Experts cite missed opportunity in NIH risk assessment of BSL-4 lab


By George Miller

A National Research Council (NRC) committee of experts provided a boost to neighbors opposing construction of a biocontainment research lab at the Boston University Medical Center by declaring in late November that a draft environmental impact report concerning the facility is “not sound and credible.”

The declaration compounds the complexity of a labyrinthine approval process whose players span neighborhood activists to officials at the city, state, and federal levels, all resulting from Project Bioshield legislation enacted following the 9/11 and anthrax letter attacks of 2001. The NRC experts viewed the report as an opportunity to quell fears about the safety of biocontainment facilities.

The National Institutes of Health (NIH) is now implementing a construction program that will complete four new BSL-4 facilities–including the $200 million BU lab, now 70 percent complete–as well as 14 BSL-3 facilities within the next few years [see “Lab Biosafety Hearings Conjure Cold War Fears,” CleanRooms, December 2007, p.7. Differences in biosafety level protocols are shown in the accompanying table].

Neighbors who oppose the facility question BU’s ability to protect their Boston neighborhood while running a BSL-4 facility, given the institution’s track record: At an existing BSL-2 lab in 2004, for example, researchers violated safety procedures and became infected with tularemia; at an advanced biomedical research building in early 2007, a medical waste fire led to the building’s evacuation.

Click here to enlarge image

Chief among the NRC expert committee’s concerns is the lack of inclusion of highly infectious agents in the NIH draft assessment, and the subsequent lack of a credible worst-case scenario. “A more acceptable analysis would have included agents that are readily transmissible and would have demonstrated that the modeling approach used recognizes biological complexities, reflecting what is known about disease outbreaks and being appropriately sensitive to population density,” according to an NRC statement.

The BU Medical Center BSL-4 biocontainment lab facility, now about 70 percent complete, is part of the Biosquare II project on Albany Street in Boston. Image courtesy of Boston University Medical Center.
Click here to enlarge image

In addition, the draft assessment contains too little information to compare the risks associated with alternative BU campus locations in suburban (Tyngsborough, MA) and rural (Peterborough, NH) settings for the laboratory. Considering pathogens that spread more easily would improve analyses of how risks vary depending on location, the committee said. It was also dissatisfied with the draft assessment’s consideration of environmental justice issues and how the biocontainment facility could affect the inner-city population in particular.

Missed opportunity

Expert committee member Gary Smith, chief for epidemiology and public health at the University of Pennsylvania School of Veterinary Medicine, said that, given the type of model that NIH researchers used in preparing the draft statement, “this seems to have been a missed opportunity, especially when the three locations were considered.” The NIH draft could have presented a more refined analysis of the risks presented by a facility like BU’s, he said, and evaluated comprehensively the impact of a worst-case scenario event on public health and safety. Doing so might have provided greater assurances for the neighbors and might also have been viewed as relevant to assessments for other biocontainment facilities.

The experts question whether the NIH fully exploited the agent-based model used in the analysis. The committee writes that such models are “particularly good at revealing the influence of heterogeneities in the host population.” Relevant examples, with respect to comparing the three locations, include host characteristics that may affect susceptibility and case fatality rates. “But there was no reference to expected or plausible differences on transmission probability for those at special risk (the very young, the very old, those with preexisting conditions, and those with compromised immune systems),” according to the report.

In addition, NIH appears to have made the assumption in its model that each person has 10 contacts per day, regardless of the population density of the location. “This assumption about the number of contacts further reduces the opportunity for transmission and effectively eliminates one of the most important differences between locations,” the report said.

Environmental justice concerns

NRC expert committee member Gigi Kwik Gronvall, assistant professor of medicine and senior associate at the University of Pittsburgh Medical Center’s Biosecurity Center in Baltimore, added during the NRC press conference that the draft NIH document also took into account neither the health status of the population, nor the Boston neighborhood’s status as a U.S. Environmental Protection Agency environmental justice community. “We didn’t see accommodations for public health access in the report,” she said. “We don’t know if it makes a difference. We just want to know that it was addressed.”

The neighborhood is acknowledged to have among the highest rates of HIV infections in Boston, as well as a high rate of intravenous drug use and correspondingly high incidence of hepatitis C.

“One of several things that affects how diseased one becomes during an outbreak is health status [of residents],” said expert committee member Smith. That status varies with age distribution, pregnancy rate, and proportion of immunocompromised individuals, among other factors.

The experts make clear in both their report and cover letter that their conclusions concern only the “scientific adequacy” of the NIH draft supplementary risk analysis, and not the previously submitted, original risk assessment and site suitability analysis document submitted by NIH as a standard part of the NEPA process.

“It is important to recognize,” the experts write, “that these conclusions are based solely on the committee’s technical review of the [NIH draft], and thus they should not be viewed as statements about the risks of proposed biocontainment facilities in Boston, or in cities more generally. The Committee acknowledges the need for biocontainment laboratories in the United States, including BSL-4 laboratories, and recognizes that BSL-4 facilities are being operated in other major urban areas.”

The NIH, while acknowledging via e-mail correspondence that “the NRC has raised important concerns,” makes no apologies for the document it drafted: “NIH followed the NEPA procedures in preparing a final environmental impact statement and in issuing a record of decision” on the BU lab, according to a statement issued after the NRC report was released in late November.

NIH said it will continue to follow the standard NEPA process and will consider and respond to all comments received, including those of the NRC experts.

For its part, the Boston University Medical Center said in a statement, “We recognize that the NRC report states concerns regarding the NIH methodology and analysis and are confident that the NIH will address those issues in its final report. In the meantime, we stand ready to provide whatever information we can in order to respond to questions and concerns, and to document that the South End site is as safe as or safer than alternative locations.”


compiled by Carrie Meadows
Gerbig Engineering introduces new cleanroom construction feature

Minnesota-based Gerbig Engineering, a specialist in the design, build, installation, and certification of cleanrooms, now offers a raceway that is integrated into the framing system of its cleanroom constructions. The raceway allows wiring, cabling, and plumbing to be threaded throughout the cleanroom and remain totally hidden. The system will work for both hardwall and softwall systems, and for portable or stationary cleanrooms. Existing AireCell Cleanrooms can be retrofitted with this raceway system.

New England Peptide opens instrumentation lab

New England Peptide, LLC (NEP), a company that designs and produces custom peptides and polyclonal antibodies for drug and vaccine discovery organizations, has opened a new production instrumentation laboratory at its Massachusetts facility. NEP’s engineering staff will use the dedicated lab to develop new instrumentation, qualify newly acquired production equipment, and efficiently bring instrumentation offline for maintenance.

David Savage lands at Ultra Clean

Ultra Clean Technology, a developer and supplier of critical subsystems for the semiconductor capital equipment industry, announced the appointment of David Savage as president and CEO, effective Jan. 8. Leonard Mezhvinsky retired from the position of president as of Dec. 31. Savage brings to Ultra Clean more than 20 years of executive experience. Before joining UCT, Savage was CEO of Litel Instruments, Inc., a semiconductor optical metrology business. He has also served as president of the Electronics Division of Meggitt USA, Inc., and as CEO at DigMedia, a media delivery business focused on broadband service providers.