Some drugs are still potent past their expiration date. The typical initial expiration date for prescription products, ie, shelf-life, is usually 12-60 months. Technically, they should not be used past their labeled expiration date. But if some drugs are still potent and potentially usable, can their expiration date be extended?
The federal government oversees a supply of medical countermeasures (MCMs) that may be used in a public health emergency such as terrorist attack, flu outbreak, earthquake, or as we know, a pandemic. Replacing expired medicines gets expensive and if some do retain potency, it would be useful if they can be used. The FDA has the following programs to extend expiration dating on certain products:
- Manufacturer initiated: the manufacturer may choose to conduct extended stability studies.
- SLEP: The Shelf-Life Extension Program (SLEP), established in 1986 by the US Department of Defense, conducts extended stability studies on drugs in federal stockpiles like the Strategic National Stockpile. It was reported that for 122 different drugs (>3000 lots), 88% of the lots were extended by at least a year past their original expiration date, with the average extension ~5.5 years. The DoD has been able to extend expiration dates on some of these drugs and save significant money.
- EUA: emergency use authorization issued by the FDA to use a product past the expiration date for CBRN (chemical, biological, radiological, nuclear) emergencies.
- Enforcement discretion: the FDA won’t take action against products that are used past their expiration date.
- Drug Shortages: The FDA posts a list of critical drugs undergoing intermittent shortages that have extended use dates generated with additional stability studies conducted by the manufacturer. The list is extensive and updated frequently.
However, while this is all well and good for the government’s drug supply, what about in the civilian environment? The American Medical Association (AMA) tried in 2001 to encourage pharmaceutical companies to conduct longer stability studies and lengthen expiration dates. While there were no data found on the clinical benefits of extending the expiration date, surely there must be an economic benefit? PhRMA, the pharmaceutical industry spokesgroup, told the AMA the following (not surprisingly):
[L]engthening expiration dating for drug products in the civilian environment would not provide the same economic benefits that SLEP has provided to the military. PhRMA contends that additional stability testing would add substantial costs to drug development and manufacturing. Furthermore, PhRMA notes that most innovator drug products that are close to expiration can be returned to the manufacturer for credit. Finally, PhRMA argues that, whereas the military stores its drug products under optimal conditions, this would be far less likely in the civilian environment. PhRMA believes this poses potential problems of reduced efficacy and safety for patients.
Some useful suggestions for extending expiration dates were offered in this 2015 commentary: 1) require drug companies to complete long-term stability testing, as they do for ongoing monitoring for adverse events; 2) create noncommercial independent testing for true lengths of stability for civilian use since SLEP cannot data be extended to this; 3) or better yet, just use the SLEP data for top performing drugs.
There are people out there trying. A study was published in 2012 that had the extend-those-expiration-dates proponents abuzz. It examined the potency of drugs found in a pharmacy that had expired 28 to 40 years previously. Out of 14 drugs tested, 86% were found to retain >90% of their initial potency. While exciting, the study was quite small.
Few if any drugs are actually harmful after they expire. Toxicity of expired medications is an area that is still not well researched. The major risk of using an expired drug is the possibility that it may lose potency and not be effective for treating the intended condition.
These types of drugs should not be used past their expiration date. Discolored, powdery, odor-emitting drugs. Injectables that are cloudy or have precipitates. Antibiotics, suspensions, insulin, and nitroglycerin can quickly lose potency after their expiration date, especially if not stored properly. Drugs with a narrow therapeutic index, such as some anticonvulsants and warfarin. Sterile ophthalmic drops can lose sterility once their preservative degrades. Some of the drugs that had the most lots fail in the initial SLEP extension studies included albuterol inhalant, diphenhydramine spray, ergotamine/caffeine tablets, isoproterenol injection, phenobarbital cartridge needle, physostigmine injection, and lidocaine/epinephrine injection.
Speaking of epinephrine, the SLEP study above also found 50% lot potency failure of epinephrine in cartridge needles (brand not specified), and another study conducted in 2000 of EpiPen and EpiPen Jr. autoinjectors that were expired by 1-90 months found significantly reduced epinephrine bioavailability compared to controls that was proportional to the length past the expiration date. However, the authors concluded that if an expired EpiPen is all that is available during an anaphylactic reaction, it is reasonable to use it if there are no discolorations or precipitates in the solution. But some good news was found in another more recently published study in the The Journal of Allergy and Clinical Immunology in 2019. It reported an analysis of epinephrine concentrations in autoinjectors (EpiPen and Adrenaclick, their authorized generic versions, and Auvi-Q) collected from friends and relatives of the authors that had been stored under “real-life conditions”. Of 46 EAIs collected and analyzed, 80% had retained >90% of their initial potency between the labeled expiration date and 24 months beyond expiry. Again, another small study, but encouraging.
So, can expired medications be used [in an austere setting when resupplies are limited]?
The British Antarctic Survey operates two ships and five bases in the Antarctic region, receiving supplies from ships (not climate-controlled) that leave the UK in September and don’t reach the bases for 2-3 months. The ships travel through the tropics twice for three week periods in transit to the bases, then the drugs may be subjected to freeze-thaw cycles when being transferred from the ships to the base. Because of the periodic and delayed nature of the supply deliveries, drugs that were delivered with an adequate remaining shelf life to the bases may expire before they are opened to be used. The stability of five drugs that were up to 51 months post-expiry and returned to the UK were reported in this study: atropine, nifedipine, flucloxacillin, naproxen, and bendroflumethiazide. All drugs were found to be stable in these tests, but this was a small study and the authors cautioned that further studies need to be conducted, especially taking into consideration factors other than temperature and expiration date that affect drug stability, such as radiation, vibration, moisture, and packaging. They did state, however, “[I]n usual medical practice, it would be entirely unacceptable to use drugs once they have passed their expiration date; however, when working as a medical practitioner in a remote environment such as Antarctica, many of the normal rules of practice must be pragmatically adapted.”
So, based on the above studies, we know that some drugs retain potency after the expiration date if they are stored properly. In the engrossing lecture at the 2021 WMS conference “Medicine at the End of the World w/COVID” by Dr. Chang, the following was asked in the chat:
Did you end up finding any good resources on which expired medications or other medical supplies might still be good to use in those austere settings? Or did you end up throwing away everything that had expired?
Dr. Chang’s response: We do have a protocol for expired medication use, and try to evaluate if expired med is better than no med.
Question 2: How can healthcare practitioners improve the use of pharmaceuticals so less ends up as waste, affecting the environment and wildlife?
In “Going Green in Your Practice”, another great lecture at the conference, Dr. Lindstadt made a helpful suggestion. Because so many pharmaceuticals can end up in the environment and wildlife through disposal or excretion into the sewage system by humans taking medications, prescribers should do the following:
- Try to minimize the use of pharmaceuticals by limiting the quantity of medications prescribed for patients
- Limit the number of refills when appropriate
- Use evidence-based prescribing practices (like not prescribing antibiotics when they aren’t necessary) to decrease the amount of medication use
In addition, all healthcare practitioners can educate themselves on and encourage patients, families, and friends on the proper disposal of medications such as in drug take-back programs.
The AMA tried again in 2018 to do something about drugs nearing expiration and drug waste, stating: “Expiration and beyond use dates are tangentially related to prescription drug donation and/or recycling because they are fundamental criteria used to establish or reaffirm the integrity of returned products.”
Their suggestions were to:
[A]dvocate for new federal legislation that would allow: 1) nursing homes to recycle prescription drugs that are unused, sealed, and dated; 2) physician offices and clinics to donate prescription drugs that are unused, sealed, and dated to patients in need who are uninsured or underinsured; and, 3) cancer programs and clinics to accept and recycle cancer-specific drugs to patients in need who are uninsured or underinsured. Both of these resolutions reflect concerns about the intersection of rising drug costs, wastage and expiration of unused pharmaceutical products prompting their disposal, and existing problems with patient access and their ability to pay for needed therapies.
FDA: Questions and Answers for the Public Donating Drugs to International Humanitarian Relief Efforts
- FDA discourages individual consumers and small groups from donating drugs to relief efforts because these donations may not meet the legal requirements for sending drugs to other countries. Generally, drug donations from individual consumers will be destroyed.
WHO and partners: Guidelines for Medicine Donations 2010
- After arrival in the recipient country all donated medicines should have a remaining shelf-life of at least one year.
- Donation of medicines just before their expiry should be avoided as in most cases they will reach patients after expiry. The argument that short‐dated products can be donated in the case of acute emergencies, because of their immediate use, is incorrect. In emergency situations the systems for receipt, storage and distribution of medicines are often disrupted and overloaded, and donated medicines tend to accumulate.
- Donations of medicines with short remaining shelf‐life have caused trouble for recipients for many years. Appropriate disposal or reverse logistics of expired products must be agreed in advance.
PQMD: The Partnership for Quality Medical Donations, Inc.
- No expired product should ever be shipped. Product with less than 12 months to expiration can be donated [with appropriate approvals].
- Products beyond their expiry date or shelf life should be separated from usable stock. Expired products cannot be sold or supplied and arrangements need to be made for their destruction.
- Ensuring the proper disposal of unused or expired products is an important aspect of any donation plan. Product that is improperly disposed of can pose significant environmental and health hazards. When pharmaceuticals are not properly destroyed, they pose a serious environmental risk and can pollute the local ground water.
So are expired drugs still immortal or still DOA? Still depends.