it while renovating or demolishing a building, it should be dealt with correctly, but proactively going into buildings and ripping out asbestos that isn't being disturbed might not be the best way to go.

But yeah also there's totally unlicensed folks ripping lagging off old boilers in a t-shirt. No worries, they usually filter it thru a cigarette.

On the issue of patent vs exclusivity https://www.fda.gov/drugs/development-approval-process-drugs...

https://www.alldaychemist.com/

They're like $6 each if you buy them from this pharmacy in India. $600 Advair inhalers are $30-ish. The website I linked doesn't even ask for a prescription.

I buy them by the dozens. I never run out anymore. (It's good to over order, as it takes 6-8 weeks for delivery to the US.)

Separately, note that there is supposedly a temporary worldwide albuterol inhaler production shortage, so maybe don't over order this quarter.

Note that almost none of the drugs offered at these shops are FDA-approved. The Indian ones are mostly produced in accordance with the regulations of the local Indian counterpart to the FDA (generically, the NRA of the country is CDSCO). Some of the Indian drugs are counterfeits though, not produced in accordance with CDSCO rules but falsely labeled as such.

The Chinese chemical distributors are even less stringent -- for those you absolutely should provide your own QA/QC by getting an HPLC/etc test done by an independent lab ($100 or so per compound tested).

But after switching I find that for me, inhalers without propellant works just as well or better than the ones without.

Since the propellant seems to be the problem in this case. It could be worth checking if the generics or even the GSK non propellant ones, are cheaper than the other one in the USA?

"New drug exclusivity" is an FDA regulation separate from patents. Basically you get a minimum of 5 year exclusivity for new molecular entities, and you can add on another couple years if it's a rare disease.

Even generic drugs get 6 months exclusivity.

Meanwhile, in Australia where I lived for several years, you could still go to a chemist and just buy an inhaler.

Someone please correct me if I'm wrong.

The Montreal Accords, a treaty signed by the US, banned CFCs. They had a clear exemption for inhalers, as long as they were necessary.

GSK invented a new delivery method. They patented this method. The existence of method made the Montreal Accords now ban CFC based inhalers.

The FDA approved the new method (makes sense).

It seems like you have an issue with the USPTO or maybe the diplomats who negotiated the Montreal Accords. The FDA wasn't stopping anyone from making generics. Although maybe once a product can no longer be legally sold it is also unapproved. It doesn't really matter which is the case, they weren't the driving force.

Every new refrigerant we use now is basically extremely flammable or volatile

The FDA doesn't control what the patent office approves.

anyway.

You seem to be somewhat unhappy with the inhalers you are using, so something that you could look into is switching to ones that don't use propellant. I find that for me, they are nicer to use than the propellant ones. I initially switched for environmental concerns, but now I would be unhappy to switch back, even if they made a propellant one that was good for the environment.

Btw. anyone that wants to try without propellant and gets pushback, play the I care about the environment, and I want to try card. Most people will fold in the face of that argument.

Even the old Intal Spininhalers look easier and they made a nice whizzing sound as the impeller span, but they had to be cleaned regularly as the powder stuck to the moving parts.

The other think I note was the nasal inhalers worked well up to the mid 1990s then became painful. If you have a sore nose duue to hay fever the last thing you want to do in inhale water up your nose. The old inhalers I now guesses used CFCs and were nice to use. The suggestion by my grandmother for hayfever was to inhale salted water up the nose, I only tried that once - it hurt.