International Harmonization Gains Importance for Global Pharmaceutical Industry

Concerns about the quality and safety of the growing volume of medicines imported to the United States, pressure to set international policies for genome editing of other scientific developments and escalating international trade disputes have prompted FDA to examine and update its programs for overseeing global operations and international affairs. The Office of Global Policy and Strategy in the newly named Office of Policy, Legislation & International Affairs (OPLIA) aims to better link consideration of international policy and trade issues with the challenges in ensuring the quality of ever-more imported medical and food products. The change reflects the global importance of FDA’s public health mission and its engagement in multiple initiatives to streamline and harmonize international standards and policies for regulated products.

A “clear global policy strategy” has never been more important, says FDA Deputy Commissioner and OPLIA Director Anna Abram, noting the need for FDA to respond quickly and effectively to international disease outbreaks such as Ebola and to deal with a soaring amount of food and drug imports. More than three-fourths of APIs are produced by firms located outside the US, Abram noted at the recent annual meeting of the Food and Drug Law Institute (FDLI) in Washington, D.C., adding that the agency’s network of foreign offices provides a valuable overseas “presence” for FDA and are important in supporting foreign inspections, obtaining feedback on international developments, and for explaining FDA actions and policies to foreign constituencies.

Mutual reliance

FDA is involved with a number of partnerships and collaborations with regulatory counterparts designed to streamline procedures for bringing new products to market in multiple regions, Abram noted. An important challenge is to inspect the thousands of foreign facilities that export to the US to ensure the quality of imported pharmaceuticals and other regulated products. As this task has expanded exponentially, FDA seeks to rely more on inspection reports produced by competent regulatory authorities in the European Union and other advanced nations. FDA and EU authorities have negotiated a mutual recognition agreement (MRA) that enables sharing of inspection reports for domestic drug manufacturers as a way to avoid duplicate inspections and to focus resources on more high-risk situations. The MRA is on track to be finalized this year following FDA’s recent announcement that it now has assessed and recognizes inspectorates in 24 of 28 EU member states.

Despite this and other collaborations, FDA still needs to monitor a vast number of drug manufacturers in China and India and other third-world nations that produce APIs and generic drugs for the US. Deborah Autor, senior vice-president at Mylan Pharmaceuticals, expects that more drugs and medical products will be coming in from overseas, as manufacturers move to more corners of the world where it is less expensive to operate. Regulatory partnerships for conducting inspections and for establishing product standards are “crucial” to advancing drug development and for expanding patient access to needed therapies, Autor observed at the FDLI meeting, so that manufacturers may satisfy registration requirements in multiple markets based on an approval one regulatory authority.

More harmonization

International standards for drug testing and manufacturing can further this goal by reducing a proliferation in divergent regulatory approaches around the world, as seen in new initiatives at the International Council for Harmonization (ICH), which has expanded to include representatives of nations from all regions of the world. ICH is shifting from establishing specific technical standards to developing more conceptual guidelines for modernizing good clinical practices, drug safety assessment, and quality production. A new draft guideline (E8) on the design and conduct of clinical trials, for example, identifies principles and practices in clinical studies that are crucial to ensuring data quality and for results to be accepted by regulators. Harmonization may extend to approaches for conducting drug-drug interaction studies, adaptive clinical trials, and for incorporating pediatric information extrapolation into drug development plans.

In the drug quality area, ICH participants are scheduled to finalize a new framework for managing post-approval manufacturing changes as a way to facilitate improvements in drug products and production methods during the product lifecycle. Additional projects aim to harmonize policies for overseeing continuous manufacturing and for bioequivalence testing of generic drugs. Also, in the works are initiatives to streamline the collection of safety data in late-stage trials and post-marketing studies, to improve validation of bioanalytical assays for non-clinical and clinical studies, and to agree on electronic standards for submitting individual case safety reports to regulatory authorities.

To further ensure that FDA policies are effective in enhancing public health at home and abroad, the agency has requested that the National Academies of Science, Engineering and Medicine review its foreign operations and how well they enhance public health. In particular, the project is assessing FDA’s ongoing efforts to build the capacity of food and drug regulatory agencies in low- and middle-income countries to help ensure the safety and quality of regulated products.