By Annette M. Boyle
FORT DETRICK, MD – Far from expiring in the one to five years stated on their labels, many prescription medications may retain their full potency for 10, 20, even 40 years.
That was underscored in a research letter recently published online in the Archives of Internal Medicine by Lee Cantrell, PharmD, of the California Poison Control System and colleagues. The group tested eight-decades-old prescription medications unearthed in a retail pharmacy and found that 12 of the 14, or 86%, of the compounds tested in the drugs retained at least 90% of their potency 28 to 40 years after their expiration dates.1
Those results came as no surprise to those involved in the DoD/U.S. Food and Drug Administration Shelf Life Extension Program (SLEP), which has been testing pharmaceuticals for more than 25 years to estimate when drugs actually will lose their potency.
The medications tested by Cantrell and colleagues contained several common ingredients. Of these, only aspirin and amphetamine had deteriorated below generally recognized minimum acceptable potency. One other, phenacetin, showed a concentration of less than 60% when tested in one medication, but 110% in another. Compounds that maintained full potency included acetaminophen, caffeine, codeine, methaqualone, butalbital, phenobarbital, pentobarbital, secobarbital, meprobamate, hydrocodone and chlorpheniramine.
“This study provides additional evidence that many prescription pharmaceuticals retain their full potency beyond their manufacturer-ascribed expiration dates,” the authors write in their research report. “Given the potential cost-savings, we suggest that current practices of drug expiration dating be reconsidered.”
Faced with huge expenses for restocking expiring pharmaceuticals, DoD came to the same conclusion in 1985.
Through SLEP, the FDA has tested scores of drugs approaching their expiration dates. In the first batch of 56 items tested, 84% were given conservative extensions of as long as three years.
The research letter authors noted that an analysis of SLEP results in 2009 showed that 88% of 122 different drugs stored in unopened, original containers in controlled environments at military facilities retained potency for at least one year past their expiration date. The average extension time for all drugs was 6.5 years, while the maximum to date has been more than 23 years.
Under current protocols, medications are not extended past 10 years from the manufacturer’s expiration date, according to materials provided by the SLEP program director, Air Force Lt. Col. Julie V. Guill, PharmD, RPh, of the Defense Medical Materiel Program Office (DMMPO) Office of the Assistant Secretary of Defense (Health Affairs) Force Health Protection & Readiness.
While many drugs have qualified for extended shelf life, not all drugs are eligible for testing through the FDA program. SLEP restricts testing to “military significant” medications, “those that are either military-unique, possessing no commercial (non-DoD) market or those drugs for which the DoD procures such large quantities for pre-positioned stocks that vendors are unwilling to accept them for credit upon expiration,” Guill told U.S. Medicine.
The FDA will not normally test medications if less than $10,000 of a lot is held by SLEP participants unless a drug in short supply is needed for a possible event or operation.
Even with a restricted number of medications eligible for the program, DoD’s savings have been substantial. According to the authors of the research letter, “each dollar spent on SLEP to demonstrate longer than labeled drug stability results in $13 to $94 saved on reacquisition costs.”
To convert those dollars to savings per drug, Guill noted that, “in 2006, we tested ciprofloxacin and extended it for two years, saving the U.S. government in excess of $1.5 million on that one product alone.”
She added that, “in Israel, the only other country with a shelf life extension program, testing of ciprofloxacin is predicted to result in savings of more than 60 million shekels [$15.3 million] over a period of 10 years.”
These extensions — and savings — are possible because the FDA does not require manufacturers to actually determine how long a drug will remain stable. The expiration date, typically 12 to 60 months from date of production, reflects a minimum window, the period through which the manufacturer guarantees the medication’s potency.
To qualify for SLEP testing, drugs must be in their original, sealed containers and have been stored continuously under conditions specified by the manufacturer. Once the drugs arrive for testing, though, the conditions change dramatically.
Most medications undergo accelerated or stress testing designed to increase the rate of chemical or physical degradation. For 60 days, each sample is stored a chamber that maintains a temperature of 122oF or 50oC and humidity of 75%. Then, the potency of the samples is compared to the standard for that medication, and the FDA calculates the extendable life based on those results.
The FDA grants extensions for all SLEP participants with inventories of the drug that match the lot number, initial expiration date and manufacturer. Medications are retested annually or biannually to confirm or further extend the expiration date. Products that fail testing or are not tested must be destroyed upon reaching their expiration date. The FDA will not test biological products such as vaccines, serums, blood products or toxoids.
“Our testing requires each of our participants to provide direct sampling of medications from inventories they have registered with SLEP,” noted Guill. “It is not unheard of to have samples from the same lot fail testing. While many medications have a strong history of successful extension, others are predictably unpredictable, meaning sometimes they can be extended the full timeframe and sometimes they fail testing with no discernible pattern.”
Extended or Not
For military pharmacists, telling whether a particular product has been extended is simple enough. The FDA Center for Drug Evaluation and Research recommends that extended medications within the DoD have the lot number, new expiration date and FDA project number imprinted on a new sticker. The original label should remain on the package, as well.
Rather than relabeling every unit in centralized storage that receives an extension, SLEP participants can label only the outer cartons of products with the updated information. Individual units must be properly labeled with stickers containing the detailed information about the extension before they leave centralized storage.
Changes in the supply system for medications during the past decade have altered the focus of SLEP.
As DoD moves from a depot-centered distribution system to one dominated by just-in-time deliveries from prime suppliers, the need to extend expiration dates on large stocks of drugs has declined. As a result, the focus of the program has shifted to war reserve; pandemic influenza; anti-malarial products and chemical, biological, radiological and nuclear medical materiel.
1. Cantrell L, Suchard JR, Wu J, Gerona RR. Stability of Active Ingredients in Long-Expired Prescription Medications. Arch Intern Med. 2012 Oct 8:1-2. doi: 10.1001/archinternmed.2012.4501. [Epub ahead of print] PubMed PMID: 23045150.