By
Laurie P. Cohen
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 $1 billion 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 over-the-counter.
The results, never before reported, show that about 90% 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.
MARKETING ISSUE
"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."
MANUFACTURERS' VIEW
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 well.
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 label.
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% of 1,000 respondents said they probably wouldn't take
a prescription drug after its expiration date; 72% said the
same of an over-the-counter remedy.
"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 results warrant.
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.
STILL GOOD
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%
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 very stable."
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 $1 billion 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 ago."
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.
STABLE MOLECULE
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 expiration dates."
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 penicillin.
BIG SAVINGS
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 expired drugs.
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 Joseph Valentino.
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 profit."
THE WALL STREET JOURNAL March 29,
2000