The complex journey of formulating vaccines

The vaccine manufacturing process involves dealing with live organisms and substances that must be rigorously purified and treated for hygiene and safety


AS THE most brilliant scientists around the world toil hard to find a cure for the Covid-19 virus, many countries have placed the hope on the discovery of a vaccine that could put an end to the outbreak which has infected millions of the population.

Today, vaccines are regarded as a vital tool in the battle against antimicrobial resistance, which will support global health security.

Vaccines are generally substances or compounds that function to form endurance.

It contains active ingredients called the antigens, which are obtained from part or all of the virus or bacteria structures that have been killed or attenuated.

The antigen in the vaccine serves to stimulate the body’s immune system to form immunity against specific infection or disease outbreaks.

Vaccines will also prevent an individual from contracting diseases, including Covid-19, hence the competition among countries to find the best solution.

According to Sanofi Pasteur Malaysia, Singapore and Brunei GM Camille de Lataillade, vaccine manufacturing is a very intricate process, which is held to the highest standard of safety.

She added that the manufacturing process involves dealing with live organisms and substances that must be rigorously purified and treated for hygiene and safety, while ensuring the efficacy of the finished vaccine.

“This means that every single step must conform to the highest levels of quality controls and stringent tests to ensure that they meet the requirements of health authorities around the world.

“Almost 70% of vaccine production time is spent on quality control, with further tests being conducted by health authorities in each country, in addition to a strict cold chain to preserve their efficacy throughout the distribution and delivery,” she told The Malaysian Reserve (TMR) in a recent interview.

De Lataillade said it usually takes between six to 36 months to produce, package and deliver high-quality vaccines to those who need them.

Taking the flu vaccine as an example, she said this process is shorter, taking only six months to accommodate the changing influenza viruses of each season.

During the two distinct influenza seasons every year, the World Health Organisation will issue their vaccine recommendation for the northern hemisphere and the southern hemisphere in February and September respectively.

The vaccines will then be manufactured, approved by the manufacturing country health authorities and delivered to the respective countries. The cycle is repeated again the following year.

As for Sanofi Pasteur, de Lataillade said the company produces 200 million doses of influenza vaccine every year, and it is a race against the clock every year.

She added that getting vaccinated saves up to three million lives every year, while an additional 1.5 million deaths could be avoided with improved vaccination coverage.

Process of Manufacturing Vaccines

Generally, the manufacture of vaccines is achieved from the four steps of propagation, isolation, purification and formulation of living organisms.

Additionally, all vaccine manufacturers are subject to national and international regulatory control and must comply with specifications for Good Manufacturing Practices.

Therefore, the process of manufacturing vaccines is conducted in a highly regulated and controlled environment.

According to the health experts from MyHealth Portal established by the Health Ministry, manufacturing is conducted in an aseptic environment and closely monitored by quality control measures.

The actual production processes may vary for different types of vaccines as some components of the manufacturing process are specific to either viral or bacterial vaccine production.

The first step, the propagation, involves the multiplication or the amplification of the living organism used in the vaccine.

During the second step, which is the isolation, the living organism used in the propagation step will be separated from the cells or growth media.

The third step requires purification, which removes all materials that may be adhering to the isolated organisms or selectively separates the portion of the living organism to be used in the vaccine.

Lastly, the formulation involves the mixing of the purified product in solutions to obtain a desired concentration.

The formulation step may also include the addition of components such as preservatives, diluents, adjuvants and stabilisers.

At the end of the manufacturing process, vaccines are typically filled in vials or syringes and packaged for shipping to healthcare providers.

It’s A Lengthy Process

The process of formulating a vaccine is time consuming, given the meticulous and complicated steps involved during the manufacturing.

According to de Lataillade, vaccine development is lengthy, as it involves complex processes, from developing, testing stages (preclinical to clinical studies phases) and regulating vaccines.

She added that it includes testing each batch of vaccine at every step of its journey, and repeat quality control of batches by different authorities around the world.

“In the vaccine field, ‘the product is the process’. This differs from other types of medication production because at the regulatory level, the manufacturing process must be registered, not just the product.

“With every minor modification of the manufacturing process, we must resubmit the marketing authorisation file to the health authorities in each country,” she said.

De Lataillade said since the manufacturing of vaccines involves dealing with viruses which are living organisms, they are less stable than synthetic pharmaceuticals.

“This complexity of working with living organisms increases the time required for vaccine production with the various quality control tests we have to do,” she said.

Additionally, de Lataillade said a vaccine is administered to a healthy person, which indicates high-quality standards.

She said in recent decades, monitoring throughout the manufacturing process of vaccines has increased which, in turn, extends the overall process.

How Does the Vaccine Work?

Apart from understanding why a vaccine takes so long to produce, it is also important to know how it will work once it is administered or injected to the human body.

De Lataillade said once injected in the body, a vaccine introduces an inactivated form of a virus into the body.

She added that the antigens in vaccines will act to stimulate the immune system to produce antibodies against specific diseases.

This will then strengthen the person’s immunity by preparing the defence cells to recognise the particular virus or bacteria so that they can better fight it in the future.

“For instance, if or when the real active virus enters the body, it is recognised by the immune system which may eliminate it.

“Vaccines will enhance our body’s natural defences without causing illness,” she noted.

The maximum effect of a vaccine will usually only take place or “kick-start” after the last dose in the schedule has been administered into the body.

Prevention Through Vaccines is Key

De Lataillade said getting vaccinated against seasonal flu protects people from the current influenza strains in circulation this year.

She said a typical influenza or flu vaccine is not effective in preventing Covid-19, as the infection is caused by two different viruses.

In terms of flu vaccines, de Lataillade said it has been used for decades with a good track record in terms of safety and efficacy.

However, in the development of the Covid-19 vaccine, manufacturers around the world are still in the process of developing and testing the vaccines to determine its safety aspect.

“It is understandable that everyone is focused on Covid-19 at the moment, but getting a flu vaccine could also help reduce false alarms at the various health screening points currently in place to monitor Covid-19 cases.

“It will also reduce the burden of seasonal influenza such as hospitalisation, which would allow healthcare services to focus their efforts on Covid-19 patients,” she said.

She also added that since flu is present year-round in Malaysia, people can take the flu vaccine any time, throughout the year.

Sanofi’s Stand on Covid-19

As a health journey partner and a vaccine manufacturer, Sanofi Pasteur has been working collaboratively with its partners on formulating the vaccine for Covid-19.

De Lataillade said the company is making great progress and its first clinical trials have begun.

“Our priority and focus are on the science that is needed to find the right vaccine.

“We have said from the beginning that we are committed to working with governments, partners and payers to ensure that when new vaccines are approved, they will be available and affordable for people at a fair and reasonable price,” she noted.

Sanofi SA is also anticipating to determine a final price for its Covid-19 vaccines at the time of its Phase 3 trials, when it has confirmed the dosing.

The company had been committed for more than 100 years to continuously invest in research and development in various fields of vaccinations.

In Malaysia, the vaccines manufactured by Sanofi range across vaccine-preventable diseases such as diphtheria, to polio, pertussis, tetanus, hepatitis A and B, meningitis, influenza.

On a yearly basis, Sanofi supplies one billion doses to people around the world and seeks to extend the benefits of vaccination to new infectious diseases, while improving existing vaccines to enhance health and wellbeing.

Read our earlier report here