Regulatory Beat: FDA Encourages Innovation in Biotech Manufacturing and Product Development

The Food and Drug Administration recently unveiled its long-awaited Critical Path Opportunities List, which maps out a number of "scientific projects" for improving the testing and production of biotech therapies. In its March report, FDA recognizes that problems in the characterization, testing, and quality management of medical products can delay clinical trials and even completely block drug development.

Jill Wechsler

At the same time, the White House officially nominated Acting Commissioner Andrew von Eschenbach to take over the top job permanently. Although von Eschenbach has provided strong support for the Critical Path initiative, his good efforts may not overcome the political issues blocking his confirmation as commissioner.

One Critical Path goal is to develop the capacity for reliable manufacturing of high-quality products at commercial scale. FDA notes that problems often occur during scale-up to mass production and that poor product design and inadequate characterization and testing can cause problems after a product comes to market.

Biotech manufacturing raises particular concerns and also presents opportunities to develop new scientific tools able to identify and characterize critical product attributes and better control product manufacturing. FDA's list calls for efforts to improve these processes by developing:

• Stable and uncontaminated cell lines able to grow influenza and other vaccine stock for easier scale-up to broad manufacturing

• New tools to assess the effect of manufacturing changes on product performance and ease scale-up of new protein products

• Microarray technologies better able to detect contamination of biological products from infectious agents found in living organisms

• New biomarkers and other approaches that use nuclear magnetic resonance, X-ray crystallography, and mass spectroscopy to characterize and standardize biological products

• Scientific tools and biomarkers to better characterize cell therapies to ensure that such treatments will reliably travel to appropriate tissues

• More reliable nonanimal-based tests of vaccine potency to spur new vaccine development

• Consensus on assessing products made from tissue engineering to ensure quality and consistency

• Research on the physical and chemical characteristics of different nanomaterials to apply this technology to the development of therapeutics and combination products

• New testing instruments for manufacturing patches, liposomes, topicals, and nasal and pulmonary inhalers that can better target the delivery of difficult-to-formulate drugs and to assess drug-device combinations products

"The aim of all these initiatives is to prevent drug manufacturing from creating a bottleneck in getting medicines to patients," said Scott Gottlieb, FDA deputy commissioner, in a recent speech on good manufacturing practices (GMPs). With more novel drug delivery systems and more complex drugs, Gottlieb noted that it is even more important to address key quality issues and to establish meaningful product specifications.

Efforts to modernize process development also continue under FDA's initiative to modernize GMPs for the 21st century. FDA plans to issue a final guidance on Quality Systems this summer and a final report summarizing its risk model for prioritizing sites for manufacturing inspections. The agency also is examining the need to revise policies governing storage and transport of temperature-sensitive drugs and biologics [see box above: Cold Chain Challenges].

Cold Chain Challenges

SPURRING COLLABORATION

FDA recognizes that it lacks the resources to tackle the many opportunities on its list and hopes to spur manufacturers and research organizations to jointly meet these challenges. As a start, FDA has linked up with the National Cancer Institute (NCI) and the Centers for Medicare and Medicaid Services (CMS) to establish the Oncology Biomarker Qualification Initiative to generate information for developing more effective cancer treatments. The group's first project is to evaluate whether PET scans can provide a marker for early drug response in non-Hodgkin's lymphoma. Success could create a new tool for assessing how well molecular imaging technology reveals drug interaction with a target. The results may be useful, moreover, for tumor staging and helping health care providers, payers, and patients make treatment and coverage decisions.

FDA deputy commissioner Janet Woodcock regards The List as an evolving document and expects to issue an update of activities underway this summer. One project on the table is an FDA-industry effort to identify biomarkers that already exist to demonstrate the practical value of such measures. FDA participated in an Institute of Medicine workshop on cancer biomarker development in March and plans to hold a workshop on what type of evidence is needed to qualify biomarkers for different purposes. This should lead to a general biomarker qualification guidance which will describe approaches for linking biomarker validation to intended uses. Additional guidances on specific qualified markers will follow, possibly starting with documents on testing for liver and kidney toxicity.

Also on the agenda is draft guidance on drug-diagnostic codevelopment. FDA published a concept paper on this topic in April 2005, but the specifics of developing a diagnostic test to fit a new therapy have been difficult to pin down.

Jill Wechsler is BioPharm International's Washington editor, 7715 Rocton Avenue, Chevy Chase, MD 20815, 301.656.4634, jwechsler@advanstar.com