Early investment in formulation strategies will maximize the chance of success.

The Earlier the Better in Formulation

Advances in simulation and the development of digital twins.

Computational Fluid Dynamics in Upstream Biopharma Manufacturing

Different methods give different answers when calculating limits for impurities.

Detecting and Determining Quantitation Limits for Impurities

Automatic visual inspection machines and AI highlight inspection deficits.

Visual Inspection: Seeing Room for Improvement?

Despite their promise, alternative drug delivery approaches are complex and must be justified.

Taking an Alternative Approach to Drug Delivery

Traditional statistical process control rules can be relaxed or adjusted to allow charting and evaluation of real-life data. 

Practical SPC Rules to Apply on Pharmaceutical Process Data

Novavax COVID-19 Vaccine Receives EUA in Indonesia

FDA Grants EUA for Pfizer-BioNTech COVID-19 Vaccine Use in Children

Recordati acquired EUSA Pharma, a pharmaceutical company specializing in developing oncology treatments, for $845 million on Dec. 3, 2021. This acquisition grants Recordati access to EUSA’s portfolio of rare cancer treatments.

Included in the portfolio are four treatments:

 is an anti-GD2 monoclonal antibody (mAb) designed for the treatment of high-risk neuroblastoma. According to a company press release, neuroblastoma is a rare form of cancer that forms as a result of immature nerve cells and predominantly affects children under the age of ten. Dinutuximab beta is currently approved in Europe and other countries

 is an anti-IL-6 mAb designed for the treatment of Idiopathic multicentric Castleman’s disease (iMCD). iMCD is a variation of Castleman’s disease, a rare lymph node cancer, that results in severe systemic symptoms. Siltuximab is the first and only approved treatment for iMCD in the United States and Europe

 is an oral small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. It is currently approved for first-line treatment of advanced renal cell carcinoma in Europe and other countries

 is an oral solution for the treatment of oral mucositis resulting from chemo- and radiotherapy. It is currently approved in the US, EU, and other markets.

“We believe that the EUSA Pharma acquisition represents an excellent opportunity to further expand and reinforce our portfolio in a new and underserved therapeutic area, rare and niche oncology, with high potential growth products and will provide a platform for potential further future expansion in these areas,” said Andrea Recordati, chairman, Recordati, in a company press release. “This is another important step forward in delivering on our strategy to increase our presence in the rare disease segment and to fulfil our mission to improve the lives of patients, delivering innovative treatments that address serious unmet medical needs.”

Articles

Recordati’s blockbuster acquisition of EUSA Pharma gives them access to a portfolio of four drugs that treat rare cancers.

Recordati Acquires EUSA Pharma for $845 Million

The Antimicrobial Drugs Advisory Committee (AMDAC) voted on Nov. 30, 2021, to recommend an Emergency Use Authorization (EUA) for molnupiravir, an experimental antiviral oral COVID-19 medication from Merck—known as MSD outside of the United States and Canada—and Ridgeback Biotherapeutics. While questions about its risks cropped up following initial positive findings, a 13-10 decision was ultimately made in favor of its recommendation.

Merck announced positive preliminary results for molnupiravir on Oct. 1st, 2021. 

, molnupiravir reduced the risk of hospitalization or death by 50% in non-hospitalized adult COVID-19 patients with mild-to-moderate symptoms. Following these results, Merck was advised to end the trial early and applied for an EUA on Oct. 8, 2021.

However, following an evaluation of the full population, this risk reduction was instead found to be approximately 30%. This reduced effectivity, in tandem with concerns about potential risks to fetuses and DNA, led to many members of the panel to believe the potential risk was not worth the demonstrated benefit.

While FDA is not required to follow the recommendations of AMDAC, they typically do. Should molnupiravir be approved, it would become the first oral treatment for COVID-19.

Following mixed results from clinical trials, a panel of outside experts voted 13-10 to recommend Merck’s pill for Emergency Use Authorization.

FDA Panel Recommends Merck’s COVID-19 Pill 

FDA approved Genentech’s rituximab (Rituxan) in combination with chemotherapy for pediatric patients (6 months of age and older to 18 years of age) with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL), according to a Dec. 2, 2021, press release.

When given as an intravenous infusion given in combination with systemic Lymphome Malin B (LMB) chemotherapy, the recommended rituximab dose is 375 mg/m

. Six total infusions of rituximab are given.

A global multicenter, open-label, randomized trial was performed, assessing patients six months in age or older with previously untreated, advanced stage, CD20-positive DLBCL/BL/BLL/B-AL. Event-free survival was the main efficacy outcome measure. This was defined as a progressive disease, relapse, second malignancy, death from any cause, or non-response as evidenced by detection of viable cells in residue after the second Cytarabine Aracytine, Ara-C, Veposide course. There were 20 deaths in the LMB chemotherapy arm compared to 8 deaths in the rituximab plus LMB chemotherapy arm at the time of the interim analysis.

Subtitle FDA approved rituximab in combination with chemotherapy for pediatric patients with previously untreated, advanced stage, CD20-positive DLBCL/BL/BLL/B-AL.

Rituximab Plus Chemotherapy Approved by FDA for Select Pediatric Cancers

On Dec. 1, 2021, Roche announced the completion of its share purchase agreement to acquire 100% of the outstanding shares of TIB Molbiol Group in a company press release. The companies will focus on the rapid development of polymerase chain reaction (PCR) assays and diagnostic tests for emerging pathogens and potential health threats, such as infectious diseases. TIB Molbiol will operate as a subsidiary within the Diagnostics division.

For more than 20 years, the companies have collaborated to address biological threats, including:

“I am very pleased that together with TIB Molbiol, we can significantly improve access for patients to a broader spectrum of diagnostic tests—from high volume routine tests to the diagnosis of rare diseases. TIB Molbiol will continue to be an innovation engine and frontrunner in our common fight against infectious diseases, such as SARS-CoV-2,” said Thomas Schinecker, CEO, Roche Diagnostics, in a company press release. “TIB Molbiol has helped to shape the future of PCR infectious disease testing and will continue to drive cutting-edge research so we can bring better healthcare outcomes to patients faster.”

The companies will focus on the rapid development of polymerase chain reaction assays for emerging pathogens and potential health threats, including biological threats.

Roche Expands PCR-Test Portfolio with Completion of Purchase Agreement of TIB Molbiol

Fujifilm Irvine Scientific, which develops and manufactures serum-free and chemically-defined cell culture media for bioproduction and cell therapy manufacturing, announced in a Dec. 1, 2021, press release that it is building an Innovation and Collaboration Center in Suzhou New District, China to help local customers design upstream cell culture processes. The company noted in the press release that the market for cell culture media is expanding due to rapid growth in China’s biopharmaceutical, vaccine, and cell and gene therapy markets.

The new center will incorporate advanced cell culture automation and analysis into process and media development to optimize cell culture media and associated workflows for upstream cell culture processes. This optimization will help achieve the quantity and product quality attributes necessary to support commercial production of new drugs. Construction has begun and is planned for completion by March 2022.

“We are increasing the number of sales and technical support staff throughout China to meet the development needs and support the antibody pharmaceutical industry in the growing Chinese market,” said Yutaka Yamaguchi, chairman and CEO, Fujifilm Irvine Scientific, general manager Fujifilm Life Sciences Business Division, in the press release.

 that it was expanding its R&D Center of Excellence at its headquarters in California to support discovery research and specialty media, technologies, and custom media services.

Fujifilm’s center adds local support in Suzhou, China for cell culture media optimization. 


Fujifilm Irvine Scientific Builds Bioprocessing Innovation and Collaboration Center in China

GlaxoSmithKline (GSK) and the University of Oxford announced a five-year collaboration to establish an institute to improve the success and speed of research and development of new medicines, which will be based at the University of Oxford, according to a Dec. 2, 2021, press release. The institute, the Oxford-GSK Institute of Molecular and Computational Medicine, will build on insights from human genetics and will use advanced technologies, such as functional genomics and machine learning.

To understand detailed patterns of disease that vary among individuals, the institute intends to evaluate and integrate new approaches in genetics, proteomics, and digital pathology. The initial research will be focused on neurological diseases, such as Alzheimer’s and Parkinson’s diseases.

In the past decade, there have been datasets of promising targets for medicine discovery. These datasets can be combined with functional genomics to provide a deep understanding of disease at a molecular level, according to the GSK press release. The institute will harness this understanding along with machine learning to learn new predictors of the disease and accelerate drug discovery.

“I am delighted to see that GSK and the University of Oxford are today taking further steps to deepen our understanding of some of the most complex diseases, such as Parkinson’s,” Prime Minister Boris Johnson said in the GSK press release. “Together they will harness the power of scientific collaboration to progress cutting-edge technologies and accelerate drug discovery—helping to cement the UK’s role as a life sciences superpower.”

This collaboration aims to better understand Alzheimer’s and Parkinson’s disease and increase drug discovery and development success rates.

GSK and the University of Oxford Join Forces to Research Treatment Potentials for Neurological Diseases

Moderna announced on Dec. 1, 2021, a revised supply agreement with the UK government for the company’s COVID-19 vaccine and possibly authorized booster vaccine candidates as well. Specifically, this supply agreement encompasses up to 60 million doses of Moderna’s COVID-19 vaccine.

In 2022, as many as 29 million doses are expected to be delivered, and up to 31 million doses are expected to be delivered in 2023. The UK government retains a right to increase or decrease its purchases in 2022 and 2023, under to the agreement, by up to 20% above or below the contracted volumes.

“We thank the UK government for their support in this supply agreement for our mRNA COVID-19 vaccine and booster candidates, if approved, in 2022 and 2023,” said Stéphane Bancel, CEO of Moderna, in a company press release. “This agreement reflects the efforts of the UK government to address the ongoing pandemic and builds on our existing collaboration to protect people in the UK.”

Moderna’s agreement with the UK government includes 29 million COVID-19 vaccine doses for delivery in 2022 and 31 million doses for delivery in 2023.

60 Million Doses of the COVID-19 Vaccine is Added to Moderna’s Supply Agreement with the UK

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

The challenges in developing gene and cellular therapies have made headlines over the past year, as biotech companies have launched a wave of development programs despite ongoing concerns about treatment safety and efficacy plus unknown long-term effects. High price tags on these breakthrough treatments, moreover, threaten to block patient access to potentially life-saving cures and treatments. FDA scientists and reviewers are working to advance the field, with new guidances and advice for manufacturers on appropriate testing of treatments to minimize risks to patients and fill gaps in data.

New gene therapies for debilitating rare conditions stand to advance from an 

FDA collaboration with the National Institutes of Health (NIH) and a cadre of pharma companies, small biotechs, and patient groups

, formally announced Oct. 27, 2021. The Bespoke Gene Therapy Consortium (BGTC) will be managed by NIH’s Accelerating Medicines Partnership program and the Foundation for the NIH and will provide public and private resources to support the development of gene therapies to treat rare diseases.

To start, the BGTC plans to initiate preclinical and clinical trials for four to six monogenetic rare diseases that currently lack any treatment. Such advances will facilitate a better understanding of the biology and production of adeno-associated virus (AAV) vectors utilized to deliver gene therapies to individual patients. The consortium will provide $76 million over five years from NIH and private partners to fund a range of research, such as establishing standardized analytical test methods to improve AAV production and use and to advance toxicology testing for preclinical development. The term “bespoke” reflects the need for efficient methods for developing highly individualized therapies to fit the genetic specifics of one or two patients.

The BGTC initiative has been under development for several months, as seen in remarks at the September 2021 PDA/FDA conference by Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), on how the program could standardize methods for developing and manufacturing bespoke therapeutics. Marks outlined efforts to leverage methods and data from one application to another to reduce prohibitive R&D costs that threaten product development and patient access. In advancing the development of gene therapies for very rare disorders, he noted the importance of collecting baseline natural history data on target diseases and of public-private partnerships to enable streamlined production through a “cookbook” for developing bespoke therapeutics.

This public-private collaboration is particularly timely in the wake of recent patient deaths and safety issues linked to experimental gene therapies involving AAV delivery. 

FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee met in early September

 to discuss these concerns, noting the limitations of preclinical animal models in predicting potential risks from viral vectors. Panel members cited the need for clearer standards related to gene therapy development, for more comprehensive patient screening, and for longer assessment of patients following treatment to better track side effects that may emerge later.

Even though the experts stopped short of recommending specifics curbs on developing these advanced treatments, 

FDA suspended further testing of an experimental gene therapy for hemophilia from BioMarin Pharmaceutical due to early safety issues

Pfizer halted studies on two experimental gene therapies

 following reports of adverse events in early studies.

Meanwhile, CBER seeks to expand the resources and expertise for its Office of Tissues & Advanced Therapies (OTAT) to better oversee and provide advice on developing genetic and other advanced products. Despite a slowdown in biopharmaceutical research due to the pandemic, CBER officials continue to see a strong flow of applications to test experimental cell and gene therapies, many requesting meetings with OTAT staff to discuss research plans. OTAT director Wilson Bryan noted the importance of transparency on safety issues related to gene therapy in a Nov. 12, 2021, presentation at a meeting sponsored by Prevision Policy. One critical issue to explore is whether the effectiveness of gene therapy treatment wears off over time, warranting re-administration. To address these unknown and continuing safety concerns, Bryan emphasized the importance of long-term follow-up of all gene therapy patients—maybe following gene therapy patients “forever,” he commented.

High price tags threaten to block patient access to potentially life-saving cures and treatments.

FDA Grapples with the Promise and Perils of Gene Therapy

Jennifer Markarian is manufacturing editor of Pharmaceutical Technology.

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.

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.