Automation has been recognized for over a century to enable consistent, efficient manufacturing. In the past few decades, even the conservative pharmaceutical industry has begun to deploy automation solutions with the goal of increasing quality and reducing cost (1). The rate of adoption is steadily increasing as not only equipment innovations, but advances in digital technologies, have led to significant improvements in efficiency, reliability, and data analytics (2,3). While many of the earliest efforts at automation of pharmaceutical manufacturing were applied to oral solid dose (OSD) production, OSD manufacturers have been slower to pursue automation solutions than biologics producers. 

What are the drivers for adoption of automation?

There are many drivers for the more widespread automation of OSD manufacturing operations, including increased drug substance and formulation complexity and pressure to reduce time and cost. Automation offers the benefits of speed, precision, consistency, and reduced manual interventions.

While time-saving and cost pressures are key motivators in adopting automation, these factors only scratch the surface of the technology’s potential, says John Nadzam, global manager, OSD equipment and novel technology in the pharma services business of Thermo Fisher Scientific. “The ability to automate processes acts as a force multiplier for efficiency, consistency, and quality in drug manufacturing. As modern pharmaceutical operations face increasing complexity, smaller batch sizes, and demands for faster scale-up from development to commercial production, automation helps reconcile these competing needs,” he observes.

From a quality perspective, automation supports right-first-time execution and data integrity by minimizing manual data entry and transcription, Nadzam explains. Automated data capture also enables real-time process understanding and tighter control, helping reduce deviations, improve compliance, and support ongoing process verification.

Automation also helps manufacturers address expanding workforce challenges. “As the industry faces workforce shortages and skills gaps, automation amplifies limited resources, allowing scientists and operators to focus on critical process understanding rather than repetitive tasks,” Nazdam notes.

While automation in small-molecule drug product manufacturing has moved well beyond the pilot phase and is now a strategic imperative, it remains underutilized and fragmented in traditional batch manufacturing.

Many operations use automation primarily for recipe management; proportional, integral, derivative loop control; and basic process data acquisition, according to Nadzam. He observes that use cases do persist across unit operations in areas like granulation, compression, and coating, but most do not currently benefit from comprehensive data integration. “In many instances, we still see reliance on paper records, manual signatures, and standalone data systems. These factors limit the ability to derive cross-unit insights or perform predictive analytics. The contrasts between biologics production and continuous manufacturing are stark compared to small-molecule batch production, which, in comparison, has been slower to modernize,” he states.

What are the benefits beyond incremental improvement?

Automation delivers precision and consistency much faster than human-driven systems. “When it comes to throughput and uptime, real-time data acquisition through automated processes enables closed-loop adjustments, reducing out-of-spec material and increasing equipment availability,” says Doug Hausner, senior R&D staff scientist in the pharma services business of Thermo Fisher. As an example, he highlights the integration of tablet press feedback with in-line hardness and weight testers to minimize rejection and downtime.

Many unit operations involved in small-molecule drug manufacturing also require tight control of critical process parameters that impact product quality attributes, and automation provides a means for improving performance by enabling real-time monitoring and adjustment of process performance (5–7).

Electronic batch records, meanwhile, increase data security and integrity by eliminating transcription errors and streamlining review by exception. “These efforts ultimately support attributable, legible and intelligent, contemporaneous, original, accurate principles and audit readiness,” Hausner states. They also support greater process understanding. Digital connection of multiple unit operations, he observes, allows teams to correlate process data, such as granule particle size distribution, tablet hardness, and coating uniformity, to reveal root causes of variability.

Automated systems with built-in analytics can also identify early signs of drift, allowing for proactive interventions (e.g., predictive maintenance and process optimization to improve quality), Hausner notes. They can also operate continuously and with minimal downtime, enabling faster cycle times, and higher output based on high-quality operational data. In tableting and encapsulation, for example, robotics can maintain consistent production rates while reducing manual handling.

Other benefits of automation include reduced waste generation, process deviations, and batch failures, all of which contribute to higher costs (6–8). The specific ways in which processes are enhanced vary for each unique unit operation, but overall, they add up to better process control and product quality. As a result, automation is becoming a necessity for small-molecule drug manufacturers seeking to establish and maintain competitive advantage.

Combination of coordinated hardware and software solutions

Effective automation in small-molecule drug product manufacturing is not achieved with a single technology. 

Both hardware and software work in concert to achieve enhanced process performance 

, robotic solutions play an increasing role in small-molecule drug product manufacturing

 (9). Examples include robotic presses and feeders used in tableting and encapsulation processes, real-time monitoring tools such as those based on near-infrared (NIR) and Raman spectroscopy across many different unit operations, and autonomous mobile robots and robotic picking systems used in warehousing and packaging.

Software solutions today are equally important, as they enable integration of disparate automated unit operations with data flowing between them and supporting a holistic approach to small-molecule drug product manufacturing. As such, software advances are equally important to the expanding adoption of automation solutions.

Nadzam highlights the growing role of artificial intelligence (AI) and machine learning (ML) in improving the effectiveness of automation systems for small-molecule drug product manufacturing operations. “Not only can these tools forecast formulation challenges ahead of time, but they also enable innovators to tackle issues around solubility, permeability, bioavailability, optimal first-in-human dosing, packaging selection, investigational new drug data generation and scale-up planning—insights that can ultimately accelerate progress from development to commercialization,” Nadzam contends.

Although the benefits of automating small-molecule drug manufacturing are increasingly clear, there are still several challenges the industry must overcome to see widespread adoption. This complex set of challenges must be navigated with care and foresight.

The two most significant challenges, according to Hausner, continue to be the high upfront investment required and the ongoing need for robust skills development. “Configuring automation requires both capital investment and technical expertise, which is why it is often outsourced due to internal resource constraints. However, the reality is that outsourcing can also increase project timelines and costs,” he observes. The need for significant upfront capital investment can also be a barrier to adoption (10), particularly for small-volume products, such as those targeting rare diseases with limited patient populations and personalized therapies.

Moving to automated small-molecule drug product manufacturing also requires a shift in perspective and often training of operators in new skill areas beyond operation of the new systems, such as in data analysis and troubleshooting. That requires effective and appropriate change management, which can be difficult to achieve but is crucial to success, Hausner says.

“Operators may initially view automation as restrictive or complex. Demonstrating how automation relieves them of repetitive documentation, enhances process visibility, and improves quality of life on the floor is key to success,” he notes.

Another challenge highlighted by Hausner is data standardization and contextualization. “Even with open protocols like open platform communications unified architecture, integrating legacy systems across vendors and facilities remains complex. Without consistent data structures, the promise of AI/ML-driven optimization remains difficult to realize,” he explains.

Regulatory expectations for validation and assurance of data security, integrity, and traceability can also create challenges as targets continue to evolve.

A defined roadmap and comprehensive strategy support success

The key to successful automation of small-molecule drug product manufacturing is to pursue the right strategy that leverages the organization’s broad expertise and process knowledge. “Automation is not simply a technical upgrade—it’s a strategic transformation,” insists Hausner. “To realize its full potential, organizations must adopt a holistic approach that blends technology, process design, and cultural readiness,” he says.

Companies should first, adds Hausner, establish cross-functional teams involving quality, information technology, regulatory, and operations personnel to ensure alignment and data integrity. Development of digital roadmaps that provide these teams with articulate short- and long-term goals for connectivity, data standards, and system interoperability will help keep manufacturing operations on track, he says.

In-depth process understanding is also essential, as it supports the use of a quality-by-design approach to process development, which in turns leads to robust, scalable processes. In addition, because human oversight remains essential for automation to be successful, developing internal automation expertise and building or training a core team capable of vendor management, configuration, and troubleshooting are essential, Hausner observes.

Drug developers should, continues Hausner, follow an approach that begins with smaller pilot projects and systems, with the ability to scale up to future needs. As an example, he suggests starting with focused automation projects such as process analytical technology (PAT) integration on a single-unit operation to demonstrate value, and then expand incrementally. Hausner notesthat working with contract development and manufacturing organizations that have these key processes in place can help make it easier for pharmaceutical and biotech organizations to adopt automation, reduce bottlenecks across the drug development continuum, and ultimately increase efficiency in bringing critical medications to patients.

Although technology is not the only crucial element to successful automation of small-molecule drug manufacturing, it is an essential component, and effective, advanced solutions are needed to ensure the maximum benefits can be realized by implementing automation.

Innovations in both equipment and software enabling smarter systems, seamless integration, and real-time responsiveness are not only improving performance, but also making implementation more accessible across scales and product types.

Several converging trends are lowering barriers to adoption of automation solutions for small-molecule drug product manufacturing operations, says Nazdam. They include a growing availability of open vendor architects as equipment suppliers increasingly support standardized communication interfaces, enabling interoperability; advanced AI/ML tools capable of predicting formulation behaviors and, therefore, addressing key challenges throughout small-molecule drug development; cloud-based manufacturing execution systems that improve scalability and enable enterprise-wide visibility; and digital twins and simulation tools that allow for virtual commissioning, predictive tuning, and training without disrupting operations.

Ongoing innovations in technology that enable better integration of automation systems, wider applications for real-time monitoring, and greater use of AI/ML are expected to not only drive greater adoption in small-molecule drug product manufacturing but increase their performance and the benefits they provide.

A broadening array of advanced PAT tools will enable more effective real-time monitoring for better process control and improved quality while supporting higher productivity through reduction in the need for traditional batch testing. Wider implementation of PAT-driven feedback control will also, notes Hausner, enable greater integration between operations, even in traditional batch environments.

Broader adoption of AI/ML is also anticipated by Hausner as these tools become more accessible. In the short term, they will support optimization of small-molecule drug product manufacturing across all unit operations by enabling real-time adjustments and predictive maintenance. Longer-term, the integration of AI-driven decision support, digital twins, and autonomous optimization loops will redefine how pharmaceutical facilities are operated, according to Hausner. “These systems will use live data streams to continually refine process parameters and minimize human intervention while maintaining compliance through automated documentation,” he notes.

“The ultimate vision,” concludes Hausner, “is a self-regulating, fully digital plant where real-time data drives dynamic control, lifecycle management, and continuous improvement.”

Bremme, L.; Darino, L.; Parry, B.; Teo, K. X. Automation and the Future of Work in the US Biopharma Industry. McKinsey & Company Insights, 2020, 

https://www.mckinsey.com/~/media/McKinsey/Industries/Pharmaceuticals%20and%20Medical%20Products/Our%20Insights/Automation%20and%20the%20future%20of%20work%20in%20the%20US%20biopharma%20industry/Automation-and-the-future-of-work-in-the-US-biopharma-industry-vF.pdf

Meticulous Research. Pharmaceutical Automation Market Size, Share, Forecast, & Trends Analysis by Offering (Solutions and Services), Mode of Automation (Semi-automatic Systems and Fully automatic Systems), End User (Pharmaceutical Industry and Biotech Industry), & Geography - Global Forecast to 2031. August 2024. 

https://www.meticulousresearch.com/product/pharmaceutical-automation-market-5280

Mirasol, F. Accelerating Adoption of Smart Tools to Advance Manufacturing. 

Tanzini, A. Robotics and Automation in Pharmaceutical Production. PDA Letter, March 7, 2023. 

https://www.pda.org/pda-letter-portal/home/full-article/robotics-and-automation-in-pharmaceutical-production

Manoj Kumar T.; Preethi, B.; Nunavath; R.S.; and Nagappan, K. Future of Pharmaceutical Industry: Role of Artificial Intelligence, Automation and Robotics. 

Journal of Pharmacology and Pharmacotherapeutics

Latzel, M. Pharmaceutical Automation: Innovations Shaping an Industry. Essert Robotics Blog, Dec. 13, 2023. 

https://www.essert.com/blog/process-automation/automation-pharmaceutical-industry/

Markarian, J. Using PAT in OSD Manufacturing. 

Pharmaceutical Technology Solid Dosage Drug Development and Manufacturing

https://www.pharmtech.com/view/using-pat-in-osd-manufacturing

Optimising the Oral Solid Dose Manufacturing Process: A Comprehensive Guide

https://upperton.com/optimising-the-oral-solid-dose-manufacturing-process/ 

Statifacts. The Rise of Pharma Robots: Transforming Drug Manufacturing and Research. 

https://www.roboticstomorrow.com/news/2025/02/07/the-rise-of-pharma-robots-transforming-drug-manufacturing-and-research/24079/

Egan, T. Navigating the Barriers to Automation in Manufacturing. 

https://manufacturingchemist.com/navigating-the-barriers-to-automation-in-manufacturing

Cynthia A. Challener, PhD, is a contributing editor to 

®
Vol. 49, No. 9
November/December 2025
Pages: 18–21

When referring to this article, please cite it as Challener, C.A. Leap Forward in Automation Anticipated for Small-Molecule Drug Product Manufacturing. 

Articles

Automation in pharmaceutical manufacturing, particularly for oral solid dose (OSD) production, is gaining traction due to its potential to enhance efficiency, consistency, and quality. Key drivers include increased drug complexity, cost pressures, and workforce challenges. Despite its benefits, automation remains underutilized due to high upfront costs and the need for skilled personnel. Effective automation requires a combination of hardware and software, with AI and machine learning playing crucial roles. Overcoming barriers involves strategic planning, cross-functional collaboration, and leveraging advanced technologies to ensure seamless integration and real-time responsiveness.

Manufacturing

Technology advances are converging with cost and time pressures and formulation complexity to drive greater adoption of automated processes.


Leap Forward in Automation Anticipated for Small-Molecule Drug Product Manufacturing

Demand for highly potent active pharmaceutical ingredients (HPAPIs) remains high in the face of a continued focus by the pharmaceutical industry on the oncology space, targeted therapies, and precision medicine. Consequently, HPAPIs account for a growing percentage of pipeline candidates. Advances in synthetic chemistry, bioproduction, continuous manufacturing, and containment technologies are increasing the feasibility of bringing these ever more-potent therapeutics to the market.

is estimated to be expanding at a compound annual growth rate (CAGR) of approximately 9% to surpass $60 billion by 2034 (1,2). Given the specialized nature of HPAPI manufacturing, this strong demand growth is also driving healthy growth for the HPAPI contract manufacturing market. One estimate pegs the global value for this sector at $8.15 billion in 2024 and expanding at a CAGR of 10.93% to reach $23 billion by 2023 (3).

A distinguishing feature of the HPAPI market is the rapid rate of change it has been experiencing over the past decade-plus. The fast pace of evolution can be attributed to several factors, according to Ester Masllorens, senior vice president of global R&D with Olon. “The HPAPI landscape is rapidly evolving, driven by breakthroughs in oncology, rare diseases, and advanced delivery platforms such as antibody-drug conjugates (ADCs) and peptides. The growing complexity and potency of these molecules requires sophisticated containment capabilities and manufacturing strategies,” she says.

At the same time, Alessandro Agosti, director of Olon’s R&D Rodano Hub, notes that regulatory scrutiny and environmental, safety, and governance (ESG) expectations are compelling contract development and manufacturing organizations (CDMOs) to operate in a cleaner, safer, and more sustainable manner.

Technological innovations are helping to both reshape HPAPI development and scale-up and addressing evolving challenges. “For example, technologies such as flow chemistry, continuous manufacturing, and advanced membrane technologies reduce operator exposure while enhancing efficiency and consistency,” comments Agosti. He also highlights the increasing importance of automation, predictive modeling, and artificial intelligence-driven design-of-experiments (DoE), particularly for high-potency compounds requiring stringent containment.

What are some technical, operational, and regulatory challenges?

Development and production of HPAPIs have always been challenging given the need for specialized expertise to ensure their safe handling with respect to both operators and the environment. The unique combination of technical, operational, and regulatory challenges faced by HPAPIs continues to increase as the diversity and higher complexity of HPAPI candidates under development today continues to widen, according to Masllorens.

“In addition to the need for robust containment, validated cleaning procedures, and strict protection of operators, HPAPI CDMOs must also be able to implement highly specialized synthesis and purification capabilities, often under extreme containment, to generate molecules from ADCs and peptides to newer types of bioconjugates,” observes Masllorens. She adds that ease of formulation, bioavailability, and supply chain security remain persistent issues as well and are further complicated by fluctuating raw material markets and global economic pressures.

Why is a multipronged approach essential?

To overcome these many challenges, HPAPI manufacturers are pursuing strategies that involve numerous independent tactics. “To address the complexity of HPAPI development, the industry is increasingly adopting modular containment systems, green chemistry approaches, and digitalization,” states Masllorens. Regardless of the specific approach taken, she emphasizes that a strong commitment to innovation, safety, and sustainability is a fundamental requirement.

Olon has found that co-locating its high-containment R&D, quality control, and good manufacturing practice (GMP)-compliant production units has streamlined tech transfer activities and enabled rapid scale-up as client candidates progress through clinical development, according to Masllorens. In a similar vein, the company has connected its global network of 14 sites through a centralized R&D hub, which has supported harmonization of processes and facilitated best-practice sharing across all technologies.

Developing processes using DoE and quality-by-design approaches and advanced modeling tools, meanwhile, ensures safety, robustness, and reliable transfer throughout the entire lifecycle of highly potent compounds, notes Agosti.

Finally, Olon believes that its integration of biological capabilities—microbial fermentation for semisynthetic APIs and bioconjugation to ADCs—with its chemical HPAPI expertise positions the company to meet evolving scientific and sustainability demands of next-generation HPAPI development, according to Agosti. He notes this integrated approach is particularly advantageous for payloads that require both biological and chemical steps such as maytansinoids and camptothecins. In addition, Masllorens believes that the vertical integration of chemical and biological capabilities allows Olon to support clients across a wide range of production volumes and modalities, from early-phase clinical batches to late-stage commercialization.

Managing the move from small- to large-scale manufacturing

Tech transfer is one of the most critical and sensitive steps in HPAPI development, particularly when moving from small-scale R&D settings to full-scale GMP manufacturing. “Key challenges include validating cleaning procedures for ultra-potent compounds, maintaining consistent containment integrity, and ensuring personnel are fully trained to handle these materials safely,” Agosti observes. He adds that for biologically derived HPAPIs, such as bioconjugates, variability in biological systems and complex purification and downstream further complicate scale-up. Here again, integration of R&D, analytical development, and GMP production in the same location ensures that R&D teams stay involved through validation and even first commercial batches, ensuring continuity of knowledge.

What are some continued CDMO investments?

The HPAPI sector is set for sustained growth, driven by a strong pipeline in oncology, rare diseases, and immune-modulating therapies, according to Masllorens. Many of these molecules, such as ADCs and peptide therapeutics, require ultra-high containment, highly specialized synthesis or fermentation, and strict regulatory compliance, which is driving demand for services from CDMOs with advanced and demonstrated capabilities, she adds.

In addition, Agosti notes that clients are increasingly prioritizing ESG performance, supply chain resilience, and digital integration; therefore, CDMOs must be positioned to address these needs as well.

In response to these evolving expectations and the healthy growth of the HPAPI market, a high level of investment by CDMOs has been observed over the past several years, including a few notable moves in the United States in 2024 and 2025.

Olon added new occupational exposure band (OEB) 5 production lines and a state-of-the-art OEB6 facility dedicated to ultra-potent compounds such as ADC payloads and payload-linkers, according to Masllorens. “The OEB6 facility integrates analytical labs, pilot units, and GMP manufacturing and leverages technologies such as flow chemistry, photochemistry, biocatalysis, and tangential flow filtration to enable safer, greener, and more scalable operations and support of the development and production of ADCs,” she says. Plans are in place to expand the OEB6 facility to meet rising demand for ultra-potent payloads and biological intermediates by 2026 and scale Olon’s bioconjugation capabilities. With respect to implementation of newer technologies, Olon has incorporated both upstream and downstream innovations including antibiotic-free processes and codon-optimized microbial expression.

In June 2025, Piramal Pharma Solutions announced it will spend $90 million to expand ADC manufacturing capability at two facilities in the US, including HPAPI production (payload-linkers) in Michigan and ADC fill/finish capacity in Kentucky (4). 

meanwhile, launched a new CGMP analytical testing laboratory dedicated to HPAPIs at its Rancho Cordova, California site in February 2025 (5).

AGC Pharma Chemicals announced in January 2025 

the expansion of its HPAPI capabilities in Barcelona, Spain with the goal of achieving “seamless scale-up from grams to tons within a single integrated ecosystem” (6). Once completed, the company’s entire development and manufacturing chain from its new R&D facility through laboratory to commercial production will be adapted to OEB5 standards.

Sterling Pharma Solutions announced in May 2024 

that it would be investing $3 million to expand its integrated ADC development and manufacturing capabilities in Wisconsin. A dedicated GMP suite including a modular isolator with containment capabilities down to less than 1 nanogram per cubic meter will be added that will enable toxin linker manufacturing up to the kilogram scale (7).

Grand View Research. High Potency Active Pharmaceutical Ingredients Market–By Product, By Drug Type, By Manufacturer Type, By Application–Global Forecast, 2025–2034. February 2025. 

https://www.gminsights.com/industry-analysis/high-potency-active-pharmaceutical-ingredients-market

Mordor Intelligence. High Potency APIs Market Size & Share Analysis–Growth Trends & Forecasts (2025–2030). 

https://www.mordorintelligence.com/industry-reports/highpotencyapis%.

Nova One Advisor. High Potency API Contract Manufacturing Market Size to Hit USD 23.00 Bn by 2034. Nov. 7, 2024. 

https://www.biospace.com/press-releases/high-potency-api-contract-manufacturing-market-size-to-hit-usd-23-00-bn-by-2034

Piramal Pharma Solutions. Piramal Pharma Solutions Breaks Ground on $90M Expansion Plan. Press Release, June 25, 2025. 

https://www.prnewswire.com/news-releases/piramal-pharma-solutions-breaks-ground-on-90m-expansion-plan-302494239.html

SK pharmteco. SK pharmteco Launches State-of-the-Art HPAPI Laboratory. Press Release. Feb. 12, 2025. 

https://www.skpharmteco.com/news-insights/news/sk-pharmteco-launches-state-of-the-art-hpapi-laboratory/

AGC Pharma Chemicals. AGC Pharma Chemicals Announces Expansion of HPAPI Capabilities in Barcelona. Press Release, Jan. 29, 2025. 

https://www.agcpharmachemicals.com/en/news/agc-pharma-chemicals-announces-expansion-of-hpapi-capabilities-in-barcelona/

Sterling Pharma Solutions. Sterling Expands HPAPI Capabilities to Further Strengthen Integrated ADC Services. Press Release, May 30, 2024. 

https://www.sterlingpharmasolutions.com/knowledge-hub/news/sterling-pharma-solutions-expands-hpapi-capabilities-in-germantown/

®
Vol. 49, No. 9
November/December 2025
Pages: 13–14, 21

When referring to this article, please cite it as Challener, C.A. Trends and Challenges Impacting Highly Potent API Development. 

The demand for highly potent active pharmaceutical ingredients (HPAPIs) is rising due to the pharmaceutical industry's focus on oncology, targeted therapies, and precision medicine. This growth is driving the HPAPI market to expand significantly, with a projected value surpassing $60 billion by 2034. Technological advancements in synthetic chemistry, bioproduction, and containment are facilitating the development of these potent therapeutics. The HPAPI landscape is evolving rapidly, with increased regulatory scrutiny and environmental expectations. A multipronged approach, including modular containment systems and digitalization, is essential to address the complex challenges in HPAPI development.

Development

Increasing demand, complexity, and potency are driving innovation and investment in HPAPIs.

Trends and Challenges Impacting Highly Potent API Development

The pharmaceutical sector continues to evolve at a remarkable pace, shaped by scientific breakthroughs, growing operational complexity, and heightened regulatory expectations. This issue highlights the industry’s ongoing effort to balance innovation with control—ensuring that as technologies and therapeutic modalities advance, manufacturing and quality systems advance alongside them.

Our cover story, “How a ‘Plan, Prevent, Prove’ Approach Helps Avoid Facility and Equipment Problems,” captures a core challenge for good manufacturing practice operations today: anticipating failure before it occurs. As facilities become more interconnected and equipment more sophisticated, risk-based planning and disciplined maintenance have become essential.

On the development front, Cynthia A. Challener, PhD, examines the increasingly complex world of highly potent APIs in “Trends and Challenges Impacting Highly Potent API Development.” The rising demand for targeted and potent therapies is driving investment in containment technologies, specialized infrastructure, and new approaches to worker and product safety. These pressures are reshaping how companies think about HPAPI innovation and scale-up.

Challener also explores the manufacturing implications of these shifts in “Leap Forward in Automation Anticipated for Small-Molecule Drug Product Manufacturing.” With formulation complexity growing and the need for efficiency intensifying, small-molecule manufacturers are turning to automation to reduce manual operations, enhance consistency, and streamline production timelines.

In “How Therapeutic and Analytical Advancements Help Drug Substance Testing Evolve,” Patrick Lavery highlights how advances in both therapies and technologies are redefining modern analytical strategies. He explores trends in sustainability, stability testing, and the emerging role of artificial intelligence in quality assessment. Rounding out the issue, the Ask the Expert feature offers an overview of batch recovery fundamentals, an essential reminder that strong foundational practices remain critical, even as the industry embraces new tools and capabilities. Together, these articles reflect an industry in transition, committed to innovation while ensuring safe, reliable, and forward-looking pharmaceutical production.

Mike Hennessy Jr is Chairman and CEO of MJH Life Sciences®.

®
Vol. 49, No. 9
November/December 2025
Page: 8

When referring to this article, please cite it as Hennessy, M. How Innovation and Risk Management Are Reshaping Modern Drug Manufacturing. 

The pharmaceutical industry is rapidly evolving, driven by scientific advancements, operational complexities, and regulatory demands. Balancing innovation with control is crucial as technologies and therapeutic modalities progress. Key challenges include anticipating equipment failures and adapting to the complexities of highly potent APIs. Automation is becoming essential in small-molecule drug manufacturing to enhance efficiency and consistency. Advances in therapies and technologies are reshaping analytical strategies, with sustainability and AI playing significant roles. Despite these innovations, foundational practices like batch recovery remain vital for safe and reliable pharmaceutical production.

From the Chairman

The articles in this issue reflect an industry in transition, committed to innovation while ensuring safe, reliable, and forward-looking pharmaceutical production.

How Innovation and Risk Management Are Reshaping Modern Drug Manufacturing

Q: What is the best way to perform batch recovery procedures for the manufacturing of pharmaceutical products?

A: Pharmaceutical batch recovery is a critical process in the manufacture of medicines. The batch recovery process is performed when there is a deviation during manufacturing, and the situation is such that there may be a potential to “recover” the batch while still ensuring the final product meets quality, safety, and compliance standards. Batch recovery involves identifying and rectifying any deviations or issues that occurred during the production of the specific batch in question by conducting a thorough investigation resulting in definitively identifying the root cause of the deviation. The investigation should involve collaboration between quality assurance, production teams, and regulatory authorities. The batch recovery process should define the details of the root cause analysis as well as any future corrective and preventive actions to prevent recurrence. This will help determine if the batch is suitable for recovery.

The main challenge in batch recovery is quickly identifying the root cause of the deviation. Investigations can sometimes be complex and may take more time to come to root cause. This impacts the ability to be able to recover the batch especially when dealing with time sensitive products that may degrade while awaiting the outcome of the investigation. Regardless of the product involved and the criticality of the situation, care must be taken to maintain consistent, thorough documentation, and timely communication with management and regulatory authorities to guarantee the recovered product meets all quality, safety, and regulatory standards, thereby ensuring patient safety.

One of the most important elements in considering batch recovery steps is making sure that a robust quality control system has been implemented across the company. The culture of the organization must be mature enough before undertaking batch recovery operations. This includes, but is not limited to, having appropriate risk analysis procedures, robust documentation and change control procedures, a highly trained staff, a comprehensive investigation process, and adherence to data integrity requirements. Continuous improvement and regular facility audits will help prevent the issue from recurring in the future.

The decision to perform a batch recovery is a difficult one. It is important to understand when a batch recovery procedure can be utilized and when it would be inappropriate to try to and recover a batch. The determination to perform a batch recovery will depend on the severity of the deviation and if the root cause that prompted the deviation was successfully identified with documented supporting evidence. Batches that have more than one deviation during that manufacturing process should not be considered suitable for batch recovery.

The ideal situation is to try and avoid batch recovery situations by having a robust quality system that values continuous process improvement based on identifying root causes for deviations and proactively implementing changes. It is essential to follow best practices and proactively address manufacturing challenges upfront. Identifying the true root cause of the deviation not only helps minimize cost, especially when expensive active ingredients are involved, but helps maintain product integrity that meets regulatory commitments. Even if you have all the necessary elements imbedded into the quality system, unexpected occurrences may lead to a scenario where the company needs to determine whether a batch can be recovered. By following best practices and employing continuous process improvements based on robust investigations and corrective and preventative actions, manufacturers can potentially recover a batch that might otherwise be rejected.

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates, a Nelson Labs Company, and a member of the 

®
Vol. 49, No. 9
November/December 2025
Page: 26

When referring to this article, please cite it as Schniepp, S.J. Fundamentals of Batch Recovery Procedures. 

Batch recovery in pharmaceutical manufacturing is crucial when deviations occur, ensuring the final product meets quality, safety, and compliance standards. The process involves identifying and rectifying deviations through thorough investigation, collaboration, and root cause analysis. A robust quality control system, mature organizational culture, and continuous improvement are essential for effective batch recovery. The decision to recover a batch depends on the severity of the deviation and successful root cause identification. Proactive measures and best practices can minimize the need for batch recovery, maintaining product integrity and regulatory compliance.

Ask the Expert

Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, a Nelson Labs Company, outlines the importance of batch recovery procedures in pharmaceutical manufacturing.

Fundamentals of Batch Recovery Procedures

Pharmaceutical manufacturers must comply with good manufacturing practices (GMPs) set by regulators in 

 (3). Pharmaceutical manufacturing buildings and equipment are governed by these regulations (4,5) and usually must comply with these rules in the form of risk-based maintenance programs.

The path to following these requirements is defined by regulators or created by the pharmaceutical company itself, according to Pranav Vengsarkar, PhD, director, process R&D and site head at Avantor. Routine inspections along with equipment calibration and cleaning must be performed and documented to demonstrate facilities and equipment are being maintained to meet regulations, Dr. Vengsarkar says. “Beyond regulatory expectations, proactive maintenance also drives operational efficiency and strengthens credibility with regulators. This enables companies to stay competitive while protecting patient safety.”

To assist in these maintenance tasks, Dr. Vengsarkar recommends the utilization of digital monitoring and artificial intelligence (AI) tools to predict when updates may be needed and to anticipate calibration problems. “This approach supports GMP compliance and minimizes downtime. It also reflects smart manufacturing—leveraging data to maintain equipment performance, improve efficiency, and scale to new modalities without compromising product quality or patient safety,” Dr. Vengsarkar says.

David Basile, VP Technical Operations, Americas at Hovione recommends a comprehensive approach that starts with specification, design, and installation and then moves through to the decommissioning of the equipment. He also suggests using modular and scalable processes to accelerate product deployment.

How much is risk mitigation involved in facility design?

Designing quality from the beginning of a facility’s creation or in the modification of an existing facility may be imperative (6). A robust quality design approach provides a blueprint for continuous improvement. A design review process should be defined in a project execution plan that includes quality reviews (6).

Mark O’Brien, Process Equipment Procurement Leader, DPR Construction, says that understanding the GMP requirements before the early facility design decisions are made can help achieve compliance. Items such as personnel flow and zoning identification can protect people and product from potential contamination. Airflow is also an important concern; therefore, HVAC system design should be taken into consideration.

Pharmaceutical facilities need reliable utility systems to purify water and have backup power supplies, O’Brien says, and a waste system should be designed to properly dispose of waste. “By making key decisions in the infancy of a project, you can deliver a facility that has been designed and built to ensure GMP regulatory compliance with minimal risk and maximum future success,” he stresses.

Risk mitigation identifies potential future problems before they arise so management strategies can be planned ahead of time. For facility design, common problems may be contamination, improper zoning, or faulty equipment. “Gaining early engagement with regulatory bodies to understand expectations and guidelines helps adherence from the start, as well as successfully commissioning, qualifying, and validating the facility at the end,” O’Brien explains. “Risk identification and mitigation isn’t just a starting process. It is an ongoing activity throughout the life of a project. Recurring GMP reviews and audits will be necessary to ensure that correct design decisions are made to allow for the successful and compliant construction of the GMP facility.”

How often should facilities and equipment be evaluated?

Pharmaceutical companies should be using a quality management system (QMS) that includes a review of the GMP facility and the equipment within that is used for GMP-regulated processes. A risk-based approach should be used to determine at what time intervals equipment should be evaluated.

According to Dr. Vengsarkar, pharmaceutical companies are expected to perform internal audits and risk assessments to ensure their operations are current. “Drivers include new technologies, scaling across modalities, or updated compliance requirements,” Dr. Vengsarkar notes. “These upgrades safeguard product quality and patient safety while also improving efficiency, flexibility, and adoption of innovative processes. A periodic review of a GMP facility is a critical process to ensure it remains in a validated state and compliant with current regulations.”

While the quality control and quality assurance departments usually oversee GMP compliance, Dr. Vengsarkar stresses it is a “cross-functional responsibility” that relies on collaboration with engineering and manufacturing departments. “This integrated approach ensures equipment is properly maintained, calibrated, and qualified while aligning facility operations with regulatory standards,” he says. “This approach reflects a culture of shared accountability that regulators expect to see across the organization.”

A dedicated reliability engineer and maintenance planner can assist in facility and equipment evaluation, according to Basile. “This is critical to shorten the mean time to repair and ensure that all tools and supplies needed for the job are available and kitted to support fast first-time-right work order execution,” he adds. “These roles are game changers to the operation and take you from walking to sprinting, especially when candidates bring hands-on experience. In fact, the best planners are usually seasoned mechanics.”

Basile also suggests having a shutdown cycle to identify potential problems with equipment as well as performing internal audits. For long-term updates in response to market demands or new products, more substantial planning may be needed.

“For example, we might have a client that has a pipeline of potent products, in which case we would evaluate the implementation of, say, airlocks, or isolators or misting stations in the relevant processing areas in the GMP facility,” Basile explains.

A site’s validation master plan includes requalification and/or assessment of GMP equipment, says Basile, and each type of equipment may need its own evaluation timeline based on a risk assessment. This can also include a review of the equipment’s historical changes, failure trends analysis, and any corrective and preventive actions performed.

“GMP manufacturing and lab equipment also require regular calibration with critical instrumentation being performed more frequently,” says Basile. “[One should take] a life cycle approach to maintaining equipment, where the equipment master serves as a birth certificate when a machine comes in, all the way through to decommissioning. This is a fundamental part of good asset management.”

How do manufacturers assure regulators that their facilities and equipment are well-maintained?

Possibly more important than setting up a maintenance schedule and having a QMS is proving to a regulatory body that these tasks are indeed being performed. Regulators insist on pharmaceutical manufacturers backing up their claims with data and proof.

“Proof of maintenance is a routine request during GMP inspections,” Dr. Vengsarkar explains. “These records should be complete, organized, and easily accessible, ideally in electronic form. They should detail the date, personnel, service performed, and verification that equipment was returned to a compliant state. A lot of companies tend to outsource their calibration and maintenance needs, which makes clear stakeholder review of these documents necessary to support compliance requirements. Strong documentation not only satisfies inspectors but also demonstrates a robust quality system—reinforcing both regulatory compliance and an organization’s commitment to operational excellence.”

“In our industry, you didn’t do it if you didn’t document it,” Basile stresses. “We compile detailed electronic records, including preventive maintenance schedules and calibration certificates. These should be presented in a clear and organized manner. In our recent inspections, we’ve seen that inspectors appreciate being able to get these records in a digital format for portability, and in case they’d like to reference them at their convenience.”

Basile also recommends using a computerized maintenance management system (CMMS) as a central repository for maintenance-related activities. “This is a key system in the efficient execution of any strong, compliant maintenance program,” he insists. “It provides detailed work order history, preventative maintenance instructions, asset specifications, scheduling, data, and spare parts inventory, so we can see trends and pick up instrument drift, for example, to clearly demonstrate that our assets remain in a state of high performance and quality operation.”

Do different stages of manufacturing have different GMP maintenance requirements?

Equipment used later in the lifecycle of a drug product carries higher risk, according to Dr. Vengsarkar; therefore, it requires more stringent maintenance requirements. Different equipment types also can have different rules for maintenance.

“Typically, analytical equipment, which is usually the last line of defense against a contaminated product, is held to a high standard from an accuracy and data integrity standpoint. Analytical instruments must be regularly calibrated and qualified to ensure accuracy and data integrity,” Dr. Vengsarkar explains. He also says that tableting and packaging equipment need preventive maintenance and rigorous cleaning to maintain consistent performance and prevent contamination.

What mistakes do manufacturers often make?

Being reactive instead of proactive when it comes to equipment maintenance is a common mistake seen by Dr. Vengsarkar, along with incomplete records. He also points to poor personnel training and inadequate cleaning procedures that can cause risk. These risks should be prevented by implementing robust cleaning practices that are consistent and by updating procedures when processes evolve.

Not performing comprehensive criticality assessments using a risk-based approach can lead to over- or under-maintenance of equipment, according to Basile. Relying only on time-based maintenance instead of a proactive approach, such as precision alignment or lubrication, can result in subpar maintenance.

“Today’s teams need to incorporate conditions-based maintenance using technologies, such as vibration analysis,” Basile advises. “They can no longer just fix things that break. They need to diagnose equipment, looking for early signs of failure before they fully develop. Other examples of this are ultrasound or infrared scanning to ensure motors and electrical systems are wired and operating properly.”

Not designing for maintainability is also a common mistake, says Basile. “During the design phase, [having] adequate space and access to equipment, standardized tools, and having the right pickups on equipment for condition-based maintenance is important. I can’t tell you how many times I’ve seen a filter housing or an instrument placed in the interstitial space above a ceiling with no way to safely access it.”

Not allowing enough time for commissioning is also a problem seen by Basile. “The lifespan of equipment can be greatly influenced during the commissioning phase; this is where maintenance reliability starts,” he says. “Too often, commissioning is rushed through, and equipment, preventive maintenance plans, and required spare parts are not thoroughly assessed. In many cases, due to limited time, the CMMS system is not fully populated with key information to perform comprehensive root cause analysis.”

How can facility and equipment problems be avoided?

Anticipating future problems using risk-based approaches can prevent facility and equipment problems. Often in pharmaceutical manufacturing, contamination control is key. Designing facilities that take into account requirements for cleanrooms and separate manufacturing areas for different types of products can keep costly contamination errors from happening…and help prevent drug shortages.

Being proactive and not reactive with equipment maintenance is key to successfully complying with regulations in a GMP environment. GMPs are there to keep patients safe, but they can also keep pharma companies from finding themselves offline.

FDA. Current Good Manufacturing Practice (CGMP) Regulations. 

https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations

https://www.ema.europa.eu/en/human-regulatory-overview/research-development/compliance-research-development/good-manufacturing-practice

WHO. Health Products Policy and Standards. WHO.int. 

https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/norms-and-standards/gmp

Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

Penko, A. Design Quality in Pharmaceutical Design: A Primer for Facility Executives. 

®
Vol. 49, No. 9
November/December 2025
Pages: 10–12

When referring to this article, please cite it as Haigney, S. How a “Plan, Prevent, Prove” Approach Helps Avoid Facility and Equipment Problems. 

Pharmaceutical manufacturers must adhere to GMPs, which are crucial for maintaining compliance and ensuring patient safety. Proactive maintenance, supported by digital tools and AI, enhances operational efficiency and regulatory credibility. Facility design should incorporate risk mitigation strategies from the outset, focusing on contamination prevention and reliable utility systems. Regular evaluations and audits, guided by a QMS, are essential for maintaining compliance. Documentation and data are critical for demonstrating maintenance activities to regulators. A proactive, risk-based approach to equipment maintenance, incorporating condition-based technologies, is vital for preventing issues and ensuring GMP compliance.

Cover Story

Starting with risk mitigation, GMP facility and equipment maintenance is all about anticipating problems before they happen and showing regulators a controlled environment.

How a “Plan, Prevent, Prove” Approach Helps Avoid Facility and Equipment Problems

Drug substance testing is a critical component of the biopharmaceutical analysis process, carrying with it inherent benchmarks of safety and efficacy that must be met. In an exclusive interview with 

, summarizes the current trends in this field and how ever-evolving regulations, as well as technologies, are moving companies forward toward greater accuracy and dependability for patients.

 Have there been notable regulatory changes in drug substance testing that have affected processes or quality issues? If not, are any expected?

 I think we are seeing four key areas of focus—it’s probably not so much about change; it’s more about concentrating on those aspects. Clearly, data integrity is a significant topic, and all agencies worldwide continue to stress the importance of data integrity throughout the lifecycle of drug substance testing. Impurity characterization and control remain significant topics of discussion. There is a trending focus on more thorough characterization of impurities, stricter controls, and an increased emphasis on understanding potential genotoxic impurities while establishing appropriate limits. Therefore, I believe this is a key focus area.

Stability requirements are evolving and being continuously refined; there’s a progression in the expectations concerning that data, necessitating support for that data, as well as support for retest periods and shelf life. And then, a higher emphasis on process understanding and control strategies. There is a clear drive toward a deeper understanding of the manufacturing process and the establishment of robust control strategies. I believe none of this is revolutionary or sweeping; however, I feel that all of these areas are worth focusing on. When we look ahead, I believe we will clearly see advanced analytical technology on the horizon. Therefore, we can expect more emphasis on the use of advanced analytical technologies like mass spectrometry and spectroscopy for improved characterization and real-time monitoring. Regarding process understanding and control strategies, advanced methodologies will certainly increase focus in that area. We can anticipate a greater emphasis on sustainability and greener technologies overall, alongside a stronger focus on sustainable manufacturing practices—we have also started to implement our My Green Lab certification in this context—along with new approach methodologies, NAMs.

In certain fields, particularly for safety testing, there is already a push to lessen reliance on animal testing. We have observed government agencies signing orders related to this and adopting new approaches. While this is more advanced in direct product testing, we may see a gradual effect on certain aspects of drug substance testing in the long term. We’ll see how this develops, but we all need to stay attentive to that progress.

Finally, with the massive cuts currently occurring at FDA under the current administration, there is reason to be concerned regarding how FDA approaches its regulatory oversight of drug substance testing (and everything else for that matter). It would not be surprising to see FDA slow down and/or become more conservative over the next 12–18 months, as it adjusts to lower headcount and support within the agency. Innovators would be wise to interact with the agency as early as possible and stay abreast of ongoing regulatory trends as the field adjusts to the new normal.

Have newer modalities caused any shift in previously standard analytical methods or procedures

We definitely see an increased emphasis on biological assays. Traditional methods often relied on physicochemical characterization, such as HPLC [high performance liquid chromatography] and spectroscopy. Newer modalities, including cell therapies, gene therapies, complex biologics like ADCs [antibody-drug conjugates] or bispecific antibodies, and importantly, peptides and oligonucleotides, necessitate a much greater focus on biological assays to assess potency, efficacy, and safety. For many of them, it’s even a question of how to best define potency and how to test efficacy on an ongoing basis.

We also observe enhanced characterization techniques. The complexities of these new modalities demand more sophisticated analytical methods for comprehensive characterization. For example, peptides, though smaller than full biologics, require rigorous analysis for sequence confirmation, impurities (e.g., related substances, residual solvents), and chirality. Techniques like mass spectrometry are essential for precise molecular weight and sequence verification, while advanced chromatography is used for separation and quantification of minor impurities. Looking at oligonucleotides (like siRNAs [small interfering RNAs], antisense oligos, and aptamers), these are complex synthetic polymers that require specialized methods to verify length, sequence fidelity, and the presence of modifications (e.g., phosphorothioate linkages, 2'-O-methyl groups). Techniques such as capillary electrophoresis and hybridization assays are crucial here, in addition to highly resolving liquid chromatography and MS. Additionally, there is an emphasis on impurity profiling specific to each modality.

Newer modalities often differ significantly from those of small molecules. We now need to factor in aspects such as process-related impurities, vector-related impurities (for gene therapy), cellular impurities, and also synthetic impurities and truncations that are characteristic of peptide and oligonucleotide manufacturing. Furthermore, we are witnessing the emergence of rapid in-process testing methodologies, which facilitate obtaining test results in real-time and potentially allow for process modifications based on those results. For some newer modalities—particularly cell and gene therapy—with short shelf lives or autologous nature, there’s a growing need for rapid testing methods that can provide quick turnaround for critical quality attributes. This need is often balanced with the highly accurate and specific testing required for oligonucleotides and peptides to confirm purity and identity before final release.

And the last thing I’d like to mention is increased regulatory scrutiny and comparability. That’s clearly an item that we have seen FDA pushing back on submissions in the past. When manufacturing processes for these complex modalities change, or when we have tech transfers, new plans, and so on, demonstrating comparability becomes increasingly critical. This applies across the board, from cell therapies down to synthetic peptides and oligonucleotides, to ensure product quality and patient safety. Rigorous analytical testing is essential, as nobody wants to repeat clinical studies for manufacturing changes. Therefore, comparability capabilities and evidence become more important.

How is artificial intelligence (AI) factoring in, now and in the future?

I firmly believe that AI, in the long run, will play an important role in revolutionizing the industry and lead to better outcomes at all levels, whether it’s yield, right-first-time, speed of tech transfer, the reduction of wet lab work necessary to develop a process, the number of tests ultimately needed to confirm quality, or overall productivity. These are just a few areas where I, or we as a company, believe that AI will significantly change our lives. We are currently in the early stages, like many others.

Drug substance testing is crucial in biopharmaceutical analysis, ensuring safety and efficacy. Current trends emphasize data integrity, impurity characterization, stability requirements, and process understanding. Advanced analytical technologies like mass spectrometry are gaining importance. Newer modalities, such as cell and gene therapies, require sophisticated biological assays and rapid in-process testing. AI is expected to revolutionize the industry by enhancing regulatory compliance and process efficiency. Tariff policy changes may impact testing costs and supply strategies. The advanced therapy market is focusing on scientifically promising assets, potentially increasing clinical success rates.

Quality, stability, sustainability, and the increased and thoughtful integration of artificial intelligence are foremost in the minds of those on the leading edge of testing trends.

Pharmaceutical Technology November December 2025

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How a “Plan, Prevent, Prove” Approach Helps Avoid Facility and Equipment Problems

How Therapeutic and Analytical Advancements Help Drug Substance Testing Evolve