Vaccines reduce the risk of getting a disease by working with the body’s natural defences to build protection blocks. Globally, there are many vaccines to prevent life-threatening diseases, helping people of all ages live longer and healthier. Immunisation currently prevents 2-3 million deaths every year from diseases like diphtheria, tetanus, pertussis, influenza and measles.

Access to quality immunisation as part of a healthcare system is an indisputable right. Vaccines are also critical to the prevention and control of infectious-disease outbreaks. Yet despite tremendous progress, far too many people – including nearly 20 million infants each year – have insufficient access to vaccines. In a highly populated, resource-constrained country like Pakistan, universal immunisation must be the cornerstone of an effective public health strategy.

Despite having one of the largest birth cohorts in the world (over 5 million annually) Pakistan has virtually no domestic vaccine production to speak of. This dependency on imported vaccines (mostly from India or China) is a health safety challenge. Pakistan’s vulnerability in this area has been further underscored in the context of the current Covid-19 pandemic. The World Health Organisation (WHO) estimates that around 1.7 million annual deaths among children under 5 years of age are due to diseases that could have been prevented by routine immunisation. The number of unimmunised children under one year of age who did not receive the three dose diphtheria, tetanus and pertussis vaccine (DTP3) was around 23 million in 2009. Up to 70 percent of these children live in ten countries including Pakistan (WHO, 2010). Amongst other constraints in the provision of public health interventions, supply and provision of vaccines remain a key component requiring attention by the government.

Due to the market dynamics of vaccination, sustainable vaccine production requires a Public-Private Partnership (PPP) approach. The private market for vaccines is minimal; the government is virtually a monopoly buyer. Vaccines are procured in bulk directly by the government from vaccine manufacturers or through coordinated multi-country programmes funded by donor agencies like the GAVI. In both cases, the supply is maintained by the EPI for distribution across the country.

GAVI vaccine prices, which are set significantly below market prices, may no longer be applicable for Pakistan when it graduates away in the next five years (as expected) with appropriate GDP increase. Given our overburdened healthcare system and scant resources, meeting the country’s immunisation requirements could become Pakistan’s most serious healthcare challenge in the medium- to long-term. According the World Health Organisation, “there is a changing dynamic in vaccine technology transfer, with joint ventures, acquisitions and establishment by multinational manufacturers of subsidiaries in developing countries becoming more frequent”.

A PPP approach seems to be practical. Several examples validate this model. About 55 countries in the world today have local vaccine production facilities. However, many production facilities cannot assure a reliable supply of existing or new vaccines. There is an increasing trend towards privatising the publicly held facilities. Recent examples include the Netherlands Vaccine Institute, now operated by Serum Institute, India. There are, however, some countries that have managed to maintain public vaccine manufacturing, albeit with the help of private sector partnerships such as the Butantan Institute in Sao Paulo, Brazil.

In Pakistan, private sector manufacturing of vaccines could supplement NIH’s existing capacity while addressing organisational, managerial and financial constraints that prevent the institution from expanding its output. This will jump-start the capacities in the overall health system to respond to national needs as well as achieving national immunoglobulin self-sufficiency. World vaccine experts recommend the following stages of local vaccine production:

At the first level, distribution of imported finished vaccine products. At the second level, packaging and labeling of imported vaccine products following national or international GMP standards. At the third level, vaccine product manufacturing from imported bulk (fill and finish) following national or international GMP standards. At the fourth level, API (active pharmaceutical ingredients) manufacturing and excipients following national or international GMP standards. Lastly, at the fifth level, research and development in new formulations, processes and new chemical or biological entities following national or international GLP/GCP and ethical standards.

The move from Level 1 to Level 4 can be undertaken over a period of five to ten years, sufficient time to ensure that local producers remain compliant with WHO standards and on-track for WHO prequalification. This should be a prerequisite for local manufacture to ensure that quality standards are not compromised in any way and the integrity of the vaccines chain is maintained.

Critical success factors for local vaccine production include long-term strategy and planning; concerted effort to invest in vaccine development and production; scientific, technical, quality and management capabilities; an enabling environment (utilities, communication means, stability in policies); functioning regulatory authorities; strong avenues of internal and external partnerships; and a viable and sustainable market.

Vaccines are public goods, and worldwide, universal vaccination is a goal that is embraced by governments. Private markets for vaccines, wherever they exist, are much smaller than the public procurement system. Thus, long-term purchase agreements for locally produced vaccines are critical in enabling domestic production to become a reality. Given the importance of universal vaccination in achieving Pakistan’s Sustainable Development Goals, the Planning Commission – as the custodian of the SDG’s for the country – may take the lead in forging a public-private partnership involving the Ministry of National Health Services, Regulation and Coordination. The private sector is needed to prioritise the antigens that need to be produced locally and develop a PPP framework to ensure the sustainability of domestic production. This includes fiscal incentives in the form of a tax holiday and duty-free import of plant and equipment, along with long-term buyback arrangements for locally produced vaccines.

Pakistan has an established network of public and private hospitals, pharmacies and labs. There is a need for the government to incentivise these and enhance capacities and capabilities. Lack of predictable policies is the biggest hindrance for any vaccine investors. In addition the public-private partnership in health must be also explored with pharmaceuticals paving the way for innovation.

Vaccines require a significantly higher level of regulation than drugs. As such, the role of the national regulator, Drug Regulatory Authority of Pakistan (DRAP), is critical in the development of an enabling environment for vaccine production. For example, no vaccine can be procured by the GAVI or international multilateral agencies or even exported to regulated markets, unless it is WHO-prequalified. In the case of vaccines, the WHO, before it can prequalify any vaccine manufacturer in a given country, has to first prequalify the monitoring, surveillance and quality assurance system of the country’s National Regulatory Authority (NRA). The National Control Laboratory for Biologics (NCLB), which is responsible for lot release of vaccines and biologics in the country, needs to build significant capacity and apply for WHO prequalification before any local manufacturer can be approved. The upgrade of NCLB needs to take place on a war footing.

International companies manufacturing WHO-prequalified vaccines should be eligible and be approached to enter into an agreement with the government of Pakistan for technology transfer to local partners. The original manufacturer of the vaccine or a manufacturer with WHO prequalification should be approached for this purpose. Local vaccine partners having validated biological production facilities, or willing to invest in the required standards would be ideal local partners for international companies providing the technology transfer. Local partner selection would be the prerogative and responsibility of the International Tech Transfer partner.

The implementation for Pakistan in the first phase is to span over an achievement time of five years. The local capability has to be up to Level 3 (vaccine product manufacturing from imported bulk). The vaccine types available for local production include vaccines currently not in EPI (not supported by the GAVI). As those would be available to the government at heavily subsidised pricing, and thus domestic manufacturing would not be feasible. One way in the first phase is to achieve up to Level 3 as indicated above and, in addition to addressing the emergency posed by Covid-19, opt for the following vaccines:

First, Hepatitis B (for children) – the Advisory Committee for Immunisation Practices (ACIP) at the CDC recommends that a birth dose of Hepatitis B single-antigen vaccine is preferred for all infants but must be administered to infants who are born to women who are Hep-B positive or whose Hep- B status is unknown. Pakistan ranks amongst the countries with the highest burden of Hepatitis B with an estimated 7-10 million people infected by the virus. Second, Pentavalent vaccine currently included in the schedule for EPI and administered to the entire birth cohort. Although, the vaccine is included in GAVI-funded support programme, local production may result in less strain on both the government and GAVI funds. Support disbursements for Penta by GAVI stood at roughly $365 million for 2000-2017 or $21.5 million annually. Third, Influenza Vaccine – Flu Vaccine is recommended for all persons 6 months and above. Influenza virus has been responsible for wide scale pandemics in recent times. In Pakistan alone, the cases for seasonal flu have soared. H1N1 cases in recent years have consistently increased and have also resulted in dozens of deaths. Pakistan’s Hajj and Umrah population is recommended a flu shot. In addition, Typhoid; Polysaccharide Typhoid vaccination is administered as a single injection and is approved for adults and children aged 2 years or older. Pakistan had the highest incidence rates for typhoid in a controlled study conducted by the WHO in five Asian countries (451/100,000). Lastly, Covid-19 vaccine. The government should urgently convene the international producers in a discussion to encourage investments in vaccine production for Covid-19 for Pakistan and the region, and ascertain the necessary support required in this regard.

The implementation of the second phase is to span over an achievement time of 7-10 years (2024-2030). The local capability is to be up to Level 5 (Vaccine product R&D and new antigens identifications and product development). Moreover, the vaccine types for local production include vaccines for the Covid-19 pandemic, the EPI and Pakistan-specific antigens. It is recommended that in the second phase, we achieve up to Level 5 as indicated above and opt for vaccines that are currently in the EPI schedule, so that Pakistan is prepared for when it graduates from the GAVI support.

Covax is co-led by the WHO, the GAVI, and the Coalition for Epidemic Preparedness Innovations (CEPI). Pakistan received 500,000 doses from SinoPharm, China which started for FLHCWs from 3rd Feb 2021 onwards.

It has secured about 17 million doses of AstraZeneca’s Covid-19 vaccine under COVAX scheme. About 6 million of the doses will arrive in the first quarter of 2021 under the scheme. These will be given to healthcare workers, senior citizens and high-risk populations.

COVAX countries will receive doses in proportion to their population size. The COVAX coverage is for 20 percent of the population prioritised for vulnerable population e.g. front-line workers and people over the age of 65. Also, Pakistan has allowed the AGP to import Sputnik vaccine from Russia. Given the financial impact of lock downs and the 11,000 plus deaths, Covid-19 vaccine will probably be deemed a good buy. The cost of the vaccine will most definitely be outweighed by the benefits.

The writer is a Pharmacy    Services Director at the The Aga Khan University Hospital, Karachi, Pakistan. He can be reached at shamimraza250@gmail.com