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Contract Topics
273 Process Analytic Technologies (PAT) for Biologics: Innovative Methods for Monitoring and Analyzing Product Quality and Safety During Manufacture of Cancer Therapeutics
Number of anticipated awards: 2
(Fast-Track proposals will be accepted.)
Budget (total costs): Phase I: $200,000;
Phase II: $1,000,000
(Note: It is strongly suggested that Proposals adhere to the above budget amounts. Proposals with budgets exceeding the above amounts may not be funded. Phase I project periods may last a maximum of 9 months.)
The deadline for receipt of all contract proposals submitted in response to this solicitation is: November 9, 2009.
Summary:
The NIH Roadmap Initiative for Medical Research emphasizes the importance of translational activities that bridge the gap between laboratory research and medical product development. In addition, the FDA has identified a growing gap between the rapid advances in drug discovery and the number of regulatory approvals for new drugs. One aspect of translational research that is frequently overlooked is the significance of the transition from a lab-scale production process to an industrial-scale manufacturing process. Production lot failures that occur during manufacturing or product testing significantly increase production costs and time-to-market. Expensive toxicology studies and clinical trial results are often brought into question during regulatory review for failure to demonstrate reliable, reproducible methods of production or for inadequate characterization of the agent used in the study. A primary roadblock in the development of new cancer therapeutics is the lack of well-defined manufacturing processes for production of high quality, safe and effective biologics. Innovative, state-of-the art technologies are critical to cost-effective, regulatory compliant pharmaceutical manufacturing at the commercial-scale.
The FDA has released a report identifying a gap between the rapid advances in the discovery of potential new therapies and actual medical product development (Challenge and Opportunity on the Critical Path to New Medical Products, FDA, DHHS, March 2004). This report identified an urgent need for applied research to guide technology development in the production of safe and effective drugs. The potential of recent advances in basic and translational research cannot be fully realized without research targeting the process of creating safe and effective drugs. To address this issue, the FDA launched an initiative to encourage development and implementation of innovative approaches to pharmaceutical manufacturing and quality assurance (Guidance for Industry, PAT-A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance, www. FDA.gov). Significant opportunities exist for improving the efficiency of pharmaceutical manufacturing and quality assurance through the innovative application of novel product and process development controls and modern analytical chemistry. The mission of the Biological Resources Branch of the NCI is to provide resources necessary for evaluation of new therapeutics in a Phase I clinical trial, including drug manufacture (http://web.ncifcrf.gov/research/brb). Consistent with this mission, the NCI seeks to fund projects that focus on the application of novel approaches to the medical product development pathway for cancer therapeutics.
Project Goals:
Effective use of science and engineering principles during the development of a drug can improve both the efficiency and reliability of the manufacturing process and thus the quality and safety attributes of the final product. The focus of this research should include the development of innovative technologies for optimizing and monitoring the manufacturing process using in-line or in-process analyzers that can provide multi-variant data to improve the efficiency of process controls and determination of production end-points. Examples of such process innovations or improvements are:
- Innovation or improved in-line monitoring of lyophilization parameters.
- Innovation or improved in-line or in-process monitoring of endotoxin levels.
- Innovation or improved in-line or in-process monitoring of product quality attributes such as activity, glycosylation, aggregation, etc.
- Innovation or improved in-line or in-process monitoring of product yields for common biologics such as antibodies, DNA plasmids, viral vectors, and recombinant proteins.
- Evidence of an existing problem which is addressed by the proposed method.
- Analysis of competitive methods to address the same problem and explanation of the technical advantages of proposed system.
Phase I will involve the development of innovative methods or improvements related to the in-line or in-process monitoring of product quality and safety attributes during manufacturing. Examples of phase I activities and deliverables:
- Scientific data demonstrating the feasibility of the in-line or in-process production process innovation or improvement.
- Scientific data demonstrating the proposed scalability of the in-line or in-process production process innovation or improvement.
- Beta-testing of the in-line or in-process production process innovation or improvement.
- Engage and obtain feedback from potential customers and users guiding the development of the product.
- Provide the program and contract officers with a letter of commercial interest.
Phase II activities and expected deliverables:
Phase II activities will include delivery of prototype with full validation of the novel technologies identified in Phase I. Examples of phase II activities and deliverables:
- Prototype with detailed specifications for hardware/software that supports the in-line or in-process production process innovation or improvement.
- Full validation of the in-line or in-process production process innovation or improvement.
- Install hardware/software at a pilot customer facility and provide NCI with a report summarizing system performance and whether it addresses customer needs.
