Jun 18 2010

DIA 2010 – Week in Review

The DIA 2010 Annual Meeting was a great success and Washington, DC was a great location.  In addition to the thousands of industry attendees, the location made it possible for this year’s meeting to include FDA representatives from all areas of the Agency.

As previously mentioned, Will Lee and I attended the meeting.  For those of you who didn’t make it, here’s our recap with the highlights of this year’s meeting.


  • While the meeting officially began with a few activities on Sunday, the real kickoff was on Monday morning, when FDA Commissioner Margret Hamburg addressed the attendees.  She spoke about two overarching goals that she’s set for the Agency.  The first is a focus on regulatory science – meaning that science-based regulatory decisions needs to be a focus for the FDA in the current technology of personalized medicine, and stem cell therapy.  Second, the globalization of medical products regulated by the FDA needs to be strengthened.  She mentioned that the recent heparin recall and melamine recall highlights the urgency and that the FDA plans to partner with regulatory bodies in other countries to prevent these situations from arising.
  • After the formal sessions ended, there was a talk by John Crowley describing his fight to get his two children suffering from Pompe’s Disease to receive innovative investigational drugs in clinical trials.  This talk, with home movie video clips, brought tears to everyone’s eyes.
  • SAS hosted an after-party at the Decatur House, a historic house built in the early 1800’s.  Former Top Chef star Spike Mendelsohn gave a cooking demonstration and everyone received an autographed copy of his cookbook.
  • GlobalSubmit (GS) hosted a Customer Advisory Council dinner.  Customers had the opportunity to meet with the GS team, provide feedback on their products, get the latest info on updates to GS software, and hear about the beta testing program for their new eCTD publishing tool, PUBLISH™.  I’ll have a separate post with more details on the Advisory Council meeting in the next few days.
  • DIA solicited ideas for themes and topics for next year’s Annual Meeting.  Possible new topics include “Inspections by Regulatory Authorities (FDA and EU),” and “Inspection Readiness by the Manufacturing Facilities and Clinical Sites,” and “Different Alliances between Big Pharma, CROs, and Patient Groups.” There is also talk of more interactive DIA sessions, more DIA topics that cut across multiple disciplines, and using social media tools to organize DIA sessions and talks.


  • The buzzword for the DIA this year was Comparative Effectiveness.  Is the evaluation of comparative effectiveness to be a regulatory decision by the FDA, a marketing decision by the pharmaceutical firms, or a decision by consumers?  How is this done in the EU or the US?  A scenario that presents a dilemma is this:  Under comparative effectiveness, if drug B is more effective than Drug A, then Drug A is pulled off the market.  At some later time, Drug B is shown to cause adverse events and is pulled off the market.  Now, both Drugs A and B are not marketed and there are no drugs available for this indication.
  • Cato Research’s Will Lee chaired a panel titled “From Bench to Bedside: Challenges in Bringing Novel Cell-based Therapies from Experimental Studies into Successful Clinical Programs.”  At the panel were two regulators, Dr. Huang  from the FDA and Dr. Narayanan from the MHRA, as well as representatives from two cell therapy biotech firms, Dr. Ladenheim from AtherSys and Dr. Watkins from Aastrom Biosciences.  The FDA and MHRA emphasized that science drives their regulatory decisions and that the regulators can be flexible.  The biotech companies emphasized that meeting with the FDA during the pre-pre-IND meetings were invaluable in the early progress of their respective cell therapies and that the interactions with the FDA were very collaborative.  The biotech companies also noted certain challenges unique to clinical trials with cell therapy.  These challenges include maintaining the blind during cell infusion and extending the duration of cell viability during transport of cell therapy from the cell processing site to the clinical site.  The panel ended by emphasizing that the recent FDA approval of Dendreon‘s Provenge® provided a shot in the arm for the entire field of cell therapy.
  • CDER’s eSubmissions team hosted two great sessions.  The first session included presentations from a CMC reviewer and a Medical Reviewer with their lists of do’s and don’ts for eCTD submissions.  Ginny Ventura also spoke about Study Tagging Files in a presentation that closely mirrors her article on the same topic in the June 2010 issue of Regulatory Focus magazine.  The second session included updates on CDER’s plan for the implementation of data standards.  The panel reiterated the FDA’s recent focus on transparency, noting that improved standards for clinical trial data will ultimately lead to a more transparent analysis and review process for the FDA.  The panel also provided an update on the ongoing development of Regulated Product Submissions (RPS), the next generation of eCTD.  As of right now, the FDA plans to implement RPS in mid-2013.


  • At a session on personalized medicine, the FDA stated that the FDA will regulate Laboratory-Developed Tests (LDTs).  LDTs refer to in vitro diagnostics that are manufactured by and offered in the same laboratory. They include some genetic tests and other tests that may lead patients to make important medical decisions.  FDA believes that LDTs that have not been properly validated put patients at risk of a missed diagnosis, wrong diagnosis, and failure to receive appropriate treatment. Therefore, FDA believes that oversight for LDTs is appropriate.
  • At a session on Modeling and Simulation, the FDA encouraged sponsors to perform modeling early in clinical development.  The FDA also gave sponsors an opportunity to meet with the FDA at the end of Phase 2a and discuss modeling and simulation approaches for the trial design of latter stage trials.  For example, the FDA will examine the pharmacokinetics data from the earlier Phase 2a trial and offer advice on dosing regimens for the Phase 2b trials.
  • At a session on biomarkers, sponsors indicated that they are now looking at biomarkers to help their decision-making on go/no-go points during early clinical development.  With easily accessible biomarkers, it is possible to conduct Phase 1 dose-escalation trials with novel trial designs.  Examples of easily accessible biomarkers are blood pressure, plasma or serum samples, or imaging.  With these novel trial designs, it is possible to produce more efficacy and toxicity data with fewer patients in a Phase 1 trial than using the traditional 3+3 design.  In addition, the FDA noted that proper storage of tissue samples is critical in order to get meaningful results from DNA or RNA analysis from these samples.


  • At a session titled “CDER Town Meeting,” about 400 conference attendees asked questions to Dr. Temple, Dr. Jenkins and Dr. Woodcock of CDER. Some of the issues discussed were:
    • Biosimilars are a huge undertaking by the FDA and an official guidance will take some time.  There are legal issues and challenging scientific complexity and CDER recognizes that each biosimilar product would have unique aspects.
    • CDER would like to see drugs approved that have a large effect in smaller targeted populations.
    • Resources are constrained for the next few years at CDER, and the greatest challenge is making the most effective use of CDER’s resources.
  • There were four take-home messages at a session titled “Clinical Trials in the Fast Lane: Is There a Speed Limit on the Road to Excellence?”.
    • Increasing the speed of clinical trials means avoiding speed bumps.  These speed bumps are delays in study start-up, delays on enrollment, and delays in resolving data queries.
    • To avoid these speed bumps, various sponsors and CROs are using metrics as indicators of the speed and quality of the conduct of a clinical trial; however, the metric must be carefully chosen.  Some suggested metrics are “Days to First Visit from IRB Submission,” or “Enrollment per Site per Unit Time,” or “Outstanding Queries per Unit Time.”
    • For these metrics to be beneficial, the metrics must be available on a day-to day basis for the clinical trial manager and the clinical research associate.  This would allow any needed corrective action early and make for a more efficiently run trial.
    • These metrics should be simple and visually displayed.

Will Lee, Ph.D. contributed to this post. Will is the Director of Regulatory Affairs at Cato Research.