Clinical

Microbiology
Newsletter
Vol. 28, No. 8 April 15, 2006

The Select Agent Rule and Its Impact on Clinical Laboratories

J. Michael Miller, Ph.D., (D)ABMM, Bioterrorism Preparedness & Response, Centers for Disease Control, Atlanta, Georgia
Abstract
The Select Agent Rule was established to protect public health and safety and was designed specifically to address the posses-
sion, use, and transfer of select agents and toxins. It was published in the Federal Register Friday, 18 March, 2005, and became
effective on 18 April, 2005. This rule applies to virtually all laboratories, including clinical, diagnostic, and research laboratories.
What has been somewhat unclear is the impact of this rule on the day-to-day operation of clinical laboratories that may, in the
course of routine analysis, isolate one of the select agents. Clearly, clinical microbiologists should be aware of the risks associated
with manipulation of any of the select agents, the precautions necessary to protect laboratory personnel, and particularly, the reg-
ulatory requirements imposed upon those laboratories that choose to maintain and work with these agents. Thus, understanding
the Select Agent Rule should be a goal of clinical microbiologists and laboratory directors that oversee diagnostic and research
procedures. For most clinical laboratories, there should be no need to register with the Select Agent Program, as long as suspected
isolates of select agents are forwarded to a registered reference laboratory for confirmatory identification and stock cultures of
these agents are not maintained. Details of the application process are available on the internet at http://www.cdc.gov/od/sap/.

The Select Agent Final Rule (actu-
ally comprised of three rules that were
promulgated and implemented simulta-
neously) was published in the Federal
Register on Friday, 18 March, 2005,
and became effective 18 April, 2005.
The Select Agent Rule was established
to protect public health and safety and
was designed specifically to address
the possession, use, and transfer of
select agents and toxins. The Centers
for Disease Control and Prevention
(CDC) Final Rule (42 CFR Part 73) is
the section of direct interest to most
laboratories and was established after
public comments were received on two
interim rules that were published in the
Federal Register on 13 December, 2002
and on 3 November, 2003, respectively.
This rule applies to academic institu-
tions; biomedical centers; commercial
Mailing Address: J. Michael Miller, Ph.D.,
(D)ABMM, Bioterrorism Preparedness &
Response, CDC 1/2011 Mailstop C-18,
1600 Clifton Road NE, Atlanta,GA 30333.
Fax: 404-639-2850. E-mail: jmm8@cdc.gov
manufacturing facilities; and federal, and toxins appear only on the HHS list,
state, and local laboratories, including some only on the USDA list, and others
clinical and diagnostic laboratories, as on both lists. Organisms and toxins that
well as research laboratories. The Select appear on both lists are referred to as
Agent Rule is a regulatory function of “overlap select agents and toxins.”
the CDC within the Department of For most clinical laboratories, there
Health and Human Services (HHS) and should be no need to register with the
is administered through CDC’s Select SAP, as long as suspected isolates of
Agent Program (SAP). select agents are forwarded to a regis-
A similar program has been promul- tered reference laboratory for confirma-
gated by the United States Department tory identification and stock cultures of
of Agriculture (USDA) through the these agents are not maintained. Accord-
Animal and Plant Health Inspection ing to the regulations, clinical laborato-
Service (APHIS) which established cor- ries must destroy isolates of select agents
responding and parallel sets of regula- within 7 working days after confirmation
tions designed to protect animal and by the reference laboratory. If select
plant health and products. These corre-
sponding USDA regulations can be
found in 9 CFR part 121 and 7 CFR
part 331. All laboratories in the United
States are required to adhere to the reg-
ulations as they apply to organisms and
toxins found on their respective lists,
whether these facilities are animal or
plant laboratories or human diagnostic
laboratories, as listed above. Confusion
may arise in trying to accommodate
both programs, because some organisms

Clinical Microbiology Newsletter 28:8,2006 © 2006 Elsevier 0196-4399/00 (see frontmatter) 57

agents are received by unregistered lab-
oratories as part of a proficiency-testing
program, the select agents identified
must be reported to the SAP within 90
days and the cultures either destroyed
or transferred to a registered facility.
This article is not intended to be the
authoritative source from which all
select agent issues are answered, but
an attempt is made to clarify those
components that directly impact the
human clinical or diagnostic laboratory.
Therefore, microbiologists should be
aware of the Select Agent Rule and its
purpose and should be knowledgeable
about how select agents and suspected
select agents are to be handled in their
laboratories, not only for academic and
clinical interest, but because of person-
nel safety and facility security. The
Select Agent Rule addresses several
areas, but the themes discussed in this
article are agents, registration and docu-
mentation, personnel, security of facili-
ties, and laboratory requirements.
Agents
The Select Agent Rules of HHS and
the USDA regulate organisms and toxins
that have severe public health, veterinary,
or agricultural impact. Interestingly,
many of the bacteria on the list are zoo-
notic pathogens, and our colleagues in
veterinary diagnostic laboratories have
been seeing these isolates routinely for
years. In addition, some states are areas
of endemicity for certain agents on the
list. For example, most animal infections
with Bacillus anthracis occur in Texas,
Louisiana, Mississippi, Oklahoma, and
South Dakota, while human infections
with Coccidioides immitis commonly
occur in the southwestern U.S., particu-
larly California and Arizona. Cultures
of these organisms are now to be han-
dled differently than before and under
secure conditions. If the laboratory
keeps stock cultures of these organisms,
it must be registered with the SAP.
58 0196-4399/00 (see frontmatter)
Table 1 lists the pertinent HHS and over-
lap select agents.
There are exclusions to the select
agent list, and it would be inaccurate to
assume that all vaccine strains are
excluded. In addition, overlap agents
eligible for exclusion require formal
exemption by both the USDA and HHS.
For example, select agents that have
been rendered nonviable, inactivated, or
dead are not considered select agents by
HHS and do not have to be listed on the
registration form. USDA, however, has
a broader interpretation of this rule. To
apply for an exclusion of an attenuated
strain of an HHS select agent, a written
request must be submitted, along with
supporting documentation. Details of
the application process are available on
the World Wide Web. The following
agents and toxins have been excluded:
Coccidioides posadasii strain Dchs5;
certain conotoxins; Junin virus vaccine
strain Candid 1; Yersinia pestis strains
that are Pgm– (EV or EV 76) or that lack
the Lcr virulence plasmid (Tjiwidej S
and CDC A1122); B. anthracis devoid
of both pX01 and pX02 and the Sterne
strain (pX01+ pX02–); Brucella abortus
strain 19 or RB51 (vaccine strain); Cox-
iella burnetii phase II, nine mile strain;
Francisella tularensis subsp. novicida
strain Utah 112; F. tularensis subsp.
holartica (live vaccine strain); F.
tularensis ATCC 6223 (also called
B38); Rift Valley fever virus vaccine
strain MP-12; Venezuelan equine
encephalitis (VEE) vaccine candidate
strain V3526; and VEE virus vaccine
strain TC-83.
There is a difference between the
terms “exclusion” and “exemption” as
used in this program. Exclusion has to
do with organisms or strains removed
from the select agent list as described
above. Attenuated strains of select
agents or organisms and toxins that
have been rendered innocuous, for
© 2006 Elsevier
example, may be excluded if an appli-
cation for exclusion is submitted to
HHS and the exclusion is granted.
Exemption is the term used to indicate
facilities and conditions under which
the entity is not required to register as
a select agent laboratory. Exemption
also applies to use of an investigational
product or to temporary relaxation of
rules during a public health emergency.
Examples would be hospitals or clinical
laboratories that do not identify or
maintain select agents. These entities
are exempted from registration with the
select agent program if they follow the
prescribed conditions for organism
destruction and reporting and meet the
requirements set forth in the Rule.
Registration and Documentation
Although not applicable to the typi-
cal clinical laboratory, documentation
required by the Select Agent Program
for a registered entity is generally
focused on five forms. The website
at http://www.selectagents.gov is the
authorized location to obtain the forms
that CDC and APHIS both use and
accept.
APHIS/CDC Form 1
The Application for Laboratory
Registration for Possession, Use, and
Transfer of Select Agents and Toxins
is a detailed guidance document and
application to register a laboratory with
the program. Registration is entity spe-
cific and organism specific and is com-
pleted by the responsible official (RO)
of the applying facility. Clinical labo-
ratories do not have to deal with this
form if they remain unregistered. Three
spreadsheets are associated with this
form but do not need further descrip-
tion here: Section 4A, Biosafety and
Laboratory Information on Select
Agents; Section 4B, Authorized Per-
sonnel Working with Select Agents;
and Section 5A are to be completed
Clinical Microbiology Newsletter 28:8,2006
Table 1. HHS select agents and overlap agents with the USDA
Overlap
HHSs (HHS &
Select agenta only USDA) Links and information
b
Abrin (>100mg) x A natural toxin found in the red seeds of the rosary pea or
jequirity pea that is similar to but more toxic than ricin
http://www.bt.cdc.gov/agent/abrin/basics/facts.asp
Bacillus anthracis x http://www.cdc.gov/ncidod/dbmd/diseaseinfo/anthrax_g.htm
Botulinum neurotoxins (> 0.5 mg) x http://www.cdc.gov/ncidod/dbmd/diseaseinfo/botulism_g.htm
Brucella abortus x http://www.bt.cdc.gov/agent/brucellosis/index.asp
Brucella melitensis x
Brucella suis x
Burkholderia mallei x http://www.cdc.gov/ncidod/dbmd/diseaseinfo/glanders_g.htm
Burkholderia pseudomallei x http://www.cdc.gov/ncidod/dbmd/diseaseinfo/melioidosis_g.htm
Clostridium perfringens epsilon toxin x From strains B and D; causes enteritis necroticans (pig bel)
(>100 mg)
Clostridium spp. that produce botulinum x
neurotoxins
Coccidioides immitis x http://www.cdc.gov/ncidod/diseases/submenus/sub_cocci.htm
Coccidioides posadasii x Formerly known as the non-California strain of C. immitis
Conotoxins (>100 mg) x Polypeptides from the venom of fish-hunting marine snails of the
genus Conus.
http://www.cbwinfo.com/Biological/Toxins/Conotox.html
Coxiella burnetii x http://www.cdc.gov/ncidod/dvrd/qfever/
Crimean-Congo hemorrhagic fever virus x http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/cchf.htm
Diacetoxyscirpenol (>1,000 mg) x Structurally similar to T-2 mycotoxin produced by Fusarium spp.
and a few other genera
Eastern equine encephalitis virus x http://www.cdc.gov/ncidod/dvbid/arbor/eeefact.htm
Ebola virus x http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola.htm
Francisella tularensis x http://www.bt.cdc.gov/agent/tularemia/index.asp
Genetic elements or nucleic acids that can x Non-modified bacterial nucleic acids are not on the select agent
produce infectious forms of any select agent list.
virus; recombinant nucleic acids that encode
functional toxins listed, whether in a vector/
host genome expressed in vivo or in vitro;
and recombinant or genetically modified
select agent organisms
Hendra virus x http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/nipah.htm
Herpesvirus B (cercopithecine Herpes x http://dcminfo.wustl.edu/occhealth/factsheet_herpesb.html
simplex virus 1)
Influenza virus (H1N1 pandemic strain of x Reconstructed forms of the virus containing any portion of the
1918) coding regions of all eight gene segments
Lassa fever virus x http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/lassaf.htm
Marburg virus x http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/
marburg.htm
Monkeypox virus x http://www.cdc.gov/ncidod/monkeypox/
Nipah virus x http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/nipah.htm
Ricin (>100 mg) x Natural toxin from the castor bean
http://www.bt.cdc.gov/agent/ricin/facts.asp
Rickettsia prowazekii x http://www.cdc.gov/ncidod/dvrd/rmsf/Organism.htm
Rickettsia rickettsii x http://www.cdc.gov/ncidod/dvrd/rmsf/Organism.htm
Rift Valley fever virus x http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/rvf.htm
Saxitoxin (>100 mg) x A paralytic shellfish poison; http://www.bt.cdc.gov/agent/saxitoxin/
Table 1 continued on page 60

Clinical Microbiology Newsletter 28:8,2006 © 2006 Elsevier 0196-4399/00 (see frontmatter) 59

Table 1. HHS select agents and overlap agents with the USDA (Continued)
Overlap
HHSs (HHS &
Select agenta only USDA) Links and information
Shiga-like ribosome-inactivating proteins x
(>100 mg)
Shiga toxin (>100 mg) x http://www.cdc.gov/ncidod/dbmd/diseaseinfo/
escherichiacoli_g.htm
South American hemorrhagic fever x http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/vhf.htm
viruses (Junin, Machupo, Sabia, Flexal,
Guanarito)
Staphylococcus enterotoxins (>5 mg) x http://www.emedicine.com/emerg/topic888.htm
T-2 toxin (>1000 mg) x A mycotoxin produced by Fusarium and other genera
http://www.cbwinfo.com/Biological/Toxins/T2.html
Tetrodotoxin (>100 mg) x A neurotoxin found in certain organs of the puffer fish
http://www.emedicine.com/emerg/topic576.htm
Tick-borne encephalitis complex viruses x http://www.cbwinfo.com/Biological/Pathogens/TBEV.html
(flaviviruses) (Central European tick-borne
encephalitis [Russian spring and summer
encephalitis, Kyasanur Forest disease,
Omsk hemorrhagic fever])
Variola major virus (smallpox) and x http://www.bt.cdc.gov/agent/smallpox/index.asp
variola minor virus (alastrim) http://www.stanford.edu/group/virus/adeno/2000/variola.html
Venezuelan equine encephalitis virus x http://www.cdc.gov/ncidod/dvbid/arbor/arbofact.htm
Yersinia pestis x http://www.cdc.gov/ncidod/dvbid/plague/
a
Applies only to confirmed identifications of organisms and toxins. Agents that are nonviable or nonfunctional, agents that occur in their natural environments, and agents that are
attenuated to the point of nonpathogenicity are excluded from regulation, but exclusions must be approved through a formal application process.
b
The amounts in parentheses indicate the amount above which the agent or toxin is regulated. Lesser amounts on hand do not require registration.

by all entities for each principal inves-
tigator. To apply for a certificate of reg-
istration that covers only HHS select
agents or toxins, an individual or entity
must submit to CDC the information
requested in this registration application
package. To apply for a certificate of
registration that does not cover only
HHS select agents or toxins (i.e., that
covers at least one overlap agent or
toxin or covers any combination of
HHS and USDA select agents or tox-
ins), this package can be submitted to
either CDC or APHIS, but not both.
APHIS/CDC Form 2
Report of Transfer of Select Agents
and Toxins. A clinical laboratory or a
registered entity is required to file this
form with either APHIS or CDC and
obtain approval prior to transfer of an
identified select agent or toxin. The
sender’s RO or facility director must
submit the form for authorization of
the transfer to either APHIS or CDC,
depending on the organism. Documen-
tation associated with the transfer of
select agents must be kept for 3 years.
APHIS/CDC Form 3
Report of Theft, Loss, or Release of
Select Agents and Toxins. An entity is
required to contact APHIS or CDC
immediately by phone, fax, or e-mail
upon discovery of a theft, loss, or
release (occupational exposure or
release of an agent or toxin outside of
the primary barriers of the biocontain-
ment area) of a select agent or toxin.
After the initial reporting, this form
should be sent directly to APHIS or
CDC, as appropriate, within 7 calendar
days after the discovery of theft, loss,
or release of select agents or toxins. A
copy of the completed form and attach-
ments must be kept by the entity for
3 years.
APHIS/CDC Form 4
The Report of Identification of a
Select Agent or Toxin in a Clinical or
Diagnostic Laboratory is used by all
entities when a confirmed identification
of a select agent sent to the laboratory in
any type of specimen has been accom-
plished either in the initial receiving
laboratory or a subsequent reference
laboratory. The form asks for informa-
tion about the facility, about the source
of the isolate, about the clinical case
from which it came, and which labora-
tory identified it. It also accommodates
proficiency-testing isolates and the final
disposition of the isolate after it was
identified. Therefore, all clinical labo-
ratories should maintain access to this
form in case a select agent is identified
in the laboratory, whether from a clin-
ical specimen or a proficiency-testing
specimen, or reported back by a
reference laboratory.
APHIS/CDC Form 5
Request for Exemption of Select
Agents and Toxins for Public Health or
Agricultural Emergency or Investiga-
tional/Experimental Product. Unless an
emergency occurs, clinical laboratories
will not need this form. It is used to
apply for exemption from the require-
ments in cases (i) of use of an investi-
gational product or (ii) due to a public
health or agricultural emergency. This
exemption request should be sent to
either APHIS or CDC, as appropriate,
for exemption consideration. For HHS
agents and toxins, the applicant should
contact CDC. For HHS/USDA overlap
agents, the applicant should contact
either APHIS or CDC. For USDA
agents and toxins, the applicant should

60 0196-4399/00 (see frontmatter) © 2006 Elsevier Clinical Microbiology Newsletter 28:8,2006

contact APHIS). Note: This form is not
for use when applying for an exclusion.
To apply for an exclusion of an attenu-
ated strain of a select agent or toxin, an
applicant must submit a written request
and supporting scientific information
to APHIS or CDC. Information in the
written request should include, at a min-
imum, the strain, how the strain was
derived, how it is ascertained that it
does not pose a severe threat to public
health or to animal or plant health or to
animal or plant products, and all cita-
tions or pertinent data to support the
request.
The reporting requirements state that
both registered and unregistered entities
must report the confirmed identification
of select agents and toxins submitted for
diagnosis, verification, or proficiency
testing. In addition, entities that presump-
tively identify select agents and toxins
in specimens submitted for diagnosis,
verification, or proficiency testing must
secure the specimen, isolate, or toxin
against theft, loss, or release during the
period between confirmatory identifi-
cation at a reference laboratory and the
transfer or final destruction of the agent
or toxin.
It is important to note that some
reports must be submitted immediately
after an agent is identified, the same
day if possible. APHIS and CDC have
combined their immediate notification
lists for overlap select agents and tox-
ins: B. anthracis, botulinum neurotox-
ins, F. tularensis, Brucella melitensis,
Hendra virus, Nipah virus, Rift Valley
fever virus, and Venezuelan equine
encephalitis virus must be reported
by the identifying laboratory and the
submitting laboratory to both agencies
immediately after confirmation of
identification. Immediately is inter-
preted as the same day as identified or
as close to the same day as possible.
Other activities and consequences
that impact clinical microbiology
laboratories are listed in Table 2.
In the event of a biocrime, a chain
of custody should be initiated. The lab-
oratory manager should be notified by
the FBI or other local law enforcement.
In some cases, law enforcement per-
sonnel will hand carry specimens that
require special attention to the labora-
tory. Specimens from known biocrime
events would normally be taken to the
nearest Laboratory Response Network
Clinical Microbiology Newsletter 28:8,2006
laboratory and not to a local diagnostic
facility.
Facilities
An individual or facility cannot
possess, use, or transfer any HHS or
overlap select agent or toxin without a
certificate of registration except under
certain conditions. This implies that
the identity of the agent has been con-
firmed. If a laboratory intends to con-
firm the identity of any select agent
and/or maintain a stock of viable select
agents under any conditions, then regis-
tration with the SAP is required. A certi-
ficate of registration is valid for 3 years.
As a condition of registration, the fol-
lowing must occur: (i) An individual
must be designated as the RO. This is
a critical position with great responsi-
bility in this program, so selecting an
assertive, reliable, and knowledgeable
RO is extremely important. (ii) A secu-
rity risk assessment must be conducted
on the facility, the RO, and the owner
of the facility. Federal, state, and local
government agencies are exempt from
this step, and rules are in place for
educational institutions and for other
complex ownership issues. (iii) An
application for registration must be sub-
mitted either to CDC or APHIS. If the
registration is only for agents on the
HHS Select Agent list, then APHIS/
CDC Form 1 must be sent to CDC.If
one or more overlap agents are included,
the same form must be submitted to
either CDC or APHIS. (iv) The facility
must have in place a security plan detail-
ing how stored select agents are secured
and protected; a biosafety plan indicating
how the laboratory meets the require-
ment of biological safety level 3 (BSL-
3) or BSL-4 facility safety, although
clinical laboratories would not have
BSL-4 capability; an incident response
plan outlining how the facility and
employees would respond to a breach
in safety or security or in emergency
situations; and any other required
documents.
The certificate of registration is valid
for only one room, building, or group of
buildings for which the RO is responsi-
ble. Even a minor change from the orig-
inal information submitted with the
registration requires the RO to submit
an amended registration form.
The SAP does not dictate what BSL
should be used when working with
© 2006 Elsevier
these agents. Rather, it refers its regis-
trants to three sources for appropriate
BSL designation and operations: (i)
the CDC/NIH publication Biosafety
in Microbiological and Biomedical
Laboratories, (ii) the Occupational
Safety and Health Administration reg-
ulations, and (iii) the NIH Guidelines
for Research Involving Recombinant
DNA Molecules. The program does
require, however, that each registered
site develop and implement a written
biosafety plan specifically designed for
the agents used by that laboratory. In
addition, the biosafety plan must be
reviewed each year and drills or exer-
cises must be conducted annually to
assess the effectiveness of the plan.
The registered site must have an
incident response plan in place, and it
must comply with any total workplace
plans currently in place. This plan must
describe the procedures to follow in
response to a theft, loss, or release of
agents; any discrepancy in inventory;
security breaches; inclement weather,
and other emergency threats. The inci-
dent response plan must contain contact
information for the RO, the building
owner and manager where applicable,
and the security officials; personnel
roles and lines of authority and commu-
nication; how to work with emergency
responders; rescue procedures; emer-
gency treatment needs; a list of personal
protective equipment and its storage
site; site security policies; and decon-
tamination procedures. This plan also
requires annual review and annual
exercises.
Personnel and Visitors
Individuals listed on the site registra-
tion must receive training annually in
select agent issues, the training must be
documented, and a means of verifying
that the employee understood the train-
ing (i.e., passing a test) must be provided.
It is the job of the RO to successfully
complete a security risk assessment,
to know the regulations of the SAP, to
ensure compliance, to ensure that annual
inspections are conducted for each labo-
ratory where select agents are stored
or used, to document the results of the
inspections, and to report the identifica-
tion and final disposition of any select
agent from a diagnostic specimen or
from a proficiency-testing specimen
using the correct reporting mechanism.
0196-4399/00 (see frontmatter) 61
 If anything in the registration certifi-
cate changes, an application for amend-
ment must be submitted and approved
by the SAP. This includes changes in
agents or activities conducted with the
agents, changes in personnel, changes
in room design or use, moving to a new
site or adding an additional site, or loss
of services of the RO.
The only individuals with access to
select agents are those specifically iden-
tified and approved in the application.
It is the responsibility of the RO to
protect the select agents from access
by anyone else, including custodial
personnel. Form 4B must list who has
access to the registered laboratory, and
nothing happens regarding laboratory
work without this form having been
submitted and approved. Visitors may
be temporarily added to the Form 4B of
a facility if the visitor has a valid and
current security risk assessment and the
information has been sent from the visi-
tor’s laboratory and approved by the
host laboratory. Once the visitor returns
home, the name must be removed from
the host’s Form 4B and the Select Agent
Program must be notified by submitting
an amended Form 4B. A person is con-
sidered to have access if the person
carries, uses, or manipulates the organ-
ism or toxin or has the ability to gain
possession. Just being in the same room
where select agents are stored provides
the opportunity to gain possession
unless the agents are held within locked
containers or closets in that room. Each
individual requesting access to select
agents must submit an application and
undergo a security risk assessment per-
formed by the FBI. Visitors without
approved access must be accompanied
at all times while in the laboratory, and
the host must keep the visitor(s) within

Table 2. Other activities and consequences that impact clinical microbiology laboratories
Laboratory event
Receiving a routine clinical specimen for diagnosis
Receiving or shipping a clinical specimen suspected of
containing a select agent
Identifying an isolate to a presumptive level and shipping
to reference laboratory for confirmation
Confirming the identity of a select agent
Receiving proficiency tests that may contain select agents
Identifying a select agent from a proficiency test sample
Storing a select agent
Receiving a known select agent in the mail
Conducting research authorized under any federal act
Participating in a public health emergency where select
agent(s) may be encountered
Shipping a select agent whose identity has been confirmed
Attending training where access to select agents will be
available in the laboratory
Working temporarily or as a visitor in a laboratory where
select agents are stored or are being used
Taking a tour within a select agent laboratory
Laboratory does not plan to confirm the identity of
suspected select agents
Laboratory is in area where a select agent may be
endemic and routinely isolated
A select agent form has been completed or an action
documented
Blood, serum, or other specimens submitted to the
chemistry or hematology laboratory from a patient
suspected of having a disease caused by a select agent
Select agent response required
None
None. Secure the specimen until results are received.
None, if the isolate is destroyed within 7 days of identification or shipped
to a registered laboratory and the CDC is notified of the disposition of the
isolate using Form 4. Certain agents must be reported immediately (see text).
Keep the agent secure until identity is confirmed and actions are completed.
Form 4 is preferably signed by the laboratory director.
Must be registered. Report agent identity to SAP on Form 4.
None
Report to SAP on Form 4 and then discard/destroy the agent within 90 days.
Maintain secure storage until final disposition.
Must be registered and use secure storage. Locks are required to secure the
room and/or the storage cabinet or device; cameras are not required.
Must be registered and notify CDC that the agent has been received.
Must be registered with SAP if research involves select agents and must
maintain documentation of the authorized research.
May request and receive a temporary exemption from the HHS Secretary.
Must be registered OR must notify CDC of the disposition of the isolate using
Form 4 if unregistered.
Prior to attending the training, the trainee must undergo a security risk
assessment and be approved by the FBI.
Prior to visiting the host laboratory, the visitor must successfully undergo a
security risk assessment (or must be escorted at all times). The host laboratory
RO must have the approval certificate on hand during the temporary work
assignment.
Visitor must sign in, be escorted at all times, and be in visual and hearing
distance of the escort. No requirement to sign out upon leaving.
None
Registration not required if the agent is sent to a reference laboratory for
confirmation, the original isolate is destroyed within 7 days, and CDC is
notified of the disposition of the identified agent.
All documents must be kept for 3 years and made available for inspection.
Handle the specimen as if it contained a highly infectious agent using
appropriate PPE and engineering controls, but no registration or reporting is
required.

62 0196-4399/00 (see frontmatter) © 2006 Elsevier Clinical Microbiology Newsletter 28:8,2006

sight and hearing distance.
Some individuals will be deemed
restricted and never allowed access to
select agents. Individuals who fall into
this category include foreign nationals
from countries flagged by the Secretary
of State as supporting terrorism, those
dishonorably discharged from the U.S.
armed forces, individuals under indict-
ment for or convicted of a crime result-
ing in a prison term of >1 year, unlawful
users of controlled substances, and
mentally impaired persons.
Clinical Microbiology Newsletter 28:8,2006
An appeals process is available and
is described in the Rule.
References and Websites:
HHS Final Rule:
Rules and Regulations, p. 13294. 2005.
Possession, Use, and Transfer of Select
Agents and Toxins. Federal Register
Vol. 70, No. 52.
USDA Final Rule:
Rules and Regulations, p. 13242. 2005.
Agricultural Bioterrorism Protection Act of
2002; Possession, Use, and Transfer of
© 2006 Elsevier
Biological Agents and Toxins. Federal
Register Vol. 70, No. 52.
HHS Select Agent Program:
http://www.cdc.gov/od/sap/
USDA Select Agent Program:
http://www.aphis.usda.gov/programs/
ag_selectagent/index.html
http://www.aphis.usda.gov/programs/ag_
selectagent/ag_bioterr_toxinslist.htm1
Exclusions:
http://www.cdc.gov/od/sap/sap/
exclusion.htm
0196-4399/00 (see frontmatter) 63