Insight: Research Edition

Fall 2005

PDM Core Helps Researchers Develop Vaccines, Therapeutics and Diagnostics

Twelve years ago, Dr. Patrick Brennan’s laboratory was looking to produce a small sample size of leprosy skin test antigens to send to Nepal for a clinical study. Such a skin test showed little upside for biomedical companies to manufacture. As leprosy is not a disease found in the United States but typically in poor countries, making a small sample of skin test antigens for early clinical trials didn’t seem economically feasible.

Dr. Brennan’s research group, based in the Mycobacteria Research Laboratories, decided that the only option was to manufacture the skin test antigens themselves, a bit of naiveté, said Becky Rivoire, a Senior Research Associate, that turned out to be their saving grace.

“Had we known at the time how difficult it was going to be to negotiate all the government regulations, and just how much time and effort this would all take, I’m not so sure we would have signed on,” said Rivoire. “But we didn’t know and, 12 years later, here we are.”

And “here we are” is a good place to be. When Colorado State University applied for a grant to become a Regional Center of Excellence, the proposed Product Development and Manufacturing Core, an extension of the Pilot Plant manufacturing facility at the Mycobacteria Research Laboratories, was a key component of the grant’s approval by the National Institute of Allergy and Infectious Diseases (NIAID), a National Institutes of Health (NIH) agency. Because the focus of the grant is the development of vaccines, therapeutics and diagnostics, already having an existing facility to produce small quantities of these products for initial pre-clinical studies in animal subjects followed by clinical studies in human populations was critical.

“The NIH charge to us was to develop vaccines, therapeutics and diagnostics for translational research,” said Rivoire, who is Co-Director of the PDM Core. “We proposed to be the bridge – to bridge the gap between research and clinical trials. We may have to work with some products start to finish, and others at different stages, depending on other public and private partnerships. We hope we can help move products through the development and manufacturing process which are not economically viable for pharmaceutical companies to produce.”

Rivoire said one of the challenges for creating a successful PDM is that Current Good Manufacturing Practices (CGMP) must be followed. That means more documentation of procedures, more federal regulations to follow, and increased reporting of process and results. It also means extensive training for the PDM staff who must learn the ins-and-outs of small-scale pharmacological manufacturing.

“We are getting assistance from pharmaceutical companies, and that is helping us to shorten our learning curve,” said Rivoire. “We also are getting incredible support and encouragement from NIH and from CSU. It’s a huge endeavor, but the challenges are not insurmountable.”

Rivoire needs only to point to the success of the leprosy skin test antigen produced at the Mycobacteria Research Laboratories to support her convictions. The research group successfully completed a Phase 1 non-endemic safety study of the test products on volunteer students at Colorado State University. The skin test antigens then entered Phase 2 of the study, which was conducted in Nepal, an endemic area with significant levels of leprosy as determined by the World Health Organization. The researchers are now at Stage C of Phase 2 where they are testing the skin test antigens on patients. The eventual goal is to show that the leprosy skin test antigens can be used to diagnose leprosy early in the course of the disease thus improving treatment and reducing long-term health risks.

“In the course of generating these leprosy skin test antigens over these many years, Ms. Rivoire educated and trained herself, often at her own expense, in the arts of CGMP, the Code of Federal Regulations and other government policies and practices pertaining to human research, such that she was perfectly poised for the opportunity presented by the RCE initiative,” said Dr. Brennan.

“She is very much admired and respected by such bodies as the Regulatory Section within the National Institute of Infectious Diseases. The special attributes of Ms. Rivoire were a major factor in the acquisition of the RCE and in its future success.”

The PDM Core, which requires Bio-Safety Level 3 (BSL3) facilities, will be located at the Bioenvironmental Health Research Building while non-BSL3 facilities will be located at the Microbiology Building until construction of the Regional Biocontainment Laboratory is completed in 2007