Regulatory minds meet in Philly

September 15, 2009 – 11:48 pm by Michael Christel

 

The City of Brotherly Love is the site of this week’s Regulatory Affairs Professionals Society’s 2009 Annual Conference & Exhibition. With much change afoot these days at FDA and healthcare reform dominating the American consciousness (more on that later), it’s no surprise the theme for this year’s event is “Succeed in the New Regulatory Landscape.” The RAPS annual meeting typically draws in folks from all over the world for what is considered the largest event of its kind devoted solely to regulatory professionals in the pharmaceutical, biotech, and medical device sectors.

 

This morning, I headed out to the Pennsylvania Convention Center to cover the event, which RAPS up tomorrow (sorry, I couldn’t resist) with a keynote address from new FDA commish Dr. Margaret Hamburg (check back here for highlights from her speech). The Convention Center was abuzz this afternoon after news spread that President Obama was dropping by the building later in the day. Of course, it’s a big building, and, no, he wasn’t there to address the RAPS faithful on healthcare reform, but instead he was in town to stump for recent party hopper Sen. Arlen Specter, who is seeking re-election. Neverthless, Philly protesters from both sides of the healthcare debate used the president’s visit to rally in the streets, attracting local news cameras and a throng of onlookers.

 

As far as the happenings inside the convention center, the RAPS conference has featured numerous educational sessions and briefings, led by representatives of regulatory agencies including FDA’s Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDHR), the European Medicines Agency, Health Canada, Japan’s Ministry of Health Labor and Welfare  and Pharmaceuticals and Medical Devices Agency, the Drugs Controller General of India, and the Dutch Healthcare Inspectorate.

 

Among the topics being explored this week are regulation of biosimilars; considerations for clinical trials of stem cell products; health technology assessment and comparative effectiveness research; global clinical trials; and regulatory challenges in emerging markets.

 

I was able to attend a few sessions covering other topics. Here are a few highlights.

 

- Dr. Axel Hoos of Bristol-Myers Squibb and co-chair of the executive committee for the Cancer Vaccine Consortium, discussed the group’s efforts to redefine clinical endpoints for cancer immunotherapy. According to Dr. Hoos, immunotherapy has different biology than chemotherapy and established endpoints may not fully reflect this biology. He notes, however, that novel tools are helping push the science forward and may improve immunotherapy development. Dr. Hoos says it is important to establish immune response assay harmonization in clinical trials, which could improve the use of T-cell response as a biomarker and accelerate the evolution of surrogate endpoints. He also points out establishing new anti-tumor response criteria is critical to help address complex patterns of clinical activity associated with oncology drug development.

 

“It’s a learning experience for all of us to be able to describe the genetics properly and design your trials having in mind that you might observe something very different than you see with chemotherapy,” Dr. Hoos said.

 

During the same session, Dr. Bindu George, medical officer/acting team leader with FDA’s Center for Biologic Evaluation and Research (CBER), presented a regulatory perspective on cancer vaccine development and CBER’s role in approving endpoints for promising new cancer therapies. She says the challenge is weighing the need to ensure the efficacy and safety of cancer biologics with the urgency to make them available to the public in a timely manner.

 

To that end, Dr. George highlighted several strategies to help optimize the outcomes of late-phase cancer trials, including doubling up the potency early in the development; doing at least one Phase II study, preferably two; attempting to get a preliminary estimate of the treatment effect; confirm the proof of concept; refine the patient population from Phase III; and understand the kinetics of an immune response.  

 

- A pair of experts presented an update on the regulatory climate in Asia, focusing in on China, Japan, and India. First, however, they outlined drug development trends concerning the overall intercontinental region market, which includes all locations outside of the United States and the European Union. According to Dr. Xin Min Yue, associate manager, intercontinental regulatory affairs, Eli Lilly and Co., there are seven official “pharmerging” markets for clinical development - China, India, Korea, Brazil, Mexico, Russia, and Turkey. Other countries considered top intercontinental markets by regulators are Canada, Japan, and Australia. Helping growth in these countries, Dr. Yue says, has been an increasingly open dialogue with FDA and wider adoption of International Conference on Harmonization guidelines.

 

“Some of them have very good communications with FDA,” Dr. Yue says. “They are doing more networking. All those agencies are making more effort to reach out and communicate with the U.S. and the EMEA.”

 

Dr. Yue cited a couple of interesting regulatory trends in Asia. She singled out Japan, China, Korea, and Taiwan as regions that have become more conservative on safety. Perhaps conversely, she pointed out that in countries such as Brazil, Argentina, Australia, and Canada, local clinical data, while helpful, is not a requirement for submission of a new drug application. Dr Yue also compared the average time it takes the respective regulatory authorities in developing nations to review new drug submissions, pointing out that Russia apparently takes the longest – anywhere from 18-24 months – while Mexico typically takes about six months to issue an approval decision.

 

Dr. Munish Mehra, managing director with Global Drug Development Experts LLC, talked about the growing yet still challenging opportunities for companies conducting trials in India. He noted that the country has 22 official languages, an aspect investigators must be aware of when selecting sites. Dr. Mehra pointed out that India has come a long way in recent years when it comes to enforcing stronger regulatory standards for drug development, issuing changes on par with some of the new regulations in the United States and Europe. In June, registration of all clinical trials in India became a mandatory requirement, and during the same month, the country issued new draft guidance for more rigorous registration criteria for CROs who wish to conduct trials in the area.

 

While India is still waiting for the first approval of a drug developed inside their borders, Dr. Mehra says there is reason for optimism with 20 promising drug presently in late Phase II and Phase III development in the country.             

 

“The feeling is that a few of these will eventually make it here and that will generate a lot of revenue for those companies,” Dr. Mehra says. “Indian companies have been increasingly collaborating with U.S. pharma on both branded generics of small molecules and biologics and also new molecular entities.”

 

- Two of the individuals who helped draft the guidance for the “animal rule” back in 2002 spoke about considerations for its use in the development and approval of counter-bioterrorism agents. Before transitioning into industry circles, Dr. Karen Goldenthal, president, Bethesda Biologics Consulting LLC, and Dr. Virginia Johnson, VP, regulatory affairs, Emergent BioSolutions Inc., helped craft the guidance documents for the animal rule while working at FDA.

 

The animal rule was put in place by FDA to provide for approval of certain new drug and biological products based on animal data when adequate and well-controlled efficacy studies in humans cannot be conducted ethically or feasibly. Human safety data is still required. In the seven years since the rule has been in place, only two drugs have been approved via this pathway, the first of which was Pyridostigmine Bromide, sponsored by the Department of the Army, for use as a pretreatment against the nerve agent Soman. In May, Human Genome Sciences Inc. submitted a biologics license application to FDA for raxibacumab for the treatment of inhalation anthrax. In July, FDA notified HGS that the application has been filed and will receive priority review.

 

According to Dr. Goldenthal, the animal rule is not automatically applied to all bioterrorism products, but is decided on a “situational” basis. Dr. Johnson outlined four important considerations for applying the animal rule to a clinical development program, including the requirement for a reasonably well understood mechanism of toxicity for the agent and the prevention or reduction of this toxicity by the product; the need for the efficacy to be demonstrated in more than once species; the animal endpoint must be clearly related to the desired benefit in humans; and the animal data must allow for the selection of an effective dose in the human clinical trials.     

 

Both speakers contend that there’s a misperception in the industry that use of the animal rule is an automatic shortcut to approval. They say the opposite is the case, with the process actually introducing a brand new layer to the development process.

 

“It’s not going to make everything easier and it’s not going to address every issue either,” Dr. Goldenthal says. “But it does allow a subset of products that might not have ordinarily been able to achieve licensure to in fact achieve that goal.”  

 

Tags: animal rule, Asia, clinical trials, endpoints, FDA, healthcare, oncology, regulatory, vaccines