In a post on the FDA's web blog FDA Voice the agency notes that early communications with agency staff - called pre-investigational new drug meetings or pre-INDs - resulted in significantly faster drug development, shaving years off of total development time:
Recently, FDA has taken a look at the development times of new drugs that were approved with the benefit of pre-IND meetings and compared them to the development times for drugs that were approved without such meetings. The findings underscore the value of early communication. For those new drugs for which a pre-IND meeting between the drug developer and FDA was held, average clinical development times were substantially shorter than when a meeting was not held. For instance, for all new drugs approved between 2010 and 2012, the average clinical development time was more than 3 years faster when a pre-IND meeting was held than it was for drugs approved without a pre-IND meeting.
For orphan drugs used to treat rare diseases, the development time for products with a pre-IND meeting was 6 years shorter on average or about half of what it was for those orphan drugs that did not have such a meeting. Early communication is especially important for orphan drugs because these products require special attention and thus early talks can be especially beneficial
The FDA believes that these meetings are particularly helpful for products that are novel, and where clear development pathways don't exist.
The FDA's data is supported by earlier work from the Tufts Center for the Study of Drug Development, which looked at FDA approvals from 1987-95 and found that average development times were 27 months - more than two years - shorter for products with pre-IND meetings. They also found that meetings at another pivot pint for drug development - the end of Phase II trials - shaved 16 months off development times.
End of Phase II meetings were also associated with higher rates of first cycle approvals, according to a Booz-Allen report. One of the FDA programs for identifying and accelerating agency communications with companies developing the most promising medicines (Fast Track) also had a higher rate of first cycle approvals (58%) compared to non-Fast Track products (42%).
This is good news, and a datapoint that industry, regulators, and patients' groups can build upon. Policymakers should ensure that FDA has the resources and staffing it needs to encourage frequent industry-FDA communications early in the drug development process, while also ensuring that clear development and approval guidelines and pathways are available for all product classes. (Incremental innovations are just as important for improving patient care as breakthrough innovations, which are much rarer.)
The most recent FDA PDUFA reauthorization contains a number of provisions that will help accelerate these trends, which we noted in post late last year:
Among other things [the legislation] it encourages the FDA to expand the use of Fast Track and Accelerated approval beyond HIV and cancer; eliminates caps on conflict of interest waivers for FDA advisory committees; creates a new breakthrough therapies designation that is supposed to allow for expedited development and review of drugs for "serious and life threatening illnesses" that show significant improvement over existing treatments in early stage testing; expands PDUFA review deadlines by 60 days to allow for additional meetings between sponsors and FDA; and requires the FDA to establish a new risk/benefit framework for describing how reviewers are actually evaluating the benefits and risks of new medicines.
Flexibility and standardization would appear to be goals that mitigate against each other. But there can also be a learning process that occurs as sponsors and regulators look back at "what works" and integrate best practices into the normal review process - in this case, adding two months to the FDA's PDUFA clock to encourage more communications between the agency and stakeholders.
Another approach would be for the agency and stakeholders to continue to look beyond the curve - on stem cells, nanotechnology, gene therapy, and other cutting edge tech - and think about how to rapidly integrate new scientific discoveries into the development and review process, so that the learning curve isn't so steep when sponsors approach the agency with "first in class" technology.
Here's one crazy idea: create a fellowship program that would allow FDA reviewers to take sabbaticals of 6 months or a year and become "fellows-in-residence" at academic centers, small biotech start-ups, and big pharma companies that are working on cutting edge products and novel technologies. Companies could create a similar high-level exchange program for the agency, so they could get a better picture of how the FDA thinks, and what kinds of information it looks for when it reviews new products. (To address conflict of interest concerns, FDA fellowship alumnae could be barred from reviewing applications from host companies.)
While the FDA already offers a Commissioner's Fellowship Program for graduate students, a fellowship/exchange program for FDA employees and industry experts would help ferment intellectual exchange between industry and the FDA, give companies better insight into regulators' concerns, and allow the agency to get up to speed faster on novel technologies months or years before companies even submit an IND.
If occasional meetings are good, wouldn't longer term educational and exchange programs be even better?