Replies to post #4552 on Opko Health Inc (OPK)

[WiseFool]

The completed and current progress with the FDA on Rayaldee has been active throughout the NDA review process.

Initially focused primarily on issues related to chemistry, manufacturing and controls (known as CMC), but has recently focused on product labeling and the proposed package insert. This would appear to bode well for a Rayaldee approval on their anticipated March 29, 2016 PDUFA date.

The proposed product labeling and package insert regulation required for an NDA are provided in 21 CFR 314 Subpart B.
The above aforementioned culminates the end process pre-approval, you may find primary items to include...safety and efficacy, components, description of methods and controls, etc...

One thing to keep in mind. Rayaldee Two Pivotal Phase 3 Trials were the subject of a Special Protocol Assessment (SPA) established with the United States (U.S.) Food and Drug Administration (FDA).

The Special Protocol Assessment (SPA) provided a mechanism for the FDA and OPKO to reach agreement on the design, size, execution and analysis of the two pivotal phase 3 trials with Rayaldee. The FDA agreed that the design and planned analysis of these studies adequately addressed the objectives necessary to support an NDA submission.

SPA in a nutshell. Representatives of GSK at the Drug Information Association’s (DIA) 45th annual meeting explained.

An SPA, they explained, is a declaration from the FDA that an uncompleted Phase III trial’s design, clinical endpoints, and statistical analyses are acceptable for support of regulatory approval later, after the trial has concluded. It’s the FDA’s way of saying: If you execute this trial exactly as you promise you will, and the data are there, this drug will get approved.

And that’s bind. Unless the science around the research changes or a new public health concern emerges that impacts the agreement, the FDA has to honor it once the Phase III trial is done. That is, as long as the sponsor has followed the agreed-upon protocol to the letter, and the data support the efficacy and safety of the product.

“It’s an opportunity to take some specific steps under SPA to cement some agreements as best as can be done during the dynamic development process,” said David Cocchetto, V.P. of U.S. regulatory affairs for GSK. During the session, he quoted a blogger as saying, “An SPA is about as binding a deal as you can get with a government agency.” Cocchetto laughed, and agreed.