Biopharmaceutical Development Program

Overview

The Biopharmaceutical Development Program offers resources for and expertise in the development of investigational biological products that move promising treatments for cancer, rare diseases, AIDS, and infectious diseases into clinical trials. 

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A scientist uses a microscope on a pink liquid

The program provides leading-edge development and analytical technologies for antibodies, recombinant proteins, peptide, DNA, and viral vaccines, oncolytic viruses, gene therapy products, cell therapies, and other biological and immunomodulating agents. 

We focus on products that are in early development, beginning with the demonstration of product feasibility. Following process development and biomolecular characterization, we move these products through manufacturing for Phase I/II clinical trials. 

We’re experienced in the transfer of manufacturing and testing methods developed to support pharma and government programs that own the licensed product rights for commercialization. We ensure compliance with FDA current Good Manufacturing Practice (cGMP).  

We work under collaborative agreements with government agencies, universities, and industry, including national and international companies. Opportunities for collaboration are reviewed and approved by the National Cancer Institute. We work with collaborators to develop a manufacturing process suitable for its intended purpose, whether pre-clinical studies or early-phase clinical trials. Project teams, consisting of representatives from the collaborator, the National Cancer Institute, and our laboratory, manage projects from inception to completion. The team addresses challenges in real time and completes projects in a milestone-based approach. 

We are developing clinical and non-clinical supplies of lentivirus vectors. If you would like more information about obtaining supplies or manufacturing and testing documentation please contact us.

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A workflow schematic showing the following steps in order: Prepare plasma, transfect HEK293T cells, suspension culture, harvest/clarification, filtration, concentration/diafiltration, chromatography, formulation, sterile filtration, and fill/finish
The Biopharmaceutical Development Program has developed a scalable serum-free 3rd generation lentivirus production platform.

Innovations

Since 1998, the Biopharmaceutical Development Program has had: 

  • More than 260 lots of product released for clinical use
  • More than 170 distinct biopharmaceuticals manufactured
  • More than 65 products in human clinical trials
  • Two products licensed and commonly used
  • More than 14 products readied for license

We developed and produced anti-GD2 ch14.18 monoclonal antibody to support clinical trials in pediatric neuroblastoma, a rare type of childhood cancer that presents poor prognosis for more than half of the children who are affected. Ch14.18 was shown to improve survivability by approximately 50 percent and is now the standard-of-care for pediatric neuroblastoma. Our program was instrumental in the successful technology transfer of ch14.18 to the commercial licensee. 

In fewer than 12 months, we established a new capability to produce a personalized cell therapy for children with acute myeloid leukemia, a particularly aggressive blood cancer. We use an engineered virus to infect certain white blood cells taken from a patient—called T cells—to make them cancer killers.  

More than 10 years ago, the National Cancer Institute asked the Biopharmaceutical Development Program to take on the development of a modified poliovirus as an investigational treatment for brain cancer. Duke University researchers sought to move “PVSRIPO”—an immune-stimulating oncolytic virus made by combining the Sabin type 1 polio vaccine strain and a human rhinovirus—into early clinical trials for glioblastoma. We developed manufacturing processes and product testing assays so the virus could be reliably reproduced for the trial. 

Focus

Process development for manufacturing 

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A technician adjusts a vat
  • Develop cell lines using small- to pilot-scale fermentation and cell cultures. 
  • Isolate and purify proteins or viruses using size-, charge- and hydrophobicity-based chromatographic methods. 
  • Enhance stability of products using formulation/lyophilization. 

Preclinical and cGMP manufacturing 

  • Manage cGMP-qualified cell banking and storage. 
  • Develop and maintain mammalian and bacterial cell cultures using fermenters (100–500 L).  and bioreactors (40–1000 L)  
  • Purify products by orthogonal methods. 
  • Fill/Finish manufacturing (up to 10,000 vials/run). 
  • Produce and purify viruses. 

Process analytics and quality control 

  • Characterize proteins through development of standardized assays 
  • Manage product release and stability testing. 
  • Analyze products using mass spectrometry. 
  • Establish bioactivity and potency testing. 
  • Analyze in-process physio-chemical components using Process Analytical Technology (PAT). 
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Technician holds a cell culture and a pipette

Quality assurance oversight and regulatory affairs 

  • Ensure all operations and products meet cGMP compliance appropriate for early-phase clinical trials. 
  • Review manufacturing and operations documents and product release records. 
  • Prepare, evaluate, and support FDA and international regulatory submissions. 
  • Provide cross reference letters to the Biopharmaceutical Development Program’s facility master file at the FDA. 

Technology transfer and cGMP training 

  • Transfer technology to companies for commercial production. 
  • Provide development and manufacturing methods, specifications, and regulatory documentation. 
  • Host and train visiting scientists, staff, and collaborators on cGMPs and Biopharmaceutical Development Program  operations.