shutterstock_73648879As global Health Authorities increase their efforts in finding ways to make promising drugs available earlier, sponsors are assessing the similarities and differences of the various programs for their impact on global marketing strategies. In mid-March, the European Medicines Agency (EMA) announced a pilot program for “adaptive licensing” which is intended to grant early access to medicines for treating unmet needs. This program has been compared to the US Food and Drug Administration (FDA)’s breakthrough therapy designation.  Under the EMA’s adaptive licensing program, innovative new drugs would be released to patients before they have been given final regulatory approval.  This approval would be followed by further evidence gathering and adaptations of approval to expand access to broader patient groups. By contrast, FDA’s breakthrough therapies pathway focuses on accelerating the existing approval process by having sponsors work closely with the Agency to develop trial designs that shorten or combine traditional phases of drug development. On the clinical side, the EMA program involves live – almost raw – data, while the FDA breakthrough therapy designation requires sponsors to submit their analysis of the data.

Can it be presumed that a product fast- tracked through one Health Authority can expect the same outcome from the other?

According to Eric Thostesen, Chair of ISPE’s Regulatory and Compliance Committee’s North American Regional Focus Group which is the group leading the ISPE Breakthrough Therapies initiative, if the principle criteria designating a product for fast- track approval in the two programs are aligned, there is a good probability that this will occur. However, this is not a given, as the assessment of medical need is based on the respective agency’s judgment. Moreover, EMA has the added factor of assessing the medical need in individual countries where existing treatment options may differ. Companies should be able to substantially align their development milestones to meeting the needs of both programs without much deviation.  The most significant difference for sponsors, according to Thostesen, is the EMA’s Conditional Marketing Authorization, which is not provided for by FDA.

Safety and Quality Issues

From a safety perspective, while there is a chance that the product approval will be granted with less “data in the bank” from phase three studies, the guiding principle behind both programs is that the benefit profile as determined by all available data significantly outweighs the potential for unknown risks that may become apparent in a larger population.  In addition, both programs require that, in most cases, the product development requirements be met before approval. Neither program offers much detail to sponsors on how to accelerate the CMC review, which puts the responsibility for quality directly into the hands of the sponsor to accelerate the completion of those activities within the new boundaries of the clinical trials.

Negotiating the Complexities of Accelerated CMC Review

ISPE’s Breakthrough Therapies Team is in the early stages of producing best practice guidance addressing the most commonly asked questions of FDA regarding the CMC review associated with breakthrough therapy designation. At the 3rd Annual ISPE-FDA CGMP Conference on 2 June 2014, the team will present theoretical- base cases outlining an accelerated CMC program and propose possible targets for developing best practice or guidance documents.  The team plans to publish initial concepts in Pharmaceutical Engineering as well as present further updates at the 2014 ISPE Annual Meeting in October.

What answers would you need from Breakthrough Therapies best practice guidance? Provide your input to the ISPE Breakthrough Therapies Team during the ISPE-FDA CGMP Conference in June, ISPE Annual Meeting in October, or by contacting ISPE.