Speeding up Covid-19 vaccine production setup with automation and digitalization



By Mr.Joseph Kong, Senior Vice President, Head of Digital Industries (DI) Siemens Thailand


If we are to list remarkable innovations done in the century, Covid-19 vaccine production would be ranked among the top of the list, if not the very top. When the novel coronavirus outbreak was declared a global pandemic by WHO in March 2020, the vaccine became the one item that was suddenly and simultaneously needed by all. While pharmaceutical firms could produce hundreds of millions of doses of Covid-19 vaccine in the matter of a few months, the world needed billions and as fast as possible.


Winning the race against time: Acceleration from development to manufacturing


Shorter time-to-market in vaccine production is crucial to save lives.  Accelerating clinical trials in the timeframes required to combat Covid-19 and ramping up production in the quantities needed are two of the biggest challenges the pharma industry has ever faced.



Ramping up Covid-19 vaccine manufacturing capabilities


The mRNA vaccine BNT162b2 (also known as COMIRNATY®) for Covid-19 by BioNTech, in collaboration with US pharmaceutical specialist Pfizer, was in extremely high demand even before it was available.


With such urgency, BioNTech converted its existing facility in Marburg, Germany, to further scale-up Covid-19 manufacturing capacity. Prior to mRNA vaccine, the Marburg facility had been producing influenza vaccines based on flu cell culture, then changed over to recombinant proteins for cancer treatments.


Besides a higher clean room(1) class required than what existed in the facility, when working with mRNA, one of the challenges faced was the need to switch from rigid to mobile production, with many single-use components(2).


mRNA vaccine production processes involve several manual work steps. Weighing is one such example. Precise measurement and reliable recording of weights are vital to ensure vaccine quality. With batch system and process orchestration, the operators get a guidance from the Manufacturing Execution System (commonly known as MES(3)) throughout the entire process on when and which actions are needed to be taken. This is enabled by the workflow management component of the software which orchestrates the various sections of the system, in ensuring the most efficient production.



Paperless production for faster and more efficient process


Paperless production offers many advantages over traditional procedures in the pharmaceutical industry.  Electronic Master Batch Record Management enables users to create, execute, review, and release Master Batch Records (MBR)(4). In addition, Electronic Batch Records (eBR)(5) are made faster. Testing is based on the principle of “review by exception” – in other words, deviations are dealt with when the system recognizes them based on exception rules. That makes the testing process less labor-intensive.


This new system and end-to-end digitalization of vaccine production enabled a conversion to “paperless documentation of production” that can immediately fulfill all documentation requirements, which is a critical component to validating vaccine efficacy.


To automate the entire facility, all systems need powerful, flexible, and scalable distributed control system that steers and controls all processes in the plant and takes digitalization to the field level. Seamless integration of automation solutions makes it possible to develop, optimize, and manage production processes efficiently.



All the improvements made at the Marburg plant are Industry 4.0 compatible.


The Marburg plant has been producing the vaccine since the end of March 2020. A digitalization and automation project of this magnitude normally takes about a year. With support from Siemens, the Marburg plant conversion was completed in just five months, with the main components of the new MES completed in only two and a half months. The Marburg facility at full operation can produce up to one billion doses annually.      


Siemens and BioNTech plan to intensify their collaboration for the rapid expansion and creation of production capacity for the Covid-19 vaccine. The aim is to establish new production sites for Covid-19 vaccine production worldwide based on the Marburg plant and its technology, starting with a production facility in Singapore. Within this cooperation, Siemens will provide the latest automation and digitalization technologies for BioNTech production sites, such as design, simulation, and engineering software as well as process control technology.




Definition of terms


(1)  Cleanroom: an engineered space, which maintains a very low concentration of airborne particulates. It is well isolated, well-controlled from contamination, and actively cleansed. Such rooms are commonly needed for scientific research, and in industrial production for all nanoscale processes, such as semiconductor manufacturing. A cleanroom is designed to keep everything from dust to airborne organisms, or vaporized particles, away from it, and so from whatever product is being handled inside it.


Source: https://en.wikipedia.org/wiki/Cleanroom


(2) Single use component: A component that is intended to be used once (single use). Specifically, single-use components include plastic bags, filters, tubing, connectors, solution-storage bottles, and sensors.


Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674654/


(3) Manufacturing Execution System (MES) are software solutions that ensure quality and efficiency are built into the manufacturing process and are proactively and systematically enforced. Manufacturing Execution Systems connect multiple plants, sites and vendors’ live production information, and integrate easily with equipment, controllers and enterprise business applications.


(4) Master Batch Record: The official written instructions or recipe for the manufacturing of each particular product part number using a specific manufacturing process. It is intended to ensure that all proper ingredients are added and that each step in the process is completed and documented.


(5) Batch record: Accurate copy or reproduction from a Master Batch Record to be associated with one particular lot number. Since the Batch Record is a copy of the Master Batch Record for each lot to be manufactured, it is filled and contains the evidence that a particular lot was done following the corresponding instructions.


Source: https://ciqa.net/what-is-a-master-batch-record/