The FDA’s push for the implementation of rapid methods as an alternative to the conventional sterility test (see my previous blog posts FDA Research: Identifying Faster Sterility Tests for Biological Products, and FDA's Proposed Changes Encourage the Use of Rapid Methods for Sterility Testing of Biologics) appears to have been the starting point for a more comprehensive scientific and quality strategy that will allow the Agency both to meet today’s public health needs and to be fully prepared for the challenges and opportunities of tomorrow.
The core responsibility of FDA is to protect consumers by applying the best possible science to its regulatory activities - from pre-market review of efficacy and safety to post-market product surveillance to review of product quality. In the last few years, rapid advances in innovative science have provided new technologies to discover, manufacture and assess novel medical products, and to improve food safety and quality; FDA must both keep pace with and utilize these new scientific advances in order to accomplish its mission to protect and promote the health of the United States.
To meet this need, FDA has developed a strategic plan for regulatory science, the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. This plan identifies eight priority areas of regulatory science where new or enhanced engagement is essential to the continued success of FDA’s public health and regulatory mission.
One of the priority areas, Support New Approaches to Improve Product Manufacturing and Quality, outlines the application of novel technologies to product development and innovative analytical approaches, including rapid methods for the detection of microbial contamination. Here is an overview:
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. In order to better reduce the risk of microbial contamination of products, the following needs will be addressed:
a) Develop sensitive, rapid, high-throughput methods to detect, identify, and enumerate microbial contaminants and validate their utility in assessing product sterility;
b) Develop and evaluate methods for microbial inactivation/removal from pharmaceutical products that are not amenable to conventional methods of sterilization;
c) Evaluate the impact of specific manufacturing processes on microbial contamination; and
d) Develop reference materials for use by industry and academia to evaluate and validate novel methods for detecting microbial contamination.
All of these needs fall within the FDA’s Quality by Design initiative, which includes 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.
How does the new strategy impact public health? Regulatory science research on novel manufacturing methods and on the analysis of products during and after manufacture will facilitate adoption of rapid microbiological methods, thus facilitating and lowering the cost of manufacturing and improving FDA’s ability to rapidly evaluate safety, efficacy, and the quality of medicinal products. If there was ever any doubt that the FDA does not embrace the implementation of rapid methods, now is the time to reconsider. The future of microbiology has been set in motion, and with the FDA and other regulatory authority’s acceptance of next generation microbial methods; the use of these technologies will soon become the norm, and not the exception.
The full plan (PDF format) may be downloaded here.
A summary of the Strategic Plan is also available in an audio Podcast. Presented by Vicki L. Seyfert-Margolis, Ph.D., Senior Advisor for Science Innovation and Policy for the FDA Commissioner’s Office, the Podcast may be accessed here.