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By Trista Morrison
Staff Writer
Last week marked the end of approvable and not-approvable letters, as the FDA's Center for Drug Evaluation and Research adopted the Center for Biologics Evaluation and Research standard of issuing complete responses.
Of course, a complete response letter still indicates that the application in question isn't ready for approval. The change in semantics removes the blurry line between what might one day be approved (pending anything from minor labeling changes to major clinical work) and what's no-way, no-how not ever getting the green light but no matter what you call it, it's not something you want to see sitting on your fax.
Yet it's not exactly an unlikely outcome. The FDA has approved just nine new drugs and biologics so far this year, putting the industry on track to hit 18 in 2008, the same as 2007 but down from 22 in 2006, 20 in 2005 and a whopping 36 in 2004. Blame it on risk aversion or the inferior quality of applications or whatever you want, but the bottom line is that FDA approval is critical to the bottom line of the industry.
There's no way to guarantee approval, but panelists at a recent breakfast meeting organized by Southern California life sciences industry association BIOCOM shared tips for increasing the odds.
Do What You're Told
One of the most important steps a company can take is to listen to and follow the FDA's advice, the panel agreed. While that might sound obvious, a survey conducted last year by Biocom and PricewaterhouseCoopers (PWC) found that half of the life science companies polled admitted to not incorporating the agency's feedback into their product development progress.
"I'm always surprised when people don't [listen to the FDA] and then they're surprised when they don't get the response they want," said Randall Woods, a serial biotech CEO who currently heads up Sequel Pharmaceuticals Inc. and previously ran Novarcardia and Corvas Inc.
But listening to the FDA isn't always easy. Elliot Parks, CEO of Hawaii Biotech Inc. and managing director of Hamilton BioVentures, acknowledged that the agency often communicates in "FDA speak," which can be "difficult to understand."
Mark Brunswick, a former FDA reviewer and current head of regulatory affairs at Arena Pharmaceuticals Inc., explained that some "FDA speak" is caused by the fact that the agency may be reviewing an application that is similar to yours, and they may have seen problems with it that they'd like you to avoid, but they can't tell you because of confidentiality conflicts.
Jeff Yuen, former FDA inspector and consultant, agreed that this is often the case, and advised companies to listen carefully when the FDA says something "might be a good idea."
Yet at the same time, it's important to recognize that "the FDA's job is not to reduce business uncertainty," said Heller Ehrman's FDA compliance specialist Natasha Leskovsek. Since new information often becomes available during the FDA review period, the agency will frequently "forestall answering a question until it has to be answered," she said.
Look Them in the Eye
Leskovsek recommended that companies improve their communications with the FDA by taking advantage of face-to-face meetings whenever possible. Although the PWC survey found that just 42 percent of life science companies had an end-of-Phase-II meeting with the agency, such meetings provide an important opportunity to read the reviewers' body language, she said.
Brunswick noted that it's also important to bring the right people to the meeting, adding that regulatory professionals are preferred because CEOs tend to have "selective hearing." He also said patient advocacy representatives can be an important ally - especially in today's safety-conscious environment - because they can "sway agency opinion by saying 'we are prepared to accept this safety risk.'"
Yuen advised bringing key opinion leaders as well, since they can help the agency understand why a certain trial design or enrollment criteria might not be reasonable for the company. Yet Brunswick cautioned that the risk of bringing an expert to an FDA meeting is that "you don't know what they are going to say" and "it's very hard to kick them under the table and tell them to shut up" without the reviewers noticing.
Use Your Time Wisely
One mistake often made by young biotechs is to start off a meeting by giving the FDA a standard corporate presentation, Brunswick said. "For the most part, they don't care" about your business objectives, so skip ahead to the data in question, he advised.
But while it's important to get straight to the point, it's equally important not to rush. Woods suggested that companies "stop talking every once in a while and check for understanding to make sure everyone is on the same page."
Parks recommended saving time during the face-to-face meeting by addressing basic questions ahead of time, either by phone or in writing. He said he's seen companies submit briefing documents to the FDA before a meeting and get "good responses" that allowed them to cross several questions off their list before the meeting even started.
And when it comes to asking questions, Woods recommended sticking to specifics. "If you ask open-ended questions, you may get an answer you don't want to be stuck with," he cautioned.
But Leskovsek warned that it's also a "fallacy" to think that just because you don't ask a specific question, you're in a "safe zone."
Mind Your Manners
Throughout all communications with the FDA, Yuen recommended that companies be collaborative and "take the mindset of how we will get the product approved working together."
The level of communication a company has with the agency may depend, at least to some extent, on the review team, Brunswick said. Some teams stay in constant contact and others just "send the final letter when they are done," he said.
But Yuen said companies should take more responsibility for maintaining the relationship. "We hear all the time that the FDA is not communicating," he said, but the company is often just sitting by the phone waiting for the agency to call instead of reaching out. "Communicating by not communicating" isn't good enough, he counseled, adding that the FDA is not going to make a note in their Outlook calendar to call you and see how you are doing. | 
