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Comment by akira2501 | Hacker News Reader

Albuterol Inhalers.

Used to use CFC as the propellant. CFCs got banned. So, the FDA lets GSK _re-patent_ the same *medication* but just with a new propellant.

What propellant did they use? R-134a. The same HFA that everyone switched to after CFC was taken out of use for refigeration.

It wasn't even a novel change.

Inhalers went from $5 generics to $90 brand name only overnight. Of course, GSK also secured further patents that prevented things from primatine mist from existing at all. Disappeared from the market and primatine tablets were the only thing left.

Oh.. and R-134a is getting phased out again soon. Just in time for the GSK patents to be renewed, I guess. So, they're going to leave people who need a simple medication for breathing issues without anything on the market, _again_. I wonder if they'll even get the single year of "generic tease" again.

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I didn’t really understand this comment so I dig into it a bit more. Here is my current understanding…

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-...

* generic

Because the old product is no longer on the market, the FDA will not approve a generic.

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.

> 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).

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.

The lawsuit implies that inhalers are a special case, where the normal FDA rules don’t apply. By adding new patents covering inhalers the manufacturer triggers FDA rules preventing the FDA from approving a generic, or so the lawsuit implies:

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.

Sure, because inhalers aren't just drugs, they are drug-device combinations.

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.

> 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 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.

---

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.

> 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.

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 is something nobody knows how to solve. The best health agencies manage to do is prohibiting some manufacturing procedure after it was shown that things built with it are ineffective.

The CFC ban really threw the baby out with the bathwater.

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.

Interestingly this did not happen with lead. The regulations for that have significant exceptions for things like medical technology, aviation, military use, and equipment only used by trained professionals. And of course the one big massive hole: aviation fuel.

Lead is still everywhere: In fishing ballast, in curtains, in camera stands, ...

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.

And soon, every single piece of electronics will be lead apatite…

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.

>> And soon, every single piece of electronics will be lead apatite…

> 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.

You are using the same logic as anti-vaxxers who point at the ingredients of vaccines and say "there's mercury in there, it MUST be bad for you!". Lead as part of a bigger molecule behaves differently from lead as a standalone metal.

It depends on the particular chemistry and whether the lead can become bioavailable.

Those things are not the same.

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.

This isn’t an alloy, it’s an ionic bond. Any acidic solution would dissolve it, releasing lead ions into solution.

like uric acid in water? https://en.wikipedia.org//wiki/Perspiration

Lead-containing compounds are toxic. In fact, as far as I'm aware, lead-containing compounds are the only toxic kinds of lead. Metallic lead is only hazardous because corrosion forms lead salts on its surface.

No longer with Aviation fuel. FAA allows unleaded AVgas now.

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.

Not aviation fuel in general. Jet fuel does not contain lead. Only aviation GASOLINE for piston engines contains lead, and that can finally be phased out now that unleaded replacements are available for the whole fleet.

You write "nothing must ever contain CFCs ever again, including critical medical products that use only insignificant amounts" while Wikipedia at https://en.wikipedia.org/wiki/Montreal_Protocol writes:

> 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?

Regarding "its on problems" I think patent commenter was primarily talking about amalgamated filings.

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.

Then why mention asbestos?

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.

The big lesson is that CFC removal has been a massive win for humanity and that kind of categorical and decisive climate action is exactly what we need in the future!

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.

> The big lesson is that CFC removal has been a massive win for humanity and that kind of categorical and decisive climate action is exactly what we need in the future!

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 lesson is that the US’s medical system is ridiculous.

The lesson has nothing to do with the CFC removal.

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.

No, the CFCs in medical inhalers were of insignificant quantity and should not have been changed. The new propellants are equal-to-slightly-inferior, in my experience.

You understand that the negative consequences of changing propellants described in the top-level comment did not occur in other societies, right?

Of course they should have been changed!

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.

The interesting thing is that most of the world kept the CFCs inhalers for many years. Immediately ceasing production so that people are thrown under the bus was a US thing.

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

Asbestos is still everywhere, but whenever it's found (at least where I live), it's red alert and specialist cleanup crews suit up and come in to dispose of it safely. Most countries banned its use, but I just read that Russia still mines and uses it in construction.

Not my experience. It’s often removed by unlicensed handy men who don’t have any training or much awareness and who will tell you candidly that they think it’s not really dangerous anyway. At least that’s been my experience as a renter here in the bay area.

For some kinds, you really don't have to worry that much, e.g. removing asbestos-containing floor tile by prying up (vs. trying to grind it away) only requires that you double-bag it when you take it to the landfill, and there's a recommendation to wet it down to prevent dust, and to wear a mask.

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.

We have sadly not applied the same ideas to asbestos. We definitely need to.

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.

Your comment creates a false appearance that FDA has anything to do with granting a patent. If you or anyone else has an issue about a patent being granted (assuming the rest of your comment is correct) then you should take it to the United States Patent and Trademark Office (USPTO) https://www.uspto.gov/.

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

But the FDA has everything to do with approval of generics, which is the real problem here, as described in this comment: https://news.ycombinator.com/item?id=36998285

Pro tip: buy them from other countries. (This doesn't solve the policy issue, but does solve the practical one.)

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.

Also https://aipctshop.com/ and https://www.reliablerxpharmacy.com/, as well as some "wholesale" distributors from China who sell directly to consumers.

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).

I've been using Ventoline (the GSK brand name they use for Albuterol or Salbutamol depending on your location), to control my asthma for years. I used to use the variant with propellant but I switched of it to the one without. The main reason I switched was environmental concerns (https://www.bbc.com/news/health-50215011).

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?

How is the FDA responsible for patent issuance? Isn't that the remit of the US Patent Office?

You are correct, but in a process that requires submission of the patent to the FDA, you can also request an FDA "new drug product exclusivity."

No, the patent has nothing to do with it.

"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.

Being an asthmatic American old enough to remember going to buy an albuterol inhaler sans prescription, thank you for bringing this up. But I think you mischaracterize it, based on my (possibly wrong) understanding: switching propellants made it a different drug. Which means prescription. Prescriptions aren't just used to limit access to dangerous substances, they're also used to grant monopolies on substances. So yes, the price went up nearly an order of magnitude, but the access was cut off. Because when the propellant formulation changed, even though the active ingredient was the same, a prescription was required in the US to acquire it.

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.

This has nothing to do with the FDA.

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.

I'll be curious what the replacement for R-134a is that's safe for inhalers

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

So, the FDA lets GSK _re-patent_ the same medication* but just with a new propellant.*

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

Its techincally not a patent but market exclusivity by the FDA

The patent is worthless if the FDA doesn't approve its use.

I’m really glad I can get my asthma medication dirt cheap on the NHS in England.

I get it for free on the NHS in Scotland. That said, ventolin inhalers are still cheap even after the propellant switch (which was in the mid 90's). Tangent, but I _despise_ the "easi-breathe" inhalers that my pharmacy gives to me (which are 10x the cost of the older ones). The feedback on the inhalation is shitty, the actual dispersion of the inhaler gets blocked, they use like 5x the plastic, and I've had to throw out most of the plastic shells before the actual inhaler is used because the little plastic tabs stop working.

anyway.

Those things are absolutely fucking useless. I've taken to just popping the top off to press the button down. Fortunately I don't need to use my inhaler more than once every few months but when I do need it it's incredibly frustrating.

I had a look at demonstration video for easi-breathe, I guess it might be useful for some people. But for me it looked most like a solution in search of a problem, and I would probably be livid if someone forced those one me.

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.

That looks really bad.

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.

The FDA is regulatory capture in its naked form.

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