June 16, 2014

Global Expansion Shapes Drug Oversight

Regulators and industry organizations explain policies and standards to manufacturers and authorities in all regions.

Few FDA officials discuss pharmaceutical regulation these days without reference to how the international reach of the biopharmaceutical industry has altered drug research, production, and regulation. At the annual meeting of the Food and Drug Law Institute (FDLI) in April 2014, FDA commissioner Margaret Hamburg concluded her keynote address by describing a “dramatically changing global marketplace” and its “huge implications” for FDA’s ability to ensure the safety and quality of products manufactured elsewhere. To better assess product risks, Hamburg proposed “enhanced intelligence” and more collaboration with regulatory partners through bilateral and multilateral agreements and through international organizations.

In addition to conducting more inspections and oversight of foreign manufacturers, FDA is working with international organizations to communicate its policies and standards more clearly and to enhance regulatory capacity in emerging countries. In a March 2014 lecture to the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA), Hamburg described efforts underway to form an International Coalition of Medical Regulatory Authorities (ICMRA), which would work to coordinate and enforce regulatory standards to ensure product safety and quality around the world.

At the same time, FDA and the European Medicines Agency (EMA) annouced plans to expand their many collaborative programs, including renewal of a pilot program that allows for parallel review and consultation on quality-by-design (QbD) components to new drug applications and supplements, an initiative designed to provide consistency and clarity to QbD policies.

At a London meeting in April, senior leadership from FDA, EMA, and the European Commission reviewed efforts to leverage each other’s inspection resources; collaboration to support global development of biosimilars; pediatric cluster meetings to encourage more common policies for pediatric studies and applications; information exchange by the EMA-FDA pharmacovigilance cluster; and broader cooperation related to veterinary medicines. The participants also discussed the creation of a EU-US Identification of Medicinal Products task force to explore adoption of US substances registration software in the EU, with an eye to forming a global identification system for medicinal products.

And last month, Howard Sklamberg, deputy commissioner for Global Regulatory Operations and Policy (GO), Janet Woodcock, director of the Center for Drug Evaluation and Research, and Karen Midthun, director of the Center for Biologics Evaluation and Research, unveiled a new initiative to collaborate more with EMA and European governing bodies to enhance pharmaceutical quality. FDA will be represented by a European-based team, with the aim of moving beyond information-sharing to “strengthen mutual reliance” on trusted regulators outside the US.

Challenges in India and China
At the MHRA meeting, Hamburg commented on her visit to India in February and FDA efforts to expand inspections and develop stronger ties with local regulatory authorities. The commissioner acknowledged that FDA has imposed import alerts on multiple drugs produced by leading Indian pharmaceutical companies such as Wockhardt Ltd. and Ranbaxy Laboratories, but emphasized that FDA was not “targeting” Indian manufacturers, but applying consistent inspection and quality evaluation standards to all products imported into the US.

FDA is expanding its presence in China even more to monitor the rising volume of APIs and medical products produced for US markets. At a hearing before the US-China Economic and Security Review Commission, held in Washington, D.C. in April 2014 to assess the safety of medical products imported from China and other health-related trade issues, this Congressionally appointed panel queried experts on the difficulties faced by FDA and manufacturers in ensuring the quality of Chinese drug products and components.

Christopher Hickey, the director of FDA’s China office, reported on increased FDA inspections in China—up to 84 in 2013 from 46 in 2010. Hickey acknowledged that his office has only two full-time field inspectors, but has plans to double FDA’s China staff, pending resolution of delays in obtaining necessary visas. He also noted formation of an FDA-China working group on economically motivated adulteration of medical products.

With some 4000 establishments producing medical products and substances intended for the US, however, Commission members concluded that FDA’s operation seems “woefully, inadequately staffed” for its job. Numerous API samples are falsified or substandard, according to research by the American Enterprise Institute. Alan Coukell of The Pew Charitable Trusts described rising concern over reliance on Chinese sources for key ingredients in older pain-relief medicines and antibiotics. He noted that more frequent FDA inspections of foreign drug establishments are important in prompting manufacturers to meet quality measures and agreed with Hickey that manufacturers of finished drugs need to do more to monitor suppliers and contractors.


Tags: drug development; regulatory agencies; bioprocess development