Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

Timothy M. Uyeki; Karl J. Erlandson; George Korch; Michael O'Hara; Michael Wathen; Jean Hu-Primmer; Sally Hojvat; Erik J. Stemmy; Armen Donabedian

Disclosures

Emerging Infectious Diseases. 2016;22(7):e1-e11. 

In This Article

Regulatory Considerations for Medical Countermeasures in the United States

Regulatory considerations for MERS-CoV medical countermeasures in the United States are focused on a pathway to human clinical trials for drugs and vaccines through submission of investigational new drug applications. Investigational new drug submissions must adhere to requirements set forth in the Code of Federal Regulations, Title 21, Part 312 (21 CFR 312; http://www.ecfr.gov/cgi-bin/text-idx?tpl=/ecfrbrowse/Title21/21cfr312_main_02.tpl). Several guidance documents exist on the FDA website related to virology, microbiology, pharmacology and toxicology, and clinical and medical considerations.[77] The most appropriate approval pathway is likely to be product-specific and will require consideration of existing product data, proposed intended use and population for use, and validated endpoints for efficacy predictive of clinical benefit, if any. Likewise, data needed for consideration of an emergency use authorization, including dose finding and dose ranging, duration, and safety, can be obtained through sources such as investigational new drug clinical trials.

Repurposing of drugs approved by the FDA for other illnesses for a MERS-CoV indication can potentially be expedited or accelerated if 1) the mechanism of action for antiviral activity is defined, 2) there is no change to the approved final drug form and route of administration, 3) dosing does not exceed the currently approved dose and duration for the currently indicated population and adequate pharmacokinetics data support this dosing, and 4) the risk–benefit profile is acceptable for the intended population and indication. For example, the risk–benefit profile for an approved drug with an oncology indication may be unacceptable if the drug is repurposed for administration to a healthy population for MERS-CoV postexposure prophylaxis. However, data requirements to initiate human trials will depend on the characteristics of the drug product and its intended use against MERS-CoV. As such, sponsors should consider prioritizing drug development on the basis of the totality of scientific evidence and merit of the drug alone, not on whether the drug has been previously approved.

In the absence of a standardized and accepted animal model that simulates human disease from MERS-CoV infection, it is unclear how the FDA may be able to expedite licensure or approval when data are lacking. The best approach may be collection of preclinical safety data and implementation of adaptive human clinical trials. This approach was taken for medical countermeasures in response to the 2013–2016 Ebola virus disease outbreak.

For diagnostic devices, the current emergency use authorization pathway serves as a fast approach to make products available for emergency public health purposes. After an emergency has been terminated, Premarket Notifications for these products should be submitted to FDA for a more thorough evaluation as 510(k)s (http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/510kClearances/default.htm).

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