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Many medical drugs contain directions to store them in certain temperature ranges - typically at room temperatures.

For Example:

drug box with "Storage" explained

Storage: Store at 20° to 25° C (68° to 77° F) excursions permitted between 15° to 30°C (59° to 86° F). [See USP Controlled Room Temperature].

Drugs are complex chemical substances, which could potentially disintegrate and lose their potency with time.

According to high school chemistry, many chemical reactions are faster when the reagents are warmer. So, if we store our drugs in the fridge, then maybe we could prolong their life further - perhaps to the detriment of the pharmaceutical companies' profits.

Are the temperature ranges provided shown to maximise the lifetime of the drugs?

HEKTO
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  • I stand to be corrected, but AFAIK a lot of 'room temperature' requirements strongly caution against higher temperatures, not so much against lower. That is not to say the efficacy of some drugs wouldn't be affected by considerably low temperatures, some harmful reactions proceed better at *lower* temperatures, not higher. – M.A.R. Aug 24 '19 at 07:56
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    I doubt that there's any general answer to this question - it's going to depend heavily on the drug in question. e.g., I would expect most tablets or other solid-form drugs to deal reasonably well with arbitrarily low temperatures, but insulin (and, I expect, most other liquid medications) can't withstand being frozen. – Dave Sherohman Aug 24 '19 at 10:18
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    @DaveSherohman, but the package explicitly says to store at above 20° and allows for short periods to be as low as 15°. This implies that being briefly exposed to 10° would be harmful, and long-term storage in a fridge at 4° would be disastrous. Yes, it doesn't make sense, which is why the OP is asking. – Ray Butterworth Aug 24 '19 at 12:42
  • Many thanks to everybody who edited my question - it became much more clear and much more politically correct! Anyway, my scepticism about drug storage rules and their usage by Big Pharma remains... Expiration date *must* depend on storage conditions. We could use thermostats to store drugs at home like wine enthusiasts do that for their collections - what is more important? But we don't have recommendations from manufacturers how to do that – HEKTO Aug 24 '19 at 20:39
  • And one interesting reference about drug expiration: https://www.propublica.org/article/the-myth-of-drug-expiration-dates – HEKTO Aug 24 '19 at 20:42
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    The [Arrhenius equation](https://en.wikipedia.org/wiki/Arrhenius_equation) applies best to simple, well-mixed chemicals; it's the thing that'd imply that cooler temperatures are better. Cooler temperatures shift phase equilibria, potentially causing mixtures to separate or solids to crack. Given this complexity, it seems reasonable that the FDA would want to focus on simple guidelines that can apply to various medicines without confusing folks. But if it's about keeping stuff simple, the truth may be more complicated -- good question! – Nat Aug 25 '19 at 11:48
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    It is worth noting that this particular drug is an ointment which is likely a suspension. The structure of that suspension could easily be susceptible to a phase change at low temperature which could alter its efficacy. The mechanism of action of some compounds (eg quat-based disinfectants) disappears entirely when they are cold though not because they are permanently degraded. The lesson is: temperature has complex effects on some compounds and reactions. – matt_black Sep 02 '19 at 16:11
  • One would think the manufacturer knows the best way to store its products ... I don't really understand skepticism on this topic, especially since storing medicine as directed is usually at worst an inconvenience. –  Mar 04 '20 at 22:16

1 Answers1

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Let's start with a simpler question, and build up.

Do drugs last longer than the expiration date?

Yes, for most but not all drugs.

The American Medical Association were concerned about the wastage of pharmaceuticals due to expiry dates. The US Department of Defense has been collecting data on this, because they stockpile a billion dollars worth of drugs (original source: Wall Street Journal).

The FDA examined the DoD data on over a hundred drugs:

Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. The [DoD] data supports the assertion that many drug products, if properly stored, can be extended past the expiration date. Due to the lot-to-lot variability, the stability and quality of extended drug products can only be assured by periodic testing and systematic evaluation of each lot.

The Wall Street Journal article quoted a former Food and Drug Administration (FDA) employee:

Joel Davis, a former FDA expiration-date compliance chief, says that with a handful of exceptions - notably nitroglycerin, insulin and some liquid antibiotics - most drugs are probably as durable as those the agency has tested for the military. "Most drugs degrade very slowly," he says. "In all likelihood, you can take a product you have at home and keep it for many years."

Davis blames the pharmaceutical company's marketing for this.

Now, let's address how the dates are determined.

In the USA, the FDA require pharmaceutical companies to perform "stability testing" on new drugs. (As I understand it, the FDA doesn't normally directly test the drugs, but requires the manufacturer to submit forms describing the testing process used.)

The standards that must be followed are listed here but in particular: Q1A Stability Testing of New Drug Substances and Products

Q1A gives some recommended (default) storage conditions to test at, including:

  • Minimum 12-month storage at a (high) room temperature: 25°C ± 2°C/60% RH ± 5% RH or 30°C ± 2°C/65% RH ± 5% RH

or alternatively:

  • Minimum 12-month storage in a refrigerator: 5°C ± 3°C

They are also expected to be tested at slightly higher temperatures and slightly higher relative humidity for shorter periods.

Note that maintaining the cold-chain for refrigerated drugs is difficult and expensive - it is under close scrutiny by the FDA. It is easier to store drugs at room temperature throughout the manufacturing and distribution process.

So, a manufacturer wants a room-temperature stable drug, and the FDA wants drugs to be tested at room temperatures - they even want refrigerated drugs to be tested at room temperatures for shorter periods.

Having two expiration dates: refrigerated and room-temperature - would require careful tracking of each package to know whether it has always been refrigerated.

How is this turned into an expiration date?

I found a confusing claim in the RAPS Summary FAQ about the regulars says:

What's the maximum level of shelf life FDA will allow?

Twice the available long-term data at the time of approval, or up to 24 months.

If this was true, if a manufacturer tests a drug for 12 months, and monitors the breakdown of the active ingredient and predicts it will remain effective for five years, they may only claim 24 months. Even if they worked out that putting it in the fridge would extend the shelf-life to 10 years, they must only guarantee it for 24 months.

So, if true, it is difficult to accept Davis's blame on the manufacturers for limitations imposed by the FDA.

However, this clashes with other information I found such as drugs.com:

The expiration date of a drug is estimated using stability testing under good manufacturing practices as determined by the Food and Drug Administration (FDA). Drug products marketed in the US typically have an expiration date that extends from 12 to 60 months from the time of manufacturer.

Australian sources (not under the FDA yoke) also describe longer expiry dates.

So, to summarise the answer to the original question:

The manufacturers probably haven't tested how long room-temperature drugs would last in the fridge, because:

  • They aren't required to conduct these (expensive) tests.
  • Even if they tested it, they might not be allowed to advertise it.
  • Refrigeration is expensive, so stockists want to avoid it.
  • Fridges are damp and that affects some drugs and paper-based packaging.
  • There is room to extend the expiration dates of many drugs at room temperature, without adding refrigeration to the mix.
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Oddthinking
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    Another reason why the high school chemistry might not be relevant is that the difference between 5°C and 30°C is really quite minor for many chemical reactions. Refrigerators are effective for slowing down *bacteria*. Drugs degrade for many reasons - only some are at risk of bacteria growth. The ones that aren't probably aren't affected much by a drop of 25°C. – Oddthinking Aug 25 '19 at 04:50
  • Don't forget that it it known that some biologics (some vaccines and drugs like insulin) are known to degrade quickly at room temperature. So, at least for those, there is *some* logic in the recommendations. – matt_black Sep 02 '19 at 16:02
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    @Oddthinking The Van ’t Hoff rule predicts that increasing temperature by 10 °C will increase reaction rates by a factor 2 to 4, so the 20 °C difference between 5 °C and 25 °C should increase it by a factor 4 to 16, leading to a notable increase in any degrading reaction rates. That’s certainly not ‘quite minor’. Most drugs are crystalline stable compounds though, that don’t decay rapidly at all so a very minor 5 °C baseline leads to a very minor increase at 25 °C. – Jan Sep 11 '19 at 17:57