Pharmaceutical products must be manufactured with perfection in mind. The slightest deviation from any production specification can quickly jeopardise the health and lives of human beings.
So, it is no wonder that regulatory authorities such as the United States Food and Drug Administration (FDA) and its European counterpart, the European Medicines Agency (EMA), keep a sharp eye on manufacturers. Pharmaceutical companies must document in painstaking detail that they have followed all regulations, from raw materials and how they are processed all the way through to product storage and transport.
In practice, this means multiple staff members must monitor production – inspecting, recording and extensively documenting all process steps. This ‘batch record’ is a kind of biography of the batch that contains a vast quantity of information and can fill up many hundreds of paper pages. Every medication has its own recipe that lists the ingredients and production steps down to the last detail – except that, unlike in the kitchen, each recipe is as long as several cookbooks.
This recipe includes not only the properties of the raw materials, but also the subtleties of how they are processed: the quantities, the ambient conditions, and exactly how they have to be mixed or fermented. Employees always have to study the detailed specifications in the batch record and then sign their names to confirm that everything was carried out within the specified parameters.
This makes it possible to make checks, such as which employee used which machine to weigh the materials. Such information allows the authorities to track the exact path that a batch took during production, should that become necessary.
Given the huge selection of medications and the wide variety of preparations – such as the distinct dosages prescribed for children and adults – pharma companies face a barrage of complex documentation requirements. At the same time, the industry is affected by ever-increasing price pressures, constantly pushing it to demand greater efficiency in production processes. With this in mind, Siemens has introduced a solution: ‘paperless pharma production’ to reduce documentation costs significantly while still complying with strict regulatory guidelines.
The basic idea is that rather than recording all data manually on paper, staff can write entries directly into a computer system. The information from production processes can even be automatically stored in an electronic batch record (eBR) and combined with data coming directly from automation and business systems. The eBR system is also able to give employees precise instructions for all workflows and process steps and can even control individual workflows without any human support.
All production information is stored in a master batch record (MBR) which works like a flowchart – plotting every production step with its specified underlying conditions and all conceivable branches that may occur during the production process – guiding employees through the process like a navigation system.
Paperless pharmaceutical production relies on the integration of various IT systems. For instance, the Manufacturing Execution System (MES) from Siemens, SIMATIC IT eBR, can communicate directly with a process control system, which, in turn, monitors the production steps and constantly records large volumes of sensor readings and other data. The smoothest integration is achieved with the Siemens Simatic PCS 7 process control system, but third-party products can also be configured to feed data into an eBR. SIMATIC IT eBR collects data through direct integration into the PCS 7 automation system.This allows a standardised data exchange of real-time process data with the MES.
The new Siemens solution is already being deployed by pharmaceutical companies in Europe, Asia, and the US. It not only shrinks paper volumes dramatically, but also reduces personnel costs: in some cases, a single employee can handle the monitoring and documentation that used to keep several people busy.
Paperless pharma production not only delivers a turbocharged efficiency boost for the production of conventional medications – it is also a prerequisite for realising one of the greatest hopes in cancer treatment
What’s more, all of this leads to much higher process quality. Software automatically detects any deviations during production and notes it in the eBR. This ‘review by exception’ identifies problems much earlier than before and helps avoid unnecessary costs. Without paperless pharma production it might take days before an error is noticed, by which time production is much further along, and, in the worst-case scenario, an entire batch may have to be destroyed. Review by exception ensures that this can no longer happen, keeping costs down in the process.
Paperless pharma production not only delivers a turbocharged efficiency boost for the production of conventional medications – it is also a prerequisite for realising one of the greatest hopes in cancer treatment – personalised medications and individualised tumour therapies. In addition, it opens the door to production of such patient-specific medications based on implementation of the same meticulous documentation standards as are applied to the production of mass-produced medications.
In Mainz, Germany, biotech company BioNTech is developing personalised cancer therapies (IVAC MUTANOME) along these lines. The therapies stimulate the immune system to effectively fight a patient’s cancer. Siemens and BioNTech have signed a strategic partnership agreement to help bring this type of customised therapy to market as quickly as possible.
The goal is a fully automated, digitised production facility for the fast, affordable, reliable manufacture of individualised BioNTech cancer vaccines starting in late 2016. Clinical studies are still in progress – but with the help of paperless pharma productions, they could go into large-scale market production after their approval and begin saving lives.
