National Institutes of Health (NIH) Office of Science Policy (OSP) Recombinant or Synthetic Nucleic Acid Research: Action Under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), 22286-22289 [2016-08810]
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[FR Doc. 2016–08691 Filed 4–14–16; 8:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institutes of Health (NIH)
Office of Science Policy (OSP)
Recombinant or Synthetic Nucleic Acid
Research: Action Under the NIH
Guidelines for Research Involving
Recombinant or Synthetic Nucleic Acid
Molecules (NIH Guidelines)
The NIH OSP is amending
portions of the NIH Guidelines in order
to provide investigators with biosafety
guidance regarding the standards for
containment of non-human primates
(NHPs) in biosafety level (BL) 4
laboratories and to make such guidance
consistent with the expectations
articulated in the Centers for Disease
Control and Prevention (CDC)/NIH
Biosafety in Microbiological and
Biomedical Laboratories 5th edition
(BMBL). Specifically, the NIH
Guidelines will allow for housing of
NHPs in open caging in a dedicated
animal holding room provided there are
two physical barriers between that
animal holding room and noncontainment space within the
laboratory, the animal holding room has
negative air pressure with respect to any
adjacent non-containment corridors,
and there are specific decontamination
protocols in place before the door to the
animal holding room is opened to allow
for the periodic transfer of new animals
into the room. These amendments do
not change the current containment
requirements in the NIH Guidelines but
rather offer an alternative for achieving
primary containment without
compromising safety.
In addition, the recertification
requirement for biosafety cabinets in
BL4 laboratories is updated in
recognition of the technological
standards for modern biosafety cabinets.
The NIH OSP also is updating the
validation requirements for equipment
responsible for centralized heat
decontamination of liquid effluents in
laboratories working with large animals.
These amendments to the NIH
Guidelines will be implemented
immediately upon publication in the
Federal Register. These changes were
developed after extensive consultation
with biosafety experts, directors of and
principal investigators in BL4 facilities
working with NHPs, and CDC’s Division
of Select Agent and Toxins (DSAT)
leadership at a public workshop and
discussion at a public Recombinant
DNA Advisory Committee (RAC)
meeting. Publication in the Federal
SUMMARY:
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Register will inform the scientific and
biosafety communities.
FOR FURTHER INFORMATION CONTACT: If
you have questions, or require
additional information about these
changes, please contact the NIH OSP by
email at SciencePolicy@od.nih.gov, or
telephone at 301–496–9838.
SUPPLEMENTARY INFORMATION: The first
three editions of the BMBL and the NIH
Guidelines were consistent in their
approach to requiring primary
containment for animal work in BL4
containment laboratories. However, in
the early 1990s, the BMBL was amended
and the fourth edition stated that
animals housed in BL4 suit laboratories
(i.e., laboratories in which Class III
cabinets are not used but instead
personnel wear positive pressure
protective suits) should be housed in a
primary containment system (such as
open cages covered with filtered
bonnets and opened in laminar flow
hoods or other equivalent containment
systems). This language remains in the
current BMBL (5th edition). With the
change in the BMBL, primary
containment caging was arguably
preferred but no longer required under
BL4 containment. In contrast, the NIH
Guidelines have always required
primary containment caging for all
animals in BL4 laboratories.
Non-human primates are social
animals and require environmental
enrichment. Researchers in several U.S.
BL4 laboratories engaged in NHP
research approached the NIH OSP with
concerns that primary containment
caging in BL4 laboratories hindered the
creation of an environment that allowed
animals to benefit from adequate social
interaction. Also based on risk
assessments and experiences comparing
several primary containment caging
systems, the researchers concluded that
primary containment caging may
actually create new hazards for
laboratory workers. These findings
included interference with observation
of the animals from outside the room
leading to more frequent entries into the
BL4 animal room to monitor the
animals, and exacerbation of cramped
working conditions created by the
additional barriers required by some
containment systems, which increases
the difficulty of working in inflated
pressure suits as well as the potential
for damage to the pressure suit. In
addition, investigators stated that
current BL4 laboratory designs
incorporate sophisticated engineering
systems, which provide biosafety
protection in a dedicated animal room
equivalent to the primary containment
caging required under the NIH
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Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 / Notices
Guidelines. On March 28, 2014, the NIH
OSP, together with the CDC Division of
Select Agents (DSAT), held a meeting
with investigators and biosafety
personnel from nine BL4 laboratories in
the U.S. and five international
laboratories (agenda and roster available
at https://osp.od.nih.gov/officebiotechnology-activities/event/2014-0328-120000-2014-03-28-211500/primarycontainment-non-human-primatesbiosafety-level-4-laboratorieschallenges-and-best-practices). That
meeting was followed by a discussion at
the June 11, 2014, meeting of the NIH
RAC regarding housing of NHPs in BL4
laboratories (a webcast of that
discussion is available at https://
videocast.nih.gov/
summary.asp?Live=14300&bhcp=1.)
As a result of these discussions and
after consultation with CDC DSAT, the
NIH OSP is amending the NIH
Guidelines to allow the housing of NHP
in open cages in a dedicated animal
room provided certain conditions as
articulated below are met.
In addition, OSP is updating the
requirement for testing and certification
of Class I and II biosafety cabinets at
BL4 from every six months to annually,
recognizing the technological advances
in biosafety cabinet design and
engineering that have occurred over the
period since this performance measure
was originally implemented.
Finally, Appendix Q of the NIH
Guidelines currently requires that the
centralized heat treatment catch tank
system in BL4 large animal laboratories
be validated every 30 days. To carry out
this testing effectively, the system
should be near capacity (i.e. ‘‘under
load’’). Some laboratories do not use
their catch tank systems on a regular
basis; therefore, a mandatory 30 day
validation would require them to
demonstrate that the equipment is
functioning when it is not in use or is
not at capacity. This will not serve the
intended purpose of demonstrating that
the equipment is functioning as
intended. Therefore, validation intervals
will need to be set based on the
utilization of the system provided it is
done at least once a year.
To implement these changes, the
following sections of the NIH Guidelines
are to be amended:
Appendix G–II–D–2–l. currently
states:
Appendix G–II–D–2–l. Laboratory animals
involved in experiments requiring BL4 level
physical containment shall be housed either
in cages contained in Class III cabinets or in
partial containment caging systems, such as
Horsfall units (see Appendix G–III–K,
Footnotes and References of Appendix G),
open cages placed in ventilated enclosures,
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or solid-wall and -bottom cages placed on
holding racks equipped with ultraviolet
irradiation lamps and reflectors that are
located in a specially designed area in which
all personnel are required to wear one-piece
positive pressure suits.
Appendix G–II–D–2–1 is amended as
follows with the addition of a new
Appendix G–II–D–2–1–(2) that will
address housing of NHPs:
Appendix G–II–D–2–l. Containment for
Animal Research
Appendix G–II–D–2–l–(1). Laboratory
animals involved in experiments
requiring BL4 level physical
containment shall be housed either in
cages contained in Class III cabinets or
in partial containment caging systems,
such as Horsfall units (see Appendix G–
III–K, Footnotes and References of
Appendix G), open cages placed in
ventilated enclosures, or solid-wall and
-bottom cages placed on holding racks
equipped with ultraviolet irradiation
lamps and reflectors that are located in
a specially designed area in which all
personnel are required to wear onepiece positive pressure suits.
Appendix G–II–D–2–l–(2). Nonhuman primates (NHP) may be housed
(1) under the containment conditions
described in Appendix G–II–D–2–l–(1)
above, or (2) in open cages within a
dedicated animal holding room that
serves as the primary barrier and in
which all personnel are required to wear
one-piece positive pressure suits. A
room serving as a primary barrier must
be air-tight and capable of being
decontaminated using fumigation. If
NHPs are to be contained in a dedicated
animal holding room serving as the
primary barrier, the following
conditions shall be met:
(i) Access to the animal holding room
from service corridors outside of the
BL4 containment space shall require
passage through two sets of doors, and
the inner most door must be an air
pressure resistant (APR) door;
(ii) For any animal holding room
considered to be a primary barrier, APR
door(s) providing direct ingress from the
exterior service corridor shall be fitted
with appropriate and redundant lockout mechanisms to prevent access when
the animal holding room is
contaminated and in use. There should
be more than one mechanism to ensure
that this primary barrier door cannot be
opened when the animal room is
contaminated and the APR door shall
not serve as an emergency exit from the
BL4 laboratory. The APR door shall be
appropriately tested to demonstrate that
in the closed, locked-out mode, the door
provides an air-tight barrier proven by
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pressure decay testing or other
equivalent method;
(iii) Any door(s) allowing access into
a corridor from which there is direct
ingress to an animal holding room must
be fitted with either (1) an APR door or
(2) a non-APR door, providing
directional airflow is maintained from
the laboratory corridor space into the
animal room. For the purpose of
fumigation, animal rooms equipped
with non-APR doors opening into the
adjacent interior corridors shall be
considered one space (i.e., areas
between air-tight doors shall be
fumigated together).
(iv) Any door(s) used for access to the
service corridor (the secondary barrier)
shall be self-closing and of solid
construction, designed not to corrode,
split or warp;
(v) Access to the service corridor
inside the secondary barrier shall be
restricted and strictly controlled when
animal rooms are in use. Whenever
possible, the secondary barrier door(s)
should be fitted with safety interlock
switches designed to prevent it from
opening when an animal holding room
door (the primary barrier) is opened
following room decontamination; if
interlock devices cannot be used,
specific administrative procedures shall
be implemented to control access to the
service corridor;
(vi) The service corridor shall
maintain a negative pressure (inward
directional airflow) relative to adjoining
traffic corridors;
(vii) Prior to fumigation of the animal
holding room, cages should be removed
for autoclaving or chemical
decontamination.
(viii) Caging should be chosen to
reduce the amount of animal detritus
that can be thrown out of the cage and
onto the floor of the animal holding
room;
(ix) The flow of personnel, material
and equipment should be directed in
order to minimize the spread of
contamination from the animal holding
room into adjacent areas of the
laboratory.
(x) Following animal room
decontamination, safeguards involving
the use of personal protective
equipment and appropriate
administrative controls shall be
implemented for the safe retrieval of
biological indicators in order to prevent
the spread of infectious agents in the
event of a decontamination failure.
With regard to the frequency of class
II biosafety cabinet recertification and
testing, the NIH Guidelines require
recertification/testing of biosafety
cabinets at six-month intervals.
However, modern biosafety cabinet
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design specifications incorporate
continuous electronic and physical
monitoring systems that track multiple
operational parameters such as pressure
differential, air flow velocity and
plenum pressure with added
capabilities for remote control and
monitoring. Continuous performance
monitoring and redundant safety
features obviate the need for frequent
testing of modern biosafety cabinets
under normal conditions of use. Also
the testing of biosafety cabinets in
biomedical high containment (BL4)
laboratories entails a complete
shutdown of the laboratory for
decontamination with appropriate
sterilants to allow technicians to access
the equipment safely. This procedure
increases risks to laboratory staff
working with the sterilants (often in the
form of toxic gasses) and requires a halt
to all research activities for an extended
period of time depending on the number
of cabinets to be tested or recertified.
The NIH is in agreement with the
recommendation of the BMBL that class
II biosafety cabinets be tested and
certified at least annually, with the
understanding that retesting may have
to be performed as needed at the
discretion of the Institutional Biosafety
Committee (IBC), if for example,
equipment is moved or subject to
unusual conditions of use.
Appendix G–II–D–4–p currently
states:
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Appendix G–II–D–4–p. The treated exhaust
air from Class I and II biological safety
cabinets may be discharged into the
laboratory room environment or the outside
through the facility air exhaust system. If
exhaust air from Class I or II biological safety
cabinets is discharged into the laboratory the
cabinets are tested and certified at six-month
intervals. The exhaust air from Class III
biological safety cabinets is discharged,
without recirculation through two sets of
high efficiency particulate air/HEPA filters in
series, via the facility exhaust air system. If
the treated exhaust air from any of these
cabinets is discharged to the outside through
the facility exhaust air system, it is connected
to this system in a manner (e.g., thimble unit
connection (see Appendix G–III–L, Footnotes
and References of Appendix G)) that avoids
any interference with the air balance of the
cabinets or the facility exhaust air system.
Appendix G–II–D–4–p is amended as
follows:
Appendix G–II–D–4–p. The treated
exhaust air from Class I and II biological
safety cabinets may be discharged into
the laboratory room environment or the
outside through the facility air exhaust
system. If exhaust air from Class I or II
biological safety cabinets is discharged
into the laboratory the cabinets are
tested and certified at minimum on a
yearly basis. More frequent testing and
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certification, based on the amount of use
or other safety factors, shall be left to the
discretion of the IBC. The exhaust air
from Class III biological safety cabinets
is discharged, without recirculation
through two sets of high efficiency
particulate air/HEPA filters in series, via
the facility exhaust air system. If the
treated exhaust air from any of these
cabinets is discharged to the outside
through the facility exhaust air system,
it is connected to this system in a
manner (e.g., thimble unit connection
(see Appendix G–III–L, Footnotes and
References of Appendix G)) that avoids
any interference with the air balance of
the cabinets or the facility exhaust air
system.
With regard to the periodic biologic
validation of the centralized heat
treatment process for all BL3 and BL4
facilities, the NIH Guidelines requires
that this process be performed every 30
days while the BMBL recommends at
least an annual biological validation.
Similar to biosafety cabinets, modern
catch tank systems for heat treatment of
all laboratory effluents have also
become more sophisticated and now
incorporate redundant monitoring
systems to track temperature and
pressure parameters during each heat
treatment cycle. In addition it should be
noted that proper validation of the heat
treatment catch tank system requires
that testing be performed when the
system is at or near capacity (i.e. ‘‘under
load’’)—more frequent validation of a
heat treatment system that is below
capacity may not serve the intended
purpose of demonstrating that the
equipment is functioning as intended.
An additional margin of safety is
achieved by monitoring sterilization
cycle parameters on a routine basis. We
are, therefore, in agreement with the
recommendation of the BMBL that
validation be performed as frequently as
necessary at the discretion of the IBC
and at least once annually to ensure that
the centralized effluent heat treatment
system is performing as intended under
the established process parameters. This
amendment shall apply to heat
treatment systems used in both large
animal BL3 and BL4 facilities.
For large animal BL3 laboratories, the
requirement for decontamination and
inactivation (BL3–N) found at Appendix
Q–II–C–1–b–(5) currently states:
Appendix Q–II–C–1–b–(5). Liquid effluent
from containment equipment, sinks,
biological safety cabinets, animal rooms,
primary barriers, floor drains, and sterilizers
shall be decontaminated by heat treatment
before being released into the sanitary
system. The procedure used for heat
decontamination of liquid wastes shall be
monitored with a recording thermometer.
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The effectiveness of the heat
decontamination process system shall be
revalidated every 30 days with an indicator
organism.
Appendix Q–II–C–1–b–(5) is amended
as follows:
Appendix Q–II–C–1–b–(5). Liquid
effluent from containment equipment,
sinks, biological safety cabinets, animal
rooms, primary barriers, floor drains,
and sterilizers shall be decontaminated
by heat treatment before being released
into the sanitary system. The procedure
used for heat decontamination of liquid
wastes shall be monitored with a
recording thermometer. The
effectiveness of the heat
decontamination process system shall
be revalidated at minimum on a yearly
basis with an indicator organism. More
frequent validation, based on the
amount of use or other safety factors,
shall be left to the discretion of the IBC.
For large animal BL3 laboratories, the
requirement for animal facilities (BL3–
N) found at Appendix Q–II–C–2–h
currently states:
Appendix Q–II–C–2–h. Liquid effluent
from containment equipment, sinks,
biological safety cabinets, animal rooms,
primary barriers, floor drains, and sterilizers
shall be decontaminated by heat treatment
before being released into the sanitary
system. The procedure used for heat
decontamination of liquid wastes shall be
monitored with a recording thermometer.
The effectiveness of the heat
decontamination process system shall be
revalidated every 30 days with an indicator
organism.
Appendix Q–II–C–2–h is amended as
follows:
Appendix Q–II–C–2–h. Liquid
effluent from containment equipment,
sinks, biological safety cabinets, animal
rooms, primary barriers, floor drains,
and sterilizers shall be decontaminated
by heat treatment before being released
into the sanitary system. The procedure
used for heat decontamination of liquid
wastes shall be monitored with a
recording thermometer. The
effectiveness of the heat
decontamination process system shall
be revalidated at minimum on a yearly
basis with an indicator organism. More
frequent validation, based on the
amount of use or other safety factors,
shall be left to the discretion of the IBC.
For large animal BL4 laboratories, the
requirement for decontamination and
inactivation (BL4–N) found at Appendix
Q–II–D–1–b–(9) currently states:
Appendix Q–II–D–1–b–(9). Liquid effluent
from containment equipment, sinks,
biological safety cabinets, animal rooms,
primary barriers, floor drains, and sterilizers
shall be decontaminated by heat treatment
before being released into the sanitary
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system. Liquid wastes from shower rooms
and toilets shall be decontaminated with
chemical disinfectants or heat by methods
demonstrated to be effective. The procedure
used for heat decontamination of liquid
wastes shall be monitored with a recording
thermometer. The effectiveness of the heat
decontamination process system shall be
revalidated every 30 days with an indicator
organism. Liquid wastes from the shower
shall be chemically decontaminated using an
Environmental Protection Agency-approved
germicide. The efficacy of the chemical
treatment process shall be validated with an
indicator organism. Chemical disinfectants
shall be neutralized or diluted before release
into general effluent waste systems.
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Appendix Q–II–D–1–b–(9) is
amended as follows:
Appendix Q–II–D–1–b–(9). Liquid
effluent from containment equipment,
sinks, biological safety cabinets, animal
rooms, primary barriers, floor drains,
and sterilizers shall be decontaminated
by heat treatment before being released
into the sanitary system. If required by
design, regulation, local ordinance or
policy, liquid wastes from shower
rooms and toilets shall be
decontaminated with chemical
disinfectants or heat by methods
demonstrated to be effective. The
procedure used for heat
decontamination of liquid wastes shall
be monitored with a recording
thermometer. The effectiveness of the
heat decontamination process system
shall be revalidated at minimum on a
yearly basis with an indicator organism.
More frequent validation, based on the
amount of use or other safety factors,
shall be left to the discretion of the IBC.
If required by design, regulation, local
ordinance or policy, liquid wastes from
the shower shall be chemically
decontaminated using an Environmental
Protection Agency-approved germicide.
The efficacy of the chemical treatment
process shall be validated with an
indicator organism. Chemical
disinfectants shall be neutralized or
diluted before release into general
effluent waste systems.
For large animal BL4 laboratories, the
requirement for animal facilities (BL4–
N) found at Appendix Q–II–D–2–i
currently states:
Appendix Q–II–D–2–i. Liquid effluent
from containment equipment, sinks,
biological safety cabinets, animal rooms,
primary barriers, floor drains, and sterilizers
shall be decontaminated by heat treatment
before being released into the sanitary
system. Liquid wastes from shower rooms
and toilets shall be decontaminated with
chemical disinfectants or heat by methods
demonstrated to be effective. The procedure
used for heat decontamination of liquid
wastes shall be monitored with a recording
thermometer. The effectiveness of the heat
decontamination process system shall be
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revalidated every 30 days with an indicator
organism. Liquid wastes from the shower
shall be chemically decontaminated using an
Environmental Protection Agency-approved
germicide. The efficacy of the chemical
treatment process shall be validated with an
indicator organism. Chemical disinfectants
shall be neutralized or diluted before release
into general effluent waste systems.
Appendix Q–II–D–2–i is amended as
follows:
Appendix Q–II–D–2–i. Liquid effluent
from containment equipment, sinks,
biological safety cabinets, animal rooms,
primary barriers, floor drains, and
sterilizers shall be decontaminated by
heat treatment before being released into
the sanitary system. If required by
design, regulation, local ordinance or
policy, liquid wastes from shower
rooms and toilets shall be
decontaminated with chemical
disinfectants or heat by methods
demonstrated to be effective. The
procedure used for heat
decontamination of liquid wastes shall
be monitored with a recording
thermometer. The effectiveness of the
heat decontamination process system
shall be revalidated at minimum on a
yearly basis with an indicator organism.
More frequent validation, based on the
amount of use or other safety factors,
shall be left to the discretion of the IBC.
If required by design, regulation, local
ordinance or policy, liquid wastes from
the shower shall be chemically
decontaminated using an Environmental
Protection Agency-approved germicide.
The efficacy of the chemical treatment
process shall be validated with an
indicator organism. Chemical
disinfectants shall be neutralized or
diluted before release into general
effluent waste systems.
Dated: April 9, 2016.
Lawrence A. Tabak,
Deputy Director, National Institutes of Health.
[FR Doc. 2016–08810 Filed 4–14–16; 8:45 am]
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[Federal Register Volume 81, Number 73 (Friday, April 15, 2016)]
[Notices]
[Pages 22286-22289]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-08810]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institutes of Health (NIH) Office of Science Policy
(OSP) Recombinant or Synthetic Nucleic Acid Research: Action Under the
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic
Acid Molecules (NIH Guidelines)
SUMMARY: The NIH OSP is amending portions of the NIH Guidelines in
order to provide investigators with biosafety guidance regarding the
standards for containment of non-human primates (NHPs) in biosafety
level (BL) 4 laboratories and to make such guidance consistent with the
expectations articulated in the Centers for Disease Control and
Prevention (CDC)/NIH Biosafety in Microbiological and Biomedical
Laboratories 5th edition (BMBL). Specifically, the NIH Guidelines will
allow for housing of NHPs in open caging in a dedicated animal holding
room provided there are two physical barriers between that animal
holding room and non-containment space within the laboratory, the
animal holding room has negative air pressure with respect to any
adjacent non-containment corridors, and there are specific
decontamination protocols in place before the door to the animal
holding room is opened to allow for the periodic transfer of new
animals into the room. These amendments do not change the current
containment requirements in the NIH Guidelines but rather offer an
alternative for achieving primary containment without compromising
safety.
In addition, the recertification requirement for biosafety cabinets
in BL4 laboratories is updated in recognition of the technological
standards for modern biosafety cabinets. The NIH OSP also is updating
the validation requirements for equipment responsible for centralized
heat decontamination of liquid effluents in laboratories working with
large animals.
These amendments to the NIH Guidelines will be implemented
immediately upon publication in the Federal Register. These changes
were developed after extensive consultation with biosafety experts,
directors of and principal investigators in BL4 facilities working with
NHPs, and CDC's Division of Select Agent and Toxins (DSAT) leadership
at a public workshop and discussion at a public Recombinant DNA
Advisory Committee (RAC) meeting. Publication in the Federal Register
will inform the scientific and biosafety communities.
FOR FURTHER INFORMATION CONTACT: If you have questions, or require
additional information about these changes, please contact the NIH OSP
by email at SciencePolicy@od.nih.gov, or telephone at 301-496-9838.
SUPPLEMENTARY INFORMATION: The first three editions of the BMBL and the
NIH Guidelines were consistent in their approach to requiring primary
containment for animal work in BL4 containment laboratories. However,
in the early 1990s, the BMBL was amended and the fourth edition stated
that animals housed in BL4 suit laboratories (i.e., laboratories in
which Class III cabinets are not used but instead personnel wear
positive pressure protective suits) should be housed in a primary
containment system (such as open cages covered with filtered bonnets
and opened in laminar flow hoods or other equivalent containment
systems). This language remains in the current BMBL (5th edition). With
the change in the BMBL, primary containment caging was arguably
preferred but no longer required under BL4 containment. In contrast,
the NIH Guidelines have always required primary containment caging for
all animals in BL4 laboratories.
Non-human primates are social animals and require environmental
enrichment. Researchers in several U.S. BL4 laboratories engaged in NHP
research approached the NIH OSP with concerns that primary containment
caging in BL4 laboratories hindered the creation of an environment that
allowed animals to benefit from adequate social interaction. Also based
on risk assessments and experiences comparing several primary
containment caging systems, the researchers concluded that primary
containment caging may actually create new hazards for laboratory
workers. These findings included interference with observation of the
animals from outside the room leading to more frequent entries into the
BL4 animal room to monitor the animals, and exacerbation of cramped
working conditions created by the additional barriers required by some
containment systems, which increases the difficulty of working in
inflated pressure suits as well as the potential for damage to the
pressure suit. In addition, investigators stated that current BL4
laboratory designs incorporate sophisticated engineering systems, which
provide biosafety protection in a dedicated animal room equivalent to
the primary containment caging required under the NIH
[[Page 22287]]
Guidelines. On March 28, 2014, the NIH OSP, together with the CDC
Division of Select Agents (DSAT), held a meeting with investigators and
biosafety personnel from nine BL4 laboratories in the U.S. and five
international laboratories (agenda and roster available at https://osp.od.nih.gov/office-biotechnology-activities/event/2014-03-28-120000-2014-03-28-211500/primary-containment-non-human-primates-biosafety-level-4-laboratories-challenges-and-best-practices). That meeting was
followed by a discussion at the June 11, 2014, meeting of the NIH RAC
regarding housing of NHPs in BL4 laboratories (a webcast of that
discussion is available at https://videocast.nih.gov/summary.asp?Live=14300&bhcp=1.)
As a result of these discussions and after consultation with CDC
DSAT, the NIH OSP is amending the NIH Guidelines to allow the housing
of NHP in open cages in a dedicated animal room provided certain
conditions as articulated below are met.
In addition, OSP is updating the requirement for testing and
certification of Class I and II biosafety cabinets at BL4 from every
six months to annually, recognizing the technological advances in
biosafety cabinet design and engineering that have occurred over the
period since this performance measure was originally implemented.
Finally, Appendix Q of the NIH Guidelines currently requires that
the centralized heat treatment catch tank system in BL4 large animal
laboratories be validated every 30 days. To carry out this testing
effectively, the system should be near capacity (i.e. ``under load'').
Some laboratories do not use their catch tank systems on a regular
basis; therefore, a mandatory 30 day validation would require them to
demonstrate that the equipment is functioning when it is not in use or
is not at capacity. This will not serve the intended purpose of
demonstrating that the equipment is functioning as intended. Therefore,
validation intervals will need to be set based on the utilization of
the system provided it is done at least once a year.
To implement these changes, the following sections of the NIH
Guidelines are to be amended:
Appendix G-II-D-2-l. currently states:
Appendix G-II-D-2-l. Laboratory animals involved in experiments
requiring BL4 level physical containment shall be housed either in
cages contained in Class III cabinets or in partial containment
caging systems, such as Horsfall units (see Appendix G-III-K,
Footnotes and References of Appendix G), open cages placed in
ventilated enclosures, or solid-wall and -bottom cages placed on
holding racks equipped with ultraviolet irradiation lamps and
reflectors that are located in a specially designed area in which
all personnel are required to wear one-piece positive pressure
suits.
Appendix G-II-D-2-1 is amended as follows with the addition of a
new Appendix G-II-D-2-1-(2) that will address housing of NHPs:
Appendix G-II-D-2-l. Containment for Animal Research
Appendix G-II-D-2-l-(1). Laboratory animals involved in experiments
requiring BL4 level physical containment shall be housed either in
cages contained in Class III cabinets or in partial containment caging
systems, such as Horsfall units (see Appendix G-III-K, Footnotes and
References of Appendix G), open cages placed in ventilated enclosures,
or solid-wall and -bottom cages placed on holding racks equipped with
ultraviolet irradiation lamps and reflectors that are located in a
specially designed area in which all personnel are required to wear
one-piece positive pressure suits.
Appendix G-II-D-2-l-(2). Non-human primates (NHP) may be housed (1)
under the containment conditions described in Appendix G-II-D-2-l-(1)
above, or (2) in open cages within a dedicated animal holding room that
serves as the primary barrier and in which all personnel are required
to wear one-piece positive pressure suits. A room serving as a primary
barrier must be air-tight and capable of being decontaminated using
fumigation. If NHPs are to be contained in a dedicated animal holding
room serving as the primary barrier, the following conditions shall be
met:
(i) Access to the animal holding room from service corridors
outside of the BL4 containment space shall require passage through two
sets of doors, and the inner most door must be an air pressure
resistant (APR) door;
(ii) For any animal holding room considered to be a primary
barrier, APR door(s) providing direct ingress from the exterior service
corridor shall be fitted with appropriate and redundant lock-out
mechanisms to prevent access when the animal holding room is
contaminated and in use. There should be more than one mechanism to
ensure that this primary barrier door cannot be opened when the animal
room is contaminated and the APR door shall not serve as an emergency
exit from the BL4 laboratory. The APR door shall be appropriately
tested to demonstrate that in the closed, locked-out mode, the door
provides an air-tight barrier proven by pressure decay testing or other
equivalent method;
(iii) Any door(s) allowing access into a corridor from which there
is direct ingress to an animal holding room must be fitted with either
(1) an APR door or (2) a non-APR door, providing directional airflow is
maintained from the laboratory corridor space into the animal room. For
the purpose of fumigation, animal rooms equipped with non-APR doors
opening into the adjacent interior corridors shall be considered one
space (i.e., areas between air-tight doors shall be fumigated
together).
(iv) Any door(s) used for access to the service corridor (the
secondary barrier) shall be self-closing and of solid construction,
designed not to corrode, split or warp;
(v) Access to the service corridor inside the secondary barrier
shall be restricted and strictly controlled when animal rooms are in
use. Whenever possible, the secondary barrier door(s) should be fitted
with safety interlock switches designed to prevent it from opening when
an animal holding room door (the primary barrier) is opened following
room decontamination; if interlock devices cannot be used, specific
administrative procedures shall be implemented to control access to the
service corridor;
(vi) The service corridor shall maintain a negative pressure
(inward directional airflow) relative to adjoining traffic corridors;
(vii) Prior to fumigation of the animal holding room, cages should
be removed for autoclaving or chemical decontamination.
(viii) Caging should be chosen to reduce the amount of animal
detritus that can be thrown out of the cage and onto the floor of the
animal holding room;
(ix) The flow of personnel, material and equipment should be
directed in order to minimize the spread of contamination from the
animal holding room into adjacent areas of the laboratory.
(x) Following animal room decontamination, safeguards involving the
use of personal protective equipment and appropriate administrative
controls shall be implemented for the safe retrieval of biological
indicators in order to prevent the spread of infectious agents in the
event of a decontamination failure.
With regard to the frequency of class II biosafety cabinet
recertification and testing, the NIH Guidelines require
recertification/testing of biosafety cabinets at six-month intervals.
However, modern biosafety cabinet
[[Page 22288]]
design specifications incorporate continuous electronic and physical
monitoring systems that track multiple operational parameters such as
pressure differential, air flow velocity and plenum pressure with added
capabilities for remote control and monitoring. Continuous performance
monitoring and redundant safety features obviate the need for frequent
testing of modern biosafety cabinets under normal conditions of use.
Also the testing of biosafety cabinets in biomedical high containment
(BL4) laboratories entails a complete shutdown of the laboratory for
decontamination with appropriate sterilants to allow technicians to
access the equipment safely. This procedure increases risks to
laboratory staff working with the sterilants (often in the form of
toxic gasses) and requires a halt to all research activities for an
extended period of time depending on the number of cabinets to be
tested or recertified. The NIH is in agreement with the recommendation
of the BMBL that class II biosafety cabinets be tested and certified at
least annually, with the understanding that retesting may have to be
performed as needed at the discretion of the Institutional Biosafety
Committee (IBC), if for example, equipment is moved or subject to
unusual conditions of use.
Appendix G-II-D-4-p currently states:
Appendix G-II-D-4-p. The treated exhaust air from Class I and II
biological safety cabinets may be discharged into the laboratory
room environment or the outside through the facility air exhaust
system. If exhaust air from Class I or II biological safety cabinets
is discharged into the laboratory the cabinets are tested and
certified at six-month intervals. The exhaust air from Class III
biological safety cabinets is discharged, without recirculation
through two sets of high efficiency particulate air/HEPA filters in
series, via the facility exhaust air system. If the treated exhaust
air from any of these cabinets is discharged to the outside through
the facility exhaust air system, it is connected to this system in a
manner (e.g., thimble unit connection (see Appendix G-III-L,
Footnotes and References of Appendix G)) that avoids any
interference with the air balance of the cabinets or the facility
exhaust air system.
Appendix G-II-D-4-p is amended as follows:
Appendix G-II-D-4-p. The treated exhaust air from Class I and II
biological safety cabinets may be discharged into the laboratory room
environment or the outside through the facility air exhaust system. If
exhaust air from Class I or II biological safety cabinets is discharged
into the laboratory the cabinets are tested and certified at minimum on
a yearly basis. More frequent testing and certification, based on the
amount of use or other safety factors, shall be left to the discretion
of the IBC. The exhaust air from Class III biological safety cabinets
is discharged, without recirculation through two sets of high
efficiency particulate air/HEPA filters in series, via the facility
exhaust air system. If the treated exhaust air from any of these
cabinets is discharged to the outside through the facility exhaust air
system, it is connected to this system in a manner (e.g., thimble unit
connection (see Appendix G-III-L, Footnotes and References of Appendix
G)) that avoids any interference with the air balance of the cabinets
or the facility exhaust air system.
With regard to the periodic biologic validation of the centralized
heat treatment process for all BL3 and BL4 facilities, the NIH
Guidelines requires that this process be performed every 30 days while
the BMBL recommends at least an annual biological validation. Similar
to biosafety cabinets, modern catch tank systems for heat treatment of
all laboratory effluents have also become more sophisticated and now
incorporate redundant monitoring systems to track temperature and
pressure parameters during each heat treatment cycle. In addition it
should be noted that proper validation of the heat treatment catch tank
system requires that testing be performed when the system is at or near
capacity (i.e. ``under load'')--more frequent validation of a heat
treatment system that is below capacity may not serve the intended
purpose of demonstrating that the equipment is functioning as intended.
An additional margin of safety is achieved by monitoring sterilization
cycle parameters on a routine basis. We are, therefore, in agreement
with the recommendation of the BMBL that validation be performed as
frequently as necessary at the discretion of the IBC and at least once
annually to ensure that the centralized effluent heat treatment system
is performing as intended under the established process parameters.
This amendment shall apply to heat treatment systems used in both large
animal BL3 and BL4 facilities.
For large animal BL3 laboratories, the requirement for
decontamination and inactivation (BL3-N) found at Appendix Q-II-C-1-b-
(5) currently states:
Appendix Q-II-C-1-b-(5). Liquid effluent from containment
equipment, sinks, biological safety cabinets, animal rooms, primary
barriers, floor drains, and sterilizers shall be decontaminated by
heat treatment before being released into the sanitary system. The
procedure used for heat decontamination of liquid wastes shall be
monitored with a recording thermometer. The effectiveness of the
heat decontamination process system shall be revalidated every 30
days with an indicator organism.
Appendix Q-II-C-1-b-(5) is amended as follows:
Appendix Q-II-C-1-b-(5). Liquid effluent from containment
equipment, sinks, biological safety cabinets, animal rooms, primary
barriers, floor drains, and sterilizers shall be decontaminated by heat
treatment before being released into the sanitary system. The procedure
used for heat decontamination of liquid wastes shall be monitored with
a recording thermometer. The effectiveness of the heat decontamination
process system shall be revalidated at minimum on a yearly basis with
an indicator organism. More frequent validation, based on the amount of
use or other safety factors, shall be left to the discretion of the
IBC.
For large animal BL3 laboratories, the requirement for animal
facilities (BL3-N) found at Appendix Q-II-C-2-h currently states:
Appendix Q-II-C-2-h. Liquid effluent from containment equipment,
sinks, biological safety cabinets, animal rooms, primary barriers,
floor drains, and sterilizers shall be decontaminated by heat
treatment before being released into the sanitary system. The
procedure used for heat decontamination of liquid wastes shall be
monitored with a recording thermometer. The effectiveness of the
heat decontamination process system shall be revalidated every 30
days with an indicator organism.
Appendix Q-II-C-2-h is amended as follows:
Appendix Q-II-C-2-h. Liquid effluent from containment equipment,
sinks, biological safety cabinets, animal rooms, primary barriers,
floor drains, and sterilizers shall be decontaminated by heat treatment
before being released into the sanitary system. The procedure used for
heat decontamination of liquid wastes shall be monitored with a
recording thermometer. The effectiveness of the heat decontamination
process system shall be revalidated at minimum on a yearly basis with
an indicator organism. More frequent validation, based on the amount of
use or other safety factors, shall be left to the discretion of the
IBC.
For large animal BL4 laboratories, the requirement for
decontamination and inactivation (BL4-N) found at Appendix Q-II-D-1-b-
(9) currently states:
Appendix Q-II-D-1-b-(9). Liquid effluent from containment
equipment, sinks, biological safety cabinets, animal rooms, primary
barriers, floor drains, and sterilizers shall be decontaminated by
heat treatment before being released into the sanitary
[[Page 22289]]
system. Liquid wastes from shower rooms and toilets shall be
decontaminated with chemical disinfectants or heat by methods
demonstrated to be effective. The procedure used for heat
decontamination of liquid wastes shall be monitored with a recording
thermometer. The effectiveness of the heat decontamination process
system shall be revalidated every 30 days with an indicator
organism. Liquid wastes from the shower shall be chemically
decontaminated using an Environmental Protection Agency-approved
germicide. The efficacy of the chemical treatment process shall be
validated with an indicator organism. Chemical disinfectants shall
be neutralized or diluted before release into general effluent waste
systems.
Appendix Q-II-D-1-b-(9) is amended as follows:
Appendix Q-II-D-1-b-(9). Liquid effluent from containment
equipment, sinks, biological safety cabinets, animal rooms, primary
barriers, floor drains, and sterilizers shall be decontaminated by heat
treatment before being released into the sanitary system. If required
by design, regulation, local ordinance or policy, liquid wastes from
shower rooms and toilets shall be decontaminated with chemical
disinfectants or heat by methods demonstrated to be effective. The
procedure used for heat decontamination of liquid wastes shall be
monitored with a recording thermometer. The effectiveness of the heat
decontamination process system shall be revalidated at minimum on a
yearly basis with an indicator organism. More frequent validation,
based on the amount of use or other safety factors, shall be left to
the discretion of the IBC. If required by design, regulation, local
ordinance or policy, liquid wastes from the shower shall be chemically
decontaminated using an Environmental Protection Agency-approved
germicide. The efficacy of the chemical treatment process shall be
validated with an indicator organism. Chemical disinfectants shall be
neutralized or diluted before release into general effluent waste
systems.
For large animal BL4 laboratories, the requirement for animal
facilities (BL4-N) found at Appendix Q-II-D-2-i currently states:
Appendix Q-II-D-2-i. Liquid effluent from containment equipment,
sinks, biological safety cabinets, animal rooms, primary barriers,
floor drains, and sterilizers shall be decontaminated by heat
treatment before being released into the sanitary system. Liquid
wastes from shower rooms and toilets shall be decontaminated with
chemical disinfectants or heat by methods demonstrated to be
effective. The procedure used for heat decontamination of liquid
wastes shall be monitored with a recording thermometer. The
effectiveness of the heat decontamination process system shall be
revalidated every 30 days with an indicator organism. Liquid wastes
from the shower shall be chemically decontaminated using an
Environmental Protection Agency-approved germicide. The efficacy of
the chemical treatment process shall be validated with an indicator
organism. Chemical disinfectants shall be neutralized or diluted
before release into general effluent waste systems.
Appendix Q-II-D-2-i is amended as follows:
Appendix Q-II-D-2-i. Liquid effluent from containment equipment,
sinks, biological safety cabinets, animal rooms, primary barriers,
floor drains, and sterilizers shall be decontaminated by heat treatment
before being released into the sanitary system. If required by design,
regulation, local ordinance or policy, liquid wastes from shower rooms
and toilets shall be decontaminated with chemical disinfectants or heat
by methods demonstrated to be effective. The procedure used for heat
decontamination of liquid wastes shall be monitored with a recording
thermometer. The effectiveness of the heat decontamination process
system shall be revalidated at minimum on a yearly basis with an
indicator organism. More frequent validation, based on the amount of
use or other safety factors, shall be left to the discretion of the
IBC. If required by design, regulation, local ordinance or policy,
liquid wastes from the shower shall be chemically decontaminated using
an Environmental Protection Agency-approved germicide. The efficacy of
the chemical treatment process shall be validated with an indicator
organism. Chemical disinfectants shall be neutralized or diluted before
release into general effluent waste systems.
Dated: April 9, 2016.
Lawrence A. Tabak,
Deputy Director, National Institutes of Health.
[FR Doc. 2016-08810 Filed 4-14-16; 8:45 am]
BILLING CODE 4140-01-P
