The fill-and-finish process is done under aseptic conditions from start to finish at the PLS plant. — Photos: Pharmaniaga
Say the word “vaccine” now and all who hear you will immediately think of the Covid-19 vaccine.
Held up as our best shot of resolving the current pandemic and getting back to some semblance of our “old” normal life, manufacturers around the world are racing to keep up with the relentless demand for the various approved vaccines on the market.
Playing its part in fulfilling our own country’s demand for these vaccines is local pharmaceutical group Pharmaniaga Bhd.
Tucked away in the middle of Puchong, Selangor, the company’s subsidiary, Pharmaniaga LifeScience Sdn Bhd (PLS), is all set to complete the production process of the CoronaVac vaccine (more popularly known as the Sinovac vaccine after its developer Beijing-based biopharmaceutical company Sinovac Biotech Limited) for local use.
About 14 million doses of the vaccine’s active ingredient are set to make their way to our shores for the final fill-and-finish process before they are ready to be distributed nationwide.
A total of 12 million doses have already been booked by the government, while the remaining two million will likely be made available for sale to companies and individuals.
Validation batch
In fact, the first batch of 200 litres, which is equivalent to about 300,000 doses, have already been filled into their vials.
Having arrived in Malaysia from China on Feb 27 (2021), the bulk batch was immediately escorted by the police to the PLS plant.
Once there, it took about four-and-a-half-days to complete the fill-and-finish process, according to Pharmaniaga Head of Manufacturing Mohd Saharuddin Othman.
He explains: “For pharmaceuticals, when you first start producing (a drug or vaccine), you have to do a process validation batch.
“But because of this validation, a lot of sampling happens (throughout the process) and this takes time.”
He estimates that once commercial production starts, the plant will be able to complete around 80,000 vials per day – easily hitting the targeted two million doses per month.
Currently, a number of the vials from this validation batch are being kept aside to monitor their stability.
“A stability study was initiated and is being monitored for this validation batch.
“This is a critical part of the process as the generated data has to be submitted to the NPRA (National Pharmaceutical Regulatory Agency) for their approval,” he says.
After the appropriate surveillance period, the vaccines from this batch will be tested to ensure that they are still stable and able to work as expected.
This is to ensure that the fill-and-finish process here does not affect the effectiveness of the vaccine.
Once approval is received from NPRA, Pharmaniaga can move full steam ahead in completing the production of the Sinovac Covid-19 vaccines for Malaysia.
In the meantime, the finished vaccine manufactured by Sinovac, which is also being distributed by Pharmaniaga, has already received conditional approval from NPRA, with 200,000 doses already available and on the ground.
Samples were frequently taken and tested during the production of the first batch of vaccines for quality control purposes.
Doing it right
Of course, the journey to this point did not start on Feb 27 (2021); it didn’t even begin on Jan 12 (2021) when the agreement with Sinovac was signed.
Opened in 2004, PLS is a specialised high-tech sterile small-volume injectable plant.
It is also the first local pharmaceutical plant to receive the European Union (EU) Good Manufacturing Practice (GMP) certificate, which was awarded to the plant in 2013.
As such, it has plenty of experience in producing injectable products in ampoules and vials.
“It is not so difficult for us to repurpose our line for vaccines,” Saharuddin comments.
He adds: “We have been doing terminally-sterilised products and aseptic fill products; and this Covid-19 vaccine is an aseptic fill product.
“In terms of the principles of managing this product, we have been trained.
“So we’re very comfortable with this filling (process).”
Despite that, he shares that true to their motto of “Do it right”, the team conducted plenty of practice runs using a placebo product before the Sinovac bulk vaccine arrived.
“A lot of man-hours has been invested in building competency in this fill-and-finish process, especially in handling biopharmaceutical products.
“We have also invested a lot of man-hours in doing risk assessment, identifying critical control points and coming up with a mitigation control plan in case anything goes wrong,” he says.
The main issue, he explains, was learning how to transfer the large amount of active ingredient from its special refrigerated container to the production line within the plant safely and sterilely.
For this, the plant had to convert to a single-use system, where the parts come sterilised and are disposed of after usage.
This system, which has been adopted widely throughout the biopharmaceutical industry internationally, has the advantage of preventing cross-contamination between different batches, eliminating cleaning and sterilisation time, and increasing process flexibility, among others.
Says Saharuddin: “We invested in a certain amount of new equipment to facilitate the change to this new single-use system.
“And also in terms of testing, there’s a lot of investment actually.
“For example, in rapid sterility testing, using the traditional method, the incubation period for the sample would take 14 days.
“But through investment, we are able to expedite the testing to within five to seven days.”
He adds that a lot of time also went into training their staff in the new technology.
Thanks to that, the production of the first batch went fairly smoothly.
While there were some minor teething challenges initially, they were quickly resolved, according to Saharuddin.
“It delayed the process, but didn’t harm or affect the quality of the product,” he adds.
“The second day onwards went really smoothly, and towards the end of the batch, we got some feedback from the team saying that they feel more confident in handling future batches.”
Knowledge transfer
Aside from lowering the cost of the vaccine and easing the logistics of distributing it, another main advantage to the partnership between Sinovac and Pharmaniaga is the knowledge transfer from the former to the latter.
According to Saharuddin, the fill-and-finish process for the first batch of Sinovac vaccines went off fairly smoothly, and the team is confident in handling future batches.
Saharuddin notes that being trained to use new equipment is one matter, but learning where things might potentially go wrong is another, and this is where Sinovac came in.
“The discussion with Sinovac was more towards identifying the critical control points – where things might go wrong – especially considering that biopharmaceutical products are highly sensitive,” he shares, adding that equipment manufacturers will not address this as they are just training you to use the equipment.
“By having these discussions with Sinovac, it really launched us to a different level in terms of understanding this new technology and the nature of biopharmaceuticals.
“It really expedited our learning curve,” he says.
In addition, the Pharmaniaga team was also able to learn and gain a better understanding of vaccine development and manufacturing.
“In terms of understanding biopharmaceutical products and the vaccine characteristics, our team also asked them how, in general, the vaccine was being manufactured and how to handle the vaccine in the correct manner,” he shares.
For example, he notes that there is actually a lot of science behind why the Sinovac vaccine needs to continuously maintained at a temperature of 2-8°C, whether during the fill-and-finish process, product storage, or transportation and distribution.
“It has also really helped us in developing our halal vaccine manufacturing blueprint.
“Because in our halal vaccine manufacturing project, not only will we do fill-and-finish from our partners, but we also have one product for which we will have our own IP (intellectual property), where we will develop it ourselves and do the manufacturing in Malaysia,” he says.
Part of Pharmaniaga’s current business strategy is to enter the halal vaccine manufacturing sector – a goal they have been working towards since 2018.
Saharuddin shares that after the first batch of Sinovac vaccines was completed, the team immediately conducted a review of the process.
“We have identified about 11 improvement ideas and action plans to be implemented in future batches.
“These action plans will really help us to further finetune our operations and improve the productivity of the fill-and-finish process.”
- It is an inactivated virus vaccine.
- It was developed by Chinese biopharmaceutical company Sinovac Biotech Limited’s Sinovac Life Sciences unit.
- It contains inactivated SARS-CoV-2 viral antigen (Wuhan strain), aluminium hydroxide, sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium hydrochloride and water.
- It requires two injected doses 14 to 28 days apart.
- The latest phase 3 clinical trial results from Turkey (as of publication time) report that it is 83.5% effective in protecting against symptomatic Covid-19, and 100% effective in protecting against hospitalisation for Covid-19.
