On Expiration Dates

Dov Michaeli

Posted 10/09/11 on The Doctor Weighs In

Have you ever looked at the label of an old medicine bottle before you deigned to take the pill?  Of course you have. You were looking for the expiration date. And how many of you threw away the bottle of aspirin because it exceeded its allotted lifetime and expired? I am sure the majority among us have done it. Now, I am not a conspiracy theorist, but having had the privilege of an inside look at the working of drug companies I can’t escape the feeling that it’s time to critically examine the process behind those menacing word of “warning: do not take after…”.

When a drug is in the process of development the company is obliged to conduct stability studies. From day 1, samples of the drug are kept at different temperatures (4-6°C, room temperature, 37°C) to simulate conditions in which the drug may be stored), and sometimes other environmental factors, like dark/ light,  relative humidity, etc. These stability studies continue throughout the development of the drug. Let’s take a typical development period of 12 years. At the end of this period the company submits an NDA or New Drug application to the FDA, and among the reams of data on what is known about the drug there is one critical page: THE LABEL. What you put in the label has to hew closely to what the data show, up to the date of submission. Everybody is involved in crafting the content of the label: the chemists who can attest to its structure, purity, and stability; the biochemists who are supposed to know about the drug’s metabolism and breakdown products in the body and in storage; the toxicologists who tested for any adverse effects on animals and humans; the clinicians who conducted the clinical trial and can attest to its efficacy.

But wait, that’s not the whole story: the marketing people weigh in as well. What does marketing have do with the label? Everything that is important to the bottom line, that’s what. Use the wrong language in the warnings section and physicians and patients will avoid you like the plague. Push the envelope a bit in your efficacy claims, and you’d gain market share worth billions of dollars over many years. Can one
blame them for trying? Of course, the FDA stands guard against such abuses, but as we all know –even they are not immune to the power of lobbying and political pressure.

So what about the stability data? If the drug had a 12-year development period, the company has only 12 years of data on stability. But that’s the maximum. The FDA encourages the company to take a conservative stance, and the company happily obliges. So they take a healthy “discount” to the stability period from the 12 years which the data show to say, 6 years. The company can claim putting patient interest as their top concern. It will also help in product liability lawsuits. And –it will induce you to throw away a perfectly good drug, and buy a replacement. And this translates into moollah.

Now, before the chemists and pharmacologists among you get their dander up, let me say that there is always a slow process of breakdown in any chemical, including drugs. But the emphasis is on ‘slow’. If it weren’t slow, it wouldn’t pass muster with the FDA. Now let’s say that in 12 years the company showed a 10% loss of efficacy. That would translate to taking 360mg of 12-year old aspirin instead of 400mg of newly synthesized aspirin. But wait: if you took that aspirin at 6 years, still within the approved period, your effective dose would be only 380mg. Now the important question: has anybody bothered to measure the differences in analgesic and anti-inflammatory activity between 360mg, 380mg, and 400mg. To my knowledge, nobody. Academic scientists wouldn’t because the difference would be so  minuscule as to be meaningless. Company scientists of course wouldn’t, because their company doesn’t want to know –it may cause a drop in sales.

The problem is that the consumer doesn’t have a way of knowing what is the real expiration date. And this is not a problem limited to consumers losing money and companies making it –it is a national problem, as a quick look at what the nation spends on medicating itself would reveal. Medicare Part D, which pays a large portion a patient’s drug bill, plays a major role in the precarious financial situation we are finding ourselves in. How much can be saved by simply keeping an effective drug a bit longer? The arithmetic is quite simple: a 10% reduction in drug consumption would translate to a 10% reduction in the national expenditure on medicines.

When we face a complex problem, like health care, we instinctively reach for complex solution. But sometimes solutions can be
simple, and they hide in plain view. All we need is to “get in the weeds,” examine our assumptions, examine the data behind the assertions and separate fact from fiction.

Dov Michaeli MD PhD is a basic researcher, writing at the Doctor Weighs In.

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