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.
FDA also resolved a critical shortage of methotrexate, also related to Ben Venue production problems, by expediting approval
of a manufacturing supplement from APP Pharmaceuticals and release of thousands of vials produced by Hospira. Preservative-free
methotrexate is needed to treat children diagnosed with acute lymphoblastic leukemia as well as other serious conditions.
FDA also is working with Mylan and Novartis' Sandoz Pharmaceuticals to increase their methotrexate production.
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."
Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, email@example.com