Increasing Processing Flexibility to Meet Demand

Flexibility and adaptation concept. Arrows on cubes following a flexible path | Image Credit: © Cagkan - stock.adobe.com

Flexibility in pharmaceutical manufacturing is becoming an increasingly pertinent requirement. Various industry trends, such as the development of increasingly complex and novel therapies, a greater focus on orphan drug designation, and the use of more highly potent ingredients, are leading to demand for adaptable and versatile processing equipment.

“For decades, large-scale drug production was the industry standard. However, the rise of rare diseases now demands increasingly expensive medications, which, in turn, require greater research and development efforts, including innovations in machine design,” remarks Andreas Mattern, vice-president Strategy and Global Product Management Pharma at Syntegon. “For example, there is now a need for machines capable of processing small and micro batches with greater flexibility. At the same time, new drugs like anti-obesity medication are sustaining the demand for high-performance equipment that can handle large batch volumes.”

Adapting to manufacturing needs

“There have been significant advances in flexible manufacturing to accommodate the rapidly changing therapeutic landscape, particularly in response to the rise of personalized medicine, biologics, gene and cell therapies, and the need for rapid responses to health crises (like the COVID-19 pandemic),” specifies Caterina Funaro, Competence Center manager at IMA Active. “These advances are helping the pharmaceutical and biotech industries adapt to smaller batch sizes, varied production processes, and the need for faster, more adaptable production cycles. Key innovations in processing equipment, facility design, and digital technologies are enabling greater flexibility in manufacturing.”

Specialized treatments are certainly driving new equipment developments, confirms Mattern, who points out that personalized therapies are becoming a focus for future treatment breakthroughs. “Many types of cancer and genetic disorders can only be treated with highly specialized drugs,” he says. “These [drugs], in turn, require production in ever smaller batch sizes.”

New therapeutic modalities, such as cell and gene therapies, require flexible equipment that can handle fast changeovers from one product batch to the next, Mattern continues. “A wide variety of products must be filled into different container sizes and types such as vials, syringes, or cartridges. Hence, it comes as no surprise that the market for ready-to-use (RTU) containers has been growing at a rapid pace over the past years,” he says.

Benefits of RTU containers include reduced time-to-market, lower cost of ownership, increased flexibility, and greater integrity of the drug product, explains Mattern. “While RTU containers have been the de-facto standard for pre-filled syringes for some time, they are now also increasingly being used for vials and cartridges in both bulk and small batch applications,” he states.

A general move away from traditional approaches to manufacturing has been trending for a while, comments Funaro. “Continuous manufacturing (CM) has gained traction as an alternative to traditional batch production,” she adds. “[CM] provides greater flexibility by allowing production to run continuously, without the need for lengthy shutdowns between batches, which is especially beneficial for both small- and large-scale manufacturing.”

Progress in continuous processes

“The industry has made significant progress in adopting continuous processes, which are progressively replacing traditional batch processes, particularly in the pharmaceutical, chemical, and food processing sectors,” explains Funaro. “Continuous processes offer enhanced efficiency, higher throughput, better product consistency, and improved energy use, driving their adoption across industries.”

For pharmaceuticals, manufacturers are employing continuous processes to API production, granulation, mixing, tableting, and coating, remarks Funaro. Through using continuous processes for these tasks, companies are being able to reduce lead times, improve product consistency, and facilitate any potential scale changes that may be required to meet therapeutic demand, such as increased production of vaccines or biologics, she confirms.

Within the oral solid dosage (OSD) space, CM has been trending for a few years, Mattern adds. “Higher flexibility, shorter development times with minimum API usage, and a direct transfer from development to production without scale-up are among the primary requirements of pharmaceutical manufacturers,” he says. “The main challenge with traditional solutions is the precise dosing of the starting materials in a constant mass flow rate of milligrams per second.” However, as the pharmaceutical industry is highly regulated, adopting newer processes can take time, Mattern specifies.

“FDA has endorsed continuous processes, recognizing their potential for faster production and more consistent product quality,” asserts Funaro. “As a result, manufacturers are investing in equipment such as continuous coaters and continuous mixers.”

Additionally, while investment in continuous processes grows, advances are also being seen in real-time data monitoring tools, which are vital in helping to control variables in CM, such as temperature, pressure, and product quality, continues Funaro. “Real-time analytics are increasingly being integrated with machine learning (ML) algorithms to allow for self-regulating systems that automatically adjust process parameters to maintain optimal efficiency and output quality,” she says.

“The shift from batch to continuous processes is well underway, but ongoing advances in processing equipment will further accelerate the transition,” asserts Funaro. “As technologies such as real-time monitoring, modular designs, AI [artificial intelligence] integration, and energy-efficient systems mature, industries will be able to harness the full potential of continuous processes, resulting in lower costs, higher productivity, and improved sustainability.”

The role of automation

“Automation is playing an increasingly critical role in processing equipment across industries such as pharmaceuticals, food and beverage, chemicals, and biotechnology,” explains Funaro. “The current trends in automation are transforming manufacturing processes by enhancing productivity, improving consistency, ensuring quality, and reducing human error.”

Through the use of automation, manufacturers can achieve a multitude of benefits. For example, Funaro points out that automated material handling, packaging, and processing reduces human intervention and speeds up cycle times. Additionally, she alludes to the fact that automation reduces variability in production processes, which ensures consistent quality.

For Funaro, the use of digital twins, which are virtual replicas of physical processes or equipment, will become more widespread within industry over time. “Digital twins allow manufacturers to simulate process changes, predict how equipment will behave under different conditions, and optimize production before making physical adjustments,” she says.

“Predictive maintenance is becoming a standard practice, leveraging AI, IoT [Internet of Things], and analytics to predict when equipment will fail, and schedule maintenance before a breakdown occurs. This reduces unplanned downtime and extends the lifespan of processing equipment,” adds Funaro. “As predictive maintenance becomes more advanced, it will shift toward prescriptive maintenance, where AI not only predicts failures but also suggests the optimal maintenance actions to take, further minimizing disruption and cost.”

While digitalization is producing large amounts of data in production every day, it will mean nothing if it cannot be viewed or used, Mattern warns. “New cloud-based software solutions, such as Synexio from Syntegon, provide a remedy by enabling the acquisition, evaluation, and visualization of equipment and production data,” he says. “[These solutions] allow for real-time monitoring of machine conditions, helping manufacturers make data-based decisions and optimize operations.”

“In sectors like pharmaceuticals, where regulatory compliance and precision are critical, automation ensures that products meet exacting standards,” continues Funaro. “Automated quality control systems, including automated visual inspection and process analytical technology (PAT), are reducing the risk of human error and ensuring that processes stay within defined limits.”

Reducing human intervention in processes is particularly helpful in high-risk environments, such as dealing with hazardous chemicals or highly potent ingredients, asserts Funaro.

“The use of robotics is taking the industry a huge step further towards even higher product protection and quality, as it eliminates the main cause for contamination (i.e., human intervention),” Mattern remarks. “This is further fueled by [the European Union’s] Annex 1 [guidance].”

Annex 1 considerations

In August 2023, the updated EU good manufacturing practice (GMP) Annex 1 guidance (1) came into operation (except for point 8.123), which has profound implications for sterile manufacturing across the global pharmaceutical sector, Mattern specifies. “One of the key challenges presented by the new Annex 1 is the requirement to separate the aseptic processing area from the operator’s environment. As a result, pharmaceutical manufacturers now need at least restricted access barrier systems (RABS) to gain approval for new products,” he says.

After the updated guidance was published, industry saw a surge in upgrades to existing cleanroom lines to incorporate RABS, Mattern notes. “Manufacturers must choose whether to upgrade their current cleanroom line for a new product or invest in new filling equipment with isolator technology or RABS,” he specifies.

“It is expected that isolator technology will become the new standard, given the added safety provided by automatic bio-decontamination processes and the pressure differential from the operator environment,” Mattern notes. “[Whereas], RABS will likely remain a preferred option for more frequent product changes and experienced operators.”

The second chapter of the revised Annex 1 guidance places a focus on automation and robotic systems, highlighting these as “Appropriate Technologies” (1), Mattern reveals. “These technologies aim to reduce, or even eliminate, the need for gloves and human intervention in barrier systems,” he says.

“Gloves pose several challenges, which are addressed in dedicated paragraphs of the [Annex 1] document,” Mattern continues. “For instance, during longer production campaigns, [gloves] must be tested in operation—a process that is difficult to achieve with current glove testing equipment without compromising the sterile environment. The shift toward gloveless systems, utilizing robotics for these tasks, is viewed as the ideal solution.”

Future advances and sustainability

There are several potential future trends that are set to impact processing equipment and pharmaceutical manufacturing in general, asserts
Funaro. “These trends are being driven by technological innovation, sustainability goals, and the need for enhanced efficiency, safety, and compliance,” she says.

Notably, automation and Industry 4.0 are set to shape the future, explains Funaro. For example, employing predictive maintenance to anticipate equipment failures before they happen, utilizing AI and robotics for fully autonomous processing systems, integrating advanced sensors and machine vision systems for greater precision and control, and analyzing vast amounts of data with ML and AI, she summarizes

“Future equipment will increasingly incorporate self-learning systems that can adjust their operation based on past performance data. This will enable greater flexibility and adaptability in production lines, particularly in industries that need to switch between different products or processes frequently,” says Funaro. “As demand for customization and flexibility grows, processing equipment will increasingly be designed with modularity in mind.”

“A persistent concern within the pharmaceutical industry and its suppliers is the need for more sustainable equipment and processes. Unfortunately, resource consumption in the sector continues to surpass that of many other industries,” stresses Mattern. “In response, drug manufacturers are intensifying efforts to reduce their carbon footprint, with the support of manufacturing companies offering services such as lifecycle assessments for their equipment.”

Adoption of more energy-efficient equipment and an overall reduction of environmental footprint is becoming a greater focus for manufacturers, confirms Funaro. “Recyclable and reusable components in machinery, as well as the use of environmentally friendly materials, are becoming more widespread,” she says.

“Given its longevity, equipment usually contributes to overall emissions over several decades,” remarks Mattern. “By continuously optimizing their machines and developing new, more energy-efficient solutions, equipment providers can help pharmaceutical manufacturing companies achieve their sustainability goals.”

“These future advances will fundamentally change how industries approach processing equipment, offering greater flexibility, efficiency, and sustainability while adapting to the needs of a rapidly evolving marketplace,” concludes Funaro.

Reference

1. EC. Annex 1 Manufacture of Sterile Medicinal Products. EudraLex Volume 4, August 2022.

About the author

Felicity Thomas is associate editorial director for Pharmaceutical Technology®.

Article details

Pharmaceutical Technology®
Vol. 48, No. 11
November 2024
Pages: 9–11

Citation

When referring to this article, please cite it as Thomas, F. Increasing Processing Flexibility to Meet Demand. Pharmaceutical Technology 2024 48 (11) 9–11.