Jennifer Markarian is manufacturing reporter for Pharmaceutical Technology.

Jennifer Markarian

Amorphous solid dispersions (ASDs) are increasingly used to address the need to enhance bioavailability of poorly soluble APIs. Contract development and manufacturing organizations (CDMOs) that have amassed knowledge and experience in this specialty area play a key role in the pharmaceutical industry by providing the capabilities of developing and manufacturing ASDs.

“The pipeline of poorly-soluble drugs continues to grow, and ASDs remain the best-in-class platform to address poorly-soluble drugs,” says Filipe Neves, strategic business senior director at Hovione. He says that spray drying has been proven as a technology for the current good manufacturing practice (CGMP) manufacture of ASDs and that pharmaceutical companies have gained confidence in the technology and its reliability. Spray drying is becoming widely accepted and is seeing a year-on-year increase in adoption, reports Neves.

“Today’s APIs are increasingly insoluble, and that can pose serious problems for formulators looking to manage the bioavailability of their formulations,” says Lieven Van Vooren, scientific director, Ardena, a Belgian-headquartered CDMO that acquired Spain-based Idifarma and its spray-drying capabilities in Sept. 2021.

“The formulation of an ASD is increasingly being recognized as one of the more reliable and efficient strategies for optimizing the solubility and dissolution characteristics of low aqueous solubility compounds,” Van Vooren explains.

“The increased development of biologic-based drugs has also fueled demand for spray drying as an alternative for the manufacturing and processing of biologics, instead of the more traditional liquid or lyophilized solid forms,” addsWilliam Wei Lim Chin, manager, global scientific affairs, Catalent. He says that additional growth in spray drying comes from the increased consideration of spray-dried intermediate powders for both local and systemic inhalation delivery of biologics.

Spray drying and hot-melt extrusion (HME) are the two most widely used technologies for CGMP manufacturing of ASDs. In spray drying, the API and excipient are dissolved in a common solvent, which is then evaporated to form ASD particles. In HME, the API is dissolved and dispersed in the molten, polymeric excipient, which is then cooled to form ASDs. An advantage of HME is that it doesn’t require the use of solvents and the additional drying step. HME has some constraints, however, particularly for thermally sensitive APIs.

“The constraints of the HME process are that both the drug and the matrix must be miscible and compatible at the temperature at which the process takes place. In addition, the components must maintain this miscibility during the cooling stage,” says Van Vooren. “Another major limitation of HME is the stability of the drug at the high temperatures at which this process is performed. On the contrary, in the case of spray drying, the evaporation process is instantaneous and therefore suitable for thermosensitive products. In addition, the control of the physical properties of the spray-dried product allows manufacturers to obtain a particle size and morphology suitable not only to meet the dissolution goals, but also to obtain density and flow characteristics that facilitate the downstream processing.”

In HME, homogeneity may be more sensitive to process parameters (such as temperature) and equipment parameters, explains Neves. He adds that spray drying is, in general, more suitable for early clinical stages because formulations can be developed and produced with minimal amounts of API.

New tools, however, may be able to address the challenge of API volume at early stages.

“There is currently a significant focus on creating advanced development tools for both spray drying and HME that allow for fast, de-risked development of ASDs using minimal quantities of API,” says Chin. “When the API is compatible with both the thermal and shear stresses of extrusion, HME offers a robust manufacturing process without the use of large volumes of solvents.”

Selecting HME or spray drying can depend on many factors, including the stage of drug development program, time, and cost, Chin concludes. Both HME and spray drying can be used in continuous solid dosage processing.

“Spray drying is a continuous manufacturing (CM) technology,” says Neves. “It offers a remarkable control over the properties of the manufactured powders, with significant downstream advantages. With adequate process development, spray drying can enable ASD formulations that are directly compressible, thus bypassing the need for granulation prior to tableting. When accomplished, this will enable much simpler CM equipment trains and processes, benefiting overall operational efficiency, speed, and conformity.”

Scaling up from development to commercial-scale spray drying present challenges related to the spray-dried bulk powder properties.

“Changes in process conditions, due to the different configuration and dimensions of the spray dryer from development to commercial scale, have a major impact on the critical quality attributes of the spray dried powder, especially on the particle size, its distribution, and residual solvent content,” says Chin. “To understand the impact of these process changes, thermodynamic and kinetic modeling techniques, supported by engineering modifications as well as exploratory laboratory work, have emerged to support a rapid and successful scale-up of spray drying processes.”

The downstream processing method should be considered in scale-up, says Neves. For example, directly compressible powders for tableting may require specific combinations of particle size and bulk density. Inhalation delivery would require different criteria, such as composite powders of small particle size, controlled within narrow ranges, explain Neves. He notes that streamlined scale-up relies on a thorough process understanding, which can be aided with advanced formulation and process modeling tools.

Formulation of ASDs involves screening APIs, excipients, and other ingredients to determine the optimal combination. The Hovione Intelligent PROprietary Screening methodology for ASDs (ASD-HIPROS) was launched in January 2021 and is offered from the company’s Lisbon, Portugal, R&D center (1).

“The service aims at developing ASDs formulations with maximum stability and performance by eliminating inviable candidates, thus saving the time and investment needed to bring the drug to the patient,” says Neves. He explains that this proprietary process can assess up to 24 formulation prototypes in six weeks, requiring as little as five grams of API.

 computational screening based on the API properties (to determine most suited polymers, surfactants, and drug loads), spray drying experimental prototyping of the most promising formulations, and analytical testing and solid-state characterization (to confirm proper dissolution in bio-relevant media as well as stability under stress conditions),” says Neves.

Van Vooren adds that in scale-up, the large number of process parameters and product characteristics add to the complexity of the spray drying process. He explains that defining a design space where the process is controlled is key.

“Approaches such as quality by design, which employs tools such as design of experiments, allow us to identify from early stages the risks related to the formulation and manufacturing process that can potentially impact product quality and, consequently, to be able to guide studies to mitigate such risks,” says Van Vooren.

Van Vooren adds that differences between laboratory and industrial-scale equipment can cause variations in evaporation rate, particle trajectory, residence time, and other factors.

“It is highly recommended to also consider the finished dosage form manufacturing requirements and technologies, since integrating the spray drying process and the finished dosage manufacturing in a single facility reduces risks and timelines, and simplifies the supply chain for the product,” concludes Van Vooren.

CDMOs have been adding capacity for both development and commercial scales to meet the expected demand for spray drying.

In November 2021, Hovione announced that the company would add commercial spray-drying capacity and equipment as part of its expansion at its facilities in the United States, Ireland, and Portugal (2). At the US facility in NJ, the company is constructing a new building and will have additional commercial spray drying capacity online by 2023. New commercial spray dryers are also slated for the Cork, Ireland and Lisbon, Portugal facilities.

Catalent acquired the manufacturing and packaging operations of Acorda Therapeutics, Inc. in January 2021, including a 90,000-ft2 CGMP facility in Chelsea, Mass. with spray drying capacity that provides Catalent with significant commercial-scale capacity for new customer programs. Catalent said that the Chelsea facility will act as a global center of excellence within the Catalent network for spray-dried dispersion and dry powder encapsulation and packaging (3).

Catalent also announced a manufacturing collaboration with clinical-stage pharmaceutical company DisperSol Technologies in August 2021 (4). DisperSol’s clinical products are made using its proprietary KinetiSol ASD platform. As part of the collaboration, DisperSol transferred its technology by setting up its proprietary equipment in a dedicated suite in Catalent’s Somerset, NJ facility. Catalent is providing staff for development, scale-up, and commercial-stage KinetiSol production.

Spray drying is suited to ASDs but is also finding use in other fields, such as microencapsulation, nanotechnology, and vaccines, according to Van Vooren. “Spray-drying stands out as an accessible, repeatable, and scalable process that offers developers a cost-effective way to improve the solubility and bioavailability of their formulations,” Van Vooren concludes. 

Hovione, “Hovione Launches ASD-HIPROS,” Press Release, Jan. 12, 2021.

Hovione, “Hovione Invests $170 million in New Capacity and Capabilities,” Press Release, Nov. 11, 2021.

Catalent, “Catalent Agrees to Acquire Dry Powder Inhaler Spray Drying, Capsule Manufacturing, and Packaging Capabilities from Acorda Therapeutics,” Press Release, Jan. 13, 2021.

Catalent, “DisperSol and Catalent Collaborate to Establish KinetiSol Technology Manufacturing Hub for DisperSol Pharmaceutical Pipeline,” Press Release, Aug. 2, 2021.

 Supplement: Bio/Pharma Outsourcing Innovation
2022 
February 2022 
Pages: s22–s24,s29

When referring to this article, please cite it as J. Markarian, “Spray Drying Finds Growing Use for ASDs,” 

Articles

CDMOs offer expertise and capacity for spray drying.

Spray Drying Finds Growing Use for ASDs

Digitalization is taking hold in many areas of the pharmaceutical industry. 

 spoke with Marcus Michel, CEO of ACG Engineering, about digitalization in pharmaceutical manufacturing equipment and ACG’s own digital transformation journey.

 What trends do you see currently in use of digitalization/Industry 4.0 technologies for the equipment you supply to bio/pharma manufacturers?

 Industry 4.0, or the ‘digital revolution’, is gaining momentum within the pharmaceutical industry. In particular, Big Data, artificial intelligence, cloud computing, continuous connectivity, and advanced analytics through the Industrial Internet of Things (IIoT) are being utilized by pharma and biopharma manufacturers to deal with issues, such as rising complexities, costs, remote connectivity, and regulations. Smart factories managed with data analytics and machine learning will lower pharmaceutical manufacturing costs, improve quality, and reduce capacity constraints. Ongoing advances in predictive analytics are enabling manufacturers to draw on vast pools of data, including information on resource consumption, machine performance, and storage conditions on shop floors to troubleshoot problems, optimize processes, and boost productivity.

With forward-thinking pharmaceutical companies expediting their plans for digital transformation following the COVID-19 pandemic, a few trends indicate the early stages of adoption of Industry 4.0 in the pharmaceutical manufacturing sector. These trends include smart connected machines and factories; the leap from a reactive to a proactive framework using data analytics; augmented and virtual reality (AR/VR) services, including remote machine maintenance, remote factory acceptance testing, and even installation and commissioning; additive manufacturing; process unit design; digital twin systems; and personalized medicine and the correct use of big data.

ACG began its digital transformation journey in 2017 with four broad objectives: 1) to use emerging digital technologies to transform manufacturing operations, 2) to enhance customer experience, 3) to build smart products and services, and 4) to create new business models. Reducing machine breakdowns and enhancing overall equipment effectiveness in capsule manufacturing were the key business drivers. While the current focus is on transforming operations, ACG is expanding into building smart connected products and services, developing customer experiences, and creating digital-led business models.

 What do you see as the biggest obstacles to the implementation of these technologies?

 The major challenges experienced by the pharmaceutical industry during this digital revolution are:

Integrating new information technology (IT) systems and updating existing systems

To completely capitalize on the potential of the IIoT, pharmaceutical manufacturers need to invest in an IIoT infrastructure that has the capacity to handle their high level of requirements. As data and network security are of paramount importance, manufacturers must also be prepared to integrate existing protocols with the latest security solutions. There must be a check on the data that is flowing out of the plants to the Cloud servers. Manufacturing shop floors typically house a wide variety of equipment and associated software, some of which are legacy systems and no longer enjoy vendor warranty. Therefore, IIoT relevant upgrades are crucial. However, these upgrades can be costly. Additionally, the workforce needs to be trained, upskilled, and educated on the importance of these technological advancements, as they are an integral part of this digital transformation.

 What do you see as needs in workforce training or changing the business and work culture to adapt to these new technologies?

 Building, deploying, and adopting Industry 4.0 initiatives requires a wide variety of technology and domain capabilities. Active collaboration with the original equipment manufacturers, continuous improvement cells, and hands-on training sessions will help in developing the required skill sets. Pharmaceutical manufacturers will have to work on developing a few core competencies, as well as flexibility, to be in the driver’s seat for successful adoption and implementation of digitalization and the technologies of the future. These competencies include:

 Industry 4.0 needs existing systems to be updated and, in some cases, entirely new IT infrastructure setups. Legacy systems are workhorses, but not high on data security, cybersecurity, and flexible communication protocols. Companies need tailored risk management systems, in addition to a strategy for cybersecurity across the organization and value chain.

 Digitalization increases the need for companies to develop new skills at an individual associate level, as well as at an organizational level. To shorten the skill development timeline, recruiting a digitally acquainted workforce and virtual training through AR/VR applications are measures being adopted by companies. This is important in terms of improving quality since we are dealing with pharmaceutical products.

 As horizontal integration will create transparency and flexibility across process chains—from procurement to production and maintenance—vertical networking opens doors to collaborate with customers and [original equipment manufacturers] to build new business models for product-based customized solutions and remote aftermarket services. Remote condition monitoring, data analytics, and sharing insights across the value chain will open avenues for different business models.

 Flexibility for adaptation will be different for different segments in an organization. R&D, services, warehousing, and production have great potential to adapt and benefit from this shift to new technologies. However, the business rules and set process standards make it difficult for warehousing, administration, and sales to transform.

 What do you see as the future in adoption of digitalization technologies in bio/pharma manufacturing?

 The Fourth Industrial Revolution is beginning to flourish within the pharmaceutical sector, which was reluctant to change before COVID-19 hit the world. Due to the pandemic, companies have realized the need for digitalization and are now focusing on a complete adoption of digital technologies. What does Industry 4.0 mean for the pharmaceutical industry? It means increased connectivity, higher productivity, simplification, and transparency in compliance, as well as consolidation and analysis of production information to optimally respond to manufacturing issues as they emerge.

Although there are challenges to be addressed, the digital transformation of equipment has begun. 

Digitalization in Pharmaceutical Manufacturing Equipment

The benefits of digital maturity in pharmaceutical manufacturing were made evident by the COVID-19 pandemic during 2020 and 2021, as the sudden need to develop, manufacture, and distribute treatments and vaccines intersected with travel restrictions, social distancing, and supply chain interruptions. Digital technologies that could meet these new challenges and aid manufacturing scale-up and speed to market, such as automated digital data collection and augmented and virtual reality (AR/VR) remote collaboration tools, were already available and had been adopted by some, but the new demand spurred greater adoption. The need to solve manufacturing challenges gave more companies the incentive to initiate or make further progress on their digital transformation journeys.

“These events directly showed the payoff of information technology (IT)/operational technology (OT) integration achieved over the last several years, but also revealed that we have an opportunity to do much more,” says Dan UpDyke, strategic marketing manager at Rockwell Automation. “The ability for the industry to pivot and quickly bring new therapies to market highlighted the need for flexible, saleable, and connected manufacturing systems. We have already seen an increase in integrating data and recipe management through a manufacturing execution system (MES) and flexible distributed control systems (DCS),” says UpDyke. “These are technologies that enable faster time to market by reducing the efforts to shift to new products.”

“As an industry, we’ve seen we need to be more efficient and we need to be able to monitor and manage processes remotely from a centralized location. People are focused on process intensification and how to better digitize and automate their processes,” says Merrilee Whitney, head of the BioContinuum Platform at MilliporeSigma, the US and Canada life science business of Merck KGaA.

The pandemic created a higher awareness of the need for digitalization, adds Dirk Wollaert, Vertical Market Pharma at Siemens headquarters in Belgium. Digital technologies were key to the success of the rapid development and rollout of the COVID-19 vaccines, facilitating cross-company collaborations even across national borders. “Globalization and industry standardization to facilitate smoother transition from one production plant to another became more important,” he explains.

Another change that accelerated in the past two years was a transition to the cloud for software solutions and data storage, adds Pamela Docherty, Life Sciences Industry Manager at Siemens USA. “The ability to push data from the manufacturing floor to the cloud creates a backbone for digitalization,” she says.

In bio/pharmaceutical manufacturing, the application of “Industry 4.0” techologies, such as digitalization, must be aligned with regulatory requirements, including good manufacturing practices (GMPs). The International Society for Pharmaceutical Engineering (ISPE) has trademarked their initiative as Pharma 4.0, also dubbed the “Smart Factory,” and has developed an operating model, which the Pharma 4.0 special interest group notes goes beyond IT to organizational, process, and resource aspects (1).

“There is a cultural aspect to digitalization because it’s a significant investment that results in changes to the operational structure of a facility; it is beneficial when the digitalization comes from the top,” explains Yvonne Duckworth, automation engineer and Industry 4.0 subject matter expert at the CRB Group, a life sciences engineering and construction company. “We are seeing more often that management is driving the adoption of digitalization in new facilities. It is becoming a standard and expected part of facility design.”

In the past five years, pharma manufacturers have been moving toward digital maturity. Assessed using the BioPhorum Group’s Digital Plant Maturity Model (2), some manufacturers are at level 1 (predigital); some are at level 2 (digital silos and islands of automation); many are at level 3 (connected plants) on their way to level 4 (predictive plant with real-time predictive analysis), and others want to adopt some aspects of level 5 (autonomous, adaptive plant), says Duckworth.

Although in past years, digitalization primarily meant moving away from paper-based systems to digital reports that were then printed to electronic or physical paper, a new paradigm enables a jump from Pharma 2.0 paper-based systems to the Pharma 4.0 operator-centric connected plant, said Gilad Langer, industry practice lead at Tulip, which supplies a cloud-based front-line operations platform (3). “This paradigm shift changes the culture and the processes, but doesn’t significantly change the operator’s workflow. Instead, digital apps are built to bring the physical world to the digital world with sensors and cameras, with digital output as the evidence. Data from equipment and human activities are collected via the industrial Internet of things (IIoT),” explained Langer.

To read the full article, which was published in the December issue of Pharmaceutical Technology, go to 

www.PharmTech.com/view/digitalization-moves-forward-in-pharma-equipment-and-processes.

The benefits of digitalization in bio/pharmaceutical manufacturing were highlighted by speed and successful integration during the COVID-19 pandemic.

Pandemic Drives Digital Transformation 

While most of the bio/pharmaceutical industry had very little time for retrospection in the past two years, stories are now beginning to be shared about the urgent, round-the-clock efforts to bring COVID-19 vaccines and therapies to market, including expanding capacity and building facilities. Some new technologies and new ways of working were tried out and proved to be successful, and others are still being developed in preparation for future crises. The following is a short selection of manufacturing topics that the 

 editorial team covered in the past year.

“Advanced Manufacturing Technologies Shift Outside the Box,”

 covered intensified and distributed manufacturing approaches including continuous manufacturing and small-scale, point-of-care systems. An October article, 

“Adopting Continuous Manufacturing for Solid-Dose Drug Products,”

 looked specifically at continuous manufacturing equipment for solid-dosage drugs. The editors also spoke with experts on this topic in interviews for INTERPHEX, such as the 

Keynote conversations with Fernando Muzzio

Equipment and process advances continue in aseptic manufacturing as well. The industry continues to move toward automation and closed systems. An INTERPHEX Keynote session with 

, for example, looked at challenges and opportunities. An October article, 

 examined the increasing use of robotics. Compounding applications are also seeing increased robotic use, as discussed in 

“Robotic Automation Boosts Efficiency and Quality in Drug Compounding.”

Digitalization was another theme for 2021, and an article in December, 

“Digitalization Moves Forward in Pharma Equipment and Processes,”

 examined industry progress toward digital maturity. Serialization is also back in the spotlight, and the editors talked to experts in an 

 focusing on the US Drug Supply Chain Security Act and the European Union’s Falsified Medicines Directive.

New technologies and methods to handle a new level of speed to market are spilling from the pandemic response into other pharmaceutical manufacturing areas; look for more coverage of this in 

New processes, automation, and digitalization were highlighted in 2021.  

Looking Back at 2021 Pharma Manufacturing Topics

Another change that accelerated in the past two years was a transition to the cloud for software solutions and data storage, adds Pamela Docherty, Life Sciences Industry manager at Siemens USA. “The ability to push data from the manufacturing floor to the cloud creates a backbone for digitalization,” she says.

Digital tools depend first on good data collection. Having equipment that is set up for data collection and data analytics is becoming increasingly important, says Duckworth. Machine sensors and process analytical technology (PAT) instruments can communicate directly with data collection systems using the IIoT. These large quantities of data are needed for machine learning (ML), including artificial intelligence (AI) systems and digital twins, which are representations of the physical world in the digital world.

Visualizing data in ways that scientists and engineers can use to improve understanding and to optimize processes is also important. Technologies can enable an “end-to-end digital thread of information,” says UpDyke. “Multi-site manufacturing in different markets is pushing the industry towards more connectivity, improved visibility across sites and organizations, and increased knowledge and information sharing that will enable expedited recipe development.” 

New England Controls, Inc. (NECI), which partners with Emerson, has developed and deployed new digital tools in the past year that enable access to data sources and aggregation into analytical tools to link the “physical plant” to the “digital plant,” says Michael Cody, director of digital and clinical manufacturing at NECI. Access to data with operational context is crucial for pharma manufacturing facilities, says Cody. “The need to aggregate and analyze data from a variety of data sources is pushing equipment and technology providers to be able to interface and communicate with those digital tools in a meaningful way,” he explains.

Digital twins are a tool being increasingly used in a wide range of scenarios, from engineering optimization of individual pieces of equipment to analysis of full manufacturing systems. Examples from the past year, says Docherty, include digital twins for process development with an innovative mixing application, a representation of a new skid to enable faster fabrication, an offline training system for a continuous direct compression line, and an alerting system to ensure that people were keeping proper distance on the manufacturing floor.

Siemens also collaborated with GlaxoSmithKline (GSK) on a digital twin pilot project that modeled and controlled the adjuvant particle manufacturing process. The project proved the concept that digital twins could be used in vaccine process development and transferred to manufacturing (4).

As biopharmaceutical facilities shift to modular, multi-product facilities, digitalization enables efficient automation. A DCS can be used to connect the components, even as the process flow changes depending on how the different production modules are combined, says Docherty. Siemens and Sartorius, for example, demonstrated a modular production system using the Siemens DCS with Sartorius’ Biostat bioreactor system. The companies set up an agreement to build standard interfaces between the Sartorius unit operations and the Siemens control system for closer integration (5). This system would allow the option of a fully paperless manufacturing facility.

AR digital tools are finding a wide range of uses in pharma manufacturing. Prior to 2020, AR was being developed for training and as an aid for technicians following standard operating procedures, for example, and it was being used for remote equipment maintenance and troubleshooting. When the pandemic suddenly made being on site impossible, AR/VR suppliers, such as Apprentice IO, stepped up with kits that included smart glasses and the technology to connect remotely (6) and pharma manufacturers and their suppliers began using them for tasks such as remote factory acceptance testing (FAT) and installations. The efficiency of these tools is expected to drive continued use. For example, reports Duckworth, using AR for FAT has now become an accepted practice.

Polpharma, a large drug manufacturer in Poland that makes APIs and generic prescription and over-the-counter drugs, began a digital transformation project of its whole business, including manufacturing operations, in 2017. To read more, go to 

www.PharmTech.com/view/digital-transformation-project-reduces-downtime

Manufacturers also began using AR/VR tools for remote inspections, audits, and facility tours. Suppliers such as Avatour offers cloud-based communication platforms with 360-degree video capabilities so that viewers can control what they are seeing. “By combining [this communication] with sensor data and geo-location stamps, these platforms provide independent third-party validation of what exactly transpired during each site visit,” asserts Devon Copley, cofounder and CEO of Avatour. 

Regulatory agencies also used these tools for what FDA calls Remote Interactive Evaluations of facilities. Although such tools will not replace physical inspections, their use is expected to continue (7).

Efficient development and tech transfer for mRNA vaccine manufacturing

The data analysis and clear communication allowed by digital tools has demonstrated its benefits for process development and technical transfer, making time to market faster. Digital manufacturing technologies were successful in helping vaccine manufacturers, such as Moderna and Pfizer, accelerate their technology transfer and manufacturing process.

“The capability to perform technology transfer from Moderna to their contract manufacturing partner, Lonza, was enabled by the digital technologies deployed in their respective facilities,” says Cody. “Both Moderna and Lonza utilize DeltaV as their process automation system and Syncade as their manufacturing execution system. NECI teams partnered with Moderna and Lonza teams to transfer equipment automation strategies and electronic batch records from company to company, accelerating the manufacturing capacity and establishing supply chain capability as the Moderna COVID-19 vaccine was completing clinical trials and FDA emergency use approval.” 

The availability of digital tools and the collaboration of implementing them in a refurbished facility was key to the speed of bringing BioNTech’s mRNA vaccine to commercial production in Europe, adds Wollaert. The process was brought online in under six months, while under normal circumstances it would have taken at least one year, he observed.

Siemens, a long-time partner of BioNTech, assisted the company in converting a facility in Marburg, Germany to mRNA vaccine production using end-to-end digitalization of production. Siemens Opcenter Excecution Pharma was chosen as the new MES, and the digital system enabled conversion to paperless documentation of production with electronic batch records. Although the process has a number of manual work steps, operators are guided through these with the software’s workflow management component. The Siemens Simatic PCS 7 distributed control system was used to automate processes (8).

FDA recognizes the role of digitalization and is working with industry suppliers to better understand these technologies. “The pandemic created significant opportunities for education and experimentation of digitalization with FDA,” says Jason Spiegler, senior director of Life Sciences Strategic Initiatives, Siemens Digital Industries. Although initial projects looking at digital twins took place within FDA’s Center for Devices and Radiological Health (CDRH) (9), the understanding developed in device manufacturing can be applied to other FDA branches, suggests Spiegler. Spiegler also co-leads a joint FDA and industry computer software assurance (CSA) team that is focused on educating and promoting the adoption of risk-based CSA best practices for the life sciences industry. “CSA is foundational for unleashing the potential of digitalization on the shop floor,” says Spiegler.

Although paper-based systems are still prevalent in the industry, the benefits of digital and automated systems were made more clear by the upheaval over the past two years, and the industry can expect more digitalization of manufacturing equipment and processes in the coming year.

“There is more of an acceptance that digital transformation is necessary and worth the investment in a regulated industry. This new awareness will help drive digital transformation and move the industry significantly forward,” predicts UpDyke.

BioPhorum Operations Group, “A Best Practice Guide to Using the BioPhorum Digital Plant Maturity Model and Assessment Tool,” 

G. Langer, “eBR in Pharma 4.0: Instrumenting the Manufacturing Processes,” Presentation at ISPE Annual Meeting, Nov. 2, 2021.

J. Markarian, “GSK Pilots Digital Twin for Vaccine Manufacturing,” 

Siemens, “Siemens Showcases its Integrated Modular Production Solution That Leverages its SIMATIC PCS 7 and SIMATIC Batch with Biostat STR DCU from Sartorius,” Press Release, Feb. 15, 2021.

PharmTech editors, “Augmented Reality Kits Deployed in the Wake of Travel Bans,” 

Siemens, “Vaccine Production: Marburg Has the Right Stuff,” 

Siemens, “Siemens Awarded $1.78M FDA Contract to Showcase Advanced Digital Design and Manufacturing,” Press Relase, Oct. 1, 2021.

Jennifer Markarian is manufacturing editor at 


Volume 45, Number 12
December 2021
Page: 16–19

When referring to this article, please cite it as J. Markarian, “Digitalization Moves Forward in Pharma Equipment and Processes,” 

Bio/pharmaceutical manufacturing harnesses the benefits of digital transformation.

Digitalization Moves Forward in Pharma Equipment and Processes 

Polpharma, a large drug manufacturer in Poland that makes APIs and generic prescription and over-the-counter drugs, began a digital transformation project of its whole business, including manufacturing operations, in 2017. The company implemented technologies that allowed it to digitize documents and activities, collect data from multiple points of the production processes, and automate data flows, says Magdalena Rzeszotalska, Corporate Communications and Corporate Social Responsibility Director. The aim was to eliminate manual activities and to develop and employ a digital twin of operations.

This article appeared as a sidebar in an article in the December 2021 issue of Pharmaceutical Technology, 

Digitalization Moves Forward in Pharma Equipment and Processes.

“In the operations area, the key benefit we were able to realize is to connect thousands of data points into a comprehensive model of manufacturing and supply chain activities that allows us to simulate, predict, and optimize underlying processes and activities in order to improve time to market, quality, and cost,” says Rzeszotalska.

One of the projects used data collected from the supervisory control and data acquisition system combined with augmented reality/virtual reality (AR/VR) to visually replicate the factory floor location and improve remote connection between subject matter experts or external service providers located outside the facility with the technicians located inside. An AR scan virtually locates the external personnel with the technician, allowing the team to more quickly communicate and resolve factory floor problems. This practice resulted in a 10–15% reduction in maintenance downtime, and was adopted across the company to help maintain social distancing during the COVID-19 pandemic, reports the company.

The biggest challenge in implementing the AR/VR project was the initial phase. “The bottleneck turned out to be the collection of the necessary materials and guidelines from end-users (maintenance services) on what exactly, and in what form, information should be represented [in] the extended/virtual environment,” notes Rzeszotalska. “It is necessary to think carefully about the organization of data and areas in the application and how to connect the environment with other systems and the metadata stored in them.”

The AR/VR solution was also used to improve the complex task of installing utilities and technical infrastructure. “AR presented key information directly at the pipelines and measuring points, without the need to reference it manually in the control room,” says Rzeszotalska. “For complicated manual procedures, AR allowed the introduction of step-by-step procedures with automatic verification of performed activities. This solution increases work safety and reduces the possibility of human error.” As a result, downtime was reduced. 

Polpharma implemented digital technologies, including a digital twin of operations.