Select Committee on Defence Appendices to the Minutes of Evidence


APPENDIX 9

Memorandum submitted by Acambis Plc (April 2002)

EXECUTIVE SUMMARY

  Acambis Plc has been asked by the Defence Select Committee to submit evidence on the issue of public health defences that can be put in place to protect against a bioterrorist attack using smallpox. Acambis is well placed to provide information on this subject as it has been selected by the US government to provide the principal medical countermeasure that the United States will use to protect its population against the threat posed by smallpox.

  However, Acambis is prevented from commenting on the detail of the UK procurement of smallpox vaccine as it is bound by confidentiality agreements with both the Ministry of Defence and the Department of Health.

  This submission makes several key assertions:

    —  The threat of a bioterrorist smallpox attack is a low probability but high consequence event that is considered credible and possible.

    —  Vaccine was proven effective to the point of eradicating the (endemic) natural-disease from the planet. Vaccination is the only medical countermeasure solution to smallpox. There is no proven therapeutic agent. We therefore applaud the UK government's decision to increase the UK's supply of smallpox vaccine.

    —  Governments around the world, concerned about the threat from smallpox, are considering following their historical reliance on vaccination and the lead taken by US to protect every one of their citizens.

    —  There is no difference in efficacy in preventing smallpox between the two strains recommended by the World Health Organisation (WHO) and most widely used to eradicate endemic smallpox during the vaccination programmes (Lister and NYCBH).

    —  We are not aware of any published data questioning the efficacy of the NYCBH strain against any of the smallpox strains. In fact, specific data indicate that it was highly effective in all of the worldwide programs in which it was actively used to control the disease.

    —  There is evidence that, because of its lower pathogenicity, the NYCBH vaccine strain is less harmful to recipients than Lister.

    —  It is critical that any new smallpox vaccine be fully clinically tested to ensure that, in improving the manufacturing process from an animal-based system to cell-culture, it has retained its key properties relating to safety, efficacy and consistency.

    —  Acambis' vaccine for the US government, based on the NYCBH strain, is being fully tested in extensive clinical trials, and will be submitted to the Food and Drug Administration for registration.

THE THREAT OF SMALLPOX

  Smallpox is one of the most devastating of all the infectious diseases. As it was finally eradicated as an endemic disease over 20 years ago people are no longer vaccinated. The WHO suggests that in most communities 90 per cent of the population is fully susceptible to smallpox and experts believe the fatality rate, which historically stood at 30 per cent, could well now be higher.

  Smallpox's potential for devastation is greater than at any time before. Its high transmission rate of 1:15 heightens its potential as a bio-weapon. After an incubation period of perhaps 14 days, infected individuals would begin to experience the symptoms of smallpox. It is likely that a further two weeks may pass before positive identification of smallpox because physicians lack familiarity with the disease.

  Following the success of the worldwide eradication campaign against the disease the WHO determined that the only remaining repository for live smallpox should be the facilities under the direct control of the United States at Centers for Diseases Control (CDC) and those of the former Soviet Union at Koltsovo. All other stocks were supposedly destroyed and the determination to destroy the remaining stocks made the responsibility of an international commission.

  However, according to many leading experts including, Dr Anthony Fauci of the US National Institutes of Health, a bioterror attack using smallpox is an "extremely realistic" possibility. The stocks of the virus held in the Russian State Research Centre of Virology and Biotechnology in Koltsovo, in the Novosibirsk region of Russia, have not been secure and represent a source of disseminated material.

  The former director of the Russian bio-weapons programme has confirmed that the Soviet Government embarked on an ambitious programme to grow smallpox virus in large quantities to use it for bombs and inter-continental ballistic missiles. The USSR was capable of producing many tonnes of smallpox virus.

  Many laboratories in Russia are now fiscally constrained and there is extensive unemployment amongst skilled scientists. The CIA estimates that there are around 11,000 former Soviet biological warfare scientists looking for work.

  Bio-weapon expertise, equipment and stocks could have moved to other countries. Dr Ken Alibek, the former Head Scientist of the Soviet Union's Biological Warfare Programme, has stated that North Korea was experimenting with smallpox in the late 1980s.

  If, as indicated by expert testimony, there is now a possibility that illegal stocks of smallpox may exist outside the registered centres in Russia and America, it is likely that it is the strain weaponised by the Russians, the so-called India-battle strain (also known as "India-1" and "India-67"). This smallpox strain was obtained by the Soviets in 1967, and identified as a particularly virulent form that was causing devastating disease in the Indian subcontinent. It is worth noting in the context of this submission that subsequent bilateral medical support efforts in India by the Soviets, using a smallpox vaccine based on the NYCBH strain (vaccine EM-63), proved spectacularly successful in controlling the disease.

THE DEFENCE AGAINST SMALLPOX

  There is no therapeutic agent to treat smallpox. The only medical countermeasure is vaccination.

  The concern about the possible return of smallpox requires prompt and extensive responses. In 1947, in response to a single case of smallpox in New York City, six and a half million people were immunised. And in Yugoslavia in 1972, faced with 140 cases the government vaccinated 20 million people.

  Around the world, governments have moved to procure vaccines for each and every citizen. America recently set contracts to procure a vaccine dose for every citizen.

  The World Health Organisation's (WHO) eradication programme began in 1958 and was intensified in 1967. Vaccination was the key element of the programme'[1].[2]. Four Vaccinia (vaccine) strains were made available through commercial, non-government, and government sources for manufacture of vaccines around the world. In addition there were specific donations from suppliers both to individual countries and through the WHO program for human immunisation. Approximately one-third of the world's population received one of these four strains. These strains were found to have varying levels of pathogenicity and propensity to cause adverse reactions.[3]
StrainPathogenicity
New York City Board of HealthLow
ListerModerate
EM-63Low
Temple of HeavenHigh


  The world expert on smallpox, Dr Donald Henderson, Director of the US Office of Health Preparedness, has said "Most countries have given little thought to the risk that's involved here and not appreciated what the problem is, and therefore they've done very little to prepare for it."[4]

TWO VACCINE STRAINS DOMINATE DEFENCES

  No strain of vaccine is officially recommended by the WHO, but in response to enquiries the Smallpox Eradication Unit advised that either the Lister or New York City Board of Health strain should be used.[5]

  There are six pertinent points:

    1.  Dr Henderson has stated that "there is not a whit of evidence" to support the Health Secretary's claim that Lister is the only "appropriate strain".[6]

    2.  Professor Oxford of Bart's and the Royal London has said that there is no medical reason to opt for the vaccine strain chosen by the UK Government rather than the one chosen by the US Government.

    3.  Dr Nedret Emiroglu, the WHO's regional adviser on communicable disease control, prevention and eradication in Europe has said "There is no difference; both are proven strains." The WHO is engaged in research to review the situation "to make doubly sure that the strains are still as effective—purely because they were used so long ago. We believe they are still valid and have no reason to think otherwise."[7]


    4.  The European Medicines Evaluation Agency (EMEA) recently issued draft guidelines for development of new smallpox vaccines. The recommendations state "that the vaccines should be derived from a viral strain used in [the] eradication program in endemic areas in order to obtain a vaccine, as close as possible to the efficacious one used in [the] eradication programme." Being based upon the NYCBH strain Acambis' vaccine fits within the EMEA guidelines.

    5.  The most credible threat comes from the Russian weapons strain of smallpox. The Soviets used EM-63 strain of vaccine which is a variant of the NYCBH strain. Evidence from the eradication campaign suggests that this strain of vaccine would be very effective against the Russian weapons strain (India 1).

    6.  The NYCBH strain has had a lower pathogenicity, in terms of the frequency of complications, than any other widely used vaccinia strain. NYCBH is less pathogenic than the Lister strain.[8] Henderson et al concluded, "the frequency of complications associated with the use of the New York City Board of Health strain is the lowest for any established vaccinia virus strain.[9]

  In the documentation concerning the use of these two vaccine strains in the eradication programme, the emergence, and apparent preponderance, of the Lister strain at the time of the intensified programme (1967) can be confusing. The WHO advocated the Lister strain at this time because of its relative ease in manufacture—not because of any perceived performance advantage in the face of the disease. In fact by the time that the Lister strain was being distributed under WHO guidelines, smallpox was only occurring in a few countries around the world. The eradication of smallpox from Europe, the Americas and most of the rest of the world (excluding Africa and India) having been achieved several decades before the involvement of the WHO, and their intensified programme, which targeted the last "pockets" of disease that might act as reservoirs for future outbreaks. In these remaining areas of endemic disease (and notably in Africa and India) the NYCBH strain, together with Lister and other strains eventually succeeded in the desired goal—defeat of smallpox.

  It is worth noting that no formal clinical trials have ever been performed. The effectiveness of different strains used for manufacture has never been directly compared.


US PROCUREMENT OF SMALLPOX VACCINE

  The United States Government has run two competitions for the procurement of smallpox. The first multi-company full and open competition was held between January and September 2000, during which a number of discussions, negotiations, and proposals were undertaken. In September of that year Acambis was awarded a contract to develop a new smallpox vaccine with provisions for the US Government to order vaccine after licensure. The estimated quantity of licensed vaccine that were expected to be ordered was 40 million doses.

  Demand increased following the events of 11 September 2001, and Acambis was requested to scale-up its pre-licensure production capacity to produce 54 million doses of vaccine under the September 2002 contract as investigational new drug (IND) material to be held in reserve for emergency use, if needed. Following that decision, the US Government solicited proposals for a selected number of qualified firms to develop a second smallpox vaccine candidate and to produce sufficient vaccine pre-licensure to supply every US citizen with a smallpox vaccine dose.

  The second US procurement process allowed interested companies to supply details regarding their proposed product and probable costs (Responses to a Request for Information and an oral presentation were allowed). Four finalists were invited to submit a formal proposal. Negotiations were carried out privately with each of the four finalists, each was given the opportunity to submit its best and final offer, and the company with the best proposal was selected based upon evaluation criteria set forth in the Government solicitation. The entire process took five weeks and work commenced immediately. The sequence of events leading up to award of that procurement are summarised below.

DateActivity
19 October 2001Request for information (RFI) sent to interested parties to assess their proposed approach and the company's ability to perform. The RFI provided a framework for responses to demonstrate capacity and capability.
22 October 2001Deadline for companies to ask questions of government.
24 October 2001US Government supplied answers to companies' questions.
25 October 2001Final RFI responses submitted.
30 October 2001Each interested party meets with CDC, deliver presentation and the opportunity to answer and ask questions.
1 November 2001Shortlist of four best-qualified companies decided by CDC (GSK, Wyeth, Merck, Acambis).
1 November 2001A 62 page Formal Request for Proposal was issued to the four companies selected to participate.
3 November 2001Technical and cost/price proposals were submitted to the US Government for evaluation.
28 November 2001Contract awarded following details negotiations, submission of revised proposals, and Government evaluation of final proposals under stated evaluation criteria for determining most advantageous proposal for award.


  For reasons of confidentiality we are prevented from supplying details of our involvement in the UK procurement process.

ABOUT ACAMBIS

  Acambis is a British company and one of Europe's leading biotechnology companies. In 2001 it was selected by the American government to supply the Centers for Disease Control (CDC) with a smallpox vaccine dose per citizen. Acambis was established in 1992 and employs 200 people. Its headquarters are in Cambridge, UK. Research and development is carried out there and at its facilities in Cambridge, Massachusetts. It also has a manufacturing facility just outside Boston, Massachusetts.



1   World Health Organization. Methodology of freeze-dried smallpox vaccines production. WHO, Geneva, SE/68.3 Rev.2) 1968. Back

2   Fenner F, Henderson DA, Arita A et al. Smallpox and its Eradication. WHO, Geneva, 1988. Back

3   From 2 above: Back

4   Donald Henderson, Panorama, "Bin Laden's Biological Threat" 28 October 2001 Back

5   see 2 above Back

6   Sunday Telegraph, 22 April 2002. Back

7   Business Weekly, 22 April 2002. Back

8   Many reports document the frequencyof cases of postvaccinal encephalopathy and encephalitis in Europe and the United States, but comparison of rates is difficult because of differing criteria for diagnosis and variability in the completeness of reporting. The usual levels of incidence, such as those reported from the Netherlands, Germany, and Austria, were initially higher than those reported in the United Kingdom, and these rates in turn were higher than those reported in the United State. (JM Lane, FL Ruben, JM Neff, and JD Millar. Complications of smallpox vaccination, 1968. National surveillance in the United States N Engl J Med 1969. 281: 1201-1208; JM Lane, FL Ruben, JM Neff, and JD Millar. Complications of smallpox vaccination, 1968: Results of ten statewide surveys J Infect Dis 1970. 122: 303-309; and JM Neff and JM Lane et al. Complications of smallpox vaccination. I. National survey in the United States 1963 N Engl J Med 1967. 276: 125-132.) Whatever the criteria and methods, differences between the rates appeared to be real, and this fact caused a number of countries, during the 1960s, to begin using the Lister strain, then in use in the United Kingdom and supplied by the WHO refrence laboratory in Bilthoven, the Netherlands. A dramatic reduction in the incidence of postvaccinal encephalitis subsequently occurred (Polak MF. Complications of smallpox vaccination in the Netherlands, 1959-1970. In International Symposium on Smallpox Vaccine. Symposia Series in Immunobiological Standardization 19: 235-242, 1973 and Berger K, Heinrich W. Decrease in postvaccinal deaths in Austria after introducing a less pathogenic virus strain. In International Symposium on Smallpox Vaccine. Symposia Series in Immunobiological Standardizaetion 19: 199-203, 1973). The incidence in the Netherlands between 1964 and 1971 appeared to approach that in the United States; 10 of 16 cases were fatal, however, compared with only four of 16 cases reported in the United States in 1968 (Henderson, DA, and Moss, B. Smallpox and Vaccinia. In: Plotkin S A and Orenstein WA: Vaccines (3rd ed.) 1999: 74-97). Back

9   Henderson, DA, Inglesby, TV, Bartlett, JG et al. Smallpox as a biological weapon: Medical and Public Health Management. JAMA 1999, 281 (2): 2127-2137. Back


 
previous page contents next page

House of Commons home page Parliament home page House of Lords home page search page enquiries index

© Parliamentary copyright 2002
Prepared 24 July 2002