Memorandum 28
Submission from the British Embassy, Washington,
United States of America
US BIOSECURITY
INTRODUCTION
Biosecurity regulation in the US is complex
and involves the participation of many different US federal agencies.
In addition, individual states and local governments may impose
their own restrictions on the types of research that can be conducted
or classes of micro-organisms entering that community. In general,
the level of regulation logically increases with the perceived
level of danger associated with a given micro-organism. The US
divides threats in terms of those posing risks to human health
and risks to animal/plant health. Human health issues are regulated
by the US Department of Health and Human Services (HHS) and animal/plant
issues are managed by the US Department of Agriculture (USDA).
In the case of HHS, most regulatory authority has been delegated
to its constituent agencies, the Centers for Disease Control (CDC)
and the National Institutes for Health (NIH). USDA utilises its
Animal and Plant Health Inspection Service (APHIS) to manage the
plant/animal dimension. The discussion in this paper will speak
generally to human, animal and plant health; however there is
a human health bias. Some variations exist for the animal and
plant health regulations.
BIOSAFETY GUIDELINES
AND CATEGORIES
Inquiry Questions: By what mechanisms are micro-organisms
classified with regards to their potential danger and their need
to be contained? What are the categories of biological containment
in use?
Published by HHS, NIH and CDC, the Biosafety
in Microbiological and Biomedical Laboratories Handbook (BMBL)
[33]has
become the cornerstone of biosafety practice in the US. It is
a key document and would be recommended for anyone wanting an
understanding of US biosafety practice. The 5th edition was last
produced in 2007 and available in pdf format.
The US uses a system of four biosafety levels
(BSLs) to describe the danger and the corresponding practices,
equipment and facilities. The BSL levels thus serve a similar
purpose to the UK's microbiological containment levels (CLs).
BSL4 represents the most dangerous pathogens while BSL1 represents
microbes that are not known to cause disease. A table summarising
the levels, equipment and practices is attached. Following from
the BSL level, equipment and facilities are further described.
In the US there are three main classes of biological safety cabinet
that are used in combination with particular types of facilities.
For example, BSL4 microbes could be used with a Class III cabinet
or Class I/II if in combination with a positive pressure personnel
suit.
SELECT AGENTS
Inquiry Question: By what mechanisms are micro-organisms
classified with regards to their potential danger and their need
to be contained?
In addition to BSL category, the US has established
a list of pathogens and toxins that it believes pose a severe
threat to public health and safety (including humans, animals
and plants). Referred to as "Select Agents,"[34]
these biological agents and toxins are given special treatment
under US law. The current list of select agents is attached to
this note. Following from this, specific agents have been identified
as having the possibility of being efficiently used for bioterrorism.
Categories of A through C help public health agencies prepare
appropriate responses.[35]
For determining select agents related to human health, HHS considered
the following:
— the effect on human health of exposure
to the agent or toxin;
— the degree of contagiousness of the
agent or toxin and the methods by which the agent or toxin is
transferred to humans;
— the availability and effectiveness
of pharmacotherapies and immunisations to treat and prevent any
illness resulting from infection by the agent or toxin; and
— any other criteria, including the
needs of children and other vulnerable populations, that HHS considers
appropriate.
POLICY HISTORY
AND FEDERAL
REGULATIONS
Following the Oklahoma City bombing in 1995,
the US Congress passed the Anti-terrorism and Effective Death
Penalty Act of 1996.[36]
In this Act, HHS was given authority to register and track dangerous
pathogens. This was soon followed by the terrorist events of September
and October 2001 with anthrax spores mailed to prominent politicians
and media personalities. In response, Congress passed three new
pieces of legislation that further strengthened oversight of dangerous
microbes and toxins. The legislation included: the Uniting
and Strengthening America by Providing Appropriate Tools Required
to Intercept and Obstruct Terrorism Act of 2001 (PATRIOT Act),[37]
the Public Health Security and Bioterrorism Preparedness and
Response Act of 2002[38]
and the Agricultural Bioterrorism Protection
Act of 2002. The provisions of these Acts were implemented through
the issuance of federal rule 42 CFR Parts 72 and 73, [39]7
CFR 331 and 9 CFR Part 121.[40]
These rules regulate the possession, use and transfer of dangerous
pathogens and toxins defined as "select agents". They
also established a national database for groups licensed to work
with the select agents and set criminal penalties for individuals
and groups that fail to comply with the rules. Under the rules,
certain US agencies have been delegated the following authorities:
— Department of Health and Human Services
(authority delegated to US Centers for Disease Control (CDC)—Responsible
for oversight of select agents effecting human health and licensing
groups to possess, use or transfer said agents/
— Department of Agriculture (authority
delegated to Animal and Plant Health Inspection Service (APHIS)—Responsible
for oversight of select agents effecting animal/plant health and
licensing groups to possess, use or transfer said agents.
— Department of Justice (authority
delegated Federal Bureau of Investigation, Criminal Justice Information
Services Division (FBI)—responsibility to conduct electronic
checks (ie security risk assessments) on groups that apply to
possess, use, or transfer select agents as well as personnel that
require access to select agents and toxins.
The regulations also contain requirements that
ensure select agents are handled safely and secured against unauthorised
access, theft, loss or release. For example, research groups and
their personnel must undergo a security risk assessment by the
FBI as part of the licensing process; groups must limit access
to select agents and implement biosafety, security and incident
response plans. In addition, all select agents must be transferred
in accordance with the regulations with any theft, loss or release
of the select agent reported to the CDC or APHIS. To assist with
the process of licensing and processing research requests, CDC
and APHIS have established the National Select Agent Registry
(NSAR). Full details of this registry can be found at: http://www.selectagents.gov/index.html
LICENSING
Inquiry Question: How are licenses to use dangerous
pathogens in research awarded? Who is responsible for overseeing
security clearance for research students working with dangerous
pathogens—what is the role of the universities in this process?
Under the select agent regulations, a research
group must register (or be licensed) to work with or have contact
with any select agent. The registration is only valid for the
specific agents, activities and location as indicated on registration.
This process is initiated by the interested entity submitting
an application to the appropriate agency (CDC or APHIS).[41]
An entity can be a government agency, academic institution, corporation,
company, partnership, society, association, firm or any other
legal entity recognised in the US. If the entity represents many
individuals, the entity must designate a responsible officer to
act on behalf of the entity. In the application, the entity must
list every individual that will have access to the select agent.
After the application is made, the FBI will conduct a security
risk assessment. This assessment includes fingerprinting all staff
listed on the application and background checks. The assessment
must be renewed and can only be issued for a period not to exceed
five years. Only individuals with a security risk assessment for
the application can be allowed access to the select agent.
INSPECTION
Inquiry Question: What is the inspection regime
for laboratories licenses to use dangerous pathogens?
Inspections are co-ordinated by CDC and APHIS.
The federal rules authorise inspections without notification to
any licensed site. Inspections are typically done prior to issuing
a license to evaluate the premises and records to ensure compliance
with rules. This includes inspection or copying any records associated
with select agent activities. A set of inspection videos can be
seen at: http://www.selectagents.gov/FacilityInspectionDVD.htm
TRAINING
Inquiry Question: What training is mandatory/recommended
for staff working in containment facilities?
As stated in the CFR rules (42 CFR 73.15),
"(a) An individual or entity . . . must
provide information and training on biosafety and security to
each individual with access approval from the HHS Secretary or
Administrator before he/she has such access. In addition, an individual
or entity must provide information and training on biosafety and
security to each individual not approved for access from the HHS
Secretary or Administrator before he/she works in or visits areas
where select agents or toxins are handled or stored (eg laboratories,
growth chambers, animal rooms, greenhouses, storage areas, etc).
The training must address the particular needs of the individual,
the work they will do, and the risks posed by the select agent
or toxins.
(b) Refresher training must be provided annually.
(c) A record of the training provided to
each individual must be maintained. The record must include the
name of the individual, the date of the training, a description
of the training provided, and the means used to verify the employee
understood the training".
CONTAINMENT
Inquiry Question: What are the regulations regarding
the storage and transportation of dangerous pathogens?
The federal regulations require that the registered
entity develop a biosafety plan that is commensurate with the
risk of the agent or toxin. This plan must provide procedures
sufficient to contain the select agent or toxin and consider in
the BMBL.[42]
The plan must also be reviewed annually.
SECURITY
Inquiry Questions: What are the regulations regarding
the storage and transportation of dangerous pathogens? What measures
are in place to be implemented when pathogenic material cannot
be accounted for?
US federal regulations require (42 CFR 73.11):
"(a) An individual or entity required
to register under this part must develop and implement a written
security plan. The security plan must be sufficient to safeguard
the select agent or toxin against unauthorised access, theft,
loss, or release.
(b) The security plan must be designed according
to a site-specific risk assessment and must provide graded protection
in accordance with the risk of the select agent or toxin, given
its intended use. The security plan must be submitted upon request.
(c) The security plan must: (1) describe
procedures for physical security, inventory control, and information
systems control, (2) contain provisions for the control of access
to select agents and toxins, (3) contain provisions for routine
cleaning, maintenance, and repairs, (4) establish procedures for
removing unauthorised or suspicious persons, (5) describe procedures
for addressing loss or compromise of keys, passwords, combinations,
etc and protocols for changing access numbers or locks following
staff changes, (6) contain procedures for reporting unauthorised
or suspicious persons or activities, loss or theft of select agents
or toxins, release of select agents or toxins, or alteration of
inventory records, and (7) contain provisions for ensuring that
all individuals with access approval from the HHS Secretary or
Administrator understand and comply with the security procedures.
(d) An individual or entity must adhere to
the following security requirements or implement measures to achieve
an equivalent or greater level of security: (1) allow access only
to individuals with access approval from the HHS Secretary or
Administrator, (2) allow individuals not approved for access from
the HHS Secretary or Administrator to conduct routine cleaning,
maintenance, repairs, or other activities not related to select
agents or toxins only when continuously escorted by an approved
individual, (3) provide for the control of select agents and toxins
by requiring freezers, refrigerators, cabinets, and other containers
where select agents or toxins are stored to be secured against
unauthorised access (eg, card access system, lock boxes), (4)
inspect all suspicious packages before they are brought into or
removed from the area where select agents or toxins are used or
stored, (5) establish a protocol for intra-entity transfers under
the supervision of an individual with access approval from the
HHS Secretary or Administrator, including chain-of-custody documents,
(6) require that individuals with access approval from the HHS
Secretary or Administrator refrain from sharing with any other
person their unique means of accessing a select agent or toxin
(eg, keycards or passwords), (7) require that individuals with
access approval from the HHS Secretary or Administrator immediately
report any of the following to the Responsible Official: (i) any
loss or compromise of keys, passwords, combination, etc, (ii)
any suspicious persons or activities, (iii) any loss or theft
of select agents or toxins, (iv) any release of a select agent
or toxin, and (v) any sign that inventory or use records for select
agents or toxins have been altered or otherwise compromised, and
(8) separate areas where select agents and toxins are stored or
used from the public areas of the building.
(e) In developing a security plan, an entity
or individual should consider, the document entitled "Laboratory
Security and Emergency Response Guidance for Laboratories Working
with Select Agents. Morbidity and Mortality Weekly Report 6 December
2002; 51:RR-19:1-6". The document is available on the
Internet at: http://www.cdc.gov/mmwr.
(f) The plan must be reviewed annually and
revised as necessary. Drills or exercises must be conducted at
least annually to test and evaluate the effectiveness of the plan.
The plan must be reviewed and revised, as necessary, after any
drill or exercise and after any incident.
ROLE OF
THE UNIVERSITY
AND NIH GUIDELINES
FOR RESEARCH
INVOLVING RECOMBINANT
DNA MOLECULES
A final point when considering US regulation
in regard to biosafety is NIH regulation on experimentation utilising
DNA recombinant molecules. With the advent of genetic engineering,
the public became concerned with the insertion of genetic material
into organisms with possibly unknown outcomes. As a result, special
guidelines were put in place to ensure that genetic manipulation
was carried out responsibly.[43]
This is particularly the case when using DNA recombinant methods
on select agents. The NIH guidelines call for the establishment
of Institutional Biosafety Committees (IBCs) that approve and
monitor recombinant research that could result in dangerous results.
The IBCs function in a manner very similar to Institutional Review
Boards (IRBs) that are established to monitor human clinical trials.
With the advent of IBCs, many institutions have
started to use the IBC to monitor both recombinant DNA work as
well as any research done with select agents. For example Boston
University discusses the function of its IBC at: http://www.bumc.bu.edu/Dept/Content.aspx?DepartmentID=357&PageID=5570
The use of IBCs is very important to universities
as federal regulations place the legal liability on the entity
licensed to conduct experimentation. The university is responsible
for all of the requirements under the regulations and also the
consequences of any failures. Thus the research institution would
need to apply for a license to APHIS/CDC for any research students
working with dangerous pathogens and those students would need
to have an FBI background check. A recent example in Texas by
Texas A&M University showed that a lab employee lacked the
clearance to work with a dangerous agent. The CDC has halted research
in the lab as a result. An article relating to this incident can
be found at: http://www.aaas.org/news/releases/2007/1121biosafety.shtml
FEDERAL AGENCY
LINKS
National Select Agent Program—http://www.selectagents.gov/
Centers for Disease Control (CDC)—http://www.cdc.gov/od/sap/
Animal and Plant Health Inspection Service (APHIS)—http://www.aphis.usda.gov/programs/ag_selectagent/index.html
National Institutes of Health (NIH) Recombinant DNA
Advisory Committee (RAC)—http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html
Federal Bureau of Investigation—http://www.fbi.gov/hq/cjisd/cjis.htm
22 January 2008
33 BMBL Handbook-http://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm Back
34
US Select Agents-http://www.cdc.gov/od/sap/docs/salist.pdf Back
35
Bioterrorism Agent Classification-http://www.bt.cdc.gov/agent/agentlist-category.asp Back
36
Anti-terrorism and Effective Death Penalty Act of 1996-http://thomas.loc.gov/cgi-bin/query/z?c104:S.735.ENR: Back
37
PATRIOT Act-http://www.selectagents.gov/resources/USApatriotAct.pdf Back
38
Public Health Security and Bioterrorism Preparedness and Response
Act of 2002-http://www.selectagents.gov/resources/PL107-188.pdf Back
39
HHS Select Agent Final Rule-http://www.cdc.gov/od/sap/42_cfr_73_final_rule.pdf Back
40
USDA Select Agent Final Rules-http://www.cdc.gov/od/sap/42_cfr_73_final_rule.pdf Back
41
NSAR Select Agent Application-http://www.selectagents.gov/resources/APHIS-CDC%20Form%201Pt1.pdf Back
42
BMBL Handbook-http://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm Back
43
NIH Guidelines-http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html Back
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