The Myth of Drug Expiration Dates • Hacker News Board

Re: The Myth of Drug Expiration Dates

#221

Post by ekianjo » Wed, Jul 19, 2017, 2:06 AM UTC

t0mbstone wrote: post #152

slr555 wrote: post #66

This issue is a conundrum. Most drugs don't fall off a cliff of efficacy when they reach their expiration date. There are drugs such as tetracyclines that should never be used past their expiration dates because they degrade into toxic compounds. Certain classes of drugs such as anti-arrhythmics or drugs like warfarin are dosing critical to the point where I would not want them if they were out of date. I worked in p…

Wouldn't the real solution here be to put real expiration dates on things that can harm you, and real expiration dates on things that haven't actually expired? Like a "dangerous to use after 01/01/2019" label on things that actually are dangerous. Other items could have labels like, "Safe for use until 01/01/2025 - Effectiveness may be degraded after 09/05/2019"

I worked on expiration dates studies in pharma. It's well known that you could probably always extend the shelf life to 3-4 years for most drugs that are supposed to expire within 2 only, because tablets for example tend to be very stable.

But nobody wants to run long stability studies, because that costs a lot of money (i.e. several batches that have to be analyzed in regular basis, documented, reported, QA'ed, inspected, etc... - and you need to place them in numerous conditions, too, ambient temperature as well as stressed conditions depending on where you intend to market the drug), and bring very little returns at the end of the day. You'd rather want your engineers to work on developing new formulations and regulatory teams to spend time on the application of new drugs rather than adding one or two years of shelf life to an existing drug on the market.

Also know that you can't "extrapolate" and need actual data based on regulations of the big 3 geographies (US, Europe, Japan). So "models" are not accepted. Also, these agencies are extremely conservative when it comes to what impurities should be considered acceptable and at what levels they should be. Not saying they are necessarily wrong, but this is another constraints. I have seen cases where it was difficult to extend one drug's shelf life because of a single impurity being a little over the tolerated limit.

Re: The Myth of Drug Expiration Dates

#222

Post by mechnesium » Wed, Jul 19, 2017, 2:25 AM UTC

kbenson wrote: post #219

t0mbstone wrote: post #152

Earlier quoted context omitted.

Wouldn't the real solution here be to put real expiration dates on things that can harm you, and real expiration dates on things that haven't actually expired? Like a "dangerous to use after 01/01/2019" label on things that actually are dangerous. Other items could have labels like, "Safe for use until 01/01/2025 - Effectiveness may be degraded after 09/05/2019"

The point is we don't necessarily know, or know to the degree of certainty the FDA requires, how many of these things degrade. Perhaps in certain conditions, they degrade at one rate, but in other conditions (such as a temperature difference), they degrade at a different rate. Testing how drugs perform years after production in multiple different scenarios is necessarily time consuming, because it takes at least that…

I'm a test engineer. Highly accelerated life testing (HALT) can probably be used to closely approximate the shelf life of medicine. You need to look at the parameters that cause degradation (humidity, temperature, light exposure, etc). HALT the samples at different temperature/humidity/lighting extremes and use mass spectrometry to check purity. Use the data to create an algorithm that approximates the product lifetime and then correlate the results with actual shelf life for verification.

Re: The Myth of Drug Expiration Dates

#223

Post by srtjstjsj » Wed, Jul 19, 2017, 2:48 AM UTC

devy wrote: post #172

Read similar article on HN before. U.S. Army was able to save millions after FDA okays them to use expired drugs.[1] [1]: https://www.thepharmaletter.com/article/fda-tests-let-milita...

yes. For the scientists in OP to say they were surprised, they completely failed sat lit review.

Re: The Myth of Drug Expiration Dates

#224

Post by ekianjo » Wed, Jul 19, 2017, 2:51 AM UTC

techthroway443 wrote: post #202

Kalium wrote: post #161

Earlier quoted context omitted.

There's also the not-irrelevant issue that testing is slow and potentially other than free. How do you find out when a drug expires? You have a bunch of it sit around and test it periodically, right? I assume that would be done after bringing a drug to market, otherwise drugs could easily be delayed 10+ years if they're shelf-stable.

Nobody said they need to find the absolute last day the drug expires before they can get it to market. If it's a new drug and they can only say for sure that it lasts 6 months then put that on the label and ship it out. But assuming the drug will be out for 10+ years they should be continually testing the expiration date and updating as they've had more time to make that determination. But like I said initially (and…

> If it's a new drug and they can only say for sure that it lasts 6 months then put that on the label and ship it out. But assuming the drug will be out for 10+ years they should be continually testing the expiration date and updating as they've had more time to make that determination.

This needs regulatory work. And this bring very little returns, so your regulatory resources are better spent somewhere else. There are other incentives in place.

Re: The Myth of Drug Expiration Dates

#225

Post by ekianjo » Wed, Jul 19, 2017, 2:52 AM UTC

yomly wrote: post #179

Kalium wrote: post #161

Earlier quoted context omitted.

There's also the not-irrelevant issue that testing is slow and potentially other than free. How do you find out when a drug expires? You have a bunch of it sit around and test it periodically, right? I assume that would be done after bringing a drug to market, otherwise drugs could easily be delayed 10+ years if they're shelf-stable.

I would expect the chemistry to be characterised well enough to the point where you shouldn't need clinical tests to know it's degredation profile...

Regulations don't want you to rely on models.

Re: The Myth of Drug Expiration Dates

#226

Post by traek » Wed, Jul 19, 2017, 3:20 AM UTC

mechnesium wrote: post #222

kbenson wrote: post #219

Earlier quoted context omitted.

The point is we don't necessarily know, or know to the degree of certainty the FDA requires, how many of these things degrade. Perhaps in certain conditions, they degrade at one rate, but in other conditions (such as a temperature difference), they degrade at a different rate. Testing how drugs perform years after production in multiple different scenarios is necessarily time consuming, because it takes at least that…

I'm a test engineer. Highly accelerated life testing (HALT) can probably be used to closely approximate the shelf life of medicine. You need to look at the parameters that cause degradation (humidity, temperature, light exposure, etc). HALT the samples at different temperature/humidity/lighting extremes and use mass spectrometry to check purity. Use the data to create an algorithm that approximates the product lifeti…

A good model really isn't good enough in medicine. Real data from clinical trials is needed, and nobody has an incentive to fund that.

Re: The Myth of Drug Expiration Dates

#227

Post by seehafer » Wed, Jul 19, 2017, 3:21 AM UTC

mechnesium wrote: post #222

kbenson wrote: post #219

Earlier quoted context omitted.

The point is we don't necessarily know, or know to the degree of certainty the FDA requires, how many of these things degrade. Perhaps in certain conditions, they degrade at one rate, but in other conditions (such as a temperature difference), they degrade at a different rate. Testing how drugs perform years after production in multiple different scenarios is necessarily time consuming, because it takes at least that…

I'm a test engineer. Highly accelerated life testing (HALT) can probably be used to closely approximate the shelf life of medicine. You need to look at the parameters that cause degradation (humidity, temperature, light exposure, etc). HALT the samples at different temperature/humidity/lighting extremes and use mass spectrometry to check purity. Use the data to create an algorithm that approximates the product lifeti…

Unfortunately, ALT is not a solution, because it's not accepted by FDA, except as a temporary measure.

Any drug submission that supports shelf life via ALT data will be expected to also say "and we're doing real time testing to support this", and FDA will expect the follow up real-time data.

Re: The Myth of Drug Expiration Dates

#228

Post by chillwaves » Wed, Jul 19, 2017, 3:34 AM UTC

civilitty wrote: post #142

PixelB wrote: post #81

Earlier quoted context omitted.

Sounds like you don't know what you are talking about. Your source is a book written with heavy influence by the Pharmaceutical industry to justify the obscene costs of their drugs, making billions in profits off of sick, poor people. You are the one who is completely wrong. The dosages most certainly do start out with a "best guess" in the pre-clinical phase. For any given drug we would guess at the doses based on o…

You and the GP talking about entirely different things. You're talking about how investigators choose the initial dose for the clinical trials, he's talking about the dosage that is actually prescribed by doctors. Hence the 'The dose we take is not a "BEST GUESS"' (emphasis mine). Unless you're a lab animal or a person in a clinical trial, the does you take is the end result of lots of money spent on first figuring o…

> Antidepressants are a unique group of drugs because the dosage is highly dependent on each person's unique brain chemistry and a huge part of a good psychiatrist's job is working with their patients to find the right dosage and combination.

How does one accomplish this absent trial and error?

This fact undermines the entirety of your argument.

"Best guess" is exactly what they do.

Re: The Myth of Drug Expiration Dates

#229

Post by chillwaves » Wed, Jul 19, 2017, 3:36 AM UTC

TeMPOraL wrote: post #28

qq66 wrote: post #20

Earlier quoted context omitted.

No drug where a 2% difference matters can be administered outside of a monitored hospital setting. There are too many variables that affect the drug uptake far more than 2%, such as body weight (100 pound person will have 3x the drug dosage of a 300 pound person), drug absorption (based on body chemistry, other food eaten, etc.) and the actual intake dosage itself (Eye drops, for example, can have a 500-fold variance…

> There are too many variables that affect the drug uptake far more than 2%, such as (...) ...or in case of tablets that come in 2x/4x the dose and you need to cut them in half/four pieces, the precision of your cut and amount of tablet dust that is lost.

And the distribution of the active ingredient vs filler.

It's a lot of guess work.

Re: The Myth of Drug Expiration Dates

#230

Post by sevenfive » Wed, Jul 19, 2017, 3:37 AM UTC

civilitty wrote: post #156

sevenfive wrote: post #148

Earlier quoted context omitted.

Excuse me, index. A dimensionless quantity. Nothing to do with potency. And you could hardly pick worse drugs to spread misinformation about.

I do not believe that you have the requisite knowledge of pharmacology to talk intelligently on these topics so you should stop correcting people who do, especially when your other comments suggest that your knowledge is based entirely on recreational drug databases. Anyone who has spent time working in the pharmaceutical industry knows that "therapeutic index" and "therapeutic ratio" are used interchangeably and tha…

But what you said was still totally wrong, regardless of whether you're talking about toxicity or anything else. LSD is not so finicky that a 25% change in the dose makes a noticeable difference -- most people would be hard pressed to tell the difference between a 100 ug tab and a 125 ug one.

It also does not follow that because a drug is active in small amounts, i.e. micrograms instead of milligrams, that a small percent change in the dosage will be more important. Full stop illogical, and also not true in practice.

So yes, I'm not a doctor and I don't know the jargon. And when I read your comment I forgot the article was about expiration dates, i.e. percent decrease. And yet you were still wrong on that particular point.