Greasing the COGs

The large scale global health vaccination programs, like those run by UNICEF, are primarily donor- (government or foundation) backed and set up the collision of two forces:  millions of people (often kids) needing vaccination and limited funds (a perpetual problem).  UNICEF has built a cracker-jack procurement agency that has done good job of projecting demand, negotiating with suppliers, and buying the meds for more than 10 years (UNICEF Supply) and regularly publishes its contractors, contracted volumes, and prices (e.g., Price Data).  Currently,  UNICEF is buying 25 vaccines (including different formulations) against 9 diseases for volume of about 2.5 billion doses and at modest prices ranging from USD .048 per dose (adult tetanus vaccine) to USD 2.80 (a strain-specific MMR [measles, mumps and rubella]) (2011 Vaccine Projection) and way below prices for the US public health market (e.g., CDC Price List).  Other low global health vaccine prices I’ve noted are $0.50 for the new meningococcal vaccine called MenAfriVac™ (my post of 12/16/10 and Synco Biopartners) and less than $3.50 for the new pneumococcal disease vaccines to be provided by GSK and others under the Advance Market Commitment pilot program of  the Global Alliance for Vaccines and Immunizations (AMC and AMC Fact Sheet).  The AMC is a new mechanism and the hope is that the program, in which initial purchases will use donor funds and later purchases will be by customers (governments) at pre-negotiated and “sustainable” prices, will accelerate the introduction of new vaccines developed for the up-market countries and (big) maybe stimulate the development of vaccines specifically for global diseases.  [Note:  the prices above do not include delivery to the recipient which is another kettle of troublesome fish.]

One consequence of having a robust global health vaccine market is that manufacturers face pressure to keep their operating costs, which are primarily for research and development of new or better vaccines, process development, and manufacturing, as low as possible and still have a sustainable business.  The big companies put their substantial profits to work, mid-sized companies may make “me-too” vaccines or operate in lower-cost countries (e.g., India vs. the US), small companies may find very venturesome venture capitalists, and all companies look for grants from governments and foundations or partner with the donor-supported product development programs (PDPs) or academics.

As for reducing manufacturing costs (aka “cost of goods” or COGs), a number of companies are developing new technologies, although their specific use and impact on global health vaccines is yet to be determined.  The major contract manufacturing companies (e.g., Lonza, and Crucell, which is being acquired by Johnson and Johnson) have been working on manufacturing improvements to lower costs for years.  Crucell, for one, is working with the Aeras TB Vaccine Foundation on a TB vaccine manufacturing process (Crucell TB Vaccine).  For the next generation influenza vaccines, Novavax (Novavax) and Technovax (Technovax) are developing processes to use virus-like particles (VLPs) to lower the time and cost of manufacture.  New manufacturing equipment is also being developed that has the advantages of being scalable, less costly to install and operate, and quickly reconfigurable for a different product (c.f., Biopharma article and Biomanufacturing meeting).  Xcellerex is developing a manufacturing system using cheaper, disposable components (Xcellerex and my post of 4/8/10).

A local company, Matrivax Research and Development Corp., also is working on a lower cost approach to making multivalent conjugate vaccines.  In these vaccines, the immunizing antigens are polysaccharide epitopes specific to the target organism, which could be bacteria, viruses, or even cancer cells, which are chemically attached to a protein, a modified, non-toxic version of diphtheria toxin called CRM197, which also helps to ramp up the immune response.  Several vaccines of this type are approved (e.g., against Haemophilus influenzae type b [CDC 1991] and 13 strains of Streptococcus pneumoniae [Vaccine Info]) and many others are under development, principally because the approach allows for immunization against multiple strains of a bug and is good at stimulating a response in children and elders who have less responsive immune systems.  Started in 2007, Matrivax is using a technology licensed out of the Mekalanos lab at Harvard (Mekalanos Projects) that entraps the polysaccharide epitopes in a protein matrix of cross-linked CRM197 to form a polysaccharide capsular matrix vaccine or PCMV (Killeen et al. 2010).  Unlike the standard process in which each epitope is added serially and with low yield, the PCMV process can add 3-4 in one step, substantially lowering the effort and, theoretically the final cost.  Matrivax is small (fewer than 10 employees) and privately funded including a Gates Grand Challenges Explorations grant it received in 2009 to work on a multivalent pneumococcal vaccine (Gates Grant), a potential competitor to the AMC’s $3.50 per dose vaccines from GSK and Pfizer.  In addition to the pneumo vax, Matrivax will be applying its technology to vaccines for  typhoid fever and bacterial meningitis, for which the current immunizations are not completely effective in response strength or breadth (multiple strain coverage).  As for commercial development, the company may attract one of the big multi-nationals as a licensee although, in my experience, pharma’s biomanufacturing guys are very conservative and resistant to the adoption of new processes.  Fortunately, the developing country-based vaccine industry is growing and has a strong interest in new products and technologies (e.g., Vaccine World Summit 2011).  Bottom line:  more grease is on the way.

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