Appendix
K-I. Selection
of Physical Containment Levels
Appendix
K-II. Good
Large Scale Practice (GLSP)
Appendix
K-III. Biosafety
Level 1 (BL1) - Large Scale
Appendix
K-IV. Biosafety
Level 2 (BL2) - Large Scale
Appendix
K-V. Biosafety
Level 3 (BL3) - Large Scale
Appendix
K-VI. Footnotes
of Appendix K
Appendix
K-VII. Definitions
to Accompany Containment Grid and Appendix K
LIST OF TABLES
Appendix K specifies
physical containment guidelines for large-scale (greater than 10 liters of
culture) research or production involving viable organisms containing
recombinant DNA molecules. It shall apply
to large-scale research or production activities as specified in Section
III-D-6, Experiments Involving More than 10 Liters of Culture. It is important to note that this appendix
addresses only the biological hazard associated with organisms containing
recombinant DNA. Other hazards
accompanying the large-scale cultivation of such organisms (e.g., toxic
properties of products; physical, mechanical, and chemical aspects of
downstream processing) are not addressed and shall be considered separately,
albeit in conjunction with this appendix.
All provisions shall
apply to large-scale research or production activities with the following
modifications: (i) Appendix K shall supersede
Appendix G, Physical
Containment, when quantities in excess of 10 liters of culture are involved
in research or production. Appendix K-II applies to Good Large Scale Practice;
(ii) the institution shall appoint a Biological Safety Officer if it engages in
large-scale research or production activities involving viable organisms
containing recombinant DNA molecules.
The duties of the Biological Safety Officer shall include those
specified in Section IV-B-3, Biological Safety Officer; (iii) the
institution shall establish and maintain a health surveillance program for
personnel engaged in large-scale research or production activities involving
viable organisms containing recombinant DNA molecules which require Biosafety
Level (BL) 3 containment at the laboratory scale. The program shall include:
preassignment and periodic physical and medical examinations;
collection, maintenance, and analysis of serum specimens for monitoring
serologic changes that may result from the employee's work experience; and
provisions for the investigation of any serious, unusual, or extended illnesses
of employees to determine possible occupational origin.
The selection of the
physical containment level required for recombinant DNA research or production
involving more than 10 liters of culture is based on the containment guidelines
established in Section III, Experiments Covered by the NIH Guidelines. For purposes of large-scale research or
production, four physical containment levels are established. The four levels set containment conditions
at those appropriate for the degree of hazard to health or the environment
posed by the organism, judged by experience with similar organisms unmodified
by recombinant DNA techniques and consistent with Good Large Scale
Practice. The four biosafety levels of
large-scale physical containment are referred to as Good Large Scale Practice,
BL1-Large Scale, BL2-Large Scale, and BL3-Large Scale. Good Large Scale Practice is recommended for
large-scale research or production involving viable, non-pathogenic, and
non-toxigenic recombinant strains derived from host organisms that have an
extended history of safe large-scale use.
Good Large Scale Practice is recommended for organisms such as those
included in Appendix C, Exemptions
under Section III-F-6, which have built-in environmental limitations that
permit optimum growth in the large-scale setting but limited survival without
adverse consequences in the environment.
BL1-Large Scale is recommended for large-scale research or production of
viable organisms containing recombinant DNA molecules that require BL1
containment at the laboratory scale and that do not qualify for Good Large
Scale Practice. BL2-Large Scale is
recommended for large-scale research or production of viable organisms
containing recombinant DNA molecules that require BL2 containment at the
laboratory scale. BL3-Large Scale is
recommended for large-scale research or production of viable organisms
containing recombinant DNA molecules that require BL3 containment at the
laboratory scale. No provisions are
made for large-scale research or production of viable organisms containing
recombinant DNA molecules that require BL4 containment at the laboratory scale.
If necessary, these requirements will
be established by NIH on an individual basis.
Appendix K-II-A. Institutional codes of practice shall be formulated
and implemented to assure adequate control of health and safety matters.
Appendix K-II-B. Written instructions and training of
personnel shall be provided to assure that cultures of viable organisms
containing recombinant DNA molecules are handled prudently and that the work
place is kept clean and orderly.
Appendix K-II-C. In the interest of good personal hygiene,
facilities (e.g., hand washing sink, shower, changing room) and protective
clothing (e.g., uniforms, laboratory coats) shall be provided that are
appropriate for the risk of exposure to viable organisms containing recombinant
DNA molecules. Eating, drinking,
smoking, applying cosmetics, and mouth pipetting shall be prohibited in the
work area.
Appendix K-II-D. Cultures of viable organisms containing
recombinant DNA molecules shall be handled in facilities intended to safeguard
health during work with microorganisms that do not require containment.
Appendix K-II-E. Discharges containing viable recombinant
organisms shall be handled in accordance with applicable governmental
environmental regulations.
Appendix K-II-F. Addition of materials to a system, sample
collection, transfer of culture fluids within/between systems, and processing
of culture fluids shall be conducted in a manner that maintains employee's
exposure to viable organisms containing recombinant DNA molecules at a level
that does not adversely affect the health and safety of employees.
Appendix K-II-G. The facility's emergency response plan shall
include provisions for handling spills.
Appendix K-III-A. Spills and accidents which result in overt
exposures to organisms containing recombinant DNA molecules are immediately
reported to the Laboratory Director.
Medical evaluation, surveillance, and treatment are provided as
appropriate and written records are maintained.
Appendix K-III-B. Cultures of viable organisms containing
recombinant DNA molecules shall be handled in a closed system (e.g., closed
vessel used for the propagation and growth of cultures) or other primary
containment equipment (e.g., biological safety cabinet containing a centrifuge
used to process culture fluids) which is designed to reduce the potential for
escape of viable organisms. Volumes
less than 10 liters may be handled outside of a closed system or other primary
containment equipment provided all physical containment requirements specified
in Appendix
G-II-A, Physical Containment Levels--Biosafety Level 1, are met.
Appendix K-III-C. Culture fluids (except as allowed in
Appendix K-III-D) shall not be removed from a closed system or other primary containment
equipment unless the viable organisms containing recombinant DNA molecules have
been inactivated by a validated inactivation procedure. A validated inactivation procedure is one
which has been demonstrated to be effective using the organism that will serve
as the host for propagating the recombinant DNA molecules. Culture fluids that contain viable organisms
or viral vectors intended as final product may be removed from the primary
containment equipment by way of closed systems for sample analysis, further
processing or final fill.
Appendix K-III-D. Sample collection from a closed system, the
addition of materials to a closed system, and the transfer of culture fluids
from one closed system to another shall be conducted in a manner which minimizes
the release of aerosols or contamination of exposed surfaces.
Appendix K-III-E. Exhaust gases removed from a closed system
or other primary containment equipment shall be treated by filters which have
efficiencies equivalent to high efficiency particulate air/HEPA filters or by
other equivalent procedures (e.g., incineration) to minimize the release of
viable organisms containing recombinant
DNA molecules to the
environment.
Appendix K-III-F. A closed system or other primary containment
equipment that has contained viable organisms containing recombinant DNA
molecules shall not be opened for maintenance or other purposes unless it has
been sterilized by a validated sterilization procedure except when the culture
fluids contain viable organisms or vectors intended as final product as
described in Appendix K-III-C
above. A validated sterilization
procedure is one which has been demonstrated to be effective using the organism
that will serve as the host for propagating the recombinant DNA molecules.
Appendix K-III-G. Emergency plans required by Sections
IV-B-2-b-(6), Institutional Biosafety Committee, and IV-B-3-c-(3),
Biological Safety Officer, shall include methods and procedures for
handling large losses of culture on an emergency basis.
Appendix K-IV-A. Spills and accidents which result in overt
exposures to organisms containing recombinant DNA molecules are immediately
reported to the Biological Safety Officer, Institutional Biosafety Committee,
NIH/OBA, and other appropriate authorities (if applicable). Reports to NIH/OBA shall be sent to the
Office of Biotechnology Activities, National Institutes of Health, 6705
Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD 20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839
(fax). Medical evaluation,
surveillance, and treatment are provided as appropriate and written records are
maintained.
Appendix K-IV-B. Cultures of viable organisms containing
recombinant DNA molecules shall be handled in a closed system (e.g., closed vessel
used for the propagation and growth of cultures) or other primary containment
equipment (e.g., Class III biological safety cabinet containing a centrifuge
used to process culture fluids) which is designed to prevent the escape of
viable organisms. Volumes less than 10
liters may be handled outside of a closed system or other primary containment
equipment provided all physical containment requirements specified in Appendix
G-II-B, Physical Containment Levels--Biosafety Level 2, are met.
Appendix K-IV-C. Culture fluids (except as allowed in
Appendix K-IV-D) shall not be removed from a closed system or other primary
containment equipment unless the viable organisms containing recombinant DNA
molecules have been inactivated by a validated inactivation procedure. A validated inactivation procedure is one
which has been demonstrated to be effective using the organism that will serve
as the host for propagating the recombinant DNA molecules. Culture fluids that contain viable organisms
or viral vectors intended as final product may be removed from the primary
containment equipment by way of closed systems for sample analysis, further
processing or final fill.
Appendix K-IV-D. Sample collection from a closed system, the
addition of materials to a closed system, and the transfer of cultures fluids
from one closed system to another shall be conducted in a manner which prevents
the release of aerosols or contamination of exposed surfaces.
Appendix K-IV-E. Exhaust gases removed from a closed system
or other primary containment equipment shall be treated by filters which have
efficiencies equivalent to high efficiency particulate air/HEPA filters or by
other equivalent procedures (e.g., incineration) to prevent the release of
viable organisms containing recombinant DNA molecules to the environment.
Appendix K-IV-F. A closed system or other primary containment
equipment that has contained viable organisms containing recombinant DNA
molecules shall not be opened for maintenance or other purposes unless it has
been sterilized by a validated sterilization procedure except when the culture
fluids contain viable organisms or vectors intended as final product as
described in Appendix K-IV-C
above. A validated sterilization
procedure is one which has been demonstrated to be effective using the
organisms that will serve as the host for propagating the recombinant DNA
molecules.
Appendix K-IV-G. Rotating seals and other mechanical devices
directly associated with a closed system used for the propagation and growth of
viable organisms containing recombinant DNA molecules shall be designed to
prevent leakage or shall be fully enclosed in ventilated housings that are
exhausted through filters which have efficiencies equivalent to high efficiency
particulate air/HEPA filters or through other equivalent treatment devices.
Appendix K-IV-H. A closed system used for the propagation and
growth of viable organisms containing recombinant DNA molecules and other
primary containment equipment used to contain operations involving viable
organisms containing sensing devices that monitor the integrity of containment
during operations.
Appendix K-IV-I. A closed system used for the propagation and
growth of viable organisms containing the recombinant DNA molecules shall be
tested for integrity of the containment features using the organism that will
serve as the host for propagating recombinant DNA molecules. Testing shall be accomplished prior to the
introduction of viable organisms containing recombinant DNA molecules and
following modification or replacement of essential containment features. Procedures and methods used in the testing
shall be appropriate for the equipment design and for recovery and
demonstration of the test organism.
Records of tests and results shall be maintained on file.
Appendix K-IV-J. A closed system used for the propagation and
growth of viable organisms containing recombinant DNA molecules shall be
permanently identified. This
identification shall be used in all records reflecting testing, operation, and
maintenance and in all documentation relating to use of this equipment for
research or production activities involving viable organisms containing
recombinant DNA molecules.
Appendix K-IV-K. The universal biosafety sign shall be posted
on each closed system and primary containment equipment when used to contain
viable organisms containing recombinant DNA molecules.
Appendix K-IV-L. Emergency plans required by Sections
IV-B-2-b-(6), Institutional Biosafety Committee, and IV-B-3-c-(3),
Biological Safety Officer, shall include methods and procedures for
handling large losses of culture on an emergency basis.
Appendix K-V-A. Spills and accidents which result in overt
exposures to organisms containing recombinant DNA molecules are immediately
reported to the Biological Safety Officer, Institutional Biosafety Committee,
NIH/OBA, and other appropriate authorities (if applicable). Reports to NIH/OBA shall be sent to the
Office of Biotechnology Activities, National Institutes of Health, 6705
Rockledge Drive, Suite 750, MSC 7985, Bethesda, MD 20892-7985 (20817 for non-USPS mail), 301-496-9838, 301-496-9839
(fax). Medical evaluation,
surveillance, and treatment are provided as appropriate and written records are
maintained.
Appendix K-V-B. Cultures of viable organisms containing
recombinant DNA molecules shall be handled in a closed system (e.g., closed
vessels used for the propagation and growth of cultures) or other primary
containment equipment (e.g., Class III biological safety cabinet containing a
centrifuge used to process culture fluids) which is designed to prevent the
escape of viable organisms. Volumes
less than 10 liters may be handled outside of a closed system provided all
physical containment requirements specified in Appendix
G-II-C, Physical Containment Levels--Biosafety Level 3, are
met.
Appendix K-V-C. Culture fluids (except as allowed in
Appendix K-V-D) shall not be removed from a closed system or other primary
containment equipment unless the viable organisms containing recombinant DNA
molecules have been inactivated by a validated inactivation procedure. A validated inactivation procedure is one
which has been demonstrated to be effective using the organisms that will serve
as the host for propagating the recombinant DNA molecules. Culture fluids that contain viable organisms
or viral vectors intended as final product may be removed from the primary
containment equipment by way of closed systems for sample analysis, further
processing or final fill.
Appendix K-V-D. Sample collection from a closed system, the
addition of materials to a closed system, and the transfer of culture fluids
from one closed system to another shall be conducted in a manner which prevents
the release of aerosols or contamination of exposed surfaces.
Appendix K-V-E. Exhaust gases removed from a closed system
or other primary containment equipment shall be treated by filters which have
efficiencies equivalent to high efficiency particulate air/HEPA filters or by
other equivalent procedures (e.g., incineration) to prevent the release of
viable organisms containing recombinant DNA molecules to the environment.
Appendix K-V-F. A closed system or other primary containment
equipment that has contained viable organisms containing recombinant DNA
molecules shall not be opened for maintenance or other purposes unless it has
been sterilized by a validated sterilization procedure except when the culture
fluids contain viable organisms or vectors intended as final product as
described in Appendix K-V-C above. A validated sterilization procedure is one
which has been demonstrated to be effective using the organisms that will serve
as the host for propagating the recombinant DNA molecules.
Appendix K-V-G. A closed system used for the propagation and
growth of viable organisms containing recombinant DNA molecules shall be
operated so that the space above the culture level will be maintained at a
pressure as low as possible, consistent with equipment design, in order to
maintain the integrity of containment features.
Appendix K-V-H. Rotating seals and other mechanical devices
directly associated with a closed system used to contain viable organisms
containing recombinant DNA molecules shall be designed to prevent leakage or
shall be fully enclosed in ventilated housings that are exhausted through
filters which have efficiencies equivalent to high efficiency particulate
air/HEPA filters or through other equivalent treatment devices.
Appendix K-V-I. A closed system used for the propagation and
growth of viable organisms containing recombinant DNA molecules and other
primary containment equipment used to contain operations involving viable
organisms containing recombinant DNA molecules shall include monitoring or
sensing devices that monitor the integrity of containment during operations.
Appendix K-V-J. A closed system used for the propagation and
growth of viable organisms containing recombinant DNA molecules shall be tested
for integrity of the containment features using the organisms that will serve
as the host for propagating the recombinant DNA molecules. Testing shall be accomplished prior to the
introduction of viable organisms containing recombinant DNA molecules and
following modification or replacement of essential containment features. Procedures and methods used in the testing
shall be appropriate for the equipment design and for recovery and
demonstration of the test organism.
Records of tests and results shall be maintained on file.
Appendix K-V-K. A closed system used for the propagation and
growth of viable organisms containing recombinant DNA molecules shall be
permanently identified. This
identification shall be used in all records reflecting testing, operation,
maintenance, and use of this equipment for research production activities
involving viable organisms containing recombinant DNA molecules.
Appendix K-V-L. The universal biosafety sign shall be posted
on each closed system and primary containment equipment when used to contain
viable organisms containing recombinant DNA molecules.
Appendix K-V-M. Emergency plans required by Sections
IV-B-2-b-(6), Institutional Biosafety Committee, and IV-B-3-c-(3),
Biological Safety Officer, shall include methods and procedures for
handling large losses of culture on an emergency basis.
Appendix K-V-N. Closed systems and other primary containment
equipment used in handling cultures of viable organisms containing recombinant
DNA molecules shall be located within a controlled area which meets the
following requirements:
Appendix K-V-N-1. The controlled area shall have a separate
entry area. The entry area shall be a
double-doored space such as an air lock, anteroom, or change room that
separates the controlled area from the balance of the facility.
Appendix K-V-N-2. The surfaces of walls, ceilings, and floors
in the controlled area shall be such as to permit ready cleaning and
decontamination.
Appendix K-V-N-3. Penetrations into the controlled area shall be
sealed to permit liquid or vapor phase space decontamination.
Appendix K-V-N-4. All utilities and service or process piping
and wiring entering the controlled area shall be protected against
contamination.
Appendix K-V-N-5. Hand washing facilities equipped with foot,
elbow, or automatically operated valves shall be located at each major work
area and near each primary exit.
Appendix K-V-N-6. A shower facility shall be provided. This facility shall be located in close
proximity to the controlled area.
Appendix K-V-N-7. The controlled area shall be designed to
preclude release of culture fluids outside the controlled area in the event of
an accidental spill or release from the closed systems or other primary
containment equipment.
Appendix K-V-N-8. The controlled area shall have a ventilation
system that is capable of controlling air movement. The movement of air shall be from areas of lower contamination
potential to areas of higher contamination potential. If the ventilation system provides positive pressure supply air,
the system shall operate in a manner that prevents the reversal of the
direction of air movement or shall be equipped with an alarm that would be
actuated in the event that reversal in the direction of air movement were to
occur. The exhaust air from the
controlled area shall not be recirculated to other areas of the facility. The exhaust air from the controlled area may
not be discharged to the outdoors without being high efficiency particulate
air/HEPA filtered, subjected to thermal oxidation, or otherwise treated to
prevent the release of viable organisms.
Appendix K-V-O. The following personnel and operational
practices shall be required:
Appendix K-V-O-1. Personnel entry into the controlled area
shall be through the entry area specified in Appendix K-V-N-1.
Appendix K-V-O-2. Persons entering the controlled area shall
exchange or cover their personal clothing with work garments such as jump
suits, laboratory coats, pants and shirts, head cover, and shoes or shoe covers. On exit from the controlled area the work
clothing may be stored in a locker separate from that used for personal
clothing or discarded for laundering.
Clothing shall be decontaminated before laundering.
Appendix K-V-O-3. Entry into the controlled area during
periods when work is in progress shall be restricted to those persons required
to meet program or support needs. Prior
to entry, all persons shall be informed of the operating practices, emergency
procedures, and the nature of the work conducted.
Appendix K-V-O-4. Persons under 18 years of age shall not be
permitted to enter the controlled area.
Appendix K-V-O-5. The universal biosafety sign shall be posted
on entry doors to the controlled area and all internal doors when any work involving
the organism is in progress. This
includes periods when decontamination procedures are in progress. The sign posted on the entry doors to the
controlled area shall include a statement of agents in use and personnel
authorized to enter the controlled area.
Appendix K-V-O-6. The controlled area shall be kept neat and
clean.
Appendix K-V-O-7. Eating, drinking, smoking, and storage of
food are prohibited in the controlled area.
Appendix K-V-O-8. Animals and plants shall be excluded from
the controlled area.
Appendix K-V-O-9. An effective insect and rodent control
program shall be maintained.
Appendix K-V-O-10. Access doors to the controlled area shall be
kept closed, except as necessary for access, while work is in progress. Serve doors leading directly outdoors shall
be sealed and locked while work is in progress.
Appendix K-V-O-11. Persons shall wash their hands when exiting
the controlled area.
Appendix K-V-O-12. Persons working in the controlled area shall
be trained in emergency procedures.
Appendix K-V-O-13. Equipment and materials required for the
management of accidents involving viable organisms containing recombinant DNA
molecules shall be available in the controlled area.
Appendix K-V-O-14. The controlled area shall be decontaminated
in accordance with established procedures following spills or other accidental
release of viable organisms containing recombinant DNA molecules.
Appendix K - Table 1. Comparison of Good Large Scale Practice (GLSP) and Biosafety Level (BL) - Large Scale (LS) Practice (See Appendix K-VI-A, Footnotes Of Appendix K)
|
CRITERION [See Appendix
K-VI-B, Footnotes of Appendix K] |
GLSP |
BL1-LS |
BL2-LS |
BL3-LS |
|
|
1. |
Formulate
and implement institutional codes of practice for safety of personnel and
adequate control of hygiene and safety measures. |
K-II-A |
G-I |
||
|
2. |
Provide
adequate written instructions and training of personnel to keep work place
clean and tidy and to keep exposure to biological, chemical or physical
agents at a level that does not adversely affect health and safety of
employees. |
K-II-B |
G-I |
||
|
3. |
Provide
changing and hand washing facilities as well as protective clothing,
appropriate to the risk, to be worn during work. |
K-II-C |
G-II-A-1-h |
G-II-B-2-f |
G-II-C-2-i |
|
4. |
Prohibit
eating, drinking, smoking, mouth pipetting, and applying cosmetics in the
work place. |
K-II-C |
G-II-A-1-d G-II-A-1-e |
G-II-B-1-d G-II-B-1-e |
G-II-C-1-c G-II-C-1-d |
|
5. |
Internal
accident reporting. |
K-II-G |
K-III-A |
K-IV-A |
K-V-A |
|
6. |
Medical
surveillance. |
NR |
NR |
|
|
|
7. |
Viable
organisms should be handled in a system that physically separates the process
from the external environment (closed system or other primary containment). |
NR |
K-III-B |
K-IV-B |
K-V-B |
|
8. |
Culture
fluids not removed from a system until organisms are inactivated. |
NR |
K-III-C |
K-IV-C |
K-V-C |
|
9. |
Inactivation
of waste solutions and materials with respect to their biohazard potential. |
K-II-E |
K-III-C |
K-IV-C |
K-V-C |
|
10. |
Control
of aerosols by engineering or procedural controls to prevent or minimize
release of organisms during sampling from a system, addition of materials to
a system, transfer of cultivated cells, and removal of material, products,
and effluent from a system. |
Minimize Procedure K-II-F |
Minimize Engineer K-III-B K-III-D |
Prevent Engineer K-IV-B K-IV-D |
Prevent Engineer K-V-B K-V-D |
|
11. |
Treatment
of exhaust gases from a closed system to minimize or prevent release of
viable organisms. |
NR |
Minimize K-III-E |
Prevent K-IV-E |
Prevent K-V-E |
|
12. |
Closed
system that has contained viable organisms not to be opened until sterilized
by a validated procedure. |
NR |
K-III-F |
K-IV-F |
K-V-F |
|
13. |
Closed
system to be maintained at as a low pressure as possible to maintain
integrity of containment features. |
NR |
NR |
NR |
K-V-G |
|
14. |
Rotating
seals and other penetrations into closed system designed to prevent or
minimize leakage. |
NR |
NR |
Prevent K-IV-G |
Prevent K-V-H |
|
15. |
Closed
system shall incorporate monitoring or sensing devices to monitor the
integrity of containment. |
NR |
NR |
K-IV-H |
K-V-I |
|
16. |
Validated
integrity testing of closed containment system. |
NR |
NR |
K-IV-I |
K-V-J |
|
17. |
Closed
system to be permanently identified for record keeping purposes. |
NR |
NR |
K-IV-J |
K-V-K |
|
18. |
Universal
biosafety sign to be posted on each closed system. |
NR |
NR |
K-IV-K |
K-V-L |
|
19. |
Emergency
plans required for handling large losses of cultures. |
K-II-G |
K-III-G |
K-IV-L |
K-V-M |
|
20. |
Access
to the work place. |
NR |
G-II-A-1-a |
G-II-B-1-a |
K-V-N |
|
21. |
Requirements
for controlled access area. |
NR |
NR |
NR |
K-V-N&O |
NR = not required
Appendix K-VI-A. This table is derived from the text in
Appendices G (Physical Containment) and K and is not to be used in lieu
of Appendices G and K.
Appendix K-VI-B. The criteria in this grid address only the
biological hazards associated with organisms containing recombinant DNA. Other hazards accompanying the large-scale
cultivation of such organisms (e.g., toxic properties of products; physical,
mechanical, and chemical aspects of downstream processing) are not addressed
and shall be considered separately, albeit in conjunction with this grid.
Appendix
K-VII-A. Accidental Release. An accidental release is the unintentional
discharge of a microbiological agent (i.e., microorganism or virus) or
eukaryotic cell due to a failure in the containment system.
Appendix
K-VII-B. Biological Barrier. A biological barrier is an impediment (naturally
occurring or introduced) to the infectivity and/or survival of a
microbiological agent or eukaryotic cell once it has been released into the
environment.
Appendix
K-VII-C. Closed System. A closed system is one in which by its
design and proper operation, prevents release of a microbiological agent or
eukaryotic cell contained therein.
Appendix
K-VII-D. Containment. Containment is the confinement of a
microbiological agent or eukaryotic cell that is being cultured, stored,
manipulated, transported, or destroyed in order to prevent or limit its contact
with people and/or the environment.
Methods used to achieve this include:
physical and biological barriers and inactivation using physical or
chemical means.
Appendix
K-VII-E. De minimis Release. De minimis release is the release
of: (i) viable microbiological agents or eukaryotic cells that does not
result in the establishment of disease in healthy people, plants, or animals; or
(ii) in uncontrolled proliferation of any microbiological agents or eukaryotic
cells.
Appendix
K-VII-F. Disinfection. Disinfection is a process by which viable
microbiological agents or eukaryotic cells are reduced to a level unlikely to
produce disease in healthy people, plants, or animals.
Appendix
K-VII-G. Good Large Scale Practice
Organism. For an organism to
qualify for Good Large Scale Practice consideration, it must meet the following
criteria [Reference: Organization for
Economic Cooperation and Development, Recombinant DNA Safety Considerations,
1987, p. 34-35]: (i) the host organism
should be non-pathogenic, should not contain adventitious agents and should
have an extended history of safe large-scale use or have built-in environmental
limitations that permit optimum growth in the large-scale setting but limited
survival without adverse consequences in the environment; (ii) the recombinant
DNA-engineered organism should be non-pathogenic, should be as safe in the
large-scale setting as the host organism, and without adverse consequences in
the environment; and (iii) the vector/insert should be well characterized and
free from known harmful sequences; should be limited in size as much as
possible to the DNA required to perform the intended function; should not
increase the stability of the construct in the environment unless that is a
requirement of the intended function; should be poorly mobilizable; and should
not transfer any resistance markers to microorganisms unknown to acquire them
naturally if such acquisition could compromise the use of a drug to control
disease agents in human or veterinary medicine or agriculture.
Appendix
K-VII-H. Inactivation. Inactivation is any process that destroys
the ability of a specific microbiological agent or eukaryotic cell to
self-replicate.
Appendix
K-VII-I. Incidental Release. An incidental release is the discharge of a
microbiological agent or eukaryotic cell from a containment system that is
expected when the system is appropriately designed and properly operated and
maintained.
Appendix
K-VII-J. Minimization. Minimization is the design and operation of
containment systems in order that any incidental release is a de minimis
release.
Appendix K-VII-K. Pathogen.
A pathogen is any microbiological agent or eukaryotic cell containing
sufficient genetic information, which upon expression of such information, is
capable of producing disease in healthy people, plants, or animals.
Appendix
K-VII-L. Physical Barrier. A physical barrier is considered any
equipment, facilities, or devices (e.g., fermentors, factories, filters,
thermal oxidizers) which are designed to achieve containment.
Appendix
K-VII-M. Release. Release is the discharge of a
microbiological agent or eukaryotic cell from a containment system. Discharges can be incidental or accidental. Incidental releases are de minimis in
nature; accidental releases may be de minimis in nature.