As a result of the new guidelines, institutions that previously handled potentially dangerous materials with little oversight must now implement extensive security measures, keep detailed inventory logs, and adopt protocols for visitors and maintenance staff working in sensitive areas. Organizations and responsible individuals failing to secure Select Agents in accordance with the new federal standards are subject to severe criminal penalties and fines up to $500,000.

"These rulings aren't about biosafety or biocontainment, they are about the protection of potentially dangerous assets," says Michael P. Kiley, Ph.D., program safety officer with the Agricultural Research Services of the United States Department of Agriculture in Beltsville, Md.

The Centers for Disease Control and Prevention (CDC) in conjunction with the Department of Health and Human Services (HHS) issued the original ruling regarding transfer of pathogens capable of mass destruction as part of the 1996 Anti-terrorism and Effective Death Penalty Act. Along with this act, the Select Agent List was created and organizations transferring any one of the agents were required to register with the CDC.

The new rule, published in the federal register December 13, 2002, is part ofthe Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (a.k.a. the Bioterrorism Act), and is in direct response to the terrorist attacks of September 11 and the 2002 anthrax attacks. It supersedes the prior ruling and establishes new rules for securing, handling, and transferring agents that could be used against human beings. Two additional rulings—7 CFR and 9 CFR—apply to agricultural threats and animal pathogens, respectively.

The new rulings impact a wide range of biotech institutions, including pharmaceutical companies, diagnostic labs, animal testing facilities, medical centers, and universities developing vaccines.

New Game, New Rules

The 82 select agents on the federal list fall into four categories: pathogens that affect humans; animal pathogens; plant pathogens; and overlap agents that are toxic to both humans and animals. According to the regulations, organizations handling any of these materials must file a site-specific security risk assessment plan with either the CDC or the Animal and Plant Health Inspection Services, depending on the substance.

All personnel, regardless of position, who have access to select agents must be cleared by an FBI background check. Organizations are also required to install security systems "proportional to the threat posed by the toxin," and designate a "responsible official" who must have the authority and latitude to implement all security measures, and is held personally responsible for their efficacy.

Though the ruling went into effect in February, organizations have until November 12, 2003 to be in full compliance.

Implications and Responses

The new ruling raises a number of facility concerns, including how and where Select Agents are physically stored; who can access them; and how to accurately account for both the assets and the access.

"Biocontaiment facility standards themselves have not changed since 2001, but what has changed with the new ruling is the nature of the security protocols, which have more effect on the way a lab might operate than on how it meets structural guidelines," says Jeff Schantz, principal architect with Lord, Aeck & Sargent Architecture.

According to Schantz, organizations must consider how increased security standards will change the design of any facility working with Select Agents.

"Designers must consider what 'appropriate security' means for each particular site. A layer approach is recommended. Security measures may range from creating a perimeter with physical barriers for vehicular traffic to video monitoring, pass cards, or other electronic security methods," he says.

Another important issue is the need to maintain accurate inventory and access logs. Different labs are developing various systems for tracking assets. Some are maintaining physical logs, others are adopting barcode scanner systems, but frost makes this difficult in facilities where agents are stored in a deep-freeze.

"Facilities planners have to consider how and where inventory information, as well as data from card key systems and video monitors, is being gathered and if those systems are secure," says Schantz.

Foreign Relations

The ruling also raises personnel concerns such as the escorting and vetting of staff, a potentially sensitive issue with long-term employees, and working with foreign students. In some cases, researchers who meet all the safety requirements and have been working inside Select Agent facilities unsupervised for years, now have to be escorted.

Facility maintenance is another area of high containment lab operations that will require re-assessment under the new rules. Previous to Part 73, some institutions had trained particular maintenance personnel to handle work in those areas.

At Duke University in Durham, N.C., a specialized four-man team of skilled tradesmen has been in place for more than 20 years conducting facility maintenance and biohazard duties such as certification of biological safety cabinets, chemical fume hoods, in-place HEPA filters and laboratory space decontamination. Because the maintenance team is dedicated to the BSL-3 labs and has specialized training in biological safety principles, no escorts were required when they entered the labs. This concept will be re-assessed in light of the new escort requirement.

"We really try to minimize the number of people who have access to those areas, so we'll be training the researchers, lab techs, and animal husbandry personnel to help with some of the minor maintenance tasks," says Steven Kridel, operations coordinator for Duke University's BSL-3 labs.

Impacts and Side Effects

According to the HHS, first year costs associated with implementing the ruling are expected to range from $23,400 for small commercial entities with BSL-3 labs, to $734,400 for medium-sized universities with more extensive BSL-2 and -3 facilities. Total annualized cost of implementation is estimated by the HHS at an average of $41 million.

As a result, companies that do not have the budget available to incorporate increased security measures and personnel background checks are having to change their line of research.

Another negative side-effect for educational institutions has been a reduction in the number of available lab workers. Many universities depend on work done by students from other countries and, under the new guidelines, persons from suspect nations are not allowed access to pathogenic agents.

"Many universities and research organizations rely on graduate students, doctoral, and post doctoral candidates to do the 'heavy lifting' of science and many of them are foreign nationals. Restrictions on student visas will make it harder to fill those positions without a concerted effort to replace those workers with domestic talent," says Schantz.

The Responsible Official

One of the key requirements of 42 CFR is that any organization handling select agents must designate a "responsible official" who is personally accountable for the implementation of all security measures.

"The responsible official is our primary point of contact. He or she is personally responsible for overseeing implementation of the new rules and the ongoing security of Select Agents at his or her institution," says Robert Hill, Ph.D., acting director for the Office of Health & Safety at the CDC in Atlanta.

"Duke's responsible official is the director of our bio-safety division, she has significant experience with oversight on this level, and it's still an incredibly daunting task. The responsibilities are extensive and there are considerable legal penalties. I can't imagine very many people would want the position," says Duke's Kridel.

The responsibilities associated with this position include filing the required site-specific security assessment and response plan; inspecting laboratories; training all individuals who work with select agents; keeping thorough records of access to Agents; and establishing protocols for reporting loss or theft of Agents. The official must also pass a thorough FBI background check.

New Designs in Security

From a design standpoint, one notable response has been a move to portable BSL lab units that are built on trailers. Such equipment can be used in different locations, and can be carted away for analysis in the event of an accident or violation.

One positive side effect from the funding surge is a focus on rebuilding of the public health infrastructure, much of which is over 30 years old, and to provide a first responder network. There has been a surge in new projects as direct result of the USA Patriot Act and the Bioterrorism Act. States that didn't have biological testing capacities prior to 2001, including New Jersey, Ohio, California, and Texas, are using new federal funds to rebuild public health infrastructure and develop BSL-3 facilities to identify and counter pathogenic threats.

"In the end, organizations can secure their facilities as much as humanly possible, but the real question is: How do you fight the intent of somebody who is committed to doing bad things?" says USDA's Kiley. "These measures can't entirely answer that question. They are a response to an immediate threat and, inevitably, systems will be adjusted and improved over time."

By Johnathon Allen