Medical Device Link.

Originally Published IVD Technology April 2003

In Person

The United States has worked to rapidly develop diagnostics technology for the protection of its 
citizens after the events of September 11.

Jerome M. Hauer is acting assistant secretary for public health emergency preparedness in the Department of Health and Human Services. He can be contacted at jerome.hauer@hhs.gov.

Repeated calls for vigilance and announcements of heightened alerts have left the United States searching for a renewed sense of safety and security. Protection may be provided by diagnostics adapted for the detection of biothreat agents. IVD manufacturers, national laboratories, and governmental agencies are collaborating to expedite the development of more-rapid and more-effective diagnostics. Governmental agencies play an important role in this process by facilitating an open exchange of ideas, offering guidance, and establishing clear objectives for manufacturers and researchers.

To illuminate the central aims and ideals of the Department of Health and Human Services for the development of IVDs for biodefense, IVD Technology editor Richard Park spoke with Jerome M. Hauer, acting assistant secretary for public health emergency preparedness in the Department of Health and Human Services (Washington, DC). In this interview, Hauer talks about the importance of diagnostics for national defense, where this technology can be most effectively used, and where further improvement is needed.

IVD Technology: Please provide some background information about yourself and the objectives of your department.
Jerome Hauer: I began my work here as an advisor to Tommy G. Thompson, the secretary of health and human services (HHS) well before September 11, 2001. In March 2001, I came on board to work on better preparing HHS to shift its focus toward bioterrorism preparedness.

The secretary and I had conducted a number of briefings on the issue of terrorism preparedness. He asked me to reorganize and better staff the department, and enhance our medical countermeasures. In the early stages of my work here, it was difficult to engage people in working on bioterrorism. Many did not perceive the risk as significant. 
It wasn’t until we testified on the Dark Winter exercise, which was a fictional scenario depicting a covert smallpox attack on U.S. citizens, that we were able to bring attention to this issue. People finally began noticing that the potential impact of a bioterrorism incident was serious and significant.

Then, we had the unfortunate attacks on September 11, just several weeks after the hearings. Because of that attack, HHS’ whole focus shifted. Soon afterwards, during the anthrax incidents in October 2001, interest in bioterrorism grew exponentially.

Once the reaction to the events of 2001 calmed down, I moved to Washington, DC, and joined HHS full-time around February of 2002. In May of 2002, I became the director of the Office of Public Health Preparedness (OPHP), replacing D. A. Henderson, who formed the office. When the bioterrorism bill passed, I was appointed acting assistant secretary for public health emergency preparedness.

Among the Ranks

How would your department rate the importance of developing diagnostics for biodefense applications?
One of the greatest deficits in our ability to respond to biological attacks lies in the conventional thinking about biological attacks; namely, that they will involve a clandestine release. There are no biological environmental detectors that provide real-time readings that can be trusted. Additionally, very few diagnostics technologies are available that allow rapid diagnostics to be performed on patient specimens. This deficit has seriously hindered our ability to rapidly recognize and validate that an adverse biological incident has occurred.

For a long while, all of the development effort was put into real-time environmental detection because most of the work was being conducted by the Department of Defense (DOD) battlefield environments, and very little work was going into rapid patient diagnostics.

Lately, a greater emphasis has been put on the use of polymerase chain reaction (PCR) and even-more-advanced technology to rapidly diagnose patients and confirm that they have a disease that is likely to be linked to a terrorist act. Maintaining this focus is absolutely critical as we look to the future.

We have a window of opportunity during which we can reduce morbidity and mortality by quickly recognizing that a biological incident has occurred. The longer it takes for us to recognize that a biological incident has occurred, the greater will be the morbidity and mortality.

It is a serious issue. We are putting an enormous amount of emphasis on the issue right now because we are moving forward very aggressively, both in DOD and in The Centers for Disease Control and Prevention (CDC), to develop rapid detection technologies, because there is a large deficit.

Do people in all levels of government appreciate the importance of the role of diagnostics in national defense?
I do realize the importance of diagnostics, and that’s why I feel there is such a great deficit right now. I think we need more rapid diagnostics. As time has gone on, there has been a greater realization that we need more than just environmental detecting; we also need rapid diagnostics to confirm patient infection.

Developing Diagnostics for Biodefense

What characteristics do you consider important for successful biodefense diagnostics?
The hallmarks of good diagnostics—specificity, sensitivity, and rapidity. In the best of all worlds, an IVD should be easy to use, so the test can be done either in the emergency room or in the smaller hospital labs that might not have 24-hour diagnostic capability for bacterial and viral specimens.

We hope that the diagnostic will be inexpensive as well. Those characteristics are very similar to those required of standard diagnostics.

What minimum performance standards have been established for biodefense diagnostics?
We are working on performance standards for some types of diagnostics. Right now, we’re focusing on rapid PCR and where it can be used.

Can first responders—police, firefighters, emergency medical technicians, paramedics, etc.—use these rapid diagnostics?
No. They wouldn’t use these devices to detect biological weapons. However, they would use tests for chemical weapons.
If there has been a clandestine release from a biological agent and environmental detectors are able to pick it up early enough, then the first people that show signs of having been exposed will show up either in an emergency room or at the office of their primary care provider. Hospital personnel and other medical staff should be provided with the rapid diagnostics, rather than first responders.

How, then, would diagnostics for biological agents be used in the field?

A clandestine release will become known because it will be picked up on an environmental detector. The area in which the release occurred can then be defined, and sampling and testing can be performed on people that might have been within the plume. But the question is: At what point do they develop recognizable and detectable symptoms?

For example, if someone released smallpox today and we picked it up on our sampler, even if we had a diagnostic that could sample people tomorrow I’m not sure that we would detect the virus in anyone. The virus may not be detectable for several days because of the way smallpox and anthrax evolve in the body. This shortcoming in our diagnostics abilities allows us to protect people by either vaccinating or chemoprophylaxing them ahead of time. Then, if a release has occurred, we can start testing people when we presume the infectious agent would become detectable in their bodies.

In addition to anthrax, what diseases does your department deem to pose significant bioterrorism threats?
All of the agents that are considered to be Category A select agents by CDC, including smallpox and tularemia, and the viral hemorrhagic fevers (VHF), are considered to be important.

Some are of greater concern. Obviously, we would like to cover anthrax, smallpox, plague, tularemia, and VHF first.

Preparing the Nation

What action is your department taking to ensure that public health systems around the nation are well equipped with the proper diagnostic tools in case of a bioterrorist attack?

We have put an enormous amount of money into enhancing the Laboratory Response Network and are continuing to strengthen it. We continue to invest in it because one of the lessons learned from the anthrax incidents was that the large volume of samples overwhelmed the limited number of laboratories that could do anthrax testing.

We are working to enable them to handle a greater capacity at both the state and local levels. We’re trying to enhance the network’s capacity by making it quicker to get specimens to a laboratory and by enabling the laboratories to conduct continuous testing. They’re constantly doing sampling to maintain their capability at the state and local levels.

What assumptions can be made about those persons using biodefense diagnostics technology? Are these people likely to have sophisticated laboratory training or are they first responders with little clinical expertise?
First responders should not be responsible for using all of the biodefense diagnostics technology. First responders, by and large, have been using handheld assays for detecting biological agents. Our department released guidance on handheld assays demonstrating that, after much testing, handheld assays are fairly uniform and unremarkable in their capability. We recommend that they not be used.

While first responders certainly have the capability to use these diagnostics, I just don’t think there is a need to have them in the hands of first responders, with one exception. That is, when biological terrorism takes the form of either packages or letters like the ones used in the anthrax attacks and that we continue to see all over the country.

In that case, having a rapid diagnostic in the hands of a hazardous-materials team could be valuable. However, available rapid diagnostics tend to be rapid PCRs. They tend to take a little time to process samples. It is generally best to take a sample to a secure lab where it can be tested in a controlled environment, rather than on-site.

If a handheld assay is developed that performs rapid on-site testing, it would enhance the capability of the first responders to deal with envelopes and packages filled with suspicious powder. But with the exception of envelopes or packages containing suspicious powder, there is little need for first responders to use rapid diagnostics because a release will generally be a clandestine release.

How do the differences between field diagnostics and laboratory diagnostics as well as between local resources and federal resources influence how new technologies are adapted for use at the local level?
Diagnostics are generally first being used at the federal level and then exported to the state and local levels. The greatest difficulty arises when diagnostics developed for the laboratory are exported to those in the field because they are often not suitable for use in field conditions.

When a technology has been developed for use at the federal level, is its durability considered before it is exported to the field or adapted for field use?
Absolutely. Anything that has to be used in the field — not used in combat settings, but used by first responders—must be transportable and durable. It must be rugged and must be unaffected when exposed to the elements. This can be a limitation for some of the technology that are available. Thus, until a better handheld assay comes out, it is better to take the sample to a laboratory where all the controls are in place and reliable tests can be performed.

Collaboration

Does your department work with diagnostic manufacturing companies in the private sector?
Yes. Primarily CDC and the laboratories at CDC. On a regular basis, we have companies come in to show us their new technologies and talk with us about technologies for new diagnostics. We are constantly looking at new diagnostics.
Many handheld assay companies will tell you that we have ignored them, but we have met with them. We simply have a difference of opinion.

What role does your department play in the efforts to develop diagnostics for biodefense?
The laboratories in the CDC network are accomplishing much of the technological development. A lot of the work is also being done in DOD, and we are working alongside DOD to look at developing technologies.

To what degree have the various government agencies been able to coordinate on developing diagnostics for biodefense?
We are working closely with DOD and DOE (Department of Energy) to exchange technologies. I have someone from DOE on my staff whose primary focus is diagnostics and laboratory capabilities.

It seems that there has been difficulty in coordinating efforts among different institutions—whether it’s EPA or CDC or FDA or DOD—to decide which direction to take when developing diagnostics for biodefense.
We haven’t had much difficulty coordinating with other departments. There is coordination within HHS, between CDC and FDA, and we do work closely with DOD. DOE is doing work on biodefense diagnostics and we are also talking with them.
Coordination doesn’t mean everybody is looking at the same thing. Different departments might be looking for different diagnostics, and that is good. I don’t think everyone ought to be myopic in their approach to developing diagnostics for biodefense.

Was the Department of Homeland Security expected to take a leadership role in coordinating efforts and determining the direction of developing diagnostics for biodefense?
That work will be accomplished by a joint effort of the secretary of homeland security and the secretary of HHS.

What future challenges do you foresee in developing diagnostics for biodefense?
We need to develop diagnostics that have the capability to adapt as organisms change. They should be able to rapidly detect genetically altered organisms, which at this point can be difficult and time-consuming. We need diagnostics that can determine susceptibilities in a very rapid fashion. The threat of genetically altered biological agents is very real, and our ability to respond should be based on the information we get from diagnostics.

Copyright ©2003 IVD Technology