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CDER 2007 Update
Scientific Research
We advance the scientific basis of regulatory practice by developing, evaluating or applying the best, most appropriate and contemporary scientific methods to regulatory testing paradigms. We provide scientific support for reviewer training, regulatory decision making and the development of regulatory policy.
We focus on creating a tighter scientific linkage between non-clinical and clinical studies, enhancing methodology for assuring product quality, building databases for improved drug development and review and providing regulatory support through laboratory testing.
Linking non-clinical and clinical studies
- Biomarkers for organ damage. We are identifying, evaluating and establishing relevant protein biomarkers in blood in both animal models and in humans. These will help detect the very earliest damage that can be caused by certain drugs to the heart, kidney, immune system and liver.
- Biomarkers for inflammation. To enhance safety within broad segments of patient populations and enable safe development of new drug classes, we are working on the identification and elucidation of associated serum biomarkers and mechanisms responsible for the development of vascular inflammation in specific organ systems.
- Medicinal plants, herbs. We established scientific research capabilities in the analyses of medicinal plant and herbal products.
- Imaging drug targets. We continue to explore noninvasive imaging technology to extend our long-standing interest in the application of accurate dose-concentration-response principles by viewing drugs and their actions directly at the level of the drug target, rather than indirectly via plasma concentrations.
- Better use of exposure-response data. We are developing a standardized approach for using exposure-response information to help evaluate the risks and benefits of drug therapies and recommending dose adjustments in special populations.
- Pediatric pharmacokinetics. We are developing a pediatric population pharmacokinetics study design template to facilitate implementation of sparse sample strategies in pediatric drug development.
Biotechnology research
We evaluate therapeutic biotechnology product submissions as well as carry out scientific research related to biologics regulatory issues.
- Immune responses. We review many submissions aimed at inhibiting unwanted immune responses, such as autoimmune diseases or rejection of transplanted organs, or aimed at enhancing desired immune responses, such as those against infections or cancer. To facilitate review of such immunology-related submissions, we study the mechanisms by which immune cells are activated, suppressed or channeled from one kind of active response to another.
- Metabolic pathways. We study the mechanisms by which various regulated products induce their intended effects, as well as unintended adverse effects. Our investigations also examine various normal and pathogenic pathways that are targeted by regulated agents.
Our research enhances the ability of our scientist/regulators to evaluate risks and benefits of biotech products, to advise industry on difficult regulatory problems, such as potency assays, and to develop hands-on expertise in the modern technologies used by sponsors of biotech products.
Informatics and computational safety analysis
- Cancer toxicity predictive software. Our cooperative research and development agreements with several commercial software developers have resulted in the development and marketing of new computer software to predict the cancer-causing potential of chemicals based on their molecular structure. The software makes use of our extensive rodent carcinogenicity database without compromising proprietary information.
- Safe starting dose models. We have successfully developed computer models to estimate the safe starting dose for clinical trials of drugs based on their molecular structure. The current method for estimating the starting dose is highly inexact and requires the use of multiple safety factors because it is based exclusively on an extrapolation from animal toxicity studies. We have begun studies to validate the new method.
How our scientific research helps us
Scientists at our own labs in Bethesda and White Oak, Maryland, and St. Louis, Missouri, perform research that helps us:
- Understand how pharmaceutical products are developed and manufactured to ensure quality and safety.
- Study specific characterizations and properties of pharmacological products in order to make sound scientific and regulatory decisions.
- Set standards for specific products based on scientific evaluation.
- Develop appropriate methodology for complex and novel products.
- Determine how best to label products.
- Address various public health issues.
- Study new technology to determine regulatory requirements.
Evaluation of new technologies
We conduct targeted research to understand how new technologies will affect future regulatory decision making.
For example, we are evaluating how microarrays that can identify thousands of genes or proteins rapidly and at the same time could improve the interface between drug development and regulatory practice.
Microbiology
We assess product sterility, maintenance of product safety and the microbiological controls used by firms for drug development and manufacturing.
Our microbiology review assures the safety of sterile and non-sterile products through scientific evaluation and communication with the industry and assures consistency through guidance documents.
We promote the development of uniform and practical test methods and criteria for our own use and through the U.S. Pharmacopoeia and the International Conference on Harmonization.
We have a new program to advance rapid microbiology test methods.
Research to support regulatory decision making
Numerous issues arise in the routine review of drug products which require us to conduct some research in order to make scientifically informed decisions regarding the marketing of a product, including its labeling.
The research often serves to provide scientific justification for policy development and enforcement actions. The research conducted in our labs covers the broad spectrum of our responsibilities, including:
- Application review. Reviewers will work with researchers to resolve specific questions having to do with a specific product before finalizing decision to approve. For example, we performed basic laboratory tests that encouraged manufacture of Prussian blue as a treatment of people exposed to harmful levels of radioactive materials and poisons and for counter-terrorism agents.
- Regulatory policy. Reviewers, research staff and researcher-reviewers will also generate research activities to determine appropriate regulatory policy. Examples include altered stability and performance of split tablets and filtration of biologics to remove viral contamination.
- Product testing. Our scientists test marketed products when there is a question of safety or quality, such as the delivery characteristics of a metered dose inhaler to make sure they meet standards.
- New technology. Our researchers help us understand new technologies and determine how they will fit into the regulatory scheme. Examples include drug delivery systems using nanoparticles, the toxicity of nanomaterial and the validation of new test methods.
- Manufacturing. We conduct research on various aspects of manufacturing to better understand a product’s critical attributes and how they affect product quality and product lifecycle. Examples include the ability of critical product attributes to stimulate an immune response and the impact of adhesion variability on transdermal patches.
- Formulation changes. We determine how certain changes in formulation, such as different inactive ingredients, affect the safety, efficacy and quality of products.
- Process analytical technologies. We research various techniques for process analytical technology, including new spectroscopy methods for characterizing tablets and future follow-on biologics.
- Mechanism of action. We research the mechanisms of action of a given product. This knowledge is critical for designing the bioactivity and potency test that is required for all biologics as well as in biomarker development.
- Biomarkers. We are developing potential safety and efficacy biomarkers to help understand how products can be better employed.
Counterterrorism biotechnology research
We have used congressionally mandated special funding to initiate research in several areas relevant to counterterrorism. Our scientists are studying:
- Microarray technologies, which could assist in identifying infectious biowarfare agents.
- Non-specific immune boosters, which could provide transient protection against such agents.
- Monoclonal antibodies as neutralizers of biological toxins.
- Various strategies to defend against anthrax.
- Development of Anthrax Toxin assays for assessment of potential therapies.
By establishing a core of scientists experienced in several areas of bioterrorism, these projects anticipate high-priority regulatory submissions likely to require rapid science-based evaluation.
Scientific collaborations
We collaborate on scientific projects in an effort to leverage our knowledge and experience with others because a single institution or firm lacks the resources to conduct some types of research. We have a number of collaborative projects that are being done under:
- Cooperative research and development agreements.
- Material transfer agreements.
- Involvement with various non-profit collaboration groups such as the National Institute for Pharmaceutical Technology and Education and the Product Quality Research Institute.
- Work with academic organizations such as the University of Delaware and Purdue University.
Collaborations bring together experts representing industry, academia and government and cover a wide array of scientific and regulatory issues related to pharmaceutical products. These collaborations help us maintain the high level of science necessary to ensure that all products are safe and effective and of high quality. A number of the Critical Path Initiatives, such as the Biomarker Consortium, are also being done through these collaborations.
Pharmaceutical analysis
We collaborate with other organizations to ensure the availability of high quality standards and calibration materials. We collaborated with state pharmacy boards to evaluate Internet pharmaceuticals. We evaluated the quality of a select group of the most-often-ordered pharmaceutical products from foreign Internet suppliers.
Laboratory support
- We assessed several technologies for rapid identification of drug products and raw materials to guard against counterfeit products. We applied near infrared, Raman, Isotope ratio mass spectrometry to the problem of distinguishing between production sources of active pharmaceutical ingredients and finished dosage forms.
- We developed methodology to better characterize nasal spray products. We evaluated a new aerodynamic particle size analyzer.
- We evaluated instrumentation for the determination of particle size and particle size distribution for cyclosporin drug products.
- We are developing physicochemical methods to assess quality changes in liposomal drug products.
- We developed methods to evaluate quality attributes of drug products and raw materials by chemical imaging. These properties include polymorphic form, hydration state, stability and purity.
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Date created: July 31, 2008 |
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