In September, the FDA issued its Proposed PDUFA V Reauthorization Performance Goals and Procedures for Fiscal Years 2013 through 2017.
There are many proposed improvements related to the FDA review procedures, including a mandate of the eCTD. This mandate will start 24-months after publication of the corresponding final guidance for marketing applications and 36-months after publication of the final guidance for commercial INDs and amendments.
The final guidance will be released no later than 12 months from the close of a public consultation period on the draft guidance. The corresponding draft guidance will be issued by December 31, 2012 at the very latest. The initial guidance will reference eCTD version 3.2.2; however, the final guidance might refer to a different standard, namely RPS, if the FDA determines the new standard is more efficient and effective. The FDA also mentions that they “shall also accept submissions using the previous version for no less than twenty-four (24) months.”
Although many of the goals for priority and standard NDA and BLA review (including Class 1 and Class 2 resubmissions, efficacy supplements, and manufacturing supplements) remain the same as under PDUFA IV, the proposed PDUFA V agreement establishes a new review model that will apply to all New Molecular Entity (“NME”) NDAs and original BLAs received from October 1, 2012 through September 30, 2017, including applications that are resubmitted following a refuse-to-file action.
The new program includes a pre-submission meeting, a mid-cycle communication, and a late-cycle meeting at which the FDA review team and the applicant will discuss the status of the review of the application. At the pre-submission meeting, the FDA and the applicant will agree on the content of a complete application for the proposed indication(s), and the applicant may also reach agreement on submission of a limited number of application components.
Another important change is the treatment of “major amendments” to pending applications.
Under PDUFA IV (and FDA’s regulations at 21 C.F.R. § 314.60), “[a] major amendment to an original application, efficacy supplement, or resubmission of any of these applications, submitted within three months of a goal date, may extend the goal date by three months. A major amendment to a manufacturing supplement submitted within two months of the goal date extends the goal date by two months” (emphasis added). Under the proposed PDUFA V agreement, however, “[a] major amendment to an original application, efficacy supplement, or resubmission of any of these applications, submitted at any time during the review cycle, may extend the goal date by three months”, and “[a] major amendment to a manufacturing supplement submitted at any time during the review cycle may extend the goal date by two months.”
It has been a while since I have updated you on the RPS project. Back in September, I had expressed cautious optimism on being able to bring RPS to vote (ballot) in May 2011. We did not make the May 2011 ballot, thus the ballot is now delayed until September 2011.
We did not make the ballot, in my opinion, since we are still working on refining all of the requirements. We have two requirements left to be finalized; namely, being able to reuse studies and all of the components in two applications and support for the new European variation legislation.
Being able to reuse studies and all of the components in two applications will allow sponsors to create a study, define all of the components (e.g. protocol, study report body, synopsis, etc) in one application (e.g. investigational application) and refer to the study in your marketing application. This benefits sponsors since it allows them to synchronize content for a study in more than one application.
The new European variation allows a sponsor to create one sequence (e.g. a manufacturing change) and apply that sequence to many products. This will benefit sponsors since they will no longer have to track multiple products for one manufacturing change.
To create the publication before the ballot opens, HL7 headquarters needs content over a month in advance. The ballot period is one month: see the following sample HL7 publishing schedule.
I feel confident that we will make the September 2011 ballot. Stay tuned for more information.
A number of good articles related to eSubmissions have been posted online recently. Below, a recap based on posts from my twitter account, www.twitter.com/kathie_clark.
In Standards news:
Finally, a few upcoming conferences have been announced:
Recently, I was providing some training to a GlobalSubmit client and one of the participants asked me about an xml document that was present in a folder along with the sample eCTD that we use for training. The document was called “porp.xml”. I explained that GlobalSubmit’s VALIDATE product can transform eCTD into RPS and when it does, it produces the XML backbone used for RPS, which is called porp.xml. This is a single xml document that replaces eCTD’s index.xml, regional xml, and study tagging files.
The next question was “Why in the world is it called porp?” I couldn’t answer that one. But recently, I attended several training classes held by the font of all RPS knowledge, GlobalSubmit’s CTO Jason Rock. I took advantage of that opportunity to gain insight into what is different about RPS xml when compared to eCTD xml. [For the record, it’s called porp.xml because it had to be different than eCTD – and porp is a combination of po, the business domain within HL7, and rp for regulated product.]
But on to bigger topics. I, along with most other remotely technical people who have dabbled in eCTD for years, am pretty comfortable with eCTD xml. I can create the xml for a sequence by hand, and I can look at a sponsor’s xml and figure out what it represents and what is wrong with it. But when I look at the xml for RPS, all bets are off. Jason walked us through the xml in our training class and here are some of the observations that I made:
The bottom line is that RPS XML is only for the brave. Most of those intrepid souls creating XML by hand for eCTD will have to give up that practice, and everyone will need to ensure that they have a publishing vendor who is highly knowledgeable concerning the standard and who is able to produce very high quality software.
For those of you who would like to see what RPS xml looks like, check out Example RPS Code: BLA Multiple Sequence along with other Informational Documents (i.e. Plans, Rosters, RPS Technical Walkthrough, Implementation Guide, etc. on the RPS wiki.
This week’s blog posting is from Rahul Mistry, CEO of GlobalSubmit, who recently was a featured speaker at the RAPS workshop entitled “Advance eCTD Submissions”. Rahul’s presentation focused on eCTD quality, a topic that obviously interested the audience based on the significant number of questions that he received.
Two weeks ago I had the pleasure at presenting at an Advanced eCTD Workshop hosted by RAPS in Rockville, MD. During the course of three days, I had the pleasure of speaking and listening with a number of people from different companies. Here is what I learned: