WHO, GSK Provide Update on Pandemic Flu Production

The World Health Organization’s Ad Hoc Policy Advisory Working Group on Influenza A (H1N1) Vaccines issued an update on May 18, 2009, on the production status of seasonal and A (H1NI) vaccines. Also, GlaxoSmithKline (GSK, London) outlined its progress in making an influenza A (H1N1) vaccine using its proprietary AS03 adjuvant system.

WHO updates
A review of 2009 production status for the Northern Hemisphere seasonal vaccine indicates that the industry plans to produce approximately 480 million doses of trivalent seasonal vaccine in 2009, according to a statement by the World Health Organization Working Group. Of this amount, 350 million and 430 million doses will be available by June 30 and July 31, 2009, respectively. For influenza A (H1N1), it is estimated that up to 4.9 billion doses could be produced over a 12-month period after the initiation of full-scale production if there is a vaccine yield equivalent to that routinely obtained for seasonal vaccine and if the most dose-sparing formulations are used. In this situation, there is potential access for the United Nations of up to 400 million doses.

The WHO Working Group said it was premature to recommend that commercial-scale production of influenza A (H1N1) vaccine should start immediately but recommended the following actions:

• The WHO Secretariat, in close coordination with its Collaborating Centers and the Essential Regulatory Laboratories of the WHO Global Influenza Surveillance Network, should recommend which vaccine viruses should be used for vaccine development as soon as possible

• Essential reagents to calibrate antigenic content should be made available as a priority

• The WHO Secretariat is encouraged to collaborate actively with its Collaborating Centers, Essential Regulatory Laboratories, and with industry, to assess the growth property of vaccine viruses and identify those with best growth potential to maximize output of a vaccine

• Manufacturers are urged to develop clinical-trial batches and accelerate initiation of clinical trials of influenza A (H1N1) vaccines and to start preparing for potential future recommendations to move to commercial-scale production

• Present production of the Northern Hemisphere seasonal vaccine should not be interfered with by activities relating to pandemic preparedness

In making these assessments, the WHO Working Group reviewed the current status of preparation of candidate vaccine viruses and said these will likely become available at the end of May 2009. Distribution of these vaccine viruses to vaccine manufacturers may need to be delayed by a further one to two weeks to allow assessment of their attenuation characteristics in appropriate animal models. Typically, one to two additional months are needed by manufacturers after they receive vaccine viruses to isolate rapid growing strains to maximum yield. Based on these considerations, the WHO Working Group said that vaccine manufacturers would not be ready to switch to large-scale production before mid-July 2009 and that moving into production now could potentially result in starting vaccine production with strains of lower growth potential and potentially could reduce global supplies of an A (H1N1) vaccine.

The WHO Working Group also emphasized that a possible declaration of pandemic influenza alert to Phase 6 does not automatically mean that WHO would recommend that manufacturers switch from seasonal to influenza A (H1N1) vaccine production. As of May 18, 2009, the pandemic status alert was still at Phase 5.

GSK works on an A (H1N1) adjuvanted influenza vaccine
GSK reported on May 15 that it expects to manufacture a candidate A (H1N1) adjuvanted influenza vaccine once a virus seed is made available by WHO. The first doses of the vaccine are expected to be available four to six months later, subject to regulatory approval.

The vaccine will consist of the antigen of the recently isolated A (H1N1) influenza strain and also contain GSK's proprietary adjuvant system AS03. An adjuvant system is added to the antigen at the time of administration to stimulate a higher immune response while using a smaller amount of antigen as compared with a formulation without adjuvant.

The new candidate vaccine will require regulatory approval. In 2008, GSK received an European license for a pandemic vaccine based on a mock-up dossier. This approval, which was based on data involving the H5N1 influenza strain, is expected to enable faster registration of a new A (H1N1) influenza vaccine and is currently being discussed with European regulatory authorities, according to GSK.

GSK has received interest from several governments seeking to stockpile the new candidate adjuvanted vaccine. The UK government is interested in purchasing 60 million doses of the candidate A (H1N1) adjuvanted influenza vaccine, the French government 50 million doses, and the Belgium government 12.6 million doses. GSK will supply the Finnish government with 5.3 million doses of H1N1 antigen, which is expected to be used in conjunction with the government’s existing stockpile of GSK’s adjuvant system.

In addition to its agreement with GSK, the UK Department of Health has an agreement with Baxter International (Deerfield, IL). The UK Department of Health reported last week that it has agreements with GSK and Baxter International for up to 90 million doses of prepandemic H1N1 vaccine. If a pandemic is declared, advance supply agreements signed by the UK Government with GSK and Baxter in July 2007 will enable the UK to purchase up to 132 million doses of pandemic-specific vaccine, when it becomes available.

GSK outlines strategy for developing nations and seasonal flu
As part of the company’s commitment to maximizing global manufacturing capacity of a pandemic vaccine, GSK says it is ready to engage in discussions with companies and governmental agencies that can combine the adjuvant system with alternatively sourced antigen. GSK also said it will convert its intended donation to WHO of 50 million doses of H5N1 prepandemic vaccine to the new candidate A (H1N1) adjuvanted influenza vaccine once production begins. In the future, as capacity increases, GSK will supply the candidate A (H1N1) adjuvanted influenza vaccine to developing countries under a tiered-pricing policy based on World Bank classifications and eligibility with the Global Alliance for Vaccines and Immunization, a private-public partnership to promote immunization by vaccines. 

GSK will continue to produce its seasonal influenza vaccine for the 2009–2010 Northern Hemisphere influenza season as planned and expects to complete production of this vaccine by the end of July. The company also continues to supply seasonal vaccine for use in the Southern Hemisphere as it enters the winter season this year. 

Baxter details pandemic flu strategy
Baxter International reported on May 7 that it is in contact with WHO and other agencies regarding the current A (H1N1) influenza outbreak. Using its Vero cell technology, Baxter has received European Medicines Agency (EMEA) approval for a mock-up pandemic vaccine, Celvapan. The qualification, development, and manufacturing processes used in gaining mockup licensure for Celvapan will apply as the company uses this new influenza A (H1N1) virus strain to develop a pandemic vaccine. The Celvapan EMEA licensure allows for fast-track approval of a pandemic vaccine containing an actual pandemic strain. “At this point, the company is taking all appropriate steps necessary to prepare for a large-scale vaccine production,” said Baxter in a prepared statement.

Read PharmTech's coverage of earlier developments on the swine flu.

Read a Q&A with Covance on manufacturing a pandemic vaccine.