By Laurie P. Cohen
The Wall Street
Journal March 29, 2000
Do drugs really stop working after the date stamped on the
bottle? Fifteen years ago, the U.S. military decided to find out.
Sitting on a one billion dollar stockpile of drugs and
facing the daunting process of destroying and replacing its supply every two to
three years, the military began a testing program to see if it could extend the
life of its inventory. The testing, conducted by the U.S. Food and Drug
Administration, ultimately covered more than 100 drugs, prescription and
The results, never before reported, show that about 90
percent of them were safe and effective far past their original expiration
date, at least one for 15 years past it.
In light of these results, a former director of the
testing program, Francis Flaherty, says he has concluded that expiration dates
put on by manufacturers typically have no bearing on whether a drug is usable
for longer. Mr. Flaherty notes that a drug maker is required to prove only that
a drug is still good on whatever expiration date the company chooses to set.
The expiration date doesn't mean, or even suggest, that
the drug will stop being effective after that, nor that it will become harmful.
"Manufacturers put expiration dates on for marketing,
rather than scientific, reasons," says Mr. Flaherty, a pharmacist at the
FDA until his retirement last year. "It's not profitable for them to have
products on a shelf for 10 years. They want turnover."
The FDA cautions that there isn't enough evidence from the
program, which is weighted toward drugs needed during combat and which tests
only individual manufacturing batches, to conclude that most drugs in people's
medicine cabinets are potent beyond the expiration date.
Still, 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, especially if it's in the refrigerator."
Drug-industry officials don't dispute the results of the
FDA's testing, within what is called the Shelf Life Extension Program. And they
acknowledge that expiration dates have a commercial dimension. But they say
relatively short shelf lives make sense from a public-safety standpoint, as
New, more-beneficial drugs can be brought on the market
more easily if the old ones are discarded within a couple of years, they say.
Label redesigns work better when consumers don't have earlier versions on hand
to create confusion.
From the companies' perspective, any liability or safety
risk is diminished by limiting the period during which a consumer might misuse
or improperly store a drug. "Two to three years is a very comfortable
point of commercial convenience," says Mark van Arandonk, senior director
for pharmaceutical development at Pharmacia & Upjohn Inc. "It gives us
enough time to put the inventory in warehouses, ship it and ensure it will stay
on shelves long enough to get used." But companies uniformly deny any
effort to spur sales through planned obsolescence.
Why Not Longer?
Now that the FDA has found that many drugs are still good
long after they have supposedly expired, why doesn't it advocate later
expiration dates for consumer drugs? One reason is that the consumer market
lacks the military's logistical reasons to keep drugs around longer.
Frank Holcombe, associate director of the FDA's office of
generic drugs, says that in many cases a manufacturer could extend expiration
periods again and again, but to support those extensions, it would have to keep
doing stability studies, and keep more in storage than it would like.
Mr. Davis adds: "It's not the job of the FDA to be
concerned about a consumer's economic interest." It would be up to
Congress to impose changes, he says. As things stand now, expiration dates get
a lot of emphasis. For instance, there is a campaign, co-sponsored by some drug
retailers, that urges people to discard pills when they reach the date on the
And that date often is even earlier than the one the maker
set. That's because when pharmacists dispense a drug in any container other
than what it came to them in, they routinely cut the expiration date to just
one year after dispensing. Some states even require pharmacists to do this.
Meanwhile, poor countries - under urging from the World
Health Organization - often reject drug-company donations of much-needed
medicines if they are within a year of their expiration dates.
It isn't known how much of the $120 billion-plus spent
annually in the U.S. on prescription and over-the-counter medicines goes to
replace expired ones. But in a poll done for The Wall Street Journal by NPD Group Inc. of Port Washington, N.Y.,
70 percent of 1,000 respondents said they probably wouldn't take a prescription
drug after its expiration date; 72 percent said the same of an over-the-counter
"People think that, upon expiration, drugs suddenly
turn toxic or lose all their potency," says Philip Alper, professor of
medicine at University of California at San Francisco. In his own practice, Dr.
Alper says, "I frequently hear - from patients who can't afford medicine -
that they have thrown away expired drugs." He says companies should be
required to test drugs for longer periods and set later expiration dates when
Some manufacturers first began putting expiration dates on
drugs in the 1960s, although they didn't have to. When the FDA began requiring
such dating in 1979, the main effect was to set uniform testing and reporting
guidelines. As now required by the FDA, so-called stability testing analyzes
the capacity of a drug to maintain its identity, strength, quality and purity
for whatever period the manufacturer picks. If the company picks a two-year
expiration date, it needn't test beyond that.
Testing for a two-year expiration doesn't initially entail
holding a drug for two years. Rather, the drug is tested by subjecting it to
extreme heat and humidity for several months, then chemically analyzing each
ingredient's identity and strength. (After the date is set and the drug is
marketed, testing continues for the full two years.) The FDA also uses chemical
analysis in testing for possible shelf-life extension; it doesn't test on human
subjects. Testing conditions are such that any medicine that meets, say, the
standards for a two-year expiration date probably lasts longer, the FDA and
drug companies agree.
Consider aspirin. Bayer AG puts two-year or three-year
dates on aspirin and says that it should be discarded after that. Chris Allen,
a vice president at the Bayer unit that makes aspirin, says the dating is
"pretty conservative"; when Bayer has tested four-year-old aspirin,
it remained 100 percent effective, he says.
So why doesn't Bayer set a four-year expiration date?
Because the company often changes packaging, and it undertakes "continuous
improvement programs," Mr. Allen says. Each change triggers a need for
more expiration-date testing, he says, and testing each time for a four-year
life would be impractical.
Bayer has never tested aspirin beyond four years, Mr.
Allen says. But Jens Carstensen has. Dr. Carstensen, professor emeritus at the
University of Wisconsin's pharmacy school, who wrote what is considered the
main text on drug stability, says, "I did a study of different aspirins,
and after five years, Bayer was still excellent. Aspirin, if made correctly, is
Only one report known to the medical community linked an
old drug to human toxicity. A 1963 Journal
of the American Medical Association article said degraded tetracycline
caused kidney damage. Even this study, though, has been challenged by other
scientists. Mr. Flaherty says the Shelf Life program encountered no toxicity
with tetracycline and typically found batches effective for more than two years
beyond their expiration dates.
Plea from the Air Force
The program dates to a U.S. effort begun in 1981 to
increase military readiness by buying large quantities of drugs and medical
devices for the armed forces. Four years later, more than one billions dollars
of supplies had been stockpiled. The General Accounting Office audited Air
Force troop hospitals in Europe and found many supplies at or near expiration.
It warned that by the 1990s, more than $100 million would have to be spent
yearly on replacements.
The Air Force Surgeon General's office asked the FDA if it
could possibly extend the shelf life of these drugs. The FDA had the equipment
for stability testing. And because it had approved the drugs' sale in the first
place, it also had manufacturers' data on the testing protocols. Testing for
the Air Force began in late 1985. In the first year, 58 medicines from 137
different manufacturing lots were shipped to the FDA from overseas storage,
among them penicillin, lidocaine and Lactated Ringers, an intravenous solution
for dehydration. After testing, the FDA extended more than 80% of the expired
lots, by an average of 33 months.
In 1992, according to the FDA, more than half of the
expired drugs that had been retested in 1985 were still fine. Even now, at
least one still is. Such results came as a revelation for Army Col. George
Crawford when he took over military oversight of the program in 1997. He is a
pharmacist, but "nobody tells you in pharmacy school that shelf life is
about marketing, turnover and profits," he says. (The drug makers don't
agree that it is, however.)
How It Works
The military's base for the program is a dingy barracks
room in Fort Detrick, Md. There, a group headed by Air Force Lt. Col. Greg
Russie, who recently took over from Col. Crawford, tracks drugs that are near
expiration at defense facilities all over the world, selecting many for
retesting. They are shipped to the FDA, which sends them to its laboratories.
The FDA's lab in Philadelphia recently tested five
automatic injectors containing an antidote to chemical poisoning, which were
purposely held for three months in conditions even hotter and more humid than
the FDA requires in consumer testing of drugs. The FDA tested the drug
contained in the injectors, pralidoxime chloride, by separating its ingredients
and measuring the strength and quality of each, then applying a computer model
to determine whether a shelf-life extension was warranted.
The injectors' original expiration date was November 1985.
The FDA had retested them periodically ever since, each time approving their
continued use. The batch, made by Ayerst Laboratories, now part of American
Home Products Corp.'s Wyeth-Ayerst unit, is 18 years old. It is 15 years beyond
the expiration date applied by Ayerst. The FDA found it is still good.
A spokesman for Wyeth-Ayerst says it "uses scientific
data to establish expiration dates" and "tries to have the longest
possible dating on products that scientific data supports." The company is
aware of the FDA retesting program. It says it can't comment specifically on the
injectors tested by the FDA.
A Few Fail
Shelf-life extensions are "intentionally
conservative," the FDA's Mr. Flaherty told military brass in a 1992
speech. He says that if the agency extended an expiration date by 36 months, it
had concluded the lot would retain all of its safety and efficacy for at least
72 months. A very few drugs aren't retested. The military has found that
water-purification tablets and mefloquine hydrochloride, for malaria, routinely
fail stability testing beyond their expiration dates, so it has removed them
from the program.
Also excluded are large-volume intravenous solutions, such
as saline. "We don't like to test those," says Col. Crawford.
"Not because we can't, but because it would be politically sensitive if
G.I. Joe was lying in bed and saw it had originally expired three years
Mr. Flaherty has said that while he tested a handful of
drug batches that didn't even make it to their expiration dates, most drugs
were "surprisingly durable." In one instance, he says, drugs labeled
for room-temperature storage had been kept for two years in a warehouse in Oman
that averaged 135 degrees Fahrenheit in the daytime. Upon expiration, the
drugs, which included the local anesthetic lidocaine and atropine, a nerve-gas
antidote also used by eye doctors to dilate pupils, "were well within the
standards for potency and other quality characteristics," he says.
One medicine the FDA has endorsed for extensions is
ciprofloxacin hydrochloride tablets, an antibiotic marketed by Bayer as Cipro.
One batch had an expiration date of March 1989. More than 9 1/2 years later,
the FDA found the tablets still good; it then extended some of them for 18 more
months and others for 24 more months.
Albert Poirier, quality-assurance director for Bayer's
pharmaceutical division, says he isn't surprised because Cipro "is a
stable drug molecule" in tablet form. "We go for a shelf life that
will be safest for patients," he says. "We want the drug to be used
up within three years. We wouldn't want a patient to have it for 10 years
because they'd have an old package insert" that might omit new information
or contra-indications and because "we'd have no control over how they'd
store the drug during this time."
Another extended drug is Thorazine, a tranquilizer
chemically known as chlorpromazine tablets. Batches bearing December 1996
expiration dates - unused and unopened, as is the case with all drugs evaluated
in the Shelf Life program - were tested in July 1998 and extended for two
years. A spokesman for the maker, SmithKline Beecham PLC, says it applies an
expiration date 24 months after manufacture. "We think that is the
appropriate expiration date," he says. "We don't benefit from short
Some other drugs the FDA has extended at least two years
beyond their expiration dates are diazepam, sold as Valium; cimetidine, sold as
Tagamet; phenytoin, sold as Dilantin; and the antibiotics tetracycline and
On a cost-benefit basis, the program's returns have been
huge. The first year, the Air Force paid the FDA $78,000 for testing and saved
59 times that sum by not needing to replace the drugs. After other services
joined, the military from 1993 through 1998 spent about $3.9 million on testing
and saved $263.4 million on drug expense, according to Lt. Col. Russie.
Says Mr. Flaherty: "We've cost the pharmaceutical
companies hundreds of millions of dollars in sales of new stuff to the
Department of Defense." More than 12 years ago, Messrs. Flaherty and Davis
explained the program to drug-company chemists at a meeting of the American
Association of Pharmaceutical Scientists in Woodbridge, N.J., going into detail
about how the FDA decided whether to extend a given expiration date. Mr. Davis
concluded by noting how much the U.S. had saved by extending shelf lives
instead of "destroying large quantities of still-useful medical products..."
Mr. Flaherty says the FDA was keenly aware that if its
methodology was flawed, or its results incorrect even once, its credibility
would be attacked. Yet FDA officials say that during the program's 15 years,
drug makers have never objected to any of its procedures or findings.
"They may not have liked what we were doing, but they weren't able to
challenge it," he says.
The Message to Civilians
While the military is finding it can keep most drugs
longer, civilians hear quite a different message. For instance, a campaign
called the National Expired and Unused Medication Drive has collected and
destroyed 36 tons of drugs since 1991, says its founder, Kathilee Champlin. Ms.
Champlin, of Colorado Springs, Colo., says her interest derives from experience
working with the elderly and seeing how hard it was for them to keep track of
all their medications. She says she wasn't aware of any FDA program to extend
drugs' shelf lives.
Her group has gained sponsorship from the some big drug
retailers, including Wal-Mart Stores Inc. It sponsors the campaign to be
"a good corporate citizen," says Frank Seagrave, vice president of
pharmacy merchandising. "
We believe that people should dispose of unused
prescription medicines a year after they get them," he says, adding that
Wal-Mart sometimes gives people a free bottle of vitamins if they bring in
Many pharmacists also play a role in shelf lives. The U.S.
Pharmacopeia, a not-for-profit scientific group that develops standards for the
drug industry, urged in 1985 that pharmacists set expiration dates at no more
than one year if they were dispensing drugs in a bottle other than the
manufacturer's original packaging. "New containers may let in more
moisture and heat than the container the manufacturer used for the stability
study," accelerating the drug's degradation, says the USP General Counsel
The recommendation became a USP requirement in 1997. As a
result, "the majority of pharmacists shorten the manufacturers' expiration
dates" on prescription drugs to one year or less, says Susan Winckler, an
official of the American Pharmaceutical Association. In fact, in 17 states,
pharmacists now are legally required to do so. Ms. Winckler says shortening the
dates makes sense because many people store drugs in moist bathrooms. She says
the one-year rule is "motivated by product integrity and not by
By Dr. Mercola
We can clearly
gain some valuable insights from this incredible piece in the Wall Street Journal and sent in by
ever-diligent Michael Belkin.The key from the article is "shelf life is
about marketing, turnover and profits." Over the course of the past two
decades, U.S. spending on prescription drugs increased from $40 billion to more
than $230 billion. If drug companies convince you to empty out your medicine
cabinets annually, those profit margins could increase even more.
I find it
absolutely incredible that the military spent from 1993 through 1998 about $3.9
million on testing and saved $263.4 million on drug expense. So, on a personal
level, unless you have nitroglycerin, insulin and liquid antibiotics, you may
be able to use your medications far beyond the expiration date on the bottle. I
believe the major tragedy is that many Third World countries needlessly discard
the drugs that are sent to them and could actually be saving lives due to lack
of appreciation of this concept.