Drug Expiration Extension Program


  • March 12, 2012

The FDA’s homepage contains an item in the Public Health Focus section from the Office of Communications entitled “Don’t Use Expired Medicine.” Given this mandate, I recall from many years ago the following conundrum.  A known hemophiliac patient, with a potent inhibitor to human factor VIII was bleeding uncontrollably, and all available porcine factor VIII in the pharmacy was out-of-date.  Porcine blood product was the only effective treatment at the time for this clinical situation in which factor replacement with human material was pointless.  Vigorous discussion ensued regarding the chances of lessened efficacy of the available vials.  This was not just an academic question, given the cost of treatment to prevent fatal bleeding in this patient was expected to be greater than $50,000.  No one considered whether the product might prove toxic, but that was because the treating physicians were relatively ignorant about the processes of drug denaturation and production of degradants, and the risks from these processes.

Reading this recent FDA communication was a reminder that expiry dates are driven by the availability of supportive stability data.  Stability studies generally are sufficient to demonstrate an economically-viable stability period such as 2-3 years, yet rarely have such studies been carried out to demonstrate the success or failure of the medication’s stability at points later than the designated expiration period.  Despite this data limitation, many thoughtful arguments have been espoused over the years regarding the potential for recycling expired medications, especially to avoid the waste of expensive and/or limited-availability drugs.  A FDA/DOD program to produce data on actual shelf lives of medications (SLEP, the Shelf Life Extension Program) has evaluated extended stability profiles for a couple of decades, finding, not surprisingly, that the majority of tested drugs retain adequate stability of at least a year, or longer, than their labeled expiration dates.  Specifically, testing 3,005 lots of 122 drug products that were near their expiration date found 88% extended beyond expiry, with most showing continued adherence to USP or product release specifications, and extended stability of 62 months.  Some medications, such as naloxone, halothane, fentanyl and others had 100% demonstrable stability of lots for at least 4-5 years after expiration.  For most drugs, however, stability beyond expiration showed considerable lot-to-lot variability such that periodic testing would be required to guarantee adequacy of the medications.

Should the military, or other entities, test and stockpile critical medications beyond the published expiration test in case of insufficient availability of within-expiration product?  Could such medications, if shown by evaluation such as SLEP to retain adequate potency, be donated to developing countries in which the usual commercial product is either prohibitively expensive or not readily available, or be used in the US during periods of critical drug shortages?  More generally for standard, common drugs used in the US, should there be an attempt to remedy the clear conclusion that expiration dating often underestimates the shelf life of products?  It seems to us that continued evaluation of shelf life extension programs makes sense to better define the benefit-risk trade-offs.  We wonder whether a mandated post-market commitment to evaluate a product’s potential for extended stability might be a reasonable consideration.

Posted by Bob Roth, Vice President and Worldwide Medical Director. For more information, please contact Bob at bob.roth@weinberggroup.com.