Section 3. Support New Approaches to Improve Product Manufacturing and Quality: Strategic Plan for Regulatory Science
Application of novel science and technologies is leading both to innovation in manufacturing and to innovative products that are often complex. In order to foster these innovations, FDA needs to do research – collaborating with industry and academia – to assess how these new technologies affect product safety, efficacy, and quality, and to use the information to inform development of regulatory policy relevant to these innovations.
In addition, analytical technologies are rapidly changing and leading to dramatic improvements in sensitivity, resolution, and precision in the determination of product structure and the detection of contaminants.
FDA will support the application of novel technologies to product development and innovative analytical approaches to improve product manufacturing and quality through active research intramurally and collaboratively with external partners by addressing each of the following needs:
- Enable development and evaluation of novel and improved manufacturing methods:
- Investigate the effects of continuous manufacturing (manufacturing using a continuous process, rather than a batch approach) on product quality;
- Examine specific novel manufacturing technologies to determine how they impact product failure rates;
- Evaluate the role of excipient ingredients and complex dosage forms on product safety, efficacy, and quality; and
- Promote two state-of-the-art manufacturing strategies – Process Analytical Technology, and Quality-By-Design approaches – for impact on manufacturers’ ability to maintain consistent quality.
- Develop new analytical methods:
- Investigate feasibility and value of using emerging and improved analytical technologies like NMR (Nuclear Magnetic Resonance), mass spectrometry, or near infrared or Raman spectroscopy for evaluating product quality of pharmaceutical agents, and evaluate whether these technologies should replace existing methods;
- Evaluate applicability of various analytic technologies for determination of the “similarity” of biosimilars to their reference products;
- Perform statistical research to support development and evaluation of new assays and tests needed to assure analytical methods give consistent reproducible results; and
- Develop improved methods and tools to detect and measure the physical structure, chemical properties, and safety of engineered nanomaterials and complex dosage forms (e.g., transdermal patches, inhalation delivery systems, and targeted drug delivery systems etc.) in FDA-regulated products.
- Reduce risk of microbial contamination of products:
- Develop sensitive, rapid, high-throughput methods to detect, identify, and enumerate microbial contaminants and validate their utility in assessing product sterility;
- Develop and evaluate methods for microbial inactivation/removal from pharmaceutical products that are not amenable to conventional methods of sterilization;
- Evaluate the impact of specific manufacturing processes on microbial contamination; and
- Develop reference materials for use by industry and academia to evaluate and validate novel methods for detecting microbial contamination.
Quality by Design
Quality by Design is understanding the manufacturing process and identifying the key steps for obtaining and assuring a pre-defined final product quality. FDA is constantly working to identify ways to improve the manufacturing process to ensure consistent product quality throughout the shelf life as well as to identify when contamination or other production failures may occur. Improved quality by design will also lower product development and manufacturing costs by reducing the likelihood of production failures during a long run and by providing opportunities for continuous improvement. As part of its Quality by Design effort, FDA is now working on three new areas to support increased manufacturing quality. The first is a continuous processing where materials constantly flow in and out of equipment. The second is the use of process analytical technology to monitor and control processes, as opposed to the current method of just testing products. The third is the development of new statistical approaches to detect changes in process or product quality.
Public Health Impact:
Regulatory science research on novel manufacturing methods and on the analysis of products during and after manufacture will facilitate adoption of these methods by industry, thus facilitating and lowering the cost of manufacturing and improving FDA’s ability to rapidly evaluate safety, efficacy, and quality of products manufactured by these methods.