Changes in select agent rules concern public health labs

Oct 10, 2012 (CIDRAP News) – The Centers for Disease Control and Prevention (CDC) has revised its list of potentially dangerous biological agents and toxins and the regulations covering them, and some of the changes have public health laboratories concerned.

The CDC has dropped 23 items from the official list of "select agents and toxins" and has added three viruses to the list: the SARS (severe acute respiratory syndrome) coronavirus and two hemorrhagic fever viruses: Lujo, from Africa, and Chapare, from South America.

"At the end of the day the list is shorter. We think it's more focused on the agents of highest concern to public health," said Rob Weyant, PhD, director of the CDC's Division of Select Agents and Toxins.

In addition, the agency has designated a new category of agents, called Tier 1, for those deemed to pose the biggest risk of deliberate misuse with potential for high casualties and economic and social disruption. Labs that handle these agents will be subject to new security requirements, including a "personal reliability" program to ensure that personnel with access to the agents are trustworthy.

It's the Tier 1 requirements that concern the Association of Public Health Laboratories (APHL), according to Chris N. Mangal, MPH, the APHL's director of public health preparedness and response. She said the association is worried that the new security requirements will prove too burdensome and may prompt labs to give up their registration with the federal Select Agent Program. And that in turn could impair their ability to respond to infectious disease threats, she said.

The Tier 1 list includes Ebola virus, Francisella tularensis (the cause of tularemia), Marburg virus, variola major and minor viruses (smallpox), Yersinia pestis (plague), Clostridium botulinum and botulinum toxin (botulism), Bacillus anthracis (anthrax), Burkholderia mallei (glanders), and Burkholderia pseudomallei (melioidosis).

The CDC detailed the select agent changes in an Oct 5 Federal Register notice. They follow the agency's biennial review of the program, which included a round of public comments. Some of the new rules take effect Dec 4, while others become effective on Apr 3, 2013, according to the notice.

There are 312 labs that participate in the CDC Select Agent Program covering human pathogens and toxins, according to CDC spokesman Jason McDonald. Another 50 labs are in involved in the animal and plant Select Agent Program under the US Department of Agriculture's supervision.

Personnel screening, physical barriers
Weyant said the personal reliability program required for labs that handle Tier 1 agents has two parts: a formal pre-access screening program and ongoing monitoring. The latter is intended to provide reporting avenues for staff members who have concerns about suspicious behavior by other lab workers, he told CIDRAP News in an interview.

Increased physical security will also be required for labs working with Tier 1 agents, Weyant said. For example, "A Tier 1 entity needs to have three demonstrable barriers between the public and regulated material. We've established a good guidance document about that."

In addition, he said, "We require that at least one barrier have an intrusion detection system, something that would tell a security function that an unauthorized person is trying to get in."

Mangal said the APHL likes some of the select agent changes. "We're definitely pleased that they've taken off Coccidioides and the Shiga toxins" from the list, she said. "These were things we had previously commented on and asked them to remove."

Coccidioides are fungi that cause respiratory disease. Mangal said a variety of treatments are available for Coccidioides infections, so it didn't make sense to keep them on the list. Shiga toxins are very difficult to aerosolize for weapon use, and Escherichia coli strains that produce Shiga toxins are not on the list, so it also made sense to drop the toxins, she added.

"Where I'm concerned is that they've retained a lot of the agents that state and local public health labs test for," Mangal said. "B anthracis is in the Tier 1 category, which means that a lot if not all of our state public health labs will be impacted by the new requirements that come along with Tier 1."

APHL sought exemptions
The APHL had formally asked the CDC to exempt Laboratory Response Network (LRN) reference labs from the Tier 1 requirements. "We based that on the existing practices in the labs, and also the fact that they possess very limited quantities of select agents," Mangal said.

The LRN is a network of about 165 labs, including 100 public health labs, designated by the CDC and APHL to help respond to potential bioterrorism events and other infectious disease threats.

The APHL also had asked the CDC to drop the nonpathogenic Pasteur strain of B anthracis, botulinum toxin, and toxin-producing strains of C botulinum from the Tier 1 list, Mangal reported. Public health labs in the LRN keep small amounts of these agents and toxins for quality-control purposes, using them to help confirm the presence of a threat agent, she explained.

The CDC turned down the APHL requests. In the Federal Register notice, the CDC said the LRN labs could use attenuated strains of select agents, which are excluded from Tier 1, for their quality-control testing purposes.

Weyant commented, "We have been working with the leadership of the LRN to identify excluded strains of select agents that can be maintained by laboratories without meeting the Tier 1 requirements. The Pasteur and Sterne strains of Bacillus anthracis are examples of these strains."

As for dropping B anthracis Pasteur strain from Tier 1, in the Federal Register the agency agreed that the strain by itself does not meet the Tier 1 criteria, but said that dropping it from the list could pose a risk of creating virulent strains through the combination of the Pasteur strain with the Sterne strain, an attenuated strain that is not in Tier 1. The CDC promised to continue evaluating exclusion requests as new information becomes available.

Mangal agreed that labs could use attenuated strains of Tier 1 agents for quality-control testing, but she said that practice raises more questions. For example, if a lab not registered with the Select Agent Program were to identify B anthracis or some other Tier 1 agent in a sample, it would be required to either destroy it or send it to another lab within 7 days, she said.

"From a scientific perspective, you may not want the lab to destroy the agent until they've had an opportunity to further characterize it and get more genetic details," she said. "We don't want to promote [the practice] that once you've identified an agent you destroy it within 7 days."

As for the new requirements for labs that handle Tier 1 agents, the APHL is mainly concerned about the personal reliability assessments, Mangal said.

"The main added requirement on this is the entity is now required to perform a pre-access suitability assessment," she said. "They [staff] already go through a background check with the Department of Justice. This is more of an entity-specific assessment. "

"The CDC has provided a guidance document, and we'll be reviewing that to gain some insights on how to perform [the assessments] and what it means to the labs in the LRNA," she said.

The bottom line is that public health labs will probably be pondering whether to continue participating in the Select Agent Program, according to Mangal.

"In coming months I anticipate significant discussion within the public health lab community as to whether to maintain their select agent registration," she said. "There's obviously value in maintaining it—there are security standards that come with that that help prevent access to select agents—but what the labs will have to look at is what are the costs to meet the new Tier 1 requirements, and what are the ongoing costs."

Adding SARS to the list
Weyant cited no specific reason for designating the SARS coronavirus a select agent, beyond comments the CDC received from experts and the public. He said the step has been considered during every biennial review of the program since the SARS epidemic in 2003.

The virus sickened more than 8,000 people and killed 916 in about 30 countries that year. The SARS virus is a coronavirus, and the emergence of another novel coronavirus in September has focused some renewed attention on SARS.

During the latest review, Weyant said, "The input we got from experts and the public really reinforced the public concern over the potential dangers of the virus. Also, we considered that there were lab-acquired infections in China and Singapore" in the aftermath of the 2003 epidemic.

CDC data suggest that more than 120 labs possessed the SARS virus at some point, and the majority of those are registered with the CDC to handle select agents, Weyant said.

"Currently it looks like a dozen or less" have the virus, he added. "Now that the [revised] rule has been published, we'll be seeking any additional labs that may have the virus."

With SARS designated a select agent, labs that possess samples will have to register with the program or else destroy the samples or ship them to another lab.

Registration is a sizable task. Labs are required to develop security, biosafety, and incident response plans, along with training programs and drills, Weyant explained.

"Anyone in these entities who would have access to regulated materials must go through a screening done on our behest by the FBI," he said. "Typically we'll do a site visit prior to providing the certificate of registration, and we'll review their physical security, biosafety, inventory control, and training programs.

"It's a fairly extensive process, and that's why we provide 180 days to come into compliance."

See also:

CDC Federal Register notice

USDA Federal Register notice on changes in animal and plant select agent program

Jun 15, 2011, CIDRAP News story about paring select agent list

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