House of Commons - Science and Technology

Select Committee on Science and Technology Eighth Report

4 RESEARCH, DEVELOPMENT AND PROCUREMENT

VACCINES

65. Vaccines are available for a surprisingly small number of infectious agents, around 10% according to PowderJect. We heard from Gail Cassel from Eli Lilly in the US that only two vaccines were available for the 13 agents on the A List (see Table 3). If vaccines are to be a major biodefence tool then a concerted research effort will be required into a range of agents that have so far received little attention owing to their low prevalence in the populations of developed countries. The US National Institutes of Health has recognised this by establishing a new Vaccine Research Center with an annual budget of $50 million. We were told during our visit in May 2003 that the Center was set up with HIV as its primary target but that biodefence was now an important objective also. The House of Lords Science and Technology Committee reports that pharmaceutical companies invest 10 or 20 times less money in vaccine R&D than in therapeutics.[59] PowderJect reports that while the timescale for developing a bioweapon on an industrial scale is 3-5 years, it takes 12-15 years to develop a vaccine.[60]Table 3: Development of vaccines for A list agents.[61]

Agent	Properties	Current vaccines
Anthrax	Non-contagious spore forming bacteria; inhalation anthrax toxaemia is lethal; 70-100% fatality if left untreated	Anthrax vaccine with 5-6 doses over 12-18 months with annual booster available; may respond to ciproflaxacin if treated early
Smallpox	Highly contagious DNA virus; variola major; 30% mortality	Wyeth: DryVax 1 shot live vaccine 10 years+; safety concerns in elderly; no known cure; treatment with antivirals may have some efficacy
Plague	Pneumonic plague; highly contagious bacterium Yersinia pestis; 80-100% mortality	No commercially available vaccine; may respond to aminoglycosides if treated early
Botulism	Non-contagious, spore-forming bacteria; toxin is lethal if enters water or food supply	No vaccine: antiserum or immunglobulin in short supply
Tularaemia	Francissella tularensis, a highly infective non-contagious intracellular bacterium	Experimental live attenuated vaccine available; If treated early will respond to antibiotics
Viral haemorrhagic fevers	Arenaviruses; Lassa fever, bunyaviruses; Rift Valley fever, filoviruses; Ebola, haemorrhagic flaviviruses; yellow fever: carried by insect or rodent vectors; highly fatal	No vaccines exist except for yellow fever and Korean haemorrhagic fever; ribavirin against hantavirus; no effective therapies

66. Dstl Porton Down has a vaccine programme as does its close neighbour CAMR. Dr Scott told us that "We are undertaking, and have been since the last Gulf War, a number of medical countermeasures development programmes to try and ensure in the biodefence area that we produce rapid acting effective vaccines". This includes, with the DoH, work on the development of the smallpox vaccine and new generations of anthrax and plague vaccines.[62] We were told by Dr Scott that he was working "very closely with our US counterparts in the DoD [Department of Defense] to generate a whole panel of defence vaccines".[63] The holy grail of vaccine development is the production of a generic vaccine that provides protection against a wide range of pathogens. We understand that Dstl is active in this pursuit. The vaccine development work by Dstl Porton Down would seem to bring closer the prospect of protection for civilians against several of the A List agents, but Dr Scott was cautious: "the strategy for producing vaccines in a military context is totally different from that which it would be in a civilian scenario".[64]

67. There has been a lot of public attention on vaccines. But, as Dr Scott said, their role needs careful thought before large amounts are invested: "Many of the current vaccines take a long time to establish immunity. Are we going to go and immunise our populus with fifteen different vaccines on the off-chance there might be a bioterrorism event using these materials? … you need to do the thinking first and then work out where you can spend the money".[65] The amount of money is substantial. As Dr Penn pointed out, "the science is there to attempt to develop safe and effective treatments or vaccines for a wide range of organisms but the risk and cost of doing so for each and every case is very high".[66] According to PowderJect, the cost of developing a new vaccine could be in excess of $350 million.[67]

68. A further problem is ensuring that large numbers of doses are available in the event of a bioterrorist attack. Either large volumes are stockpiled or there needs to be the capability to produce large amounts very quickly.

69. We share Dr Scott's concern that too much attention may be given to vaccination. Nevertheless, it is prudent to marshal available resources without compromising research programmes into vaccines for infectious diseases such as HIV, malaria or even SARS. The decision by DoH to ask CAMR to provide a Strategic Response Capability to concentrate on those micro-organisms rarely encountered in the UK seems sensible.

Rapid Response Vaccine Facility

70. In September 2002 CAMR submitted to the DoH a draft business case for a Rapid Response Vaccine Facility. The proposal was for the design and build of a state-of-the-art manufacturing facility capable of operating at Pathogen Containment Levels 3 and 4 (the degree to which the worker is protected from the agent) and suitable for process development and production of vaccines for emergency use. The projected cost was £30 million.

71. The Government has not accepted the business case in its current form. Hazel Blears, giving evidence to the House of Lords Science and Technology Committee on 8 April 2003, said that the DoH was keen that the development time should be reduced below six months and they had concerns about the cost. Ms Blears said "That does not mean the door is closed on it and I am certainly still happy to consider it with advice from the HPA and to see if there is a way forward on this". The House of Lords Science and Technology Committee did not give explicit support to the proposal in its report Fighting Infection but said it was pleased that the DoH would consider a further submission.[68] Dr Pat Troop, Chief Executive of the Health Protection Agency told us that the proposal "was not turned down, but there were some issues in the business plan that we felt needed further clarification and discussion".[69] Dr Harper from the DoH told us that "we have asked specifically that the Health Protection Agency considers the vaccine production facility in the round, looking at what is available in dialogue with industry and with the wider academic community as well".

72. The evidence we have received on the proposal from the pharmaceutical industry displays little enthusiasm. Philip Wright from the Association of the British Pharmaceutical Industry (APBI) said "I think it would be very interesting if a public body could actually out-compete some highly competitive industries across the globe".[70] Nick Higgins from Acambis questioned the proposed speed of development. He said that his company had been able to produce a bottled vaccine within 10 months of getting the contract: "CAMR typically has not worked at that sort of breakneck speed and I think generally industry tends to work faster".[71] Dr Scott from Dstl dismissed the idea that the public sector could not match the speed of industry, but tellingly, he refused to be drawn on the merits of the facility, maintaining that "we need to establish the case".[72]

73. We too have concerns about the creation of a Rapid Response Vaccine Facility. There is merit in a publicly funded vaccine development facility. As the APBI indicated, "only a few member companies in the UK have category three facilities and none have category four", which are necessary for handling the most dangerous biological agents. CAMR has many qualities but we believe that this venture would be better conceived as a partnership between CAMR and industry. Given the Government's policy of keeping the pharmaceutical industry at arms' length on this issue, this was not an avenue that CAMR could pursue.[73] John Hutton indicated that the DoH was planning a more constructive (and long-overdue) dialogue with industry. This is an opportunity to rethink the proposed Rapid Response Vaccine Facility. We recommend that the HPA develop with industry a fast efficient vaccine production facility which combines a service to the tax-payer and benefits participating companies. This should form part of a long-term vaccine development strategy for Government.

Vaccination policy

74. While vaccines generally offer better protection against infection if administered before exposure, they can have value in limiting the effects after exposure. In the case of smallpox, current vaccines can keep a patient alive although they do not prevent them being carriers, which has implications for restricting the spread of the disease. The DoH have published a smallpox strategy, based upon regional teams of vaccinated staff, ring-fenced vaccination around any outbreak and the procurement of additional vaccine stocks. The Prime Minister said that the Government's policy on smallpox vaccination was consistent with WHO guidelines.[74] These state that:

75. Smallpox has attracted a lot of attention on account of its virulence and the potential susceptibility of the population. There has not been a case in the UK since 1978. As a result, medical practitioners have no licensed vaccine available to them. With no incidents of infected individuals, it is not possibile to test a vaccine to regulatory standards in an ethically acceptable manner. There are two commercially available vaccines. The purchase by the UK Government of the product produced by PowderJect was highly contentious and the subject of a National Audit Office (NAO) inquiry.[76] This issue will not be considered here. Representatives from the companies (the other one was Acambis) insisted to us that there was nothing to choose between their products and we have no reason to doubt them.[77]

76. The US Government has decided on a mass vaccination campaign and inevitably this has focused attention on UK policy. The medical community is largely supportive of the UK position. Vivian Nathanson from the BMA told us that "Smallpox vaccine is a dangerous vaccine and if nobody has smallpox in the community you do not give it to people who are not at front line risk". But there could be a mass vaccination programme with "the right kind of agent and the right kind of vaccine".[78] We note that the US smallpox vaccination programme has been making slow progress, with less that 40,000 individuals (excluding the military) as of September 2003.[79]

Regulation

77. Dr Paul Drayson, Chief Executive of PowderJect, said that the smallpox vaccine that PowderJect produced was unlicensed and that it had provided for an emergency response situation against a potential biodefence threat. He said that the responsibility for compensation and indemnification lay with the medical practitioner who administered the vaccine, who would be a Government employee. Issues of indemnification and vaccine damage payments would therefore come under the responsibility of Government. We were reassured to hear the Minister, John Hutton, confirm to us that all healthcare workers taking the smallpox vaccine would be compensated for any side effects.[80] Evidence from the US military vaccination programme suggests that adverse side effects have been lower than expected and there have been no deaths among the 450,000 who have been vaccinated.[81]

78. The Committee heard during its visit to the US of the Food and Drug Administration's (FDA's) ability to invoke the "animal rule".[82] This enables it to approve critical drugs and vaccines based on evidence of their effectiveness in animal tests rather than on extensive human studies. This permits scaled-back human trials, especially for products to counter biological and chemical weapons. The equivalent body in the UK is the Medicines and Healthcare products Regulatory Agency (MHRA), which has recently been formed by the merger of the replaced the Medical Devices Agency and the Medicines Control Agency. The MHRA tells us that "When the CSM [Committee on Safety of Medicines] considers the application on the basis of quality, safety, efficacy and the risk:benefit of the product, it takes into account the data submitted and also the reasons for absence of full data. This is then factored into evaluation of risk:benefit before a decision is taken". At a European level, we understand that the European Medicines Evaluation Agency already has a provision for marketing authorisation under exceptional circumstances.[83] How this applied is another matter. The vaccine manufacturer Acambis reports that guidance from the European Medicines Evaluation Agency is that any new smallpox vaccine needs to be fully tested as a 'new vaccine', which would involve Phase I trials of a hundred or so people, Phase II of several hundred and Phase III of many thousands to show that it is safe.[84]

79. The Government's decision not to conduct a mass vaccination programme for smallpox is correct in our view. The reported side effects of the vaccine make this option unattractive. Should a safer vaccine become available, we would expect the Government to reconsider this policy yet the Minister refused to address this point. We have heard of doctors' concerns about the "worried well".[85] A safe vaccine might prove cost effective, provide reassurance to millions and possibly act as a deterrent to any attack.

PERSONAL PROTECTION AND DECONTAMINATION

80. A DoH working group was looking at the procurement of personal protective equipment (PPE) at the time of 11 September 2001. While the new specification was being established, the NHS procured PPE as an interim measure, the process starting in October 2001 and finishing in March 2002, at a cost of £16 million.[86] It became apparent that these interim suits were faulty, as David Harper from the DoH explained to us:

81. This is an embarrassing episode for the DoH. We can understand the desire to be seen to be doing something in response to the 11 September 2001 attacks but the Department has succeeded only in undermining confidence in its competence. An NAO review of NHS preparedness reports the concerns of the London Ambulance Service about "the recurring costs associated with maintaining and replacing the one-off Department of Health issue".[88] The most curious aspect of the affair is that the suits were tested by Dstl.[89] Either Dstl did not identify the problem or its advice was ignored. We were also surprised that in the first instance the Fire Service was not consulted.[90] Its demands are likely to be more in line with the health service than the military.

82. In law the DoH is responsible for the decontamination of the public.[91] The DoH and the OPDM have signed a Memorandum of Understanding in respect of mass decontamination. It outlines the basis on which the Fire Service will assist the Department of Health by providing and staffing mass decontamination facilities at a CBRN incident.[92]

83. The NAO review found that existing provision to deal with contamination incidents was inadequate and that there was a fragmented approach, which had led to individual NHS trusts procuring different types and quantities of PPE and decontamination facilities. Only after this review were national specifications developed.[93] The review concluded that the situation concerning PPE and decontamination equipment was continuing to improve.

84. In its initial procurement of personal protective equipment after 11 September 2001, the DoH acted too hastily and without consulting sufficiently widely. We are content that problems are being remedied but at considerable expense and at a cost to the public's and health professionals' confidence in the Department's competence.

59 House of Lords, Fourth Report of the Select Committee on Science and Technology, Session 2002-03, Fighting Infection, HL Paper 138,para 8.3 Back

60 Ev 202 Back

61 Ev 202 Back

62 The new anthrax vaccine about to enter phase 1 clinical trials; the plague vaccine is about to enter phase 2 clinical trials Back

63 Q 265 Back

64 Q 251 Back

65 Q 248 Back

66 Q 44 Back

67 Ev 202 Back

68 House of Lords, 4th Report of the Select Committee on Science and Technology, Session 2002-03, Fighting Infection, HL Paper 138, para 4.12 Back

69 Q 693 Back

70 Q 199 Back