DTP’s Biological Resources Branch oversees the Biopharmaceutical Development Program (BDP), which provides biopharmaceutical development expertise and production capability to all NIH-supported investigators. The BDP produces a variety of clinical-grade biological agents from bacterial, yeast, and mammalian cells; natural products from various organisms; and DNA, RNA, and viral materials under current Good Manufacturing Practices for phase I/II human clinical trials or advanced preclinical animal testing.
Researchers have attempted to design targeted cancer therapies to avoid toxicities associated with standard chemotherapeutic agents. BL22, one such targeted treatment, originated in an intramural NCI laboratory and was developed through DTP’s biologicals production facility.
The BDP was able to develop a complete, simple, and scalable clinical manufacturing process for BL22 immunotoxin production. A novel hydrophobic chromatography method was incorporated into the process to clearly separate the product, which elutes in a separate peak from the impurities. The new protocol almost tripled the yield of the final product and lowered the cost of production. This novel purification method has also been applied to other similar antibody-conjugated toxins, facilitating the manufacture of immunotoxin anticancer drugs in large scale.
BL22 showed promising results in a phase I trial: 11 of 16 patients with chemotherapy-resistant hairy cell leukemia have shown complete remission, lasting up to 18 months, mostly without major side effects. An improved version, HA-22, has subsequently been developed that has higher affinity targeting to the CD-22 antigen. This drug is has been licensed to MedImmune, a subsidiary of AstraZeneca. Using material made by the BDP at NCI-Frederick, HA-22 is in clinical trials at NCI and elsewhere in the U.S. and Europe in patients with hairy cell leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. The program’s labs, production suites, and offices are located on the NCI-Frederick campus and are currently operated under a contract with SAIC-Frederick.
Five years of success for DTP’s RAID concept prompted the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to suggest a similar program for diabetes therapeutics. The Type 1 Diabetes Rapid Access to Intervention Development Program (T1D-RAID) is a cooperative program between DTP, which manages the technical resources, and NIDDK, which prioritizes and funds the projects. Like DTP’s parent program, RAID, T1D-RAID makes available NCI resources for the preclinical development of drugs, natural products, and biologics on a competitive basis. DTP support includes high-throughput screening, animal studies, drug formulation, pharmacology and toxicology studies, and bulk substance acquisition.
T1D-RAID, begun in 2003, is intended to remove the most common barriers novel diabetes therapeutics face before entering clinical trials.
This program is not a grant-making mechanism. T1D-RAID is open to extramural investigators from academic institutions, nonprofit research institutions, and biotechnology and pharmaceutical companies. Requests are accepted twice a year, on November 1 and April 1. Each request is reviewed by a panel of extramural experts for the strength of the scientific hypothesis and scientific novelty as well as cost-benefit considerations.
NIH-RAID Pilot Program Office
A new pilot program announced in December 2004—NIH Rapid Access to Intervention Development (NIH RAID)—opens the door to DTP’s drug-development expertise to the other NIH institutes and centers. Intramural researchers outside of NCI now have access to DTP know-how in acquiring preclinical information in support of an IND application. They also will have DTP support with scale-up synthesis of the drug substance, dosage form development and manufacture, and development of analytical methods to characterize the drug substance/dosage form, assay the compound in tissues and body fluids, and carry out toxicological studies with correlative pharmacology and histopathology assessment.
Emphasis is on high-risk ideas or therapies for uncommon disorders that frequently do not attract private sector support at early stages of development. In these cases, government resources provide a means to acquire further information to assess the potential of these approaches and facilitate clinical evaluation.
The program accepts applications for these resources biannually. Two review cycles have been completed. Five institutes are sponsoring or cosponsoring the four proposals accepted for implementation.
NIH RAID is part of NIH’s Roadmap Initiatives. Projects are jointly funded by the sponsoring institute and the Roadmap Office. The purpose of the Roadmap Initiatives is to identify major opportunities and gaps in biomedical research that no single institute at NIH could tackle alone but that the agency as a whole must address to make the biggest impact on the progress of medical research.
NIH RAID is not a grant program. Successful projects will gain access to the government’s resources as well as assistance of the NIH in establishing and implementing a product development plan.
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