West Coast Editor

SAN FRANCISCO - "You have five people looking at the same accident and they all see something different," said Edward Korwek, partner in the Washington-based law firm Hogan & Hartson LLP.

He wasn't talking about a personal-injury case. He was talking about the varied impressions of spectators at FDA advisory panel meetings, and how those differences can affect what the subject company does afterward - not to mention what investors do.

Korwek's metaphor came during a panel discussion at the Emerging Company Investor Forum, presented by the Biotechnology Industry Organization here and hosted by five banks. The subject was how to get approval of a drug candidate with multiple potential indications, though his remarks proved relevant to the nitty-gritty of regulatory challenges overall.

Having practiced in FDA matters for more than 20 years, Korwek was well positioned to point out trouble spots in such procedures as what he called the "black hole" of advisory panel meetings.

"You can never predict where panel discussions will go and what you'll end up having to do after the panel meeting, whatever the FDA says or does not say," he said, allowing that the hearing is "bound to go better if you have a new variation on a previously approved drug," as the Section 505 (b) (2) new drug application provides for.

"You want to go with the indication that will get you out there [on the market] the quickest, even if it's a smaller population," he said, focusing on a hypothetical situation in which the small start-up firm has a peroxisome proliferator-activated receptor (PPAR) compound that might work against Type II diabetes and acromegaly. "Then you can do some variations in the life-cycle management of the product and deal with different issues of changing dosage forms, route of administration - various aspects like that."

The rule permitting Section 505 (b) (2) NDAs, "which has been the subject of a lot of controversy today, primarily in the area of follow-on biologics," has been around since 1984. It's "largely an effort to copy a product in some way by making slight or different variation of it in dosage form perhaps, or route of administration, or new indication, and this is obviously possible for some of these PPAR products that are already approved," Korwek said.

Using Section 505, "you rely in some way on the prior approval of another product that's similar in some way to not repeat all the safety and efficacy studies" - often by coming up with a new route of administration - thus cutting down on preclinical route and possibly avoiding an advisory panel hearing, which adds six months to the review process, he noted.

But Korwek warned that it's "not clear how long this will be an option if it's challenged in court, and innovator companies are raising significant issues" about them.

Another tricky area is manufacturing capability, which "always tends to get the short end of the stick, but how you make the product, where you make it, who makes it are very important considerations, particularly if you make it abroad," he said. "You need pre-approval inspections, which takes time."

Getting the drug made properly can be even more crucial in the case of an orphan drug, Korwek said.

"If your supplier is nailed by the FDA for violations in [Good Manufacturing Practices] or has other serious problems and your supply is cut, your orphan drug exclusivity can be lost," he said. "You have to be very careful, particularly in the orphan drug area, about supply issues if you're not doing it yourself."

Not that orphan drug status is the key to everything anyway, Korwek added.

"It's a very common misunderstanding that because you have orphan drug status you are entitled to priority review," he said. "That is not correct." The FDA gives priority review to drugs that show significant improvement over marketed products.

"Obviously, if there's an orphan population, there probably aren't any marketed products or few, but you never know," Korwek said. More important is the factor of "significant improvement," which must be proved to the agency's satisfaction.

Still, gaining orphan drug status is one option for getting the FDA's attention.

"We could talk for hours about each of these options and what they entail or don't entail," Korwek said, adding that, in general, "you should avail yourself of any pathway that will get the FDA involved in the process as quickly as possible" so that approval requirements can be pinpointed early and met.

With 1,110 registrants, the three-day BIO conference continues through today.