Biosecurity:

How Export Controls impact the

Life Sciences

Betty Lee, Ph.D.

Chemical and Biological Controls Division
Bureau of Industry and Security
Department of Commerce
2nd International Conference on Systems and Synthetic Biology, Aug 18-20, 2016
London, UK
 TOPICS

• Definition of Biosecurity,
Dual Use Research, Multi-
Lateral Regimes

• Export Control as a tool for

Biosecurity

• Summary
 Biosecurity
• Defined as measures taken to limit the threats
posed by
• Pandemic outbreaks
• Theft of biological agents
• Bioterrorism

• Biosecurity is important for public health and the

agriculture industry
 Dual Use Research
‘Encompasses biological research with legitimate
scientific purpose, the results of which may be
misused to pose a biologic threat to public health
and/or national security’

www.biosecurityboard.gov/faq.asp#14.
 Publications of Dual Use
Research
natural template. Science. 297(5583):1016-1018.
• In 2002, researchers published the results of the synthetic
reconstruction of poliovirus (J.Cello, et al Science 297(5583):1016-
1018)

• Life Sciences is interdisciplinary-includes computational biology,

systems biology, nanotechnology and synthetic biology

• Dual use research can produce biological organisms and knowledge to

improve health or harm others

• Such research should not be prohibited but it requires increased

scrutiny (Biotechnology Research in an Age of Terrorism, National
Research Council, 2004)
 Biosecurity and
Non-Proliferation

Multilateral Regimes Dual Use Research

Control Lists Controlled Technology

Export
Control

Biosecurity and Non-

Proliferation
 Multilateral Regimes and
Export Control
• Australia Group (AG)-41 members and the EU
• Missile Technology Control Regime (MTCR)-35
members
• Nuclear Suppliers Group (NSG)-48 members
• Wassenaar Arrangement (WA)-41 members
 Emerging Technologies

• New Technologies may have dual use implications

e.g. Synthetic Biology, Gene Editing (CRISPR) ,
etc

• Biosecurity and Biosafety could be affected by

nefarious use of such technologies by terrorists
 Export Control as a Tool

• Impede the proliferation of Dual Use

Technologies by terrorists

• Enhance Biosecurity by controlling listed

pathogens and genetic elements for legitimate
uses

• Ensure that entities are vetted and not on Denied

Parties or Sanctions lists
 Chemical and Biological
Controls

• AG Common Control List-updated to include

emerging technologies

• US Commerce Control List-updated according to

the AG List
 Mission of BIS

Advance U.S. national security, foreign policy, and

economic objectives by ensuring an effective export
control and treaty compliance system and promoting
continued U.S. strategic technology leadership.
 Department of Commerce
Export Controls
• Commerce Control List (CCL)
• Dual-use biological material
• subject to BIS regulatory jurisdiction
• predominantly commercial/academic uses
• could also be used in military applications
• listed in the Export Administration Regulations (EAR)
by Export Control Classification Number (ECCN)
• May require export license
• Other Controls– USML (CAT XIV), OFAC
Biological Agents and Toxins
• 1C351 and 1C354
• Human, Animal and Plant Pathogens Australia Group (AG)
controlled -
• Select Agents not on the AG list are also controlled
• Select Agent (SA) exempt strains ARE controlled for export
• 1C353
• Genetic Elements for controlled agents/toxins
• Genetically Modified controlled organisms
• 1C991
• Vaccines if licensed or IND
• Medical toxins
• EAR99
• Killed pathogens with destroyed genetic elements
• Technology for vaccine production
 Current Control Language for Genetic
Elements and Genetically-Modified
Organisms:
• Genetic elements that contain nucleic acid sequences
associated with the pathogenicity of any of the
microorganisms in the list.
• Genetic elements that contain nucleic acid sequences coding
for any of the toxins in the list, or for their sub-units.
• Genetically-modified organisms that contain nucleic acid
sequences associated with the pathogenicity of any of the
microorganisms in the list.
• Genetically-modified organisms that contain nucleic acid
sequences coding for any of the toxins in the list or for their
sub-units.
 Genetic Elements and Genetically-Modified
Organisms

Technical note:
Nucleic acid sequences associated with the pathogenicity of any of
the micro-organisms in the list means any sequence specific to the
relevant listed micro-organism:
• that in itself or through its transcribed or translated products
represents a significant hazard to human, animal or plant health;
or;
• that is known to enhance the ability of a listed micro-organism, or
any other organism into which it may be inserted or otherwise
integrated, to cause serious harm to human, animal or plant health.
Genetic Element Exports
• Whole Nucleic acids – not controlled if
• Certified non-infective and chemically treated to be
non-recoverable
• Chimeric Viruses- controlled if
• Based on a controlled virus
• Has controlled virus element in non-controlled virus
• Plasmids - controlled if
• Promoter present
• Complete gene or Viral Particle
• Replication competent
 Chimeric Viruses
Ebola Virus
NP VP35 VP40 GP/SGP VP30 VP24 L

N P M G
GP/SGP L

Genetically modified Vesicular stomatitis virus

(controlled as genetically modified VSV)

If the Ebola Virus GP were incorporated into a non-

controlled virus, this would be still controlled as a genetic
element.
 Expression Plasmids

Controlled Plasmid (1C353) Non-Controlled Plasmid (EAR99)

pXX-hpai-HA pXX-hpai-HA

HA
promoter

HA from High-path Avian HA from High-path Avian

Influenza Influenza

HA + promoter = complete gene (replication Without the promoter, the

competent) element is not replication
competent
Intangible Technology Transfer (ITT) and
The Commerce Control List(CCL)
 Technology Definitions
• Definitions used in the EAR are consistent with the control
language used by the multilateral export control regimes.

• Intangible Technology Transfer (ITT): Controlled technology

that is transferred by
-Electronic means, email, telephone conversation, cloud access,
etc.
-Technical assistance-instruction : training, working knowledge,
consulting services.
 Technology Considerations
• Is the technology related to controlled biological processing
equipment?
• “Development”
• “Production”
• “Use”
• Is the technology related to manipulation of controlled
biologicals that is not public domain or fundamental
research?
• Where is the transfer taking place?
• Deemed export vs. tech transfer
 SUMMARY

• Export Control is one tool for maintaining Biosecurity and

Non-Proliferation

• Control lists are updated on an annual basis-items can be

added or deleted

• Multilateral regimes review emerging technologies for their

potential dual use implications
 Additional Information
BIS Biological Controls:
www.bis.doc.gov/index.php/policy-guidance/product-guidance/chemical-andbiological-controls

Deemed Export:
www.bis.doc.gov/index.php/policy-guidance/deemed-exports/deemed-exports-faqs

NIH DURC:
http://osp.od.nih.gov/office-biotechnology-activities/biosecurity/dual-use-research-concern

Regulation updates:
6/7/2016
81 FR 36458
Implementation of the February 2015 Australia Group (AG) Intersessional Decisions
and the June 2015 AG Plenary Understandings

6/3/2016
81 FR 35586
Revisions to Definitions in the Export Administration Regulations
 THANK YOU

Questions ?

Contact Information: Betty.Lee@bis.doc.gov

 Scenario 1

• Researcher working with Yellow Fever Virus

• Exports strain to colleague in Kenya for use in

vaccine production

• Foreign student in lab on different project

• Research increases Yellow Fever virulence

generating a monovalent vaccine candidate
 Scenario 2
• Researcher ships new YF strain to Kenya

• Foreign student (from Malaysia) is learning to

increase YF virus pathogenicity

• Colleague in Kenya asks for unpublished

methodology on increasing Yellow Fever
virulence
 Scenario 3

• Malaysian student becomes a permanent

resident. Additional student from Canada joins
lab learning manipulation techniques

• Paper on research is published. Researcher gets

request from multiple countries for the YF strain