Welcome to our new website! If this is the first time you are logging in on the new site, you will need to reset your password. Please contact us at firstname.lastname@example.org if you need assistance.
Your membership opens the door to free learning resources on demand. Check out the Member Knowledge Center for free webcasts, publications and online courses.
This comprehensive resource covers product change evaluation, postmarket surveillance, audit/inspection compliance, and various other laws and regulations pertaining to maintaining a product on the market.
Hear from leaders around the globe as they share insights about their experiences and lessons learned throughout their certification journey.
Regulatory News | 18 January 2016 | By Michael Mezher
Officials from the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have shared their perspectives on evaluating treatments for Ebola in two articles appearing in Clinical Trials.
The articles discuss some of the challenges the Ebola outbreak presented for studying drugs and vaccines to treat the disease. At the time the outbreak began, no products existed to treat Ebola, and those that were in development had not been tested in humans.
While a randomized controlled trial is considered the gold standard for drug and vaccine development programs, public health authorities had to consider other alternatives during the Ebola epidemic due to ethical and practical concerns.
In addition to weakened public health infrastructure in affected countries, declining infection rates and changes in epidemiology were major challenges to studying Ebola treatments.
In the articles, both EMA and FDA authors support the notion that randomized controlled trials continue to be the most effective at demonstrating efficacy. However, both note that in public health crises, alternative trial designs should be considered when randomized controlled trials are not ethical or feasible.
One example of an alternative approach to a randomized trial in the FDA article points to a design that first assigns all patients to the experimental treatment.
"Based on continuous monitoring of how the survival rate contrasts with an assumed control survival rate of 50%, the multi-stage approach discards the experimental therapy, moves to a sequential RCT [randomized clinical trial] to confirm potential benefit, or proceeds to a confirmatory single arm study to confirm likely benefit," they wrote.
The FDA officials noted that the design in this example is dependent on the validity of the assumed comparator event rate and "can miss the mark in determining whether a drug is safe and effective when the assumed comparator event rate is not appropriate for the patients who are enrolled in the study."
Both FDA and EMA discuss alternative regulatory pathways sponsors could follow to get products authorized more quickly in the context of the Ebola outbreak.
In the US, sponsors can seek accelerated approval using a surrogate endpoint to support a product's use before conducting additional confirmatory trials to demonstrate the product's efficacy.
During the Ebola outbreak, FDA also published guidance on the "Animal Rule," which allows sponsors to use data from "relevant animal species" to support approval when conducting studies in humans that would be unethical. As with accelerated approval, products approved under the Animal Rule would also require additional study to confirm their safety and efficacy.
In Europe, EMA suggests two potential regulatory pathways, conditional marketing authorization and marketing authorization under exceptional circumstances. According to the EMA perspective, "both these regulatory options could be used either in the context of an EU marketing authorisation or for a scientific opinion for a so-called Article 58 procedure, in collaboration with WHO and for use only outside the EU."
While neither FDA nor EMA authorized any drugs or vaccines to treat Ebola, the US Department of Health and Human Services (DHHS) did shield the manufacturer of the investigational Ebola virus treatment ZMapp from legal liability under a federal law intended to incentivize the development of new medical products for medical emergencies.
EMA in their perspective argues that "an authorization in EU and/or North America would have enhanced the process of making these vaccines and drugs available, providing reassurance to local health authorities and funders."
A US Food and Drug Administration perspective on evaluating medical products for Ebola
A viewpoint on European Medicines Agency experience with investigational medicinal products for Ebola
Tags: Ebola, Emergency Use Authorization, Animal Rule, Conditional marketing authorisation, Accelerated Approval