Late last year, an FDA official told the New York Times that the drug shortage issue was abating. But two drugs commonly used in rheumatology, injectable methotrexate and methylprednisolone acetate injection, remain in short supply. Why do shortages happen, and what can be done?
Late last year, an FDA official told the New York Times that the drug shortage issue was abating. But two drugs commonly used in rheumatology, injectable methotrexate and methylprednisolone acetate injection, remain in short supply.
What can you expect for the future about drug shortages? Here, a few answers:
Why do shortages occur?
Often, the cause is unknown. Manufacturers aren’t required to report the reasons, though some do. The stated reasons vary: Increased demand (especially for anticancer and rheumatology drugs), shortage of raw materials, manufacturing problems.
Among the larger issues:
• Steadily increasing demand for anticancer and rheumatology drugs strains manufacturers’ capacity.
• Especially for low-cost generics, where profit margins are slim, manufacturers have little economic incentive to expand capacity rapidly enough to assure a continuous supply (2011 report on drug shortages from the Department of Health and Human Services).
• Manufacturers of generics tend to keep a relatively low inventory (2012 analysis by FDA authors in Clinical Pharmacology & Therapeutics).
• Oral products are less vulnerable than injectable because it is easier to ramp up production quickly for tablets or liquids than for injectables.
Which rheumatology drugs are most often in short supply?
Generics and injectables account for about 2/3 of shortages (Government Accounting Office, 2011). For example:
Methylprednisolone acetate injection: Linked to the recent fungal meningitis outbreak, this is in short supply from manufacturers Sandoz and Teva, after the FDA closed the New England compounding firm responsible for the contamination. Sandoz and Teva “could not provide a reason for the shortage” (American Society of Health System Pharmacists). Both companies report that this drug is on back order; neither has estimated a release date.
Methotrexate injection: A diverse list of reasons.
• Sandoz recalled their 2 mL and 10 mL methotrexate preservative-free vials in October, 2010, without saying why.
• Manufacturer APP discontinued the 2 mL vials at 25 mg/mL (with preservative); 10 mL vials are on shortage due to increased demand.
• BenVenue (Bedford Labs) of Ohio voluntarily suspended all manufacturing and distribution in mid-November, 2011, responding to FDA quality concerns.
• Hospira had methotrexate on shortage due to "manufacturing delays".
• Mylan Institutional acquired methotrexate supplier BioNiche in 2011 and has not explained the shortage since then.
The American Society of Health System Pharmacists maintains a complete list of drug shortages.
What is being done to alleviate the problem?
The Food and Drug Administration Safety and Innovation Act (FDASIA), passed in July 2012, provides the FDA with additional authority to prevent and rectify drug shortages. By August of last year the Agency said the new law had helped it to prevent 100 drug shortages.
Among other changes in authority, FDASIA:
• Requires all manufacturers (no longer just the sole manufacturer of a drug) to notify FDA of anticipated discontinuances, whether temporary or permanent;
• Includes mandatory reporting for biological products in short supply (previously exempted);
• Requires FDA to issue a public non-compliance letter to manufacturers who fail to comply;
• Requires FDA to establish a strategic plan for enhancing response to drug shortages by July 2013;
• Allows FDA to expedite review of applications that may mitigate or prevent a shortage;
• Requires the Agency to maintain an up-to-date list of drugs in shortage, including the cause and estimated duration, and to establish a mechanism for third parties to report shortages. (However, the list is only for "medically necessary" drugs and may not be complete.)
If you encounter a shortage, you can try:
Prescribing a different dosage schedule
Using a different mode of administration, if possible
Looing for a different supplier (Often alternatives are suggested at the ASHP website)