FDA Waves a Big Stick - Pharmaceutical Technology

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FDA Waves a Big Stick
Agency officials and manufacturers anticipate stricter enforcement of drug safety and quality.

Pharmaceutical Technology
Volume 33, Issue 6, pp. 30-35

Global challenges

Legislative efforts and FDA initiatives reflect the effect of global drug manu-facturing on ensuring product safety and quality. Such "supply-chain fragmentation and geographic dispersion of drug manufacturing add new risks," said CDER Director Janet Woodcock at the FDLI meeting. Foreign drug-manufacturing sites now outnumber registered domestic facilities (an estimated 3700 overseas and 2500 in the US, according to 2008 figures), and the volume of drug products made overseas continues to rise. Registered drug manufacturers in India increased 25-fold from 2001 to 2007, and China has experienced a 7-fold increase during the same period.

Woodcock described many drug products as "world travelers," with the API made here, vials there, and labeling elsewhere. Autor advised manufacturers to look for red flags indicating problems such as the widespread swine flu and the heparin contamination crisis. These crises provide an "open invitation to dishonest activity," she said, emphasizing the importance of corporate responsibility to protect against product contamination and unethical behavior.

Adulteration. More cases of apparently intentional contamination of imported food and drug products involving melamine and heparin, respectively, have prompted FDA to focus on the factors behind incidents involving dilution or substitution of ingredients in food and drugs primarily to increase profits. At a public meeting last month, agency officials heard from manufacturers and other interested parties about ways to predict, prevent, and address economically motivated adulteration (EMA). Attendees discussed which types of products are most vulnerable, how manufacturers track and verify product components and ingredients, where supply chains are open to abuse, and what analytical methods can best detect contamination.

Randall Lutter, FDA deputy commissioner for policy, defined EMA as the "fraudulent, intentional substitution or addition of a substance in a product for the purpose of increasing the apparent value of the product or reducing the cost of its production, i.e., for economic gain." This action may involve diluting or watering down drugs, possibly by increasing the inactive ingredient in a product.

FDA noted that dramatic shifts in product supply, perhaps from the entry of additional companies or a shift of production to new regions could signal fraudulent activity. EMA may involve expensive biologics that are relatively easy to engineer, or less costly medicines that are widely used. Although Lutter wants manufacturers to report any signs of fraud or product adulteration, he noted that confidential information that might be useful to the adulterers should not be revealed.

At the public meeting, academic experts described models for detecting shifts in supply chains that can signal fraudulent activity. Roger Williams, CEO of the US Pharmacopeia (USP), urged broader FDA and industry support of efforts to update USP monographs that set drug quality standards. USP was in the process of revising its heparin monograph when the contamination crisis happened, he explained, noting that "that revision came too late."

Supply-chain validation. Manufacturers voiced support for wider use of accredited third-party inspectors to audit foreign producers of active and inactive ingredients, as well as required registration of all ingredient producers and stiffer penalties for drug counterfeiting and adulteration. Martin Van Trieste, vice-president for quality at Amgen and member of the Pharmaceutical Research and Manufacturers of America (PhRMA) Quality Technical Group, backed the development of a proposed Qualified Trusted Importer Program, a voluntary certification program for qualified and compliant importers.

Van Trieste also described industry efforts to form the Rx–360 consortium, which aims to develop best practices for supply-chain management and new approaches to supplier auditing and adulteration detection. The group is holding a launch meeting in Washington, DC, on June 5, to discuss audit models and methods for monitoring suspicious events. Such efforts, he noted, would benefit from assurance that manufacturers can share information on suppliers and other issues without running afoul of antitrust laws.

Criminal elements have entered into the drug supply chain, warned Van Trieste, and it's only a question of when and where EMA will occur again. The short supply of antivirals during a pandemic influenza outbreak, he said, provides the "perfect opportunity for someone to come in and make a quick buck." Industry and FDA, he said, need to think like the criminals to detect adulterated products.

Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634,


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