FDA Drug Shortage Strategy: Enforcement Discretion, Patient Public Relations

Rapid approval of a new, preservative-free generic methotrexate and permission to import an unapproved version of doxorubicin touted at press conference as FDA emphasizes the success of administrative efforts.

FDA’s efforts to combat drug shortages include a flexible regulatory approach towards getting alternatives towards market and muscular public relations activity aimed at making the public aware of its efforts as it pushes for legislation to expand its powers.

The most recent example of that one-two punch at the problem was an unusual Feb. 21 public press conference in which FDA announced that has its has allowed the importation of an unapproved version of a widely used cancer drug and speeded approval of a generic version of a different cancer drug to address scarce supplies of both.

The drugs in question are Janssen Biotech Inc.’s Doxil (doxorubicin), an anthracycline topoisomerase inhibitor indicated for ovarian cancer, AIDS-related Kaposi’s Sarcoma and multiple myeloma, and methotrexate, a chemotherapeutic agent used in combination with other drugs to treat a variety of cancers.

The agency will temporarily allow Sun Pharma Global FZE and its authorized distributor, Caraco Pharmaceutical Laboratories Ltd., to import their unapproved liposomal version of doxorubicin to address a shortage (Also see "The Drug Shortage Problem: Good Solutions are as Hard to Find as Some Critical Products" - Pink Sheet, 1 Oct, 2011.).

“When a critical drug is unavailable, and the [unapproved] substitute can produce a comparable outcome and has been evaluated by us for quality and for safety, we do have enforcement discretion to allow for its temporary and limited use,” FDA Commissioner Margaret Hamburg said at the press conference.

As for methotrexate, Hamburg said the agency’s 11-member drug shortage team has been at work with alternate manufacturers to address supply problems stemming from Ben Venue Laboratories Inc., which agreed to voluntarily shut down its plant in Bedford, Ohio Nov. 19. The agency was working with generic manufacturers Hospira Inc., Mylan NV and Sandoz International GMBH months before the plant shutdown, Hamburg said. Ben Venue has agreed to release emergency supplies of preservative-free methotrexate, and FDA granted accelerated approval of APP Pharmaceuticals Inc.’s preservative-free version Feb. 17. “We prioritized this application, as with any drug in short supply,” Hamburg said.

Patients’ Families Front And Center

At the news conference, FDA featured Sara Stuckey, mother of a six-year-old cancer patient son named Nate, to emphasize the need for action on drug shortages. “There are too many families like the Stuckeys worried that they won’t have the medication they need for the next treatment, or perhaps may have to stop a course of treatment, and are understandably anxious … about switching to a treatment that may have more side effects or may be less effective. Clearly, this is not acceptable,” Hamburg said.

She cited the Stuckeys again in discussing the progress FDA has made since last Oct. 31, when President Barack Obama signed an executive order on addressing drug shortages (Also see "Obama's Drug Shortage Efforts Focus On Personnel, Persuasion" - Pink Sheet, 31 Oct, 2011.). “There were 195 drug shortages in 2011, and 111 drug shortages have been prevented since the executive order back on Oct. 31, 2011, when we made the call for early notification,” she said. “Since then, we’ve seen a six-fold increase in voluntary reporting drug shortages. But more needs to be done so Nate doesn’t miss his next treatment.”

“As a follow-up to President Obama’s executive order, FDA is releasing draft guidance on mandatory and voluntary notification related to drug shortages,” Hamburg noted. The draft guidance fleshes out an interim final rule FDA released in December that increased the number of manufacturers that must report drug shortages to the agency (Also see "FDA’s Drug Shortage Reg Adds More Manufacturers, Products To Notification List" - Pink Sheet, 19 Dec, 2011.).

“We fully support bipartisan legislation to require drug manufacturers to report all prescription drug shortages to the FDA and give the FDA new authority to enforce these requirements,” Hamburg said.

The Role Of Industry

Congressional discussions are under way on including such language in the pending Prescription Drug User Fee Act reauthorization, and legislation aimed at expanding the notification requirements has bipartisan sponsors. But many Republicans are skeptical of placing the responsibility on FDA and are pushing for regulatory and reimbursement reforms to emphasize a market-based response (Also see "GOP Drug Shortage Strategy Pushes FDA Reform, Reimbursement Over Notification" - Pink Sheet, 13 Feb, 2012.).

FDA press conference featured firms praising their work with the agency, and naturally using the stage to note their own efforts to address the shortages. APP Pharmaceuticals’ Mitchell Ehrlich noted that the company “took a two-pronged approach” to the methotrexate shortage. “First, we began the process of significantly increasing the production of the preservative-containing methotrexate injection, taking our output over the next few weeks to nearly four times our historical rate.” The second prong was the rapid approval of the preservative-free version. Production began immediately, and the company will be able to begin supplying the product “in next four to six weeks.”

“APP Pharmaceuticals has attempted to fill the void left by other companies” for other drugs as well, Ehrlich said. For example, APP used to provide only 10% of the market demand for doxorubicin. This has now been increased to 60%. The story is similar for two other cancer drugs, etoposide, where the company went from 2.5% to 29% of the market, and cisplatin, where it went from 37% to 64%.

“APP believes that in-house manufacture is a more reliable way to supply the market than a virtual supply chain based on overseas, third-party production facilities,” Ehrlich said.