Tim Sandle's Blog recently made us aware of an FDA scientific poster that considers rapid sterility testing (thanks Tim!). The FDA routinely conducts their own internal studies on new technologies, and to better understand how these programs work, I am providing a brief overview of the Science & Research initiative at FDA, as well as the work being conducted within CBER, the Center that performed the sterility testing studies. Links to the relevant FDA websites, as well as the sterility test study, are also provided below.
Relevant Links (as of August 10, 2011)
About Science & Research at FDA
The mission of the Food and Drug Administration (FDA) is the protection and advancement of public health by helping speed innovation on FDA regulated products. To accomplish this, FDA makes risk assessment/risk management decisions on safety, efficacy, and quality of the products it regulates. Evaluation of FDA regulated products requires application of the latest technology and standards pertinent to the particular regulatory challenges, e.g., in review of new products (drugs, biologics, medical devices or food additives) or in the resolution of compliance/safety issues of a marketed/regulated product.
Underlying FDA regulatory decisions are the application of advanced technology and science based standards. Examples include the pre-market and post-market evaluation and approval of new technologies in the products, in addressing the many compliance issues that arise in the marketed products FDA regulates, and the use of new technologies in the manufacture and evaluation of innovative products. The burden for FDA is to ensure the acceptance of our science-led regulatory decisions by the U.S. consumer and the respective scientific communities and thus maintaining scientific credibility, accuracy and predictability of the decision making process.
Science & Research (Biologics)
In order to provide effective regulatory review of biological products, the Center for Biologics Evaluation and Research conducts active mission-related research programs. This research greatly expands our knowledge of fundamental biological processes and provides a strong scientific base for regulatory review.
A wide variety of changing technical and scientific issues related to the safety, potency and efficacy of novel biological products requires knowledge of new developments and concepts of basic research in the relevant biological disciplines. Because of the rapid advancement in both conventional and new biotechnologies, the scope of research is both diverse and dynamic.
Innovation and Regulatory Science
CBER plays a critical role in the development of biological products that are at the cutting edge of 21st century medicine.
The center regulates preventive and therapeutic vaccines, blood and blood products, and cell, tissue, and gene therapies. Therefore, its research focuses on creating new knowledge in the fields of diagnostic and therapeutic product innovations and the regulatory science needed to ensure those products are safe, effective, and available to the public.
CBER scientists facilitate the development of new and promising biological products and technologies by increasing the understanding of existing products through mission-related research that advances regulatory science. For example, CBER scientists are actively engaged in developing in vitro (“test-tube”) tests and animal models used to study new therapies and product testing methods, assays, and standards. This work supports the development of CBER-regulated products by enabling the development of manufacturing methods and providing tools to assess product safety, efficacy and manufacturing consistency. CBER scientists also evaluate potential methods for improving ongoing monitoring of the safety of products that CBER has approved for use.
The web site provides both summaries of recently published research conducted by CBER scientists, as well as posters developed to highlight some of this work. These web pages will keep you informed of current research being done at CBER that is helping to bring safe and effective products to the public.
POSTER REVIEW
Identifying Faster Sterility Tests for Biological Products
Seema Parveen, Simleen Kaur, James L. Kenney, William M. McCormick, Rajesh K. Gupta. Center for Biologics Evaluation and Research, FDA, Rockville, MD.
The two‐week sterility test incubation period can be a significant limiting factor in the timely release of biologicals, particular for pandemic vaccines and products with short shelf lives. Researchers in the Division of Product Quality (DPQ) in the Office of Compliance and Biologics Quality (OCBQ) are working to resolve this problem by evaluating rapid microbial methods that significantly reduce the time needed for sterility testing of biologicals. Several alternative rapid tests to detect microorganisms in either solid or liquid media were compared.
Microorganisms were spiked into 10 ml of Fluid A with & without 100 ppm thimerosal, and then evaluated for detection by Compendial Sterility Methods (Filtration and Direct inoculation method) and Rapid Sterility Methods:
1. Milliflex Detection System (ATP bioluminescence)
2. BacT/Alert (detection of carbon dioxide)
3. BACTEC (detection of carbon dioxide)
Three rapid microbial methods and the compendial sterility method were comparatively evaluated for the sensitivity and speed of detection of spiked
microorganisms.
The research team developed criteria for an alternate rapid sterility method to be equivalent in sensitivity and accuracy to the Compendial Method, but provides results within seven days rather than two weeks. To compare the various methods they spiked growth media with various organisms and used the methods to detect, isolate and identity the spiked organisms.
CONCLUSIONS:
The compendia method, Rapid Milliflex, BacT/Alert, and BACTEC showed equivalent sensitivity at detection of lowest spiked microorganism level.
The Milliflex Detection System detected the lowest spiked of P. acnes and B. vulgatus within 5 days versus 9‐10 days for compendial sterility method, BacT/Alert, and BACTEC.
The Milliflex system consistently detected spiked organisms at 1 CFU/10 ml within 5 days (usually 1‐3 days). Similar results were obtained at 10 and 100 CFU/10 ml.
Solid media (TSA, SDA, and SBA) showed faster growth of spiked organisms (within 5 days) compared to liquid medium.
The Milliflex Detection System appears to be a promising alternative to the compendial sterility test for filterable biological products.
Additional information about the group's RMM research may be obtained by contacting Dr. Rajesh Gupta at rajesh.gupta@fda.hhs.gov.