By: Melinda K. Plaisier, MSW, Associate Commissioner for Regulatory Affairs
Consumers must have confidence in the safety and quality of generic medicines. They also rely on FDA’s regulatory systems to ensure the quality and safety of globally produced drugs even before those products are on the market. Generic drugs are just as safe and effective as their brand counterparts and FDA stands behind the rigorous standards and regulatory inspections that go into ensuring the safety and quality of all generic drugs. These standards and inspections apply equally to generic and innovator drugs — domestically and around the world.
FDA has implemented a modernized approach to ensure and enhance adherence to these standards and to keep up with continuous globalization and increasingly complex supply chains. Through Program Alignment, FDA’s Office of Regulatory Affairs (ORA) has modernized its workforce and approach to improve public health in a way that keeps pace with the acceleration of scientific innovation, global expansion of markets, and new programmatic mandates.
In the two years since implementing Program Alignment, FDA has achieved many of the original goals, providing greater focused expertise for our investigators across all products that fall under FDA’s purview, and the FDA’s regulation of generic drugs has never been stronger, more strategic, more risk-based, or more efficient than it is today.
Employing a Risk-Based Approach to Global Inspections
The FDA maintains global vigilance through a risk-based inspection strategy to focus inspectional resources on higher risk facilities. FDA uses a risk-based site selection model for prioritizing and scheduling drug manufacturing inspections at higher risk facilities. The FDA prioritizes inspections of sites regardless of their location and through this model we have achieved parity of inspections. Depending on the risk-based assignments FDA may now do more foreign inspections than domestic — and both are of the same scope and intensity.
For manufacturing facilities in other countries, inspections may be conducted by investigators stationed in an FDA foreign office, by investigators assigned to a dedicated foreign inspection cadre, or staff that travel internationally to conduct the inspection.
To add greater transparency around FDA’s site selection model, the agency published its internal policy for how manufacturing facilities are prioritized and scheduled for surveillance inspections. Our policy explains how a facility’s compliance history, recall trends, time since last inspection, inherent risk of the drug being manufactured, processing complexity and other factors are all weighed and considered.
The FDA’s inspections program is a large-scale endeavor. As of fiscal year 2018, there were 4,676 human pharmaceutical sites worldwide subject to routine surveillance inspection — 61 percent of those were foreign-based. For that year, the FDA conducted 1,365 human drug Current Good Manufacturing Practice (CGMP) surveillance inspections, of which 739 were conducted at facilities outside the U.S., to ensure manufacturers were following CGMP requirements and maintaining high quality standards.
The globalization of the manufacturing industry and supply chain is simply huge, and no one inspectorate can inspect it all. Wherever possible, inspectorates need to share information and discuss respective regulatory decisions so that global partners can learn from each other. For FDA, this means we are continuing to leverage and expand partnerships. Two important investments are the Mutual Recognition Agreement with the European Union (EU) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S).
The Mutual Recognition Agreement implemented in 2017 allows FDA and the EU drug investigators to rely upon information from drug inspections conducted within each other’s borders. Ultimately, this will enable FDA and the EU to avoid the duplication of drug inspections, lower inspection costs, and enable regulators to devote more resources to other parts of the world where there may be greater risk. This agreement allows FDA to receive EU regulators inspection reports and use the information to influence or inform the risk-based site selection model.
The second is the Pharmaceutical Inspection Co-operation Scheme (PIC/S), a multilateral group of inspectorates from 52 countries, which seeks to lead the international development, implementation, and maintenance of harmonized good manufacturing practice standards and quality systems of medical product inspectorates.
With membership in PIC/S, FDA further supports the specialization of its drug investigators by investing in training to harmonize drug inspection programs across all sites of manufacture, domestic and foreign, so that the agency can inspect regulated products in the same way as our PIC/S partner countries. The FDA strongly supports the development of a training curriculum for inspectorates, and we are committed to contributing our technical expertise and support to the working group and training sub-committee.
By maintaining global vigilance over the generic manufacturing industry, in close collaboration with our international regulatory partners, FDA provides confidence in the quality of these medicines while helping patients realize more of the benefits from high quality, low cost generics. Through Program Alignment, coordination with FDA’s Center for Drug Evaluation and Research and Office of Global Policy and Strategy, as well as more global partnerships, we can continue to take enhanced steps to address the increasing challenges posed by a global supply chain and encourage the adoption of new advanced manufacturing methods. These actions are key parts of our commitment to ensure high-quality manufacturing, and to make sure Americans have confidence in the quality of products in their medicine cabinets — regardless of where they were manufactured.