By Laurie P. Cohen
The Wall StreetJournal March 29, 2000
Do drugs really stop working after the date stamped on thebottle? Fifteen years ago, the U.S. military decided to find out.
Sitting on a one billion dollar stockpile of drugs andfacing the daunting process of destroying and replacing its supply every two tothree years, the military began a testing program to see if it could extend thelife of its inventory. The testing, conducted by the U.S. Food and DrugAdministration, ultimately covered more than 100 drugs, prescription andover-the-counter.
The results, never before reported, show that about 90percent of them were safe and effective far past their original expirationdate, at least one for 15 years past it.
In light of these results, a former director of thetesting program, Francis Flaherty, says he has concluded that expiration datesput on by manufacturers typically have no bearing on whether a drug is usablefor longer. Mr. Flaherty notes that a drug maker is required to prove only thata drug is still good on whatever expiration date the company chooses to set.
The expiration date doesn't mean, or even suggest, thatthe 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 theFDA until his retirement last year. "It's not profitable for them to haveproducts on a shelf for 10 years. They want turnover."
The FDA cautions that there isn't enough evidence from theprogram, which is weighted toward drugs needed during combat and which testsonly individual manufacturing batches, to conclude that most drugs in people'smedicine cabinets are potent beyond the expiration date.
Still, Joel Davis, a former FDA expiration-date compliancechief, says that with a handful of exceptions - notably nitroglycerin, insulinand some liquid antibiotics - most drugs are probably as durable as those theagency has tested for the military. "Most drugs degrade very slowly,"he says. "In all likelihood, you can take a product you have at home andkeep it for many years, especially if it's in the refrigerator."
Drug-industry officials don't dispute the results of theFDA's testing, within what is called the Shelf Life Extension Program. And theyacknowledge that expiration dates have a commercial dimension. But they sayrelatively short shelf lives make sense from a public-safety standpoint, aswell.
New, more-beneficial drugs can be brought on the marketmore 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 handto create confusion.
From the companies' perspective, any liability or safetyrisk is diminished by limiting the period during which a consumer might misuseor improperly store a drug. "Two to three years is a very comfortablepoint of commercial convenience," says Mark van Arandonk, senior directorfor pharmaceutical development at Pharmacia & Upjohn Inc. "It gives usenough time to put the inventory in warehouses, ship it and ensure it will stayon shelves long enough to get used." But companies uniformly deny anyeffort to spur sales through planned obsolescence.
Why Not Longer?
Now that the FDA has found that many drugs are still goodlong after they have supposedly expired, why doesn't it advocate laterexpiration dates for consumer drugs? One reason is that the consumer marketlacks the military's logistical reasons to keep drugs around longer.
Frank Holcombe, associate director of the FDA's office ofgeneric drugs, says that in many cases a manufacturer could extend expirationperiods again and again, but to support those extensions, it would have to keepdoing stability studies, and keep more in storage than it would like.
Mr. Davis adds: "It's not the job of the FDA to beconcerned about a consumer's economic interest." It would be up toCongress to impose changes, he says. As things stand now, expiration dates geta lot of emphasis. For instance, there is a campaign, co-sponsored by some drugretailers, that urges people to discard pills when they reach the date on thelabel.
And that date often is even earlier than the one the makerset. That's because when pharmacists dispense a drug in any container otherthan what it came to them in, they routinely cut the expiration date to justone year after dispensing. Some states even require pharmacists to do this.
Meanwhile, poor countries - under urging from the WorldHealth Organization - often reject drug-company donations of much-neededmedicines if they are within a year of their expiration dates.
It isn't known how much of the $120 billion-plus spentannually in the U.S. on prescription and over-the-counter medicines goes toreplace 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 prescriptiondrug after its expiration date; 72 percent said the same of an over-the-counterremedy.
"People think that, upon expiration, drugs suddenlyturn toxic or lose all their potency," says Philip Alper, professor ofmedicine 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 berequired to test drugs for longer periods and set later expiration dates whenresults warrant.
Some manufacturers first began putting expiration dates ondrugs in the 1960s, although they didn't have to. When the FDA began requiringsuch dating in 1979, the main effect was to set uniform testing and reportingguidelines. As now required by the FDA, so-called stability testing analyzesthe capacity of a drug to maintain its identity, strength, quality and purityfor whatever period the manufacturer picks. If the company picks a two-yearexpiration date, it needn't test beyond that.
Testing for a two-year expiration doesn't initially entailholding a drug for two years. Rather, the drug is tested by subjecting it toextreme heat and humidity for several months, then chemically analyzing eachingredient's identity and strength. (After the date is set and the drug ismarketed, testing continues for the full two years.) The FDA also uses chemicalanalysis in testing for possible shelf-life extension; it doesn't test on humansubjects. Testing conditions are such that any medicine that meets, say, thestandards for a two-year expiration date probably lasts longer, the FDA anddrug companies agree.
Consider aspirin. Bayer AG puts two-year or three-yeardates 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 "continuousimprovement programs," Mr. Allen says. Each change triggers a need formore expiration-date testing, he says, and testing each time for a four-yearlife would be impractical.
Bayer has never tested aspirin beyond four years, Mr.Allen says. But Jens Carstensen has. Dr. Carstensen, professor emeritus at theUniversity of Wisconsin's pharmacy school, who wrote what is considered themain text on drug stability, says, "I did a study of different aspirins,and after five years, Bayer was still excellent. Aspirin, if made correctly, isvery stable."
Only one report known to the medical community linked anold drug to human toxicity. A 1963 Journalof the American Medical Association article said degraded tetracyclinecaused kidney damage. Even this study, though, has been challenged by otherscientists. Mr. Flaherty says the Shelf Life program encountered no toxicitywith tetracycline and typically found batches effective for more than two yearsbeyond their expiration dates.
Plea from the Air Force
The program dates to a U.S. effort begun in 1981 toincrease military readiness by buying large quantities of drugs and medicaldevices for the armed forces. Four years later, more than one billions dollarsof supplies had been stockpiled. The General Accounting Office audited AirForce 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 spentyearly on replacements.
The Air Force Surgeon General's office asked the FDA if itcould possibly extend the shelf life of these drugs. The FDA had the equipmentfor stability testing. And because it had approved the drugs' sale in the firstplace, it also had manufacturers' data on the testing protocols. Testing forthe Air Force began in late 1985. In the first year, 58 medicines from 137different manufacturing lots were shipped to the FDA from overseas storage,among them penicillin, lidocaine and Lactated Ringers, an intravenous solutionfor dehydration. After testing, the FDA extended more than 80% of the expiredlots, by an average of 33 months.
In 1992, according to the FDA, more than half of theexpired drugs that had been retested in 1985 were still fine. Even now, atleast one still is. Such results came as a revelation for Army Col. GeorgeCrawford when he took over military oversight of the program in 1997. He is apharmacist, but "nobody tells you in pharmacy school that shelf life isabout marketing, turnover and profits," he says. (The drug makers don'tagree that it is, however.)
How It Works
The military's base for the program is a dingy barracksroom in Fort Detrick, Md. There, a group headed by Air Force Lt. Col. GregRussie, who recently took over from Col. Crawford, tracks drugs that are nearexpiration at defense facilities all over the world, selecting many forretesting. They are shipped to the FDA, which sends them to its laboratories.
The FDA's lab in Philadelphia recently tested fiveautomatic injectors containing an antidote to chemical poisoning, which werepurposely held for three months in conditions even hotter and more humid thanthe FDA requires in consumer testing of drugs. The FDA tested the drugcontained in the injectors, pralidoxime chloride, by separating its ingredientsand measuring the strength and quality of each, then applying a computer modelto 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 theircontinued use. The batch, made by Ayerst Laboratories, now part of AmericanHome Products Corp.'s Wyeth-Ayerst unit, is 18 years old. It is 15 years beyondthe expiration date applied by Ayerst. The FDA found it is still good.
A spokesman for Wyeth-Ayerst says it "uses scientificdata to establish expiration dates" and "tries to have the longestpossible dating on products that scientific data supports." The company isaware of the FDA retesting program. It says it can't comment specifically on theinjectors tested by the FDA.
A Few Fail
Shelf-life extensions are "intentionallyconservative," the FDA's Mr. Flaherty told military brass in a 1992speech. He says that if the agency extended an expiration date by 36 months, ithad concluded the lot would retain all of its safety and efficacy for at least72 months. A very few drugs aren't retested. The military has found thatwater-purification tablets and mefloquine hydrochloride, for malaria, routinelyfail stability testing beyond their expiration dates, so it has removed themfrom the program.
Also excluded are large-volume intravenous solutions, suchas saline. "We don't like to test those," says Col. Crawford."Not because we can't, but because it would be politically sensitive ifG.I. Joe was lying in bed and saw it had originally expired three yearsago."
Mr. Flaherty has said that while he tested a handful ofdrug batches that didn't even make it to their expiration dates, most drugswere "surprisingly durable." In one instance, he says, drugs labeledfor room-temperature storage had been kept for two years in a warehouse in Omanthat averaged 135 degrees Fahrenheit in the daytime. Upon expiration, thedrugs, which included the local anesthetic lidocaine and atropine, a nerve-gasantidote also used by eye doctors to dilate pupils, "were well within thestandards for potency and other quality characteristics," he says.
One medicine the FDA has endorsed for extensions isciprofloxacin 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 moremonths and others for 24 more months.
Albert Poirier, quality-assurance director for Bayer'spharmaceutical division, says he isn't surprised because Cipro "is astable drug molecule" in tablet form. "We go for a shelf life thatwill be safest for patients," he says. "We want the drug to be usedup within three years. We wouldn't want a patient to have it for 10 yearsbecause they'd have an old package insert" that might omit new informationor contra-indications and because "we'd have no control over how they'dstore the drug during this time."
Another extended drug is Thorazine, a tranquilizerchemically known as chlorpromazine tablets. Batches bearing December 1996expiration dates - unused and unopened, as is the case with all drugs evaluatedin the Shelf Life program - were tested in July 1998 and extended for twoyears. A spokesman for the maker, SmithKline Beecham PLC, says it applies anexpiration date 24 months after manufacture. "We think that is theappropriate expiration date," he says. "We don't benefit from shortexpiration dates."
Some other drugs the FDA has extended at least two yearsbeyond their expiration dates are diazepam, sold as Valium; cimetidine, sold asTagamet; phenytoin, sold as Dilantin; and the antibiotics tetracycline andpenicillin.
On a cost-benefit basis, the program's returns have beenhuge. The first year, the Air Force paid the FDA $78,000 for testing and saved59 times that sum by not needing to replace the drugs. After other servicesjoined, the military from 1993 through 1998 spent about $3.9 million on testingand saved $263.4 million on drug expense, according to Lt. Col. Russie.
Says Mr. Flaherty: "We've cost the pharmaceuticalcompanies hundreds of millions of dollars in sales of new stuff to theDepartment of Defense." More than 12 years ago, Messrs. Flaherty and Davisexplained the program to drug-company chemists at a meeting of the AmericanAssociation of Pharmaceutical Scientists in Woodbridge, N.J., going into detailabout how the FDA decided whether to extend a given expiration date. Mr. Davisconcluded by noting how much the U.S. had saved by extending shelf livesinstead of "destroying large quantities of still-useful medical products..."
Mr. Flaherty says the FDA was keenly aware that if itsmethodology was flawed, or its results incorrect even once, its credibilitywould 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 tochallenge it," he says.
The Message to Civilians
While the military is finding it can keep most drugslonger, civilians hear quite a different message. For instance, a campaigncalled the National Expired and Unused Medication Drive has collected anddestroyed 36 tons of drugs since 1991, says its founder, Kathilee Champlin. Ms.Champlin, of Colorado Springs, Colo., says her interest derives from experienceworking with the elderly and seeing how hard it was for them to keep track ofall their medications. She says she wasn't aware of any FDA program to extenddrugs' shelf lives.
Her group has gained sponsorship from the some big drugretailers, including Wal-Mart Stores Inc. It sponsors the campaign to be"a good corporate citizen," says Frank Seagrave, vice president ofpharmacy merchandising. "
We believe that people should dispose of unusedprescription medicines a year after they get them," he says, adding thatWal-Mart sometimes gives people a free bottle of vitamins if they bring inexpired drugs.
Many pharmacists also play a role in shelf lives. The U.S.Pharmacopeia, a not-for-profit scientific group that develops standards for thedrug industry, urged in 1985 that pharmacists set expiration dates at no morethan one year if they were dispensing drugs in a bottle other than themanufacturer's original packaging. "New containers may let in moremoisture and heat than the container the manufacturer used for the stabilitystudy," accelerating the drug's degradation, says the USP General CounselJoseph Valentino.
The recommendation became a USP requirement in 1997. As aresult, "the majority of pharmacists shorten the manufacturers' expirationdates" on prescription drugs to one year or less, says Susan Winckler, anofficial of the American Pharmaceutical Association. In fact, in 17 states,pharmacists now are legally required to do so. Ms. Winckler says shortening thedates makes sense because many people store drugs in moist bathrooms. She saysthe one-year rule is "motivated by product integrity and not byprofit."
By Dr. Mercola
We can clearlygain some valuable insights from this incredible piece in the Wall Street Journal and sent in byever-diligent Michael Belkin.The key from the article is "shelf life isabout marketing, turnover and profits." Over the course of the past twodecades, U.S. spending on prescription drugs increased from $40 billion to morethan $230 billion. If drug companies convince you to empty out your medicinecabinets annually, those profit margins could increase even more.
I find itabsolutely incredible that the military spent from 1993 through 1998 about $3.9million on testing and saved $263.4 million on drug expense. So, on a personallevel, unless you have nitroglycerin, insulin and liquid antibiotics, you maybe able to use your medications far beyond the expiration date on the bottle. Ibelieve the major tragedy is that many Third World countries needlessly discardthe drugs that are sent to them and could actually be saving lives due to lackof appreciation of this concept.
The key from the article is "shelf life is about marketing, turnover and profits. 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.
We can clearly gain some valuable insights from this incredible piece in the Wall Street journal and sent in by ever diligent Michael Belkin.
Unless you have nitroglycerin, insulin and liquid antibiotics, you can pretty much be safely assured that your medication expires years beyond the date it says it does. 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.