Susan Haigney

Hand holding a stylus over a tablet with futuristic risk management icons such as warning signs, data charts, and safety symbols on a dark background. | Image Credit: ©ImageFlow -stock.adobe.com

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. 

Articles

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.

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

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 that it will be providing agency staff with agentic artificial intelligence (AI) capabilities that will enable the creation of complex AI workflows, harness AI models, and assist with multi-step tasks. The deployment is part of FDA’s initiative to embed AI more deeply into workflows to achieve operational efficiency.

“FDA's talented reviewers have been creative and proactive in deploying AI capabilities — agentic AI will give them a powerful tool to streamline their work and help them ensure the safety and efficacy of regulated products,” Chief AI Officer Jeremy Walsh stated in a press release (1).

Agentic AI are advanced AI systems used for planning, reasoning, and executing multi-step actions with built-in guidelines for reliable outcomes. A two-month Agentic AI Challenge will be launched by the agency to encourage staff members to build Agentic AI solutions that will be demonstrated at the FDA Scientific Computing Day in January 2026.

While use of the Agentic AI will be optional and voluntary for FDA staff, the agency says it will help staff with meeting management, pre-market reviews, validation reviews, post-market surveillance, inspections, compliance, and administrative functions. Models will be built within high-security GovCloud environments and will not train on input data, or any submitted regulatory industry data, ensuring sensitive research is safe.

“We are diligently expanding our use of AI to put the best possible tools in the hands of our reviewers, scientists, and investigators,” FDA Commissioner Marty Makary, MD, MPH, said in the release. “There has never been a better moment in agency history to modernize with tools that can radically improve our ability to accelerate more cures and meaningful treatments.”

, a generative AI tool for staff use. Elsa was also built within a high-security GovCloud environment for staff to securely access internal agency documents. Elsa is being used by FDA to accelerate clinical protocol reviews, scientific evaluations, and identify inspection targets.

Elsa is a large language model (LLM) designed to assist with reading, writing, and summarizing to support safety profile assessments, label comparisons, and help develop databases for nonclinical applications.

“Following a very successful pilot program with FDA’s scientific reviewers, I set an aggressive timeline to scale AI agency-wide by June 30,” Makary said in a press release at the time (2). “Today’s rollout of Elsa is ahead of schedule and under budget, thanks to the collaboration of our in-house experts across the centers.”

What is AI’s impact on the pharma industry?

AI has been a hot topic at many recent industry conferences and events. It is becoming more widely used in the industry in a variety of areas. There were a variety of discussions on AI’s use in bioanalysis at the 

 conference, which was held in November 2025. 

® spoke with Long Yuan, PhD, director of the Department of Drug Metabolism and Pharmacokinetics at Biogen about how AI, machine learning, and LLM are being utilized for bioanalysis.

“There is significantly increased interest and a great potential for AI to make a significant impact on various aspects of bioanalysis, including improving the quality, efficiency, compliance, and also reducing human errors,” Dr. Yuan said (3). 

The full interview can be watched on PharmTech.com.

FDA. FDA Expands Artificial Intelligence Capabilities with Agentic AI Deployment. Press Release. Dec. 1, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-expands-artificial-intelligence-capabilities-agentic-ai-deployment

FDA. FDA Launches Agency-Wide AI Tool to Optimize Performance for the American People. Press Release. June 2, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-launches-agency-wide-ai-tool-optimize-performance-american-people

Haigney, S. How AI, Machine Learning, and Large Language Models Enhance Bioanalysis. 

https://www.pharmtech.com/view/how-ai-machine-learning-and-large-language-models-enhance-bioanalysis

The FDA is integrating agentic AI to enhance operational efficiency, allowing staff to create complex AI workflows and assist with multi-step tasks. This initiative aims to streamline processes such as meeting management, pre-market reviews, and compliance. The agency will host an Agentic AI Challenge to encourage staff innovation. Additionally, the FDA has launched Elsa, a generative AI tool, to aid in clinical protocol reviews and scientific evaluations. AI's impact on the pharmaceutical industry is significant, improving bioanalysis quality, efficiency, and reducing human errors.

The agency is expanding its use of artificial intelligence (AI) with the deployment of agentic AI for staff to create more complex AI workflows and harness AI models.

FDA Deploys Agentic AI Capabilities for Agency Staff

Close-up view of doctor's hand in a white glove holding syringe | Image Credit: ©ra2 studio - stock.adobe.com

Eli Lilly and Company (Lilly) announced on Dec. 1, 2025 that the first patient visit for the SURMOUNT-REAL UK five-year, randomized, real-world clinical trial has taken place. The study, which is expected to include up to 3000 participants in the Greater Manchester, United Kingdom region, will evaluate the long-term effectiveness of tirzepatide on obesity outcomes when the drug is given in primary care settings. The trial will also evaluate the drug’s potential to delay the progression of type 2 diabetes.

“Obesity is a pressing health challenge both in the UK and globally,” Professor Rachel Batterham, Senior Vice President for International Medical Affairs at Lilly, said in a press release (1). “Lilly is committed to working with partners across the health system to better understand and address its complexity. With SURMOUNT-REAL UK, we aim to generate real-world evidence on the long-term health impacts of obesity management medications—evidence that can help shape future care pathways and improve health outcomes for people living with obesity.”

Lilly, the trial sponsor, is partnering with other organizations on the trial, which will also look at impacts of obesity-related complications, such as quality of life, work productivity, and hospital visits. Trial delivery, data flows, technology, and patient recruitment will be led by North West EHealth. System engagement and communications support for the trial is being provided by Health Innovation Manchester. The Chief Investigator for the trial, Martin Rutter, Professor of Cardiometabolic Medicine at the University of Manchester, is being hosted by the University of Manchester.

“In addition to endpoints assessing weight reduction and progression to type 2 diabetes, SURMOUNT-REAL UK will assess the broader health and healthcare impacts in a diverse group of individuals living across Greater Manchester,” Rutter stated in the press release. “The trial is particularly important because it will contribute to the evidence base on intervening comparatively early in the progression of obesity. It’s fantastic that Greater Manchester was selected for the trial because of the excellent research infrastructure and the availability of primary care data for research across the region.”

“As a GP, I see patients bring more than symptoms—they bring hopes, challenges, and the realities of their communities. They trust our practice as a familiar and accessible space. This is why I am proud to be involved in this trial, which extends participation opportunities to groups often under-represented in research,” Dr. Imran Ghafoor, GP Partner at Peterloo Medical Centre and Principal Investigator for the trial, noted in the release. “Research in primary care gives the potential to address health inequalities we witness firsthand. By involving our practice, we can amplify patient voices, identify barriers, and test solutions tailored to real lives. This approach ensures research is inclusive and that the evidence generated reflects the diverse population we serve.”

The study team will identify eligible participants for the trial based on predefined criteria. The results of the trial will be published in peer-reviewed journals.

What is the latest on tirzepatide in the United States?

that it is lowering the price of single-dose vials of tirzepatide in the United States, which is marketed under the name Zepbound, via the company’s digital healthcare platform, LillyDirect (2) (see Table). This action follows 

the reduction in price of Zepbound multi-dose pens 

in November, which is subject to FDA approval (3).

Table: Updated prices for 2.5mg and 5mg doses via Self Pay Journey Program via LillyDirect for Zepbound single-dose vials. Source: Eli Lilly and Company (2).

“Far too many people who need obesity treatments still face cost and coverage barriers,” said Ilya Yuffa, executive vice president and president, Lilly USA and Global Customer Capabilities, in the press release (2). “Today’s action underscores Lilly’s commitment to improving access across the obesity care landscape. We will keep working to provide more options—expanding choices for delivery devices and creating new pathways for access—so more people can get the medicines they need.”

Eli Lilly and Company. Lilly Announces First Patient Visit in SURMOUNT-REAL UK Trial. Press Release. Dec. 1, 2025.

Eli Lilly and Company. Lilly Lowers the Price of Zepbound (tirzepatide) Single-Dose Vials. Press Release. Dec. 1, 2025. 

https://investor.lilly.com/news-releases/news-release-details/lilly-lowers-price-zepboundr-tirzepatide-single-dose-vials

Eli Lilly and Company. Lilly and US Government Agree to Expand Access to Obesity Medicines to Millions of Americans. Nov. 6, 2025. 

https://lilly.mediaroom.com/2025-11-06-Lilly-and-U-S-government-agree-to-expand-access-to-obesity-medicines-to-millions-of-Americans

Eli Lilly and Company has initiated the SURMOUNT-REAL UK trial, a five-year study in Greater Manchester, UK, to assess tirzepatide's long-term effectiveness on obesity and its potential to delay type 2 diabetes progression. The trial, involving up to 3000 participants, aims to generate real-world evidence on obesity management. North West EHealth and Health Innovation Manchester are key partners in trial management. Concurrently, Lilly has reduced the price of tirzepatide in the US to improve access, reflecting its commitment to addressing obesity treatment barriers.

The first patient visit has taken place for the SURMOUNT-REAL UK clinical trial of Eli Lilly and Company’s weight-loss drug, tirzepatide. 

Lilly Launches UK Trial of Weight-Loss Drug as US Price Drops

Ask the Expert November 2025: Audits, Inspections, and CDMOs

Contract development and manufacturing organizations (CDMOs) typically have multiple clients who each have specific needs. When regulators perform audits and inspections of CDMOs, it is sometimes unclear who is responsible for any deviations the inspector might have. However, ultimately, the sponsor company is responsible for ensuring that any contract organizations are following good manufacturing practices.

But what happens when a CDMO has a client that has specification and/or requirements that infringe on that contractor’s ability to work with other clients? How should the CDMO respond to audits and their clients? In this episode of Ask the Expert, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, a Nelson Labs company (RCA); Siegfried Schmitt, vice president Technical at Parexel, and Anita Michaels, executive pharma compliance expert and principal consultant at RCA, give advice on how contractors and clients can work together to prepare for inspections and address regulatory actions.

“A lot of CDMOs utilize their clients' inspections to prepare for inspection. But I think you could level up, level that up higher,” Michaels says. “The first thing is you want to have a robust quality system. And you also want to integrate the other five systems into your facility. Then you'll receive, if it's a regulatory authority like the FDA, they could come to inspect you for a GMP or pre-approval inspection, which will be specific to the product they're covering. And then the GMP portion, if you have been approved for a United States product, would cover the six systems. So, I think holistically, a CDMO should prepare, number one, to handle a GMP covering the six systems and have a robust quality system, such as policies in place for your CAPAs [corrective and preventative actions], investigations, deviations, your KPIs, your tracking, and trending holistically across your facility. And then also understanding the approach for a preapproval inspection for your clients.”

Click the video above to watch Sue, Siegfried, and Anita answer the following question:

“How does a CDMO organization handle multiple client input and perspective with regard to general GMP inspections without compromising or setting up different standards within their Quality Management System?

Susan J. Schniepp, Distinguished Fellow, Regulatory Compliance Associates, a Nelson Labs company

Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates and a member of 

Siegfried Schmitt, PhD, Vice President, Technical at Parexel

Siegfried Schmitt, PhD, is vice president, Technical at Parexel and a member of 

Anita Michael, executive pharma compliance expert and principal consultant, Regulatory Compliance Associates, a Nelson Labs company

Anita Michael is RCA’s Executive Pharma Compliance Expert & Principal Consultant. She has 24+ years of global regulatory and quality experience, including 16 years direct FDA experience operating globally as their Pharmaceutical Expert, FDA Investigator and FDA Pre-Approval Manager. Anita has excellent interpersonal, empathetic communication and client management skills that enable her to skillfully coach and collaborate with clients at the highest levels of an organization and prepare them for successful FDA inspections (ANDA/NDA/BLA/PMA Pre-Approvals) and global regulatory and quality assurance audits across Biotech, Biologics, Sterile Operations, Drug Substances, and 503A/B. She has been Keynote Speaker for the Pharma Industry and internally to the FDA throughout her career.

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to 

, and it may appear in a future episode or print column.

Videos

In this episode of the Ask the Expert video series, Susan J. Schniepp, Regulatory Compliance Associates (RCA), Siegfried Schmitt, Parexel, and Anita Michaels, RCA, explain how CDMOs can best handle regulatory inspections and client expectations. 

Audits, Inspections, and CDMOs

Cropped shot of doctor holding transparent glass medical vial in hand, focus on bottle | Image Credit:  ©MYDAYcontent - stock.adobe.com

, which is being held from Nov. 9–12 in San Antonio, outlined a streamlined approach to identifying and mitigating the presence of visible particles in biologics. Eda Fenercioglu, Scientist, Formulations at Pfizer, explains how the workflow was applied to biologic formulations (1). The process was developed to reduce time and resources and maintain quality and data generation relevance. The approach used aligns with Six Sigma methodology, Define, Measure, Analyze, Improve, Control (DMAIC). A structured path offered particulate detection through root cause resolution. For this study, particulates were observed after manufacturing steps and in drug product that had been frozen and was then thawed.

How does the workflow help with assessment of particulates in product?

Visual inspection and microscopy imaging was first used to assess particulate morphology so that reason for the particulates could be determined. After this step, the isolated particulates were re-imaged and measured. Spectroscopic analysis, such as Fourier-transform infrared (FT-IR) spectroscopy, was used to ascertain the biochemical composition of the particulates. This allowed the particulates to be classified as either inherent, intrinsic, or extrinsic for targeted follow-up studies to determine the origin particulates and prevent recurrence. While FT-IR spectroscopy was used in this study, the workflow developed allows for the primary identification tool to be adapted, as necessary.

For non-polar or symmetric molecules, Raman spectroscopy is recommended, while scanning electron microscopy with energy dispersive X-ray spectroscopy is suggested for identifying trace metals or inclusions not visible under optical microscopy (1). More detailed characterization of fiber types is achieved with polarized light microscopy. This tool also helps differentiate between protein and nylon when it is used with FT-IR spectroscopy.

During mixing and settling studies, particulate count, size distribution, and morphology were assessed by high-accuracy light obscuration (HIAC-LO) and microflow imaging (MFI) to determine particulate formulation and possible process changes that would eliminate particulate formulation in future batches.

The study showed that particulates were inherent and their morphology and spectra were consistent with the components of the drug product. HIAC-LO and MFI were then used to identify that shear stress from mixing was the cause of the particulate formulation in the product. HIAC-LO was used to conduct a settling study that showed that turning off the mixer at a certain stage of manufacturing preserved solution homogeneity, therefore preventing the particulates from generating. The settling study also found that the drug product remained homogeneous over the hold time without continuous mixing; therefore, a process change could be made.

What does this mean for product inspection?

The study showed that an integrated approach to the identification and classification of particulates can assist in timely process improvements and process control. The use of analytical tools within the DMAIC framework provides efficient root cause analysis that can enhance the quality of the product. Robust control strategies can be established by defining and measuring particulate characteristics followed by analyzation of their composition that leads to the implementation of process improvements.

Fenercioglu, E. A Streamlined Workflow for Visible Particulate Indentification and Root Cause Mitigation in Biologic Drug Products. AAPS PharmSci 360 Poster Presentation. Nov. 11, 2025. 

https://aaps2025.eventscribe.net/fsPopup.asp?PosterID=764134&mode=posterInfo

A streamlined approach for identifying and mitigating visible particles in biologics was presented, utilizing a workflow aligned with Six Sigma's DMAIC methodology. This process, applied to biologic formulations, aims to reduce time and resources while maintaining quality. Visual inspection, microscopy, and spectroscopic analysis, including FT-IR, were employed to classify particulates as inherent, intrinsic, or extrinsic. The study identified shear stress from mixing as the cause of particulate formation, leading to process changes that preserved solution homogeneity. This integrated approach enhances product quality through efficient root cause analysis and process control.

In a poster presentation at AAPS PharmSci 360, Eda Fenercioglu, a scientist at Pfizer, outlines a streamline workflow for identifying and mitigating visible particles in biologic drugs.

Using A Streamlined Workflow to Identify Particulates in Biologic Drugs

AAPS PharmSci 360 2025: Instrumentation Innovation for Bioanalysis

The field of bioanalysis in the development of bio/pharmaceutical products is quickly advancing, and a variety of techniques is available to those working in the field. To learn more about the types of instrumentation used in bioanalysis, 

® spoke with Steve Lowes, senior director of Scientific Affairs at IQVIA Laboratories, as part of our coverage of 

According to Lowes, techniques like flow cytometry and polymerase chain reaction (PCR) are commonly used in bioanalysis; however, they challenge some of the established platforms mentioned in guidance documents. “The way to employ such alternative technologies is through an a 

 SOP [standard operating procedure]-driven and defendable assay validation that clearly defines the capabilities of the assay itself,” Lowes suggests.

“New LBA [ligand binding assay] platforms are also presenting some attractive strengths in terms of their sensitivity and even multiplexing,” Lowes continues. “For example, the proximity extension assay Olink has caught a lot of attention of late associated with the selectivity, the ability to do some multiplexing, and significantly, the sensitivity capabilities derived from the DNA tag hybridization that can be subsequently amplified using PCR. So many of these types of techniques are evolving from the proteomics field, but we are now adapting them to regulated bioanalysis, and when it comes to selectivity, liquid chromatography–mass spectrometry continues to be the benchmark.”

Steve will be monitoring the Rapid Fires: AI/ML in Bioanalysis session on Monday, Nov. 10, 2025 at 3PM CT at AAPS PharmSci 360 2025, being held Nov. 9–12 in San Antonio, Texas.

Click the video above to watch the interview.

Steve Lowes is Senior Director, Scientific Affairs at IQVIA Laboratories

Steve Lowes is Senior Director, Scientific Affairs at IQVIA Laboratories. Steve has 30+ years’ experience in bioanalysis with a focus on LC-MS and regulatory aspects and has been with the legacy LC-MS regulated bioanalytical lab of IQVIA Laboratories in Ithaca, NY since 1995. He is a regular presenter and author of publications on regulated bioanalysis, is co-editor of the text “Regulated Bioanalysis: Fundamentals and Practice,” and is the primary contributor to the popular 

 bioanalysis blog from IQVIA Laboratories. His most recent interests are the application of LC-MS to regulated bioanalysis of biologics and biomarkers. He received his bachelor’s degree in Analytical Chemistry at Sheffield Hallam University in the UK (1987) and a PhD in Biochemistry from the Open University, Milton Keynes, UK (1991).

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Hi, I'm Steve Lowes, Senior Director of Scientific Affairs at IQVIA Laboratories. I'm delighted to talk with you today.

We've seen a plethora of techniques and platforms targeted at biological analytes that have entered our bioanalytical laboratories, flow cytometry, PCR, in particular, are commonly discussed and applied, although they do challenge the established biological guidance precedents that I've already mentioned, the way to employ such alternative technologies is through an a priori, SOP driven and defendable assay validation that clearly defines the capabilities of the assay itself.

New LBA ligand binding platforms are also presenting some attractive strengths in terms of their sensitivity and even multiplexing.

For example, the proximity extension assay olink has caught a lot of attention of late associated with the selectivity, the ability to do some multiplexing, and significantly, the sensitivity capabilities derived from the DNA tag hybridization that can be subsequently amplified using PCR. So many of these types of techniques are evolving from the proteomics field, but we are now adapting them to regulated bio analysis and when it comes to selectivity, liquid chromatography, mass spectrometry continues to be the benchmark.

Again, proteomic originating LC-MS technologies are finding their way into the bioanalytical laboratories. A good example of this is high resolution mass spectrometry that we iqvia are heavily invested in for the primary reason that it can do things that a triple quadrupole instrument cannot do.

Now, historically, HRMS has been heavily applied to the characterization of peptides and proteins we now see in these instruments being routinely applied to quantitative bio analysis. Oligonucleotides and siRNA determinations are particularly well suited to HRMS, where conventional CID fragmentation in a triple quadrupole instrument may not always deliver the sensitivity that is required

Instead, high resolution and mass accuracy can address these assay needs. The antibody drug conjugate assays that I just mentioned are another good example here where the selectivity and the multiplexing flexibility of LC-MS can be further leveraged with high resolution mass spectrometry, and then many large molecule biomarker quantitative assays are also being demonstrated with HRMS. I think this is an exciting time for mass spectroscopists with a continuing pipeline with technology advancements finding practical application in our biological labs.I will go on to point that low flow rate chromatography with microflowrates. Now there's sub milliliter per minute and true nanoflow sub microliter per minute flow rates delivers increased sensitivity, but historically, such advanced LC techniques have presented some practical challenges around run times and robustness. Some interesting developments are coming along now, and hitting the market that are truly democratizing low flow chromatography.

I see these as having practical utility, even in high throughput bioanalytical labs. There's even a technology platform now that proposes doing away with chromatography altogether, using acoustic ejection droplets from a sample to enable sub second per sample bioanalytical quantitation for the right applications, and these were primarily in the discovery stages.

While it's difficult to envisage this having universal application in bio analysis, when combined with alternative separation technologies such as ion mobility, the scene is truly set for an evolution of rapid throughput improvements in the LC-MS laboratory, simplifying and standardizing LC-MS has been a trend from manufacturers for some time now.

This year, already, we are seeing the LC-MS systems that are being launched that are targeted at clinical laboratories with full integrated sample preparation, chromatographic separations and mass spec detection.

Bringing LC-MS into the scope of a traditional clinical analyzer is a very interesting concept, and I'm sure we'll all be watching this very closely.

Pharmaceutical Technology® spoke with Steve Lowes, senior director of Scientific Affairs at IQVIA Laboratories, ahead of AAPS PharmSci 360 to discuss some of the unique instruments used to conduct bioanalysis. 