By Prof P.T. Thomas

The whole world is anxiously waiting for the COVID-19 vaccines to be made available in their own countries. Many parties may resort to obtaining these vaccines as quickly as possible out of fear, and so it is imperative that the public learn about the complex supply chain that governs the production and distribution of these vaccines.

Because demand will outweigh supply initially, vaccine administration must also be prioritized so that the most vulnerable in the population – the elderly and frontliners – receive vaccination first.

The Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK was the first regulatory agency in the world to approve a vaccine, the Pfizer-Biontech (Pfizer) vaccine, for use.

Subsequently, the US Food and Drug Administration (FDA) approved two vaccines – Pfizer and Moderna – for emergency use.

More recently, the European Medicines Agency (EMA) and the Health Sciences Authority (HSA) in Singapore have also approved the Pfizer vaccine for use.

The vaccine has already been administered to hundreds of thousands of individuals.

A third candidate, the AstraZeneca-University of Oxford (AstraOxford) vaccine has just been approved for emergency use by the MHRA.

There are other vaccines produced in China and Russia which have been administered largely in their own populations. However, these have not been subjected to same level of scrutiny as have been the Pfizer, Moderna and AstraOxford vaccines.

Malaysia has committed to purchasing the Pfizer, AstraOxford vaccines and others which have not been identified yet through the COVAX initiative of the Act-Accelerator Partnership (an undertaking of the WHO and Bill and Melinda Gates Foundation).

However, the Drug Control Authority (DCA) of Malaysia has not yet approved any COVID-19 vaccine.

Recently, it was reported that Pfizer had already submitted a dossier for evaluation to the National Pharmaceutical Regulatory Agency (NPRA) for evaluation.

The Malaysian government is also in final stages of negotiations with two vaccine manufacturers from China, Sinovac and CanSinoBio, as well as Gamaleya from Russia to purchase their vaccines.

The production and approval of a vaccine, its marketing and administration to a healthy individual is all part of a complex supply chain process influenced and subject to different practices meant to ensure that the vaccine is safe, efficacious and of quality. 

Weaknesses in the supply chain can affect the safety, quality and efficacy of a vaccine, hence it is important to pay attention to various components of the supply chain as detailed here.

Good Manufacturing Practice (GMP)

GMP is essential for all medical products because the way in which they are manufactured will have a significant impact on the final product. This is especially important in a medical product because its quality (or lack of it) will have a direct impact on morbidity and mortality.

Large scale vaccine production must ensure the safety, quality and efficacy of each unit/vial.

The quality of a product is influenced not only by the manufacturing process but also the physical facilities, quality of raw materials, personnel, documentation, training and quality systems, as well as packaging material.

While Malaysia currently does not have any manufacturers of vaccines, two local manufacturers in Malaysia (Pharmaniaga and Duopharma) have already indicated that they have the necessary facilities to fill and finish vaccines.

Malaysia is part of the internationally recognized Pharmaceutical Inspection Cooperation Scheme (PICs) and thus Malaysian manufacturers and finish and fill facilities approved by the NPRA will be in line with international standards.

The importance of GMP was highlighted recently when a mistake was made in the filling of the vaccine dose in an Astra manufacturing facility where the AstraOxford vaccine was manufactured for clinical trials.

The dose filled in the vial was lower than what was stated on the label. By the time the mistake was discovered the vaccine had already been administered to subjects in the clinical trial.

As serendipity would have it, a low dose of the first injection followed by a "normal" dose of the second injection gave an efficacy rate of 90% whereas, two equal doses (as planned) produced an efficacy rate of 70%.

However, despite the possible positive outcome, the filling of the lower dose is a serious breach of GMP.

Good Distribution Practice (GDP)

This refers to the practices in the distribution of the product from the time it leaves the manufacturing site to the point of administration to the patient/healthy individual. It includes transport by road, rail, water (sea and river) and air.

In the case of the COVID-19 vaccine, the maintenance of a cold chain through refrigeration and storage at very low temperatures is essential to ensure global access to the vaccines.

Both the Pfizer and Moderna vaccines require storage below freezing temperature, -70°C and -20°C respectively. Thus, they are packed with dry ice in sealed thermal shipper boxes and shipped in refrigerated containers.

Any excursions from the cold chain will have detrimental effects on the vaccine. The thermal shipper boxes of the Pfizer vaccine have GPS enabled thermal sensors that will track the location and temperature of the vaccines that are shipped across the globe.

All logistic companies like FedEx and DHL, importers and distributors of the vaccine must have suitable storage facilities and refrigerated transport facilities.

There are a few companies in Malaysia who have indicated interest to import vaccines for supply, primarily for the private sector. They will need to have the required facilities for proper storage of the vaccines for distribution.

Internet sales

Buying medicines or medical products over the internet is to be done with caution.

While it is illegal to sell prescription medicines (including vaccines) over the Internet, the sale of health supplements and products not containing controlled substances is permitted. However, the safety, efficacy and quality, and authenticity of products sold over the Internet cannot be guaranteed.

Soon after the approval of the Pfizer vaccine by MHRA and US FDA, there were reports of products claiming to be vaccines being sold on the Internet. The Malaysian public should be educated and warned not to buy vaccines on the Internet.

Unfortunately, a good supply chain does not by itself ensure access to the vaccine to all who require it.

The Malaysian Government has already announced that vaccines will be provided free for citizens and in anticipation of regulatory approval from the DCA, the government has placed advance orders for the Pfizer and Astra vaccines, and vaccines from the COVAX initiative, and is in negotiation for orders of vaccines from China and Russia.

Reports indicate that the advance orders will cater to up to 82.8% of the Malaysian population. It is believed that when 80% of a population is vaccinated, the population will achieve herd immunity.

However, in view of the latest highly transmittable mutation of the virus, countries like Singapore think that 90% the population will need to be vaccinated for effective herd immunity.

Rich countries like the UK, US, European countries and Canada have placed orders for vaccine doses up to nine times what is required for their populations. This will result in poorer countries probably not having vaccines in a timely manner.

According to some estimates, their populations may only be fully vaccinated in 2024! Some developing countries like India have the facilities, capacity, and expertise to manufacture affordable versions of the COVID-19 vaccines at lower cost. However, for them to be able to do that, the World Trade Organization (WTO) must waive intellectual property protection.

We can only hope that all nations and pharmaceutical companies look at this collectively as a global problem and work in concert, with the rich helping the poor, for greater global good as opposed to profit, to ensure everyone has access to an effective vaccine as soon as possible.

(Prof P.T. Thomas is the Executive Dean and Professor at the Faculty of Health and Medical Sciences, Taylor's University and Director of the Taylor's University APEC-LSIF Centre of Excellence for Global Supply Chain Integrity.)