By Nicholas Borgert

 FDA changes and user fees help shrink review times for emerging infectious disease tests
Organizational changes within the Food and Drug Administration are combining with more user-generated funding to shorten the review process for new diagnostic tests on emerging infectious diseases.

These infectious diseases pose serious risks to people of all ages, races, genders, ethnic heritages, economic status and lifestyles. According to the National Institute of Allergy and Infectious Diseases (NIAID), emerging infectious diseases include diseases that are new to the population as well as re-appearances by some old diseases reflected in hikes in the number of cases or the geographic range affected.

New diseases include West Nile virus. The first cases of the West Nile encephalitis in the U.S. were confirmed in 1999 by the Centers for Disease Control and Prevention. While patient history and clinical symptoms are considered, lab testing is the only way to positively diagnose WVN. The most common test is the IgM-antibody test of blood or cerebrospinal (CSF) fluid. According to the CDC, the test is positive in 90 percent of infected people within eight days of the onset of symptoms.

Among the potential resurgents is the variola virus that causes smallpox. Routine vaccinations against the virus ended two decades ago. Long considered the most devastating of all infectious diseases, smallpox was declared eradicated in 1980 by the World Health Organization. By the mid-80s, no country in the world was vaccinating against smallpox. But today, concerned with the use of smallpox as a possible agent of bioterrorism, plans for vaccination are being debated.

Other emerging infectious diseases include drug-resistant forms of malaria, tuberculosis and a number of strains of bacterial pneumonias.

Today, leading companies in the in vitro diagnostics industry are pushing ahead — working with appropriate regulatory agencies to streamline the approval process tests on emerging infectious diseases.

While the WVN IgM antibody test is widely used by the CDC and local and state health laboratories, it is not yet available to all private laboratories. When WNV was first diagnosed in the U.S., all human cases were confirmed by the CDC reference laboratory. Widespread training has given most states the capability to identify IgM antibody in the blood or CSF of suspected human cases.

Shrinking the review pipeline
In recent years, the FDA has fine-tuned its process for approving new drugs, biologics and diagnostic products. Its goal is to help get new products developed, reviewed, put through clinical trials and approved for the market in less time.

This fall, the FDA’s Center for Devices and Radiological Health (CDRH) established a new office-level group called the Office for in Vitro Diagnostic Device Evaluation and Safety.

FDA officials believe the new office will concentrate its efforts on consolidating all premarket, compliance and postmarket IVD regulatory activity into a single functional unit. They’re pursuing a “seamless and interactive regulatory process that focuses on total product life cycle.” The office’s product line approach involves complete integration of all regulatory oversight for any product line within a common unit, with hopes of building on a common pool of expertise.

“We’re trying to be creative because of a public health need,” said Donald St.Pierre, Deputy Director of FDA’s Division of Clinical Laboratory Devices.

This new initiative reflects an organizational change within CDRH. Now, instead of different FDA groups handling the varied tasks concerned with enforcement, premarket and postmarket process, the FDA will use the same group of reviewers to track a newly developed diagnostic device or reagent all the way through the process. This approach, characterized by St.Pierre as “one-stop shopping,” will serve to streamline each function within the process.

Accompanying the change to the new office, according to St.Pierre, is the shift from a

premarket focus to a postmarket one. FDA says it is committed to promoting and protecting public health in the least burdensome and most appropriate manner possible. As a result, the agency is continuing to rethink its existing processes and procedures with future demands in mind. According to St.Pierre, attempts to streamline most premarket reviews is pushing the focus in the future on postmarket and enforcement.

How long it takes to get a new diagnostics products through review and approved for introduction, said St.Pierre, depends on its how it is classified. Class II premarket notification typically runs 75 days. For higher-risk Class III products, market introduction averages 220 days, he said.

In dealing with testing for infectious diseases, the FDA at times will expedite the review program for Class III products and push the product to the top of the list. The denovo classification provides the agency with the flexibility to reclassify some Class III lower threshold test products not already in the market as Class II.

The FDA maintains a good working relationship with the vast majority of the companies it regulates, St.Pierre said. “Informal meetings are often scheduled to give us a heads up on their plans for test development,” St.Pierre said. “Our goal is simple: get good products on the market quicker and keep bad products off the market.”

New user fees bring more reviewers
A source close to the FDA, who has first-hand knowledge of conditions there, was encouraged by recent changes. But the key to FDA’s ability to review new devices and diagnostics is less time, the source said, is increased money to pay for additional reviewers.

“For a long time, they (FDA) had to deal with increasing numbers of reviews without the necessary additional resources from Congress to hire more reviewers available,” the source said. “PDUFA and its user-fee system is providing the needed funding.”

First introduced in 1992 and renewed twice, the Prescription Drug User Fee Act gave the FDA the power to collect fees from companies who produce certain human drug and biological products. Before that, taxpayers alone paid for product reviews.

The intention of that law was to give the FDA the additional revenues it needed to hire more reviewers and support staff and upgrade its technology to speed up the application process — without compromising review quality. The law set specific time targets for the agency to complete reviews, depending on product type.

The latest renewal of PDUFA took effect October 1 of this year and will extend for five years. For the first time, manufacturers of clinical devices such as diagnostic tests for emerging infectious diseases will pay user fees to the FDA to help pay for product reviews. Small companies will pay lower fees; large companies higher fees.

“I think the diagnostics industry has seen the light and has accepted the user fee system,” the source said. “The first user fees — for drug reviews — reduced the average review time for drugs from more than two years to less than one year.”

Recent organizational changes, the source said, suggest the FDA is “taking a longitudinal focus instead of a narrow one — that’s good news.”

Bioterrorism is a, major concern for the FDA/Center for Biologics Evaluation and Research. The President’s initiative on Countering Bioterrorism is comprised of a number of essential elements for which CBER plays an integral role, including the expeditious development and licensing of products to diagnose, treat or prevent outbreaks from exposure to the pathogens that have been identified as bioterrorist agents. These products must be reviewed and approved prior to the large-scale productions necessary to create and maintain a stockpile. Staff must guide the products through the regulatory process, including the manufacturing process, pre-clinical testing, clinical trials, and the licensing and approval process. This process is extremely complex and early involvement by FDA staff is crucial to the success of the expedited review process.