This campaign includes several projects designed to "move manufacturing into the 21st century" by developing standards for
laboratory and production analytical methods. To encourage the adoption of process analytical technology, for example, FDA
is partnering with pharmaceutical and instrument manufacturers to test validation reference systems. The aim is to establish
specifications for imaging methods such as near-infrared, mid-infrared, Raman chemical imaging (RCI), and terahertz technologies.
Standards that ensure proper calibration and instrument qualification would lead to FDA guidance for adopting such methods
in continuous quality-controlled manufacturing processes.
Other collaborations with industry and academia aim to ensure that policy development, training, and regulatory practices
are consistent with state-of-the-art science. FDA has signed Cooperative Research and Development Agreements (CRADAs) with
Pfizer and Novartis to expand understanding, and ultimately control, of material transformation. Another CRADA with Conformia
Software seeks better understanding of the challenges and bottlenecks that influence pharmaceutical development. Additional
PAT-related research ventures involve FDA and Duquesne University, the Center for Pharmaceutical Processing Research, the
National Institute for Pharmaceutical Technology and Education, and the Engineering Research Center for Structured Organic
New dosage forms.
FDA also is encouraging new standards and methods for novel drug dosage forms to expand options for drug delivery. One project
aims to refine and validate the use of RCI to establish scientific standards for chemical identity, particle size, and distribution
characteristics of active pharmaceutical ingredients in aqueous nasal-spray suspensions. If successful, this approach could
be applied to dry-powder and metered-dose inhalers. Another FDA–industry collaboration is developing methods to assess the
adhesive properties and permeation of various transdermal products. The objective is to compare drug diffusion and skin permeation
through different in vitro methods, an exercise that eventually could lead to American Society for Testing and Materials standards and agency guidance
for these products.
FDA also is working to characterize liposomal drug products for their encapsulation efficiency, leakage, and particle size.
The project involves testing performance under various physiologic stress factors, with an eye to developing in vitro cell-line bioassay methods to assess changes in liposomes under different conditions.
A high-profile project is to establish standards for multi-color flow-cytometry measurements in various laboratories and
across instrument platforms. Because flow-cytometry data are important for developing many medical products, FDA is collaborating
with instrument makers and the National Institute of Standards and Technology (NIST), the Centers for Disease Control and
Prevention, the Environmental Protection Agency, the NIH, the International Society of Cytometry, and the Clinical Cytometry
Society to develop, test, and validate standards that will ensure comparability of such measurements.
Similarly, a Microarray Quality Control Project involving scientists at federal agencies, academia, and pharmaceutical companies
is testing the reliability of microarray tools in measuring gene expression. Initial tests showed that these data can be reproducibly
measured across multiple drugs and laboratories.
Several projects seek to modernize vaccine production. FDA is supporting research to shift influenza-vaccine production from
egg-based systems to cell-culture substrates and to establish libraries of possible pandemic influenza virus strains to help
manufacturers test new vaccines for potency and efficacy more quickly. These projects can support efforts to produce safe
and low-cost vaccines for developing countries such as new vaccines for meningitis and tuberculosis. FDA scientists also are
collaborating on research to evaluate the efficacy of mumps vaccines and to develop biomarkers to evaluate the stability and
safety of future vaccines for malaria and leishmaniasis.
Related efforts aim to improve the safety of biotechnology manufacturing processes, including those used in vaccine production.
An FDA collaboration with the National Institutes of Allergy and Infectious Diseases is examining methods for detecting infectious
contaminants in cell cultures and whether such contaminants increase the risk of causing tumors. Additional projects seek
to improve the characterization of complex biological products. FDA is exploring how to adapt high-tech imaging methods such
as nuclear magnetic resonance spectroscopy to better characterize glycoprotein vaccines, allergen extracts, and other complex
products. Similarly, a collaboration of FDA, NIH, and other partners is evaluating how well new microarray technologies and
other tools can better predict the quality of cell substrates used to manufacture vaccines, protein drugs, and gene vectors.
The discovery of specific gene-expression patterns or the identification of clusters of specific genes may help characterize
cell substrates and serve as biomarkers of manufacturing quality.