Patrick J. Scannon, M.D., Ph.D.CSO, XOMAStanford University, October 2015

Technology Impact on Biosecurity Policy and Practice

“D.A. Henderson, Scientist Who Helped Eradicate Smallpox, Says U.S. Is Unprepared For Bioterrorism” Huffington Post , Feb 6, 2012

“California nurses go on strike over lack of Ebola preparedness” Fortune, Nov 11, 2014

Biosecurity - Technology - Public Policy Biosecurity (adapted from NIH): Taking appropriate

measures to address life sciences research (eg, human, animal, plant) with the potential to be misused to threaten public health or national security. 

Technology (adapted from Merriam Webster): the science of the application of knowledge to practical purposes – often building upon prior generations of science and technologies

Public Policy (adapted from study.com): the means by which a government maintains order or addresses the needs of its citizens, through actions defined by its constitution.

Biotechnology Advances over Past Ten Years: Faster, Cheaper, Mobile and Global

Many biotechnologic advances:• Accelerated research technologies: • Accelerated development technologies• Internet: Methodologies widely published

The Impact:• Good: Greater innovation, faster and cheaper• Bad: Greater innovation, faster and cheaper: non-state

rogues

Biosecurity: Animals – Plants – Humans

Recent Biosecurity-Related Topics in Medical News

Key Biosecurity Public Policy Questions to Ask:

What is/should be the United States’ overarching policy for biosecurity, even if not formally stated? And what role does Technology play?

Some Desirable Properties of Public Policy Forward looking and strategic guidance, ideally with declared

objectives, from government to its society - guidance has some reasonable/likely life span

Guidance results in enhancing society’s protection or well being Guidance anticipates scope Guidance acknowledges all processes necessary to meet

objectives Guidance should recognize required leadership Fiscally manageable and timely Guidance is directional but also adaptive

Can’t write Public Policy in a Vacuum

Written Here

Needed Here

Key Biosecurity Public Policy Concerns Management of concept of near-zero probability X high societal impact:

Many known, and perhaps more unknown, all rare biothreats: what is real and what is “crying wolf”? Fear tactics quickly tachyphylax audiences.

Some factors concerning biothreats: natural vs intentional vs accidental causes, disease toxicity/pathology/mortality, disease speed in affected host, ease of dissemination across populations, impact on health care system – how to prioritize across so many possibilities?

Prevention versus treatment strategies: when is each appropriate? Available resources – how much to allocate? Long lead times and big costs with new drug development – how to allocate

time? Disease boundaries do not respect State boundaries – how encompassing

should public policy be? Country-wide? Global? Role of technologies: often rapidly evolving – how to capture in public

policy?

Examples of Biothreats

Anthrax: October 2001 Intentional

Flu: 1997, 2005, 2011, 2015 &

ongoing Natural

Ebola: 2015 & Ongoing Natural

Examples of Post Event Comments

REGARDING THE “BIG ONE”

Missed that Bullet…

Hasn’t happened yet…..

What are the odds: won’t happen on my watch…

NIAID Category A, B, and C Priority PathogensCategory A Priority PathogensBacillus anthracis (anthrax)Clostridium botulinum toxin (botulism))Yersinia pestis (plague))Variola major (smallpox) and other related pox virusesFrancisella tularensis (tularemia))Viral hemorrhagic fevers

Arenaviruses Junin, Machupo, Guanarito, Chapare (new in fiscal year (FY) 14), Lassa, Lujo (new in FY 14)

Bunyaviruses Hantaviruses causing Hanta Pulmonary syndrome, Rift Valley Fever, Crimean Congo Hemorrhagic Fever

FlavirusesDengue

FilovirusesEbolaMarburg

Category B Priority PathogensBurkholderia pseudomallei (melioidosis)Coxiella burnetii (Q fever)Brucella species (brucellosis)Burkholderia mallei (glanders)Chlamydia psittaci (Psittacosis)Ricin toxin (Ricinus communis)Epsilon toxin (Clostridium perfringens)Staphylococcus enterotoxin B (SEB)Typhus fever (Rickettsia prowazekii)Food- and waterborne pathogens

Bacteria Diarrheagenic E.coliiPathogenic VibriosShigella species Salmonella Listeria monocytogenesCampylobacter jejuniYersinia enterocolitica

Viruses CalicivirusesHepatitis A

Protozoa Cryptosporidium parvumCyclospora cayatanensisGiardia lambliaEntamoeba histolyticaToxoplasma gondiiNaegleria fowleri (new in FY 14)Balamuthia mandrillaris (new in FY 14)

Fungi Microsporidia

Mosquito-borne encephalitis viruses West Nile virus (WNV) LaCrosse encephalitis (LACV)California encephalitisVenezuelan equine encephalitis (VEE)Eastern equine encephalitis (EEE)Western equine encephalitis (WEE)Japanese encephalitis virus (JE)St. Louis encephalitis virus (SLEV)

Category C Priority Pathogens

Nipah and Hendra virusesAdditional hantavirusesTickborne hemorrhagic fever viruses

Bunyaviruses Severe Fever with Thrombocytopenia Syndrome virus (SFTSV), Heartland virus

Flaviruses Omsk Hemorrhagic Fever virus, Alkhurma virus, Kyasanur Forest virus

Tickborne encephalitis complex flaviviruses Tickborne encephalitis virusesEuropean subtypeFar Eastern subtypeSiberian subtypePowassan/Deer Tick virus

Yellow fever virusTuberculosis, including drug-resistant TB Influenza virusOther RickettsiasRabies virusPrions Chikungunya virusCoccidioides spp.Severe acute respiratory syndrome associated coronavirus (SARS-CoV), MERS-CoV, and other highly pathogenic human coronaviruses (new in FY 14)Antimicrobial resistance

Pharma will not proceed for rare IDs without USG Funding: NIH, CDC, DoD

Biothreats From Any Direction

Not just on the NIAID Priority List

+

Global Realities Impacting Bioresponse Strategy

Diseases do not recognize national borders

Multiple Populations: Civilian (children, elders, immunocompromised), Military

Inability to stockpile vaccines/therapies for all possible disease

US Strategic National Stockpile (SNS): STRATEGIC CHALLENGES

Public Policy Requires Many Inputs for Cohesive Integration and Implementation

TECHNOLOGIES

TIME

DEMAND

INTEGRATION:Public Health Dept

Hospitals1st Responders

…

PRIORITIZATION

EFFECTIVEPUBLIC POLICY

DISEASE(S)

Possible Barriers to the Inclusion of Transformational Technology into Policy

Only one of many variables which need integration Policy Makers may not recognize what is reasonable to

request Technologies “move too fast” – when is good, good

enough?• Proven “Bird in the Hand” technologies: ready to go• Unproven “Birds in the Bush” – what are risks?

Time/cost to develop and implement new technologies

RESULT: Potential default to existent technologies which MAY not meet Policy Objectives – modify objectives?

Can or should Technology affect Public Policy? Can or should Public Policy affect Technology?

Consider impact, cost, timing of increasing mfg capacity(10x mfg cGMP capacity), yield (10x vaccine/liter from fermenter), potency (1/10 dose)/person.

Technologies Encompass the Entire Biosecurity Path Rapid and distributed detection systems

Rapid Discovery of new vaccines (prevention) and therapeutics (treatment)

Development

Manufacturing Clinical Trials

Regulatory

FDA approval

Distribution

Administration to Patients

Technical Impacts at Each Step: Speed, Scale, Safety, Efficacy, Cost

From Another Angle: Same Need for Technology

Bill Gates, N Eng J Med, 372;15 April 9, 2015

Getting to Some Answers

What makes a rare biothreat disease “bad” for society?

• Mortality: 0% or 100% for individual, variable % for society• High Morbidity: overwhelming the health care system, eg,

ventilators, isolation units, trained personnel (3 shifts)• Contagiousness: high transmission (plague, smallpox) vs low

transmission (anthrax)• Lack of existent prevention and treatment

Example 1: Disease Transmission, independent of disease, May Affect Policy

Example 2: Disease Morbidity, independent of disease, May Affect Policy

Disease Profiles, independent of disease, May Affect Policy

High transmission x high morbidity

High transmission x low morbidity

Low transmission x high morbidity

Low transmission x low morbidity: probably not a meaningful societal threat

Necessary But Not Sufficient: How are bioresponses affected?

Possible Profile Categories – each with different impact

Different Disease Categories Suggest Different Medical (Technical) Responses Concept: Diseases with high transmission and

substantial morbidities affecting large populations, especially where time is critical, may be best addressed by a “bioresponse” prevention plan which includes novel vaccines

Complementary Concept: Diseases with low transmission and substantial morbidities may be more practically approached by a “bioresponse” treatment plan which includes novel therapeutics

Impact of Technology: Two Scenarios for a highly contagious, high morbidity pathogen

Scenario 1: Previously unknown pathogenNo vaccine or therapy known

Scenario 2Known pathogenExistent vaccine

The “Simple Case”: Scenario 2 Options

In Place Vaccine but Stores Insufficient 10X10,000 L bioreactors available 1 microgram dose, single vaccine (no booster

required) Availability 1: 100 million doses given by shot

Availability 2: 1 billion doses given by pill

How extensive would the public policy be for each?

Policy concerns (inversely proportional to number of doses and route of administration)

100,000,000 doses IM Prioritization for

administration (eg, first responders, elderly, children, military)

Availability of 100,000,000 needles, syringes and sufficient cold storage

Availability of hospitals, MDs, technicians….

1 billion doses PO Deliver everywhere

ASAP Make available to ROW

Conceptual Public Policy Bifurcation for Different Biothreats:

Disease Transmission x Morbidity

Requirement for Rapid Response

High Transmission x High Morbidity

Low Transmission x High Morbidity

Technology Implications:•Identification/Detection•Rapid Vaccine Development•Medical Supportive Care: Quantity + Quality•Distribution/Administration

Technology Implications:•Identification/Detection•Rapid Therapy Development

Current focus appears to be on categories of diseases (eg, NIAID, CDC, CDC/USDA select agent/toxin listings) and specific diseases within.

Alternatively, “USG bioresponses to disease” driven by disease profile and technology, rather than disease specifics, may beneficially impact USG response, eg, vaccine, therapy and relative funding to support different scenarios.

USG’s Overarching Biosecurity Policy?

Pathogen

Response in place eg, SNS

No Response in place, eg, new

High Transmission, High Morbidity, eg, pandemic

Low Transmission, High Morbidity, eg, containable

Vaccine Therapy, eg, siRNA, mAb

Technology-Driven Bioresponse to Pathogen Profile Provides Direction

Key Biosecurity Public Policy Questions to Ask:

What is/should be the United States’ overarching policy for biosecurity, even if not formally stated? And what role does Technology play?

Who is in charge? And do the involved departments know what the other departments’ responsibilities are?

Multiple Federal Agencies Are Involved: But who should be in charge of biosecurity?

Key Biosecurity Public Policy Questions to Ask:

What is the United States’ overarching policy for biosecurity? And what role does Technology play?

Who is in charge? And do the involved departments know what the other departments’ responsibilities are?

What does it take to be ready?

Preparing for unknown biothreats: Where to Start?

First, recognize and accept such biological threats can happen anywhere and anytime: natural, accidental, intentional

Assess our limitations on global scale, and determine which are addressable by investments in technology: • Timely Biothreat identification• Current Bioresponse Capabilities/ Capacities• Public health care and logistical response structures – not made for rapid

and large scale emergencies Develop Overarching Biosecurity Public Policy as broadly as

practical: • Top down leadership with long term commitment• Greater communication nationally and internationally • Large and distributable technology platforms adaptable for rapid

implementation when needed

Progress into Preparedness

“An epidemic is one of the few catastrophes that could set the world back drastically in the next few decades. By building a global warning and response system, we can prepare for it and prevent millions of deaths.” Bill Gates, N Eng J Med, 372;15 April 9, 2015

An example of an Overarching Biosecurity Public PolicyStatement

My Viewpoint

Responses cannot be developed for questions not asked. Biosecurity Public Policy makers should not permit public policy to be driven solely by present day technologies but, rather, must create the needed vision in order to challenge technologists to address biothreats both today and tomorrow.

An Adaptable Strategy for Addressing Unknown Biothreats on a Global Scale Depends on

Technology Advances and Leadership at Every Step

Cooperative communication network

Early-warning biosurveillance

Public Health response system for pandemics

(Global)Vaccine/Therapy response plan

Response plan for unknown biothreats

International Cooperation of governments, policymakers, public health

systems, industry and academia

Prepared for the Unknown on Global Scale