Frequently Asked Questions: Biological Safety Practices

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Oct 23, 2013 (3 years and 8 months ago)

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Frequently Asked Questions:


Biological Safety Practices

for Research with Potentially

Highly Pathogenic Influenza
Virus Strains












NIH Office of Biotechnology Activities

-

Biological Safety
Practices for Research with Potentially Highly Pathogenic Influenza Virus Strains



1

Frequently Asked Questions
:

Biological Safety Practices f
or Research with

Potentially Highly Pathogenic Influenza
Virus
Strains


The National Institutes of Health (NIH) Office of Biotechnology Activities (OBA) periodically

receives questions

about the appropriate containment for various types of influenza strai
ns used in
recombinant DNA research. This is especially true for non
-
contemporary human influenza strains
(including but not limited to H2N2 and 1918 influenza virus) and circulating highly pathogenic
avian influenza

(HPAI) viruses
. The following frequentl
y asked questions are intended to assist
investigators and Institutional Biosafety Committees (IBCs) in making
decisions

about
containment
and biosafety practices
for research with

these pathogenic strains or their genetic
elements.


1.

What regulations

and g
uidelines

pertain to research

with non
-
contemporary strains of
influenza

virus
?


The principal policies addressing

the biosafety and biosecurity considerations relating to
research with

non
-
contemporary strains of influenza are the
:



NIH Guidelines for Research Involving Recombinant DNA Molecules

(
NIH
Guidelines
);



Department of Health and Human Services (HHS)
Centers for Disease Control and
Prevention

(CDC)

and US Department of Agriculture Animal (USDA)
Animal and
Plant Health Inspection Service

(APH
IS)

Select Agent Rul
es;

and



CDC/NIH publication
Biosafety in Microbiological and Biomedical Laboratories

(BMBL) 5
th

Edition.



Certain
NIH Institutes and Centers may have their own terms
and conditions of grant award
in
addition

to the standards

articulate
d

by the
policies above

(see question 5 below)
.

2.

What should be considered when conducting a risk assessment for research with non
-
contemporary strains of influenza?

T
he
NIH Guidelines

address research with influenza viruses to the extent they have been
genetically modified with recombinant DNA or are being used with transgenic animals. The
NIH Guidelines
describe

four levels of Risk Groups into which
infectious agents are placed

in
ac
cordance with their potential impact on human health
,

as well as

four biological safety
levels, in keeping with the risk of the re
search.
Appendix B

of the
NIH Guidelines

lists
Ort
homyxoviruses

(influenza) types A, B, and C as Risk Group 2 agents. Users of the
NIH
Guidelines

should understand, however, that Risk Group assignments are just the starting point
for the risk assessment process, and for the determination of the appropriat
e biosafety level at
which to conduct research with pathogenic agents.








A comprehensive risk assessment of research involving a potentially highly
pathogenic influenza strain would generally lead to the conclusion that the work
should be conducted at B
iosafety Level 3 or higher.

NIH Office of Biotechnology Activities

-

Biological Safety
Practices for Research with Potentially Highly Pathogenic Influenza Virus Strains



2

As noted in
Section II
-
A
-
3

of the
NIH Guidelines
, risk assessments should include a
thorough
consideration of such
factors as virulence, pathogenicity, infectious dose, environmental
stability, route of spread, communicability, quantity, availability of a vaccine or treatment,
toxicity, physiological activity, and allergenicity. Any stra
in that is known to be m
ore
hazardous than the parent (w
ild
-
type) strain should be considered for handling at a higher
containment level than typicall
y assigned to its Risk Group.


In deciding on the appropriate containment for an experiment involving non
-
contemporary
strains of influenza

virus
, an initial risk assessment must be conducted based on the known and
potential properties of the agent. This should be followed by a thorough consideration of how
the agent is to be manipulated.


Important considera
tions in working with these strains include:




The number of years since an antigenically related virus last circulated and the potential
for presence of a susceptible population;



Whether an efficacious vaccine is available and whether the agent is likely t
o be
susceptible to current antivirals;



The gene constellation used;



Whether there is clear evidence of reduced virus replication in the respiratory tract of
appropriate animal models, compared with the level of replication of the wild
-
type
parent virus fr
om which it was derived; and



The degree of clonal purity and phenotypic stability.













3.

What are the current
CDC/
NIH
recommendations for working with non
-
contemporary
strains of influenza

viruses
?



The BMBL recommends Biosafety Level 3

and Animal Biosafety Level 3
practices,
procedures and facilities with rigorous adherence to
clothing change protocols
and
additional
respiratory protection
such as that afforded by n
egative pressure, HEPA
-
filtered respirators or
positive ai
r
-
purifying respirators (PAPRs).

Any researc
h involving
reverse genetics

of the 1918 influenza strain

in particular

should
proceed with extreme caution. The risk to laboratory workers is unknown at the present time
,

but the pandemic potential is thought to be significant. Until further risk assessment data are
In general, non
-
contemporary human influenza virus strains, HPAI viruses,
and chimeras containing genetic elements from highly pathogenic influenza
virus strains present more significant biosafety and public health
considerations than seasonal influenza st
rains and should be
contained under

Biosafety Level 3
conditions.
More stringent biosafety controls may be
appropriate, depending on the outcome of the risk assessment. If adequate
risk assessment data are not available, a more cautious approach utilizin
g
higher
biosafety l
evels and additional practices is warranted.


NIH Office of Biotechnology Activities

-

Biological Safety
Practices for Research with Potentially Highly Pathogenic Influenza Virus Strains



3

available, the following practices and conditions

at a minimum

are recommended for
manipulation of these viruses and
for the use of
laboratory animals infected

with these viruses:



Biosafety Level 3

and
A
nimal Biosafety Level 3

pract
ices, procedures and facilities;



Large laboratory animals such as nonhuman primates should be housed in primary
barrier systems in
Animal Biosafety Level 3
;



Rigorous adherence to add
itional respiratory protection and clothing change prot
ocols;



Use of negative pressure,
high efficiency particulate air (
HEPA
)
-
filtered respirators or
positive ai
r
-
purifying respirators (PAPRs
);



Use of HEPA filtrati
on for treatment of exhaust air;

and



Amendment of personnel practices to include personal showers prior to exiting the
laboratory.


4.

What are the specific biosafety recommendations for handling Highly Pathogenic Avian
Influenza (HPAI)

viruses
?

Manipulating

HPAI
viruses in biomedical research laboratories requires extreme caution
because some strains may pose increased risk to laboratory workers and have significant
agricultural and economic
consequences
.
The BMBL recommends a minimum of Biosafety
Level 3

and
Anim
al Biosafety Level 3

practices, procedures and facilities along with clothing
change and personal showering protocols. Negative pressure, HEPA
-
filtered respirators or
positive air
-
purifying respirators are recommended for
HPAI
viruses with potential to inf
ect
humans.

Detailed b
iosafety recommendations for work with various human and animal influenza
viruses, including HPAI viruses, can be found in the
agent summar
y statement

for
i
nfluenza
virus in the 5
th

edition

of the BMBL.
Readers should also be aware

that HPAI

viruses

are
agricul
tural
Select Agents
requiring registration
under the
USDA/APHIS Select Agent
rule
.
A
ll work with
HPAI
strains of influenza (including non
-
HPAI) requires
an

APHIS
-
issued
permit.

In addition,
other strains of avian influenza are covered by
USDA
regulations
pertaining to the interstate transport
of

avian influenza viruses

generally
.

5.

Are there are parti
cular

terms and conditions of award
that NIH places on work with
non
-
contemporary strains of influenza

viruses
?


As
stated in
Section I
-
D

of the
NIH
Guidelines

and

reiterated

in the
NIH Grants Policy Manual
,
as a condition for NIH funding of recombinant DNA research, institutions shall ensure that
such res
earch conducted at or sponsored by the institution, irrespective of the source of
funding, shall comply with the
NIH Guidelines
.


NIH Institutes and Centers may have their own
term
s

and condition
s

of grant award

in addition
to the standards

articulate
d

by
the BMBL and the
NIH Guidelines
.
You should consult with
your NIH program officer for information on any such terms and conditions.

6.

Are there are special occupational health considerations that should be considered when
working with

non contemporary human

strains of influenza

viruses
, including
recombinants and reassortants;

with HPAI

viruses
; or with

viruses created by reverse
genetics of the 1918

strain
?

NIH Office of Biotechnology Activities

-

Biological Safety
Practices for Research with Potentially Highly Pathogenic Influenza Virus Strains



4

According to the BMBL, i
nstitutions performing work with HPAI

viruses
; non
-
contemporary
human influen
za strains, including recombinants and reassortants; and viruses created by
reverse genetics of the 1918 pandemic strain should consider developing and implementing a
specific medical surveillance and response plan. These plans may include:



Storage of base
line serum samples from individuals working with these influenza strains;




Annual vaccination with the currently licensed influenza vac
cine for such individuals;




Providing employee counseling regarding disease symptoms including fever, conjunctivitis
and
respiratory symptoms;



Establishing a protocol for monitoring personnel for these symptoms; and



Establishing a clear medic
al protocol for responding to suspected laboratory
-
acquired
infections. Antiviral drugs (e.g., oseltamivir, amantadine, rimantadine, zanamivir) should
be available for treatment and prophylaxis, as necessary. It is recommended that the
sensitivities of the

virus being studied to the antivirals be ascertained.

In addition, all personnel should be enrolled in an appropriately constituted respiratory
protection program.


7.

Where can I find out more information on conducting a risk assessment with
non
-
contemporary influenza strains?


Information on risk assessments may be found in the
NIH Guidelines

for Research Involving
Recombinant DNA

Molecules

Section II: Safety Consideration
s
.


Information on agent risk assessments may be found in the
Agent Summary Statements

of the
CDC/NIH publication
Biosafety in Microbiological and Biomedical Laboratories
.


Further guidance on agents may be obtained thro
ugh:




National Institutes of Health Offi
ce of Biotechnology Activities

Phone: 301
-
496
-
9838

Email:
oba@od.nih.gov

Web Site:
http://www4.od.nih.gov
/oba




Centers for Disease
Control and P
revention Select Agent Program

Phone: 404
-
718
-
2000

Email:
lrsat@cdc.gov

Web Site:
http://www.cdc.gov/od/sap/




U
nited States Department of Agriculture Animal and Plant Health Inspection Service,
Select Agent Program

Phone: 301
-
734
-
5960


Email
:
Agricultural.Select.Agent.Program@aphis.usda.gov

Web

Site:
http://www.aphis.usda.gov/programs/ag_selectagent/