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FDA and the US Congress support innovation and access to cheaper medicines.
The recent surge in demand for certain common medicines hyped as potential COVID-19 therapies led to serious drug shortages at hospitals and pharmacies, notably for the common malaria treatment hydroxychloroquine and antibiotics such as azithromycin. Widespread use of ventilators to relieve respiratory distress in very ill patients, moreover, depleted supplies of sedatives and painkillers administered with such equipment.
These supply problems highlight the reliance of the US healthcare system on generic drugs, many produced overseas or made with imported APIs. Manufacturers have rushed to fill the gaps, particularly to aid patients already relying on these medicines to treat serious medical conditions. FDA issued guidances on developing generic versions of chloroquine phosphate and hydroxychloroquine sulfate to help address the shortages (1). Even so, policymakers continue to lament the nation’s unreliable supply chain for vital medicines, many made in India, China, and other regions.
These developments reflect the importance of regulatory and legislative policies in facilitating generic-drug development and market approval. FDA has expanded and reorganized its Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research (CDER) to streamline and accelerate the approval process for follow-on medicines, supported by generic-drug user fee revenues. A sign of success is FDA’s record-breaking approval of more than 1000 abbreviated new drug applications (ANDAs) in 2019 (2). An important gain is OGD’s ability to process and approve more ANDAs in one review cycle by encouraging manufacturers to file more complete applications that avoid time-consuming discussions on application shortcomings.
FDA also seeks to advance the development and approval of more complex generics, such as topicals and inhaled products, as outlined in the agency’s Drug Competition Action Plan of 2017 for facilitating access to less expensive alternatives to a broader range of innovator therapies (3). FDA has published lists of more than 500 drugs that lack competition and warrant extra agency assistance in determining what tests and data are needed to gain market approval. Multiple guidances on developing specific complex therapies support the program, including an advisory issued in March 2020 outlining the process for a manufacturer to seek designation for a product as a Competitive Generic Therapy that warrants expedited development and review (4).
The development of complex generics also has support from FDA research that addresses technical and scientific issues related to testing innovative generic products. At an FDA public workshop in May 2020, agency scientists sought further industry input on research priorities and challenges related to developing complex generics, drug-device combination products, new bioequivalence testing methods, and new data analysis and modeling strategies to support these initiatives (5).
Congress also has furthered generic-drug development in approving the long-debated CREATES Act in December 2019 as part of a must-pass budget bill. The measure helps generic-drug makers access innovator supplies needed for bioequivalence testing and product approval, even when the brand is subject to a risk evaluation and mitigation strategy (REMS). The legislation also provides flexibility in establishing shared REMS programs for innovators and generics, another effort to avoid roadblocks to accessing less costly prescription drugs (6).
To further identify and prevent looming drug shortages, moreover, the legislators also included a provision in the CARES Act, the $2-trillion COVID emergency bill enacted in March that supports FDA efforts to monitor medical product supply chains and ensure access to both drugs and APIs imported from abroad. The bill expands FDA authority to require information on where problems might interrupt access to APIs, as well as drugs, and calls on firms to establish back-up plans for ensuring supplies of critical products (7).
Generic-drug development also may advance from global agreement on standards for testing and regulating these medicines. A new project of the International Council for Harmonization (ICH) aims to establish bioequivalence standards for immediate-release solid oral dosage forms to support generic product development and approval in multiple regions (8). Additional ICH guidelines for generics are expected, as the group explores opportunities for standards related to a number of complex generic medicines.
These and other initiatives were discussed at an FDA Generic Drugs Forum, which attracted more than 4000 registrants from 73 countries to the online program held April 15–16, 2020. FDA staff provided practical advice to manufacturers on minimizing deficiencies in applications and described opportunities for OGD assistance in developing complex generic products and on navigating the regulatory process (9).
1. FDA, “Product-Specific Guidances for Chloroquine Phosphate and Hydroxychloroquine Sulfate,” www.fda.gov, April 13, 2020.
2. FDA, 2019 Office of Generic Drugs Annual Report, www.fda.gov, Feb. 19, 2020.
3. FDA, FDA Drug Competition Action Plan, www.fda.gov, April 8, 2020.
4. FDA, Competitive Generic Therapies, Guidance for Industry (CDER, March 2020).
5. FDA, FY 2020 Generic Drug Regulatory Science Initiatives Public Workshop, online, May 4, 2020.
6. GovTrack, H.R. 965: CREATES Act of 2019.
7. 116th Congress, H.R.748–CARES Act.
(Jan. 31, 2020).
9. FDA/SBIA, Generic Drugs Forum, online (April 15–16, 2020).
Vol. 33, No. 6
When referring to this article, please cite it as J. Wechsler, "Generic Drugs in Spotlight as Pandemic Creates Shortages," BioPharm International 33 (6) 2020.