AGGRAVATING SHORTAGES

DEA quotas on active ingredient supplies and production volume for schedule II drugs also have drawn scrutiny as factors contributing to shortages in critical drugs. Manufacturers claim that such controls have reduced supplies for treatments for attention-deficit/hyperactivity disorder (ADHD), which often contain amphetamines. DEA can amend aggregate drug production quotas during the year when there is a "legitimate need," explained Boggs. But he noted that it's hard to quantify such need, and the amendment process involves a lengthy comment-and-rulemaking procedure. FDA has been able to work with DEA to prevent shortages in several cases, notes Valerie Jensen, associate director of CDER's drug-shortage program, and Congress may modify the DEA quota-setting policy as part of legislation to address drug shortages in development on Capitol Hill.

FDA is moving aggressively to deal with shortages of critical drugs on all sides, as witnessed in recent actions to ensure access to two key cancer medicines. Commissioner Margaret Hamburg announced at a February 2012 briefing that FDA remedied a serious shortage in a version of cancer drug Doxil (doxorubicin hydrochloride liposomal injection) by authorizing Caraco Pharmaceutical Laboratories to temporarily import a replacement drug, Lipodox, produced overseas by India's Sun Pharma Global FZE. Serious manufacturing problems at contract supplier Ben Venue Laboratories, a division of Boehringer Ingelheim, dried up Doxil production for Johnson & Johnson's Janssen Products, leaving physicians desperate for supplies of this important cancer and AIDS treatment. FDA officials emphasized that import of this unapproved foreign drug will be a temporary, limited arrangement and was authorized only after the agency evaluated Sun to ensure the quality and safety of the product.

Hamburg said that FDA is dealing with these problems by expanding its drug-shortage team, providing guidance to industry on drug shortage notification procedures, and backing legislation to expand required reporting. By working closely with generic- and brand-drug makers, FDA has prevented 114 shortages since October 2011, Hamburg pointed out.

Yet, the commissioner also noted in a speech to the annual meeting of the Generic Pharmaceutical Association in February that the majority of drug shortage problems are related to compliance issues affecting product safety and quality. On almost the same day that APP announced expanded methotrexate production, FDA issued a scathing Warning Letter citing the company for significant manufacturing violations at its Grand Island, NY. facility, primarily related to heparin production. Hospira was able to ship some 65,000 vials of methotrexate in February because it obtained additional supplies of active ingredient and invested hundreds of millions of dollars in extensive plant remediation efforts to resolve serious quality manufacturing issues cited multiple times by FDA.

Manufacturers of medically necessary drugs "must invest in their manufacturing facilities," Hamburg advised the generic-drug manufacturers, noting that "quality is crucial for all products," and that visible shortages involving generic drugs could lead to public "to equate generics with quality concerns."