Stakeholders continue to look for ways to streamline drug development, but FDA has determined that using its existing formal meeting opportunities can drastically cut the time needed to complete development and get regulatory approval.

New molecular entity and novel biologic application sponsors that conducted pre-IND meetings with FDA saw shorter clinical development times. They also had more first-cycle approvals than “complete response” letters and other regulatory actions.

Rare disease sponsors saw a dramatic difference in clinical development time – more than 10 years – if they conducted a pre-IND meeting with the agency. The same sponsors also showed a more than four-year difference in development time if they had an end-of-phase II meeting with FDA.

It is more evidence that communication with FDA, especially early in development, can streamline the regulatory process. Increased communication is something FDA has particularly pushed in the last couple years, especially as user fee programs neared reauthorization.

“Everyone’s so interested in expediting drug review, this is important data,” Larry Bauer, senior regulatory project manager in the FDA Rare Diseases Program, said Oct. 24 during a conference on rare diseases and orphan drugs, sponsored by the Drug Information Association and National Organization for Rare Disorders.

2010-2011 Mean Clinical Development Times For NMEs and New BLAs
Meeting Status	All Applications	Rare Disease Applications	Non-Rare Disease Applications
Pre-IND meeting	6.1 years	6.3 years	5.9 years
No Pre-IND meeting	11.1 years	16.9 years	9.0 years
End of Phase II meeting	8.9 years	9.8 years	8.4 years
No End of Phase II meeting	10.1 years	14.0 years	7.1 years

Source: FDA

In 2010 and 2011, the 10 rare disease drug applications that had a pre-IND meeting had a mean clinical development time of 6.3 years. The mean clinical development time for the nine submissions that did not have a pre-IND meeting was more than twice as long, 16.9 years, according to FDA data released at the conference.

Similar times were found with non-rare disease applications. Sponsors having a pre-IND meeting had a mean clinical development time of 5.9 years, while those that did not had a mean of 9.0 years.

Across all 54 applications in the cohort during the two-year time period, the mean development time for those with a pre-IND meeting was 6.1 years and 11.1 years for those not having the meeting.

The message appears to be that FDA is willing to point sponsors in the right direction for their clinical program, if sponsors meet with them.

“Believe it or not … sometimes when we’re out we’ve heard rumors that [you should] try to minimize your contact with the FDA,” said Bauer, who presented the data, during the conference. “Part of the reason I focused on this is that I really wanted to dispel this myth [and show] that it’s actually just the opposite.”

Conducting pre-IND meetings also resulted in more approvals. Data from 2009 and 2010 indicated there were more than double the number of approvals as “complete responses” if the meeting was held. There were no first-cycle approvals among the applications that did not have a pre-IND meeting.

Increasing communication between FDA and sponsors has been a focus lately, particularly because it may be able to shorten development and review times.

Among the most significant changes to FDA’s regulatory pathway out of this year’s FDA Safety and Innovation Act was the addition of mid- and late-cycle meetings during NME and novel BLA reviews to talk about potential problems. The hope is that some issues could be corrected without forcing a second review cycle.

FDA also will conduct a pre-submission meeting with those sponsors to talk about what will be included in the application package, including items that can arrive late Also see "Buying Time: Industry Sacrifices Early To Gain Later With PDUFA V Review Model" - Pink Sheet, 1 October, 2012..

The agency has also released data showing that applications not requiring multiple amendments after submission have a better chance of an on-time approval Also see "Want A Predicable Review For Your NDA? Use eCTD And Don't Amend It" - Pink Sheet, 1 June, 2011..

End-Of-Phase II Meetings Provide Similar Benefit

In addition, FDA-sponsor interaction later in the development process had a positive effect, according to Bauer’s data.

Sponsors taking advantage of the end-of-phase II meeting saw shorter development times, again with the most dramatic difference coming among rare disease applications.

The 12 rare disease applications that had an end-of-phase II meeting in 2010 and 2011 saw a mean clinical development time of 9.8 years, while the seven that did not had a mean time of 14.0 years.

The same was not true of non-rare disease applications. The 26 applications where the meeting was held had a mean clinical development time of 8.4 years, but the nine applications without the meeting had a mean of 7.1 years.

However, the benefit for the rare disease applications was enough to pull up the average for all applications. Across all applications, the development time was shorter for applications where an end-of-phase II meeting was conducted (8.9 years), than those not conducting it (10.1 years).

Data Comes As Industry Gains More Expedited Approval Pathways

Data showing that the existing FDA processes, if used, can reduce development time is interesting given the strong effort by industry to create new methods to streamline the approval process.

Increased development time has been blamed, along with cost, as a driver of investment away from the biotech sector. FDA’s lack of regulatory flexibility in orphan drug reviews has also been identified as a suspect in decreasing investment Also see "How Bad Are Biomedical Innovation Problems? Metrics Needed To Know For Sure" - Pink Sheet, 29 June, 2012..

FDASIA, which reauthorized the prescription drug and medical device user fees and created new programs for generic drugs and biosimilars, also included several policy changes intended to speed approvals.

Congress pushed FDA to increase its use of the accelerated approval pathway in the bill. It also created the breakthrough therapy designation for drugs that show dramatic improvements over existing therapies, which could allow much smaller clinical trials and earlier involvement by senior FDA officials Also see "Industry Wants A Breakthrough Therapy, Even Without All The Standards" - Pink Sheet, 29 October, 2012..

FDA is developing a comprehensive guidance to clarify the use of all its expedited approval pathways Also see "FDA To Provide Expedited Approval Desktop Reference" - Pink Sheet, 29 October, 2012..

Pre-IND, End-Of-Phase II Meetings Can Decrease Development Time, FDA Says

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