Avian Flu: a Global PerspectiveAvian Flu: a Global Perspective

Peter D. Rumm, MD, MPHPeter D. Rumm, MD, MPHDeputy Director, DGRND, FDA, DHHSDeputy Director, DGRND, FDA, DHHS

Peter.Rumm@FDA.HHS.GOVPeter.Rumm@FDA.HHS.GOV

GoogleGoogle™™ Search: World Preparedness for Search: World Preparedness for Pandemic Flu – about 1,190,000 ResultsPandemic Flu – about 1,190,000 Results

• WHO | Pandemic preparedness In the 20th century, the greatest influenza pandemic occurred in 1918 -1919 and caused an estimated 40–50 million deaths world wide. ...www.who.int/entity/csr/disease/influenza/pandemic/en/index.html - 25k - Cached - Similar pagesWHO | Avian influenza frequently asked questions

• Despite an advance warning that has lasted almost two years, the world is ill-prepared to defend itself during a pandemic. WHO has urged all countries to ...www.who.int/csr/disease/avian_influenza/avian_faqs/en/index.html - 42k - Cached - Similar pagesMore results from www.who.int

• President Outlines Pandemic Influenza Preparations and Response The website will keep our citizens informed about the preparations underway, ... There is no pandemic flu in our country or in the world at this time -- but ...www.whitehouse.gov/news/releases/2005/11/20051101-1.html - 45k - Cached - Similar pages

• Life Sciences & Health Care - Business Preparations - Pandemic Flu ... Business Preparations for Pandemic Flu. Survey finds concern, uncertainty among US employers. Business Preparations for Pandemic Flu ...www.deloitte.com/dtt/research/0,1015,sid%253D42469%2526cid%253D107442,00.html - 52k - Cached - Similar pages

Avian flu "the next emerging disease" to Avian flu "the next emerging disease" to threaten humans and worldthreaten humans and world

Humanity risks being overrun by diseases from the animal world, according to researchers who have documented 38 illnesses that have made that jump over the past 25 years.

There are 1,407 pathogens -- viruses, bacteria, parasites, protozoa and fungi -- that can infect humans, according to Mark Woolhouse of the University of Edinburgh in Scotland.

Of those, 58% come from animals. Scientists consider 177 of the pathogens to be "emerging" or "re-emerging," although most will never cause pandemics.

However, experts fear bird flu could prove an exception as recent advances in the worldwide march of the H5N1 strain have rekindled fears of a pandemic. The virus has spread across Asia into Europe and Africa in recent months.

• http://www.24dash.com/content/news/viewNews.php?navID=47&newsID=3256 (Feb 22, 2006)

Avian Flu – an epidemic of birds Avian Flu – an epidemic of birds with human sufferingwith human suffering

• Since late 2003, avian influenza has been devastating to several countries in SE Asia, where over 140 million chickens and ducks have died from the disease or have been culled.

• The economies of those countries have suffered greatly, with lost revenue estimated at over US$10 billion. In the affected countries, 200 million depend on poultry for their livelihoods and nearly 80% of the population live in rural areas. [FAO, Director, 11/05]

Estimated minimal costs of Estimated minimal costs of controlling the avian virus in poultrycontrolling the avian virus in poultry

Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO20 June 2006

Country 

2003 2004 2005 2006 Total

cases deaths cases deaths cases deaths cases deaths cases deaths

Azerbaijan 0 0 0 0 0 0 8 5 8 5

Cambodia 0 0 0 0 4 4 2 2 6 6

China 0 0 0 0 8 5 11 7 19 12

Djibouti 0 0 0 0 0 0 1 0 1 0

Egypt 0 0 0 0 0 0 14 6 14 6Indonesia 0 0 0 0 17 11 34 28 51 39

Iraq 0 0 0 0 0 0 2 2 2 2

Thailand 0 0 17 12 5 2 0 0 22 14

Turkey 0 0 0 0 0 0 12 4 12 4

Viet Nam 3 3 29 20 61 19 0 0 93 42Total 3 3 46 32 95 41 84 54 228 130Total number of cases includes number of deaths.

Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO19 September 2006

Country 

2003 2004 2005 2006 Total

cases deaths cases deaths cases deaths cases deaths cases deaths

Azerbaijan 0 0 0 0 0 0 8 5 8 5

Cambodia 0 0 0 0 4 4 2 2 6 6

China 1 1 0 0 8 5 12 8 21 14Djibouti 0 0 0 0 0 0 1 0 1 0

Egypt 0 0 0 0 0 0 14 6 14 6

Indonesia 0 0 0 0 19 12 46 37 65 49

Iraq 0 0 0 0 0 0 3 2 3 2

Thailand 0 0 17 12 5 2 2 2 24 16Turkey 0 0 0 0 0 0 12 4 12 4

Viet Nam 3 3 29 20 61 19 0 0 93 42

Total 4 4 46 32 97 42 100 66 247 144

Peak of Human Outbreak was 2 years agoPeak of Human Outbreak was 2 years ago

• An outbreak of highly pathogenic avian influenza A (H5N1) spread to poultry in 9 Asian countries. H5N1 infections caused >52 human deaths in Vietnam, Thailand, and Cambodia from January 2004 to April 2005. Genomic analyses of H5N1 isolates from birds and humans showed 2 distinct clades with a nonoverlapping geographic distribution. All the viral genes were of avian influenza origin, which indicates absence of reassortment with human influenza viruses.

• All human H5N1 isolates tested belonged to a single clade and were resistant to the adamantane drugs but sensitive to neuraminidase inhibitors. Most H5N1 isolates from humans were antigenically homogeneous and distinct from avian viruses circulating before the end of 2003.

• Some 2005 isolates showed evidence of antigenic drift. An updated nonpathogenic H5N1 reference virus, lacking the polybasic cleavage site in the hemagglutinin gene, was produced by reverse genetics in anticipation of the possible need to vaccinate humans [EID, Vol. 11, No. 10October 2005]

WHO RoleWHO Role

• WHO is coordinating the global response to human cases of H5N1 avian influenza and monitoring the corresponding threat of an influenza pandemic

Global Outbreak Alert & Response Global Outbreak Alert & Response NetworkNetwork

• The Global Outbreak Alert and

Response Network (GOARN) is a technical collaboration of existing institutions and networks who pool human and technical resources for the rapid identification, confirmation and response to outbreaks of international importance.

• The Network provides an operational framework to link this expertise and skill to keep the international community constantly alert to the threat of outbreaks and ready to respond.

The World Health Organization Global The World Health Organization Global Influenza Program Surveillance NetworkInfluenza Program Surveillance Network

• The WHO Global Influenza Surveillance Network was established in 1952. The network comprises 4 WHO Collaborating Centres (WHO CCs) and 116 institutions in 87 countries, which are recognized by WHO as WHO National Influenza Centres (NICs).

• These NICs collect specimens in their country, perform primary virus isolation and preliminary antigenic characterization. They ship newly isolated strains to WHO CCs for high level antigenic and genetic analysis, the result of which forms the basis for WHO recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year.

WHO Announcement – a country in WHO Announcement – a country in conflict faced a new threatconflict faced a new threat

• 19 September 2006 • The Ministry of Health in Iraq has retrospectively confirmed the

country’s third case of human infection with the H5N1 avian influenza virus. The case, a 3-year-old boy, was hospitalized in Baghdad on 15 March 2006. His illness was mild and he fully recovered.

• During its outbreak, which is now considered over, Iraq faced problems in the shipment of specimens for external verification of diagnostic tests.

• For the retrospectively confirmed case, initial test results were inconclusive, possibly as a result of sample deterioration during shipment. Repeated testing, using different methods, was needed for diagnostic confirmation.

• The two cases previously confirmed in Iraq occurred in January 2006. Both cases were fatal.

Most discussed scenario - Kubu Most discussed scenario - Kubu Sembelang Sembelang

• Indonesia, June 2006: WHO reported evidence of human-to-human spread. In this situation, 8 people in one family were infected. The first family member (37 y/o female) is thought to have become ill through contact with infected poultry (not confirmed). This person then infected six family members.

• One of those six people (a child) then infected another family member (his father). Much of the investigation was done by a combined WHO/CDC team. No further spread outside of the exposed family was documented or suspected.

• http://www.cdc.gov/flu/avian/outbreaks/current.htm#assess

WHO Model PlanWHO Model Plan

• Released August 2005: – Responding to the Avian Influenza Threat -

recommended strategic actions

• http://www.who.int/csr/resources/publications/influenza/WHO_CDS_CSR_GIP_05_8-EN.pdf#search=%22country%20plans%2C%20avian%20influenza%22

The Five WHO Strategic GoalsThe Five WHO Strategic Goals

• Reduce opportunities for human infection• Strengthen early warning systems• Contain or delay spread at the source• Reduce morbidity, mortality and social

disruption• Conduct research to guide response

measures

Last three situational assessmentsLast three situational assessments

• Early warning system is weak• Preventive intervention is possible but

untested• Reduction of mortality and morbidity will

be impeded by inadequate medical supplies.

Global Strategy for the Progressive Control of Highly Global Strategy for the Progressive Control of Highly Pathogenic Avian Influenza (HPAI)Pathogenic Avian Influenza (HPAI)

• Published in May 2005 by the Food and Agriculture Organization (FAO, Rome) and the World Organization for Animal Health (Office International des Epizooties - OIE, Paris) in collaboration with the World Health Organization (WHO, Geneva).

• This 85-page document details a strategy for controlling highly pathogenic avian influenza (HPAI), worldwide. It draws on recommendations made during the 2nd FAO/OIE Regional Meeting on Avian Influenza Control in Asia (February 2005) held in Ho Chi Minh City, Vietnam and was prepared in consultation with key partners from Asia

Time PeriodsTime Periods

• Specifically, the resource (since updated with some appendices) provides approaches and implementation plans for the global control of avian influenza, which will be implemented over 3 time frames: immediate to short (1-3 years), short to medium (4-6 years) and medium- to long-term (7-10 years). This process will be carried out at various levels

Levels - NationalLevels - National• A typical country-specific project will adopt a task-force

approach, guided by a national steering committee, which will comprise key decision makers and stakeholders and may include national experts, research institutes, non-government organizations (NGOs) and the private sector.

• A key focus here is on improving capacity at the national level in diagnosis, epidemiology, disease surveillance, and early detection and reporting and disease information systems (which will "provide better analytical capacity to enable the country to participate in disease information sharing within the region, thereby contributing towards progressive regional control and eradication.")

Regional LevelRegional Level

• Establishment of coordination units - networks - that will promote open and transparent dialogues on improved disease information sharing, standardization and regulatory frameworks for the management of animal movement and the control of trans boundary animal diseases (TADs), and adherence to OIE guidelines to facilitate regional trade.

Update: Since May 2005Update: Since May 2005

• Goals of no spread to Indonesia have not been met

• However, a project called the GLEWS is coming along.

The Global Early Warning System for Animal The Global Early Warning System for Animal

Diseases (GLEWS) including ZoonosesDiseases (GLEWS) including Zoonoses • The Food and Agriculture Organization of the UN (FAO),

OIE (World Organization for Animal Health) and WHO are currently developing the GLEWS as a joint system that builds on the added value of combining and coordinating the alert and response mechanisms of the three organizations.

• The response component of the GLEWS is being established and will be complementing the existing response systems of FAO, OIE, and WHO in order to deliver rapid coordinated international response to animal disease emergencies

Area of Current Greatest Risk – Area of Current Greatest Risk – Asia/Indonesia and S. PacificAsia/Indonesia and S. Pacific

• Asia to date has accounted for 122/144 deaths. There is been a lot of focus on China and Central Indonesia but concern is mounting about smaller islands.

• The World Health Organization (WHO) on 9/19/06 urged small Pacific islands nations to do more to prepare emergency plans for a possible bird flu outbreak and human influenza pandemic, warning no nation could be immune.

Some Individual Country and Some Individual Country and Collective Partnerships in the EastCollective Partnerships in the East

• Australia has sent teams of epidemiologists and purchased 50,000 doses of Tamiflu for Indonesia [Xinhua, 2/2006)

• Singapore is considered to have one of the most advanced plans in the world and has stockpiled Tamiflu for 10% of its population. [Bloomberg News, 9/2005]

• China is actively subsidizing research and vaccine production capabilities.

Asian Tracking by WHO (Clades)Asian Tracking by WHO (Clades)

• Asian lineage HPAI A(H5N1) is divided into two antigenic clades. "Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia.

• Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa.

• The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO.

• Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections:– Subclade 1, Indonesia – Subclade 2, Middle East, Europe, and Africa – Subclade 3, China

Status of rest of world’s Status of rest of world’s surveillance – European Unionsurveillance – European Union

• Surveillance of sick and dead birds (wild and domestic) for highly pathogenic avian influenza (HPAI) is particularly strong.

• This mechanism in 2006 monitored the extension of the H5N1 virus from the East in wild birds including non-migratory species in 13 countries.

• Some domestic poultry have also been infected. Surveys of healthy wild birds in the EU have so far indicated that H5N1 infection is very rare [https://cms.bmaa.gv.at/up-media/2365_ec_regional_response.pdf ].

Africa – the forgotten continent?Africa – the forgotten continent?• Surveillance in Africa is especially weak, but there is

evidence of widespread infection in domestic poultry in parts of north, west and central Africa.

• Prospects of control are bleak there because of weaknesses in veterinary services, and a number of competing animal and human health problems.

• There is little evidence that migratory birds are playing a big role in transmission here: trade and movement of poultry, has been and is likely to be the most important driver [media/2368_thailand.pdf https://cms.bmaa.gv.at/up-media/2382_african_union.pdf}

• Sudan reports bird flu outbreak14/09/2006 08:43  - (SA News Service)  

Bird flu found in Sudan: SA to do bird flu tests

Juba - Authorities in autonomous southern Sudan said on Wednesday that they had confirmed an outbreak of the H5N1 strain of bird flu in poultry, with two other suspected cases of the virus potentially fatal to humans.

Louis Morris Kyanga of south Sudan's ministry of animal resources and fisheries said the tests confirmed that several chickens from a residential backyard in the southern Sudanese capital of Juba had died from H5N1 on August 03.

Why do some scientists consider Why do some scientists consider Africa at high risk?Africa at high risk?

• Concentration of poverty• War and civil unrest• Burden of HIV/AIDS in some countries• Regional partnerships may “protect” other

parts of the world

A sample concernA sample concern“ That AH5N1 has now been found in Africa is particularly

frightening. I would think it would be appropriate for the U.S. government and the other European Economic Community players to declare some kind of emergency program to do more comprehensive sentinel surveillance in Africa and see what's happening beyond the commercial farms in which AH5N1 has been found. And that means mobilizing funds as well as people.” [Harvard Public Health Review spoke with the Harvard School of Public Health's Max Essex, the John LaPorte Given Professor of Infectious Diseases]

Early Surveillance of a Human Early Surveillance of a Human Case AfricaCase Africa

• “In Africa, diagnosing that a villager has died from avian flu would be a lot harder than in Turkey, Thailand, and China, for example, because there are fewer medical experts and so, fewer chances that AH5N1 would be suspected and investigated as a cause of death. And so I would not in any sense rule out that people have already been infected with the virus in Africa--even dozens of them. I think that's a very likely possibility.”

Once potential source of infectionOnce potential source of infectionExperts divided in role of the flyways in

transmission.When evaluating the risks of migratory

birds spreading the HPAI H5N1 virus, many factors must be taken into account. There is considerable variation between species susceptibility and response to any given disease.

This, combined with the different behaviors, ecology, geography, migratory pathways, and interactions among and between species, presents a very complex picture of avian influenza and associated risks for spread via migratory birds.

For more information about wild birds and H5N1, see ProMED-mail, June 25, 2005 (http://www.promedmail.org, archive 20050625.1786)

Efforts to strengthen warning Efforts to strengthen warning systems - GAINSsystems - GAINS

• In an effort to improve the tracking of avian influenza, the United States Agency for International Development (USAID) has awarded $5 million in support for a new initiative that will monitor wild bird populations for the disease around the globe, according to the New York-based Wildlife Conservation Society (WCS), which will spearhead the project involving more than a dozen private and public partners.

• Called the Global Avian Influenza Network for Surveillance (GAINS), the initiative has also received an additional $1 million from the Centers for Disease Control (CDC) to continue global monitoring and surveillance efforts underway by WCS and its network of partners.

GAINSGAINS• Many migratory species nest thousands of miles

from where they spend the winter, and it is difficult to determine which groups come from which areas, said Dr. John Takekawa, one of the wild swan study scientists, who is with the USGS Western Ecological Research Center in California.

• "We are marking swans with very small GPS transmitters that are similar to navigation systems on cars, but that also transmit the data through weather satellites so we can track their movements."

GAINSGAINS

US Funding to Assist World EffortUS Funding to Assist World Effort

• President Bush requested and got approved $7.1 billion in emergency funding to immediately begin implementing a national strategy for pandemic influenza. This funding includes $251 million to detect and contain outbreaks before they spread around the world.

• The United States is implementing the $25 million that the President earlier signed in an emergency supplemental to prevent and control the spread of avian influenza in Southeast Asia

• . . . in addition to providing more than $13 million in technical assistance and grants to affected countries in Southeast Asia and to the World Health Organization for influenza pandemic preparedness in the past year. [http://www.pandemicflu.gov/global/]

USAIDUSAID

• USAID has provided foreign assistance for AI activities in 46 countries and has allocated $158 million in assistance and grants to affected and at-risk countries and to WHO, FAO, and private sector partners for pandemic preparedness and response in the past year. [http://usinfo.state.gov/usinfo/Archive/2006/Feb/23-495816.html]

Six Focus AreasSix Focus Areas

• Surveillance - USAID is supporting animal and human surveillance efforts in Asia and the Near East, Europe and Eurasia, Africa, and Latin America and the Caribbean. The Agency is working with host governments, NGOs, and private sector and international partners to enhance the ability of affected countries to rapidly detect H5N1 outbreaks in animals and humans by supporting community-level early warning networks

Planning and PreparednessPlanning and Preparedness

• USAID is supporting multi-sectoral national planning and preparedness efforts for AI control and outbreak response in each of its regions and is focused on strengthening human disease surveillance systems and laboratories. In collaboration with WHO, FAO, and other partners, USAID is working with governments to develop and support national AI task forces and preparedness plans in 46 countries

Outbreak ResponseOutbreak Response• USAID is funding international animal and human H5N1

response efforts. On the animal side, these funds are used to support efforts for better culling and disposal procedures and for better biosecurity practices in poultry-raising settings in 20 countries.

• On the human side, USAID provides support in nine countries for commodities such as diagnostic equipment; training in case management and infection control procedures for health facilities; and assistance in developing procedures for health facilities at the central and peripheral levels

Commodity StockpileCommodity Stockpile• USAID is building a global stockpile of 1.5 million

sets of personal protective equipment (PPE) and 15,000 decontamination kits for rapid deployment to those responding to AI outbreaks.

• To date, USAID has deployed more than 65,625 PPE sets for first responders to outbreaks in 54 countries in Asia and the Near East, Europe and Eurasia, and Africa.

• The Agency also provides technical assistance for AI control and is deploying kits for proper sample collection and transport to laboratories for verification of H5N1

CommunicationsCommunications

• USAID is supporting AI-related communications and public outreach activities in 34 countries and in global programs.

• The Agency is working with private partners, NGOs, and local governments to develop communications strategies and campaigns in each region.

Rapid ResponseRapid Response

• USAID has set aside funds for emergency rapid response and management to address outbreak situations throughout the world

DOD/GEIS ProgramDOD/GEIS Program• The DoD Influenza Surveillance Program is a laboratory based

influenza surveillance program that was begun in 1976 as Project Gargle under the direction of the Air Force (AF) Surgeon General.

• The goals of the program are threefold: (1) detect local respiratory outbreaks; (2) provide isolates to the World Health Association (WHO); (3) detect emerging strains.

• There are 19 AF sentinel bases (9 stateside, 3 Europe, 7 Asia) and additional sites that have been established in cooperation with the Army and the Navy. These include sites located at a travel clinic in Nepal, the Kwai River Christian Hospital on the Thai-Burmese border, and at Lima, Peru.

• At Walter Reed Army Institute of Research the Army oversees 6 oversees laboratories and advanced virology testing under the Global Emerging Infectious Disease Surveillance System (GEIS) that is being integrated into the larger DOD program.

Food and Drug AdministrationFood and Drug Administration

• Recent events our Center has been involved with include:– Input into a family leave program that is changing

rules to provide coverage for pandemics.– Creation of a database of codes and contacts of

manufacturers to draw on emergency supplies for disasters.

– New rules to allow employees to work from home in a pandemic and to develop IT capacity to enhance this.

Testing: FDA and CDCTesting: FDA and CDC

HHS' Food and Drug Administration (FDA) today (Feb 6, 2006) announced the approval of a new laboratory test to diagnose H5 strains of influenza in patients suspected to be infected with the virus.

The test was developed by another HHS agency, the Centers for Disease Control and Prevention (CDC).

The product approved today is called the Influenza A/H5 (Asian lineage) Virus Real-time RT-PCR Primer and Probe Set. The test provides preliminary results on suspected H5 influenza samples within four hours once a sample arrives at the lab and testing begins. Previous testing technology would require at least two to three days to render results. If the presence of the H5 strain is identified, then further testing is conducted to identify the specific H5 subtype (e.g., H5N1).

Rule Making and Regulatory Rule Making and Regulatory GuidanceGuidance

“The Food and Drug Administration today (March 20, 2006) published a proposed final rule to prohibit the extra label use in poultry of two classes of approved human antiviral drugs in treating influenza. FDA is taking this measure to help preserve the effectiveness of these drugs for treating or preventing influenza infections in humans.

Specifically, the order prohibits the extra label use by veterinarians of anti-influenza adamantane (amantadine and rimantadine) and neuraminidase inhibitor (oseltamivir and zanamivir) drugs in chickens, turkeys, and ducks. Extra label use is the actual use or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling.”

Public AdvisoriesPublic AdvisoriesFDA: Bird flu 'remedies' not so helpfulBy Audrey Gruber and Randi Kaye

CNNWednesday, May 24, 2006; Posted: 12:37 p.m. EDT (16:37 GMT)

SPECIAL REPORT NEW YORK (CNN) -- Type "avian flu" or "bird flu" into an Internet

browser, and you will find Web sites selling "generic Tamiflu," herbal cures, and many other ways to fight the illness.

But these products offer little protection against the H5N1 virus that causes bird flu, federal health officials say.

"None of them have any scientific evidence to show that they are safe and effective for the treatment of bird flu," said David Elder, director of enforcement at the U.S. Food and Drug Administration.

Contain or delay spread at its Contain or delay spread at its source – best option is vaccinesource – best option is vaccine

• In an ideal world we would have a vaccine and it would not have to be a perfect match to most likely help contain a pandemic.

• Some encouraging computer simulation results show that advance preparation of a modestly effective vaccine in large quantities appears to be preferable to waiting for the development of a well-matched vaccine.

"Because it is currently impossible to predict which of the diverging strains of avian H5N1 influenza virus is most likely to adapt to human transmission, studies of broadly cross-reactive avian-influenza based vaccines with even modest immunogenicity in humans are important," Ideally, both vaccine strategies would be done in parallel. Our models show that if we could stockpile a modestly effective vaccine to use while the better matched one is being developed, we could abate many outbreaks in countries of the world”. (Macken J, Los Almos National Laboratory, April 3, 2006)

New WHO Document – Vaccine New WHO Document – Vaccine DevelopmentDevelopment

• Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as pre-pandemic vaccines, 8-18-2006

• http://www.who.int/csr/disease/avian_influenza/guidelines/recommendationvaccine.pdf

BarriersBarriers

• Progress is needed on three fronts. First, countries experiencing outbreaks need to rapidly share human and animal viruses with laboratories in the WHO Global Influenza Surveillance Network. Analysis of these viruses determines the possible need for changes in the prototype vaccine “seed” strains which WHO makes available to the pharmaceutical industry.

• Second, companies need to engage in research on pandemic vaccine development that includes pilot production of small batches for clinical testing. National licensing agencies in Europe and North America have developed regulatory guidelines for industry.

BarriersBarriers• Third, public health agencies need to engage in discussions with

pharmaceutical companies to explore areas of common interest in vaccine development and identify areas where support is needed. Since 2003, when two cases of human H5N1 infection occurred in Hong Kong SAR, WHO has worked to identify and resolve problems in order to pave the way for rapid development and production of a pandemic vaccine.

• Vaccine manufacturers respond to market forces. Companies may be reluctant to produce a vaccine for an event, such as a pandemic, that cannot be predicted with any certainty and might not be caused by currently circulating strains. Some uncertainty has also centered on rights to use the special technique of reverse genetics, a patented procedure, that is needed to produce the prototype “seed” vaccine against H5N1.

Progress on a vaccineProgress on a vaccine

• Under NIH Funding researchers at Johns Hopkins have protected ferrets and mice with a live attenuated vaccine in phase one trials. [http://www3.niaid.nih.gov/news/newsreleases/2006/fluvax9_06.htm]

• Chinese researchers have developed a low dosage vaccine that showed considerable promise in Phase I trials [Lancet: 9/7/06]

ApproachesApproaches

• Changing technology from cell culture to genetic

• Use of Adjuncts• Ramping up production capability• Regulation of manufacturing capacity

Harmonizing RegulationHarmonizing Regulation

• Currently, the situation calls for individual regulation of pandemic vaccines that are in clinical trial.

• For example, the FDA, European Medicines Agency, and the Pharmaceutical and Medical Devices Agency (Japan) have to approve vaccines for their jurisdictions and usually require their own clinical trials.

Current situationCurrent situation

• Most other countries accept FDA trials but not vice – versa.

• The FDA is working through HHS and international partners to work to study feasibility of accepting foreign trials. Benefits would also incur during annual flu seasons.

• Currently, the FDA has developed a Rapid Response Team to evaluate and encourage the development of safe and effective vaccines and look at coordinating with other countries. [FDA 10.2005]

Current SituationCurrent Situation• FDA has issued regulatory guidance on vaccines that

would need regulatory review as a new product, depending on similarity to current methods.

• Europe has the potential problem of requiring special approval of “reverse engineered” vaccines, and the problem of upgrading laboratory facilities for genetic vaccines. Would also most likely require any vaccine to be considered a new product.

• Issues in any country to be over-come include those of intellectual property, cost for developing countries and sharing of the vaccine to areas that need it most. These could over ride other concerns to abate an epidemic.