Low costs solve global vaccine access---eliminates supply AND innovation constraints

The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers.

Vaccine rollout in low- and middle-income countries (LMICs) routinely lags far behind rollout in high-income countries. As of 2010—a full decade after its introduction—87% of high-income countries included the pneumococcal conjugate vaccine in their immunization schedules, compared with only 2% of low-income countries.1 Although the Haemophilus influenzae type b (Hib) vaccine was being widely used in wealthy countries by the early 1990s, Hib vaccine coverage in Africa was estimated at 24% as of 2006.2 Twenty years after licensure of the hepatitis B vaccine, vaccine coverage was estimated at 90% in the Americas as opposed to only 28% in Southeast Asia, where hepatitis B is endemic.1 These timelines, unfortunately, are the norm rather than the exception for adoption of new vaccines in LMICs. The inequities of this situation are all the more indefensible because the vast majority of mortality from vaccine-preventable diseases occurs in LMICs3; it is estimated that more than 90% of deaths from pneumococcal disease,4 95% of deaths from Hib,5 and 80% of deaths from hepatitis B5 occur in developing countries.

In May 2012, the 65th World Health Assembly endorsed the Global Vaccine Action Plan (GVAP),6 a document that sets ambitious vaccination goals for the upcoming decade. The GVAP reflects the growing recognition by governments, international agencies, and civil society of the importance of vaccines not only for achieving international health priorities but for addressing global issues such as poverty, hunger, education, and gender equality.7 One of the key objectives outlined by the GVAP is for all immunization programs to have sustainable access to universally recommended vaccine technologies within 5 years of licensure. There is an enormous gap between this goal and the current reality of new vaccine rollout in LMICs, and the GVAP recognizes that innovative mechanisms will be needed to support scale-up of new vaccines within the proposed timeline. The Decade of Vaccines collaborative that created the GVAP has proposed the goal of achieving universal vaccine access by 20208; it is estimated that this goal will cost more than US $57 billion, with new vaccines responsible for over half the cost.9

Although there are numerous social and logistical obstacles to the adoption of new vaccines in LMICs, a clear consensus has emerged that one of the greatest barriers is vaccine pricing.10–15 This problem is being compounded by the increasingly high costs associated with recent vaccine innovations. The newly developed human papillomavirus (HPV) vaccine, for example, is the most expensive vaccine in history16; this is particularly problematic because the overwhelming majority of cervical cancer cases occur in developing countries.17 Like many new vaccines, the high cost of the HPV vaccine will be most prohibitive in exactly the places it is most needed, and it is unlikely that expensive new vaccines such as the HPV vaccine will become widely accessible in LMICs without extensive external funding.

Currently, the most important source of external funding for vaccines in low-income countries is the Global Alliance for Vaccines and Immunizations (GAVI). GAVI’s critical role in the introduction of new vaccines to low-income countries, most recently with its commitment to introducing the HPV vaccine,18 cannot be overstated; however, there are significant limitations inherent in this support. First, new vaccine introduction is only 1 component of GAVI’s vaccination programs, and the decision to introduce a new vaccine is based on numerous factors, which inevitably include the price of the vaccine and GAVI’s current financial status. In 2010, GAVI was facing a serious budget shortfall of over $4 billion, which threatened to limit future plans to introduce new vaccines.19 GAVI was able to raise sufficient funds to overcome this budgetary crisis; however, the shortfall highlights concerns regarding the long-term stability of GAVI’s subsidies for the future introduction of new vaccines. In any event, LMICs that are not eligible for GAVI funding are likely to have difficulty financing new vaccines without assistance,12 and the GVAP notes that innovative pricing strategies will be particularly important for those LMICs that do not have access to GAVI pricing and procurement mechanisms. In addition, the subsidies provided by GAVI to finance new vaccines are intended to be limited to a 5-year period, with the expectation that, over that time, prices will fall, allowing donors and national governments to continue vaccine financing. To date, however, this expectation has not been realized. Once it became apparent that vaccine prices were not dropping rapidly enough, GAVI was forced to revise its support timelines. Thus, a critical limitation to GAVI’s role in promoting access to new vaccines is the failure to establish mechanisms ensuring sustainable vaccine pricing once the initial period of support has ended.

There is an emerging consensus that the most important factor in achieving sustainable vaccine pricing is the market entry of developing-country vaccine manufacturers (DCVMs).1,20–23 I propose an intellectual property, technology, and know-how (IPTK) bank as a novel strategy to enable early market entry of multiple DCVMs to facilitate rapid rollout and sustainable pricing of new vaccines in LMICs.

In January 2010, a consultation meeting convened by Médecins Sans Frontières and Oxfam brought together experts from around the world to discuss strategies for improving access to vaccines in LMICs.20 New vaccines were a major focus of this meeting, which included representatives from key players such as the Netherlands Vaccine Institute, the International Vaccine Institute, Third World Network, Program for Appropriate Technology in Health, and the World Health Organization (WHO). The consultation meeting report concluded that although organizations such as the Pan American Health Organization Revolving Fund—which effects reduced prices through bulk procurement systems—are key players in improving vaccine access, such entities have not proven sufficient to ensure affordable prices for new vaccines. The report further noted that success with tiered pricing approaches has been mixed and has not consistently resulted in sustainable prices, particularly for new vaccines. It concluded that future strategies to improve access to new vaccines will need to include (1) streamlining regulatory pathways for biosimilar vaccines, (2) addressing intellectual property barriers, and (3) reducing the barriers and timelines to the entry of multiple new suppliers by transfer of technology and know-how. Before addressing each of these strategies in detail, I will briefly discuss the implications of the fact that vaccines are biologics rather than small-molecule drugs.

Vaccines as Biologics and Implications for Access Strategies

The presence of multiple DCVMs has been identified as a critical factor in generating sustainable vaccine prices. It is now widely recognized that the advent of generic drug production, but more importantly the market entry of multiple generic drug suppliers, is the best mechanism for rapidly achieving dramatic price reductions. The major expansion of HIV/AIDS treatment in LMICs, for example, was made possible through the entry of generic manufacturers in countries such as India and Brazil; with the advent of robust generic competition, prices of first-generation antiretroviral drugs fell by more than 99%, from $10 000 annually per patient in 2000 to less than $70 in 2014. Strategies to improve access to medicines have thus coalesced around the goal of enabling generic production. This has led many of these efforts to focus on patent protection as a key barrier to the availability of affordable generic medicines. A crucial assumption that underlies this strategy is that it is fairly straightforward to reverse engineer a given drug; in concept, the problem is not that generic drug manufacturers would be unable to exactly replicate a drug, it is that they are prohibited from doing so by patent law. Although this is generally the case for small-molecule drugs, this basic assumption does not hold true for biologics, including vaccines.

The majority of medications in common use are small-molecule drugs, which are generally low-molecular-weight organic compounds synthesized by chemists. Biologic drugs, a category that includes vaccines, are generally produced by living cells and are significantly larger and structurally more complex than small-molecule drugs. To successfully reverse engineer a small-molecule drug, it is not necessary to precisely duplicate the manufacturing process in order to guarantee an identical product. In the case of vaccines, however, an identical product is not necessarily guaranteed if an alternative production process is used. The details of the vaccine production process can affect variables such as 3-dimensional structure and posttranslational modifications, which are important determinants of vaccine immunogenicity. Detailed information on vaccine production processes is usually not patented. Instead, this information is protected by trade secret law, under which it is never made publicly available because, unlike patent protection, there is no scheduled expiration after a preset term.24 This perpetual monopoly prevents replication of the production process, thus precluding straightforward duplication of the vaccine.25 Furthermore, because vaccine manufacturing is often highly complex, significant know-how may be required to reproduce a vaccine, necessitating direct input from the original product developer.