Many Medicines Are Potent Years Past Expiration Dates
By LAURIE P. COHEN Staff Reporter of THE WALL STREET JOURNAL
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.
Johnson & Johnson's Janssen Pharmaceutica unit, a drug maker, also sponsors Ms.
Champlin's campaign. "We think it's important to educate the public about the
risk of taking drugs that are expired and to raise public awareness," says a
spokesman for Janssen. Both Wal-Mart and J&J say that supporting the campaign to
discard expired drugs has nothing to do with their sales efforts.
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."
Even the FDA has sometimes pushed for throwing out drugs at their expiration
date. Last October it co-sponsored, with the National Association of Chain
Drugstores and others, a campaign that urged women not to use medications beyond
the expiration dates because, as the brochure put it, "they may not work." Mr.
Davis says this shows just how obscure the military Shelf Life Extension Program
is. "Many people at the FDA have absolutely no idea this program exists," he
says.
http://www.mercola.com/2000/apr/2/drug_expiration.htm
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