How digital container twins can improve pharma manufacturing

Manufacturing Intelligence: Digital Twins Meet Pharma Containers

Navigating FDA Shakeups and Obesity Drug Wars

Behind the Headlines Episode 28

Ask the Expert

How evolving regulatory expectations are reshaping pharma development and manufacturing.

Drug Digest April 2026

How It Helps Avoid Facility and Equipment Problems

A “Plan, Prevent, Prove” Approach

Adam Goldstein is senior director, R&D, Thermo Fisher Scientific.

Michelle Nolasco is staff engineer, systems design engineering, Thermo Fisher Scientific.

3D Render of Therapeutic Antibody binding do PD-1 Molecule | Image Credit: ©Alpha Tauri 3D -stock.adobe.com. 

Downstream purification is increasingly defining the pace and performance of biologics manufacturing. However, as upstream processes deliver higher titers, downstream capacity and throughput have not kept pace, creating bottlenecks that delay clinical timelines, inflate manufacturing costs, and limit commercial potential. This mismatch is particularly acute as antibody-drug conjugates (ADC) and multispecific antibodies move toward commercialization, especially as each modality demands unique purification strategies, control parameters, and quality attributes.

Addressing these challenges requires a combination of process intensification, flexible system design, and smarter integration of analytics and automation. Developers who build scalability into their early process design, supported by real-time analytics, advanced process control, sustainable practices, and deep understanding of the design space, can successfully move from early-stage success to commercial manufacturing with significantly less rework and risk.

How Do Upstream Gains Create Downstream Constraints?

Over the past decade, upstream productivity improvements—largely driven by advances in cell line development, media, and perfusion—have fundamentally shifted the manufacturing balance. While upstream titers are continuing to rise dramatically,with typical fed-batch processes producing approximately 3–5 g/L and some optimized processes achieving up to 10–13 g/L

, downstream purification technologies have not scaled at the same rate, particularly in single-use environments.

For monoclonal antibodies (mAbs), the bottleneck is often capacity related. Larger product loads are processed through chromatography, filtration, and ultrafiltration/diafiltration (UF/DF) with finite throughput and footprint. In contrast, emerging modalities such as multispecific antibodies, ADCs and cell and gene therapies (CGTs) present purification challenges that are less about larger volumes and more about separation of these more complex molecules as compared to standard mAbs. Closely related impurities, structurally complex molecules, and sensitivity to processing conditions frequently force manufacturers to balance purity, yield, and process robustness.

How can Downstream Processing Be Intensified Without Increasing Complexity?

To keep pace, manufacturers are increasingly adopting downstream intensification strategies that reduce physical footprint while increasing effective throughput. Higher-capacity chromatography resins, flow-through polishing steps, and optimized clarification approaches enable more material to be processed with smaller columns and lower buffer volumes.

Providers should focus on enabling these strategies through scalable, single-use downstream systems that support higher productivity without adding operational burden. For example, chromatography platforms are designed to operate across a wide range of column sizes, allowing manufacturers to move from clinical to commercial scale using consistent hardware and control strategies. Similarly, advances in clarification technologies, such as integrating centrifugation and filtration, help deliver cleaner feed streams to downstream operations, reducing filter fouling and improving overall process efficiency.

Inline buffer dilution and the use of concentrated buffers further simplify operations by reducing buffer preparation and storage requirements, which are often overlooked contributors to downstream bottlenecks.

What Are the Benefits of Real-Time Analytics?

As downstream processes become more integrated, real-time insight is increasingly critical. Inline and at-line analytics allow manufacturers to monitor critical quality attributes in real time during processing rather than relying on offline sampling and delayed decision-making.

Raman-based process analytical technology (PAT) is being applied in downstream unit operations like UF/DF to monitor protein concentration and buffer composition in real time. By integrating these analytics directly with automation platforms, manufacturers can define precise process endpoints, reduce over-processing and minimize yield losses, particularly during final formulation steps where recovery from errors are difficult.

Over the past several years, PAT has become a critical enabler for accelerating development timelines and supporting scalable manufacturing. When paired with artificial intelligence (AI) and machine learning (ML), PAT data can be transformed from raw sensor readings into actionable process insights. This closed-loop approach shifts PAT from a passive monitoring tool to an active lever for de-risking scale-up and accelerating the path to commercial readiness.

While AI and ML are still emerging in downstream applications, manufacturers are already using advanced data analytics to accelerate process development and optimize operating parameters, driving smarter, faster decision-making at every stage of the purification train.

Scaling with Confidence from Clinical to Commercial

Designing downstream systems that scale smoothly remains a priority for biologics manufacturers. Consistency in materials, equipment, and control strategies across development stages simplifies technology transfer and reduces validation risk.

Platforms that can scale to support both small-scale development and large-scale commercial production, using the same core systems, allows teams to focus on process optimization rather than requalification at each scale. Implementing approaches that emphasize modular, scalable downstream solutions that can be deployed in flexible manufacturing environments helps support rapid transitions as pipelines evolve.

Single-use, skid-based purification systems with standardized interfaces enable manufacturers to quickly adapt their strategies as new modalities move through development, reducing capital investment and downtime between batches. By designing downstream platforms for flexibility from the outset, developers can accelerate commercial readiness while future-proofing their manufacturing strategy as the CGT landscape expands.

Regulatory expectations continue to support innovation when manufacturers demonstrate strong process understanding and control.

 For intensified or integrated downstream processes, this means validating unit operations individually while clearly defining their interactions within the overall process. Regulators expect detailed risk assessments and well-documented data flows that show how each purification step contributes to final product quality.

 They are also continuing to raise the bar on extractables, leachables, and overall sustainability, driving manufacturers and technology providers to innovate materials that meet stringent requirements while maintaining performance and reliability.

Collaboration, transparency, and rigorous validation enable manufacturers to gain speedy regulatory acceptance for new equipment and digital solutions, unlocking the full potential of next-generation downstream platforms.

Sustainability Through Process Efficiency

Sustainability considerations are becoming inseparable from downstream process design. Water and buffer consumption represents a significant portion of a facility’s environmental footprint, particularly for traditional bind-and-elute chromatography workflows.

Process intensification strategies, such as higher-capacity resins and flow-through chromatography, can dramatically reduce buffer usage. In some cases, switching from bind-and-elute to flow-through polishing steps can reduce water consumption by up to 70%,

 delivering both environmental and economic benefits. These gains illustrate how efficiency-driven downstream design aligns sustainability goals with operational performance.

Beyond buffers and water, energy consumption during purification—driven by extended cycle times, multiple chromatography runs, and inefficient unit operations—represents a hidden but substantial environmental cost. Continuous purification workflows, optimized chromatography cycles, and intelligent automation can reduce process duration and energy intensity compared to traditional batch approaches. At commercial scale, these efficiency gains translate into measurable reductions in carbon footprint alongside lower operating costs.

Progress in downstream purification depends on close collaboration between manufacturers, technology providers, regulators, and even competitors. While novel approaches may demonstrate technical promise in laboratory settings, broad adoption, and regulatory confidence typically follow once technologies are proven in real manufacturing environments. This reality underscores why industry partnerships and transparent data-sharing are essential to accelerating innovation across the sector.

The industry is increasingly coming together to define clear benchmarks for quality, share research on new materials and methods, as well as align on best practices for validation and process transfer. These collaborative efforts are driving the development of new standards and accelerating adoption of best-in-class solutions. By establishing common frameworks and shared learning, manufacturers reduce the risk and cost of technology implementation while building collective confidence in emerging approaches.

The most successful organizations recognize that transformation happens incrementally, not overnight. Rather than making sweeping changes that introduce unnecessary risk, they focus on scalable improvements that embed new technologies and practices alongside existing operations. This measured approach allows manufacturers to validate innovations in parallel, build internal expertise and scale solutions as confidence and capability grow.

During the next several years, downstream purification is likely to be shaped by incremental but impactful improvements rather than wholesale disruption.

Greater integration of unit operations, reduced pool volumes through single-pass tangential flow filtration (TFF), wider use of inline analytics, and continued movement toward semi-continuous processing will define near-term progress. These advances will be accelerated by industry collaboration across manufacturers, contract development and manufacturing organizations, technology providers, and regulators to establish common standards, share validation data, and reduce risk.

Perhaps most importantly, flexibility will be central to future downstream strategies. As therapeutic modalities diversify, manufacturers must be prepared to deploy different purification tools, such as columns, membranes, or alternative formats, within adaptable facilities. This requires intentional design choices during early process development, where scalability and modularity are embedded rather than retrofitted later.

Investments in flexible systems, integrated analytics and scalable platforms today will position manufacturers to meet the evolving demands of next-generation biologics, all while reducing rework, accelerating timelines, and managing costs. Developers who prioritize process understanding, build automation into their workflows, and design with commercial scale in mind will gain significant competitive advantage.

The path forward is not about finding the single best solution, but building resilient, adaptable operations capable of evolving alongside the rapid transformation of the biologics industry.

Sargent B. The current landscape of monoclonal antibody production

https://cellculturedish.com/the-current-landscape-of-monoclonal-antibody-production/

Bokelmann C, Ehsani A, Schaub J, and Stiefel F. Deciphering metabolic pathways in high-seeding-density fed-batch processes for monoclonal antibody production: A computational modeling perspective. 

Sponchioni M, Cavazzini A, and Catani M. 

Guidance for Industry: Process Validation: General Principles and Practices

https://www.fda.gov/files/drugs/published/Process-Validation--General-Principles-and-Practices.pdf

Sharma N, et al. Systematic Approaches on Extractable and Leachable Study Designs in Pharmaceuticals and Medical Devices: A Review. 

Journal of Packaging Technology and Research

6. Rivera MN, Siemers A, Pleitt K, and Becerra A. Leveraging 3 distinct resins to provide effective impurity removal for mAbs and novel antibody derivatives. 

, Thermo Fisher Scientific, accessed February 20, 2026, 

https://www.bioprocessonline.com/doc/leveraging-distinct-resins-to-provide-effective-impurity-removal-for-mabs-and-novel-antibody-derivatives-0001

Articles

Downstream purification has become the principal rate-limiting step in biologics manufacturing as upstream titers surge, especially for ADCs and multispecifics that require tighter separations and gentler conditions. Closing the gap hinges on downstream intensification, modular single-use system design, and deployment of real-time analytics with automation to enable tighter control and faster scale-up. Regulatory acceptance increasingly depends on demonstrated process understanding, unit-operation interaction risk assessments, and robust extractables/leachables strategies. Efficiency-led redesign also advances sustainability by reducing buffer, water, and energy consumption.

Building resilient, adaptable operations capable of evolving alongside the rapid transformation of the biologics industry is key for downstream processing.

Transforming Downstream Purification: Trends Shaping the Future of Biologics Manufacturing

FDA headquarters at White Oak Campus in Silver Spring, Maryland, USA - January 13, 2020. The United States Food and Drug Administration (FDA) is a federal agency. | © JHVEPhoto - stock.adobe.com (330225712)

Following the resignation of FDA Commissioner Marty Makary, the FDA has replaced the acting heads of its two primary product review centers, continuing a pattern of leadership instability that has characterized the agency under the second Trump administration.

 The changes affect the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). The turnover raises practical questions about regulatory continuity and the pace of decision-making during what is already a complex period for the industry.

Tracy Beth Høeg, who had been serving as acting director of CDER, 

stated on social media that she was fired.

 Katherine Szarama, acting director of CBER, will depart her leadership role but remain at the agency. Michael Davis steps in to lead the drug evaluation center, while Karim Mikhail takes over the biologics division. Lowell Zeta has also been named acting chief of staff. The agency's official organizational chart was updated within days of the announcement.

FDA Overview Organization Chart, Content Current as of 05/18/2026 | Image Credit: FDA

What Does Repeated Leadership Turnover Mean for Regulatory Timelines?

The leadership changes are not occurring in isolation.

 They follow the resignation of commissioner Marty Makary, who departed after reports emerged that President Trump sought to remove him from the position. A senior administration official has indicated that a new permanent commissioner nominee could be named within weeks, though that individual would still require Senate confirmation, which adds further uncertainty to the timeline. CDER has now seen several acting directors since January of last year, a level of churn that is unusual by historical standards.

How Stable Is the Broader Public Health Leadership Environment?

The situation at the drug and biologics centers reflects a wider vacancy problem across federal health agencies.

 The administration is simultaneously working to fill the director position at the CDC and the office of the surgeon general, suggesting that the leadership gaps extend well beyond the FDA's immediate remit.

Within CBER specifically, the past year has seen multiple individuals rotate through leadership, including Vinay Prasad, who left, returned, and ultimately departed again following a series of public controversies.

 That kind of instability in the division responsible for vaccine regulation creates difficulties for manufacturers navigating complex biologics pipelines, where long-term regulatory relationships and scientific consistency are closely tied to development strategy and investment planning.

The pharmaceutical industry's ability to plan around regulatory interactions depends heavily on predictable institutional structures.

 While the FDA's career staff provides a degree of continuity that political appointees do not, senior leadership sets the tone for enforcement priorities, review standards, and external engagement. Until a confirmed commissioner is in place and both centers have settled leadership, manufacturers and developers will need to be on top of the continuous rotation of the staff at the FDA, as the choices for those roles carry massive repercussions for the entire pharmaceutical industry.

Peebles A. FDA shuffles top drug, biologics leaders in latest shakeup. CNBC. May 15, 2026. 

https://www.cnbc.com/2026/05/15/fda-shuffles-top-drug-biologics-leaders-in-latest-leadership-shakeup.html

FDA overview organization chart. U.S. Food and Drug Administration. May 18, 2026. 

https://www.fda.gov/about-fda/fda-organization-charts/fda-overview-organization-chart

Peebles A. FDA vaccine head will step down in April after string of controversial decisions. CNBC. March 6, 2026. 

https://www.cnbc.com/2026/03/06/fda-vaccine-head-prasad-step-down.html

Repeated leadership turnover is reshaping oversight at CDER and CBER, with acting directors replaced shortly after the commissioner’s departure. Tracy Beth Høeg reported being fired as acting CDER head, while Katherine Szarama is leaving the acting CBER role but staying at FDA. Michael Davis and Karim Mikhail will lead the drug and biologics centers, respectively, alongside a new acting chief of staff. The churn extends across federal health agencies and heightens uncertainty for sponsors reliant on stable review expectations, engagement norms, and timing predictability.

The FDA replaced acting heads of its drug and biologics centers, deepening leadership instability that raises concerns for pharmaceutical developers.

Everything to Know about FDA's Personnel Shifts

Discover how Piramal Pharma Solutions is innovating in integrated CDMO services, leveraging their Science Collective of experts to streamline drug substance and drug product programs from early development through commercialization.

CDMO Innovations in Integrated Services

In this video, Jean-François Carniaux, a vice president and global API technical lead at Piramal Pharma Solutions, discusses how the company is advancing its CDMO landscape through integrated service delivery. Operating across approximately 15 sites in India, Europe, and North America, Piramal provides a global infrastructure supporting multiple modalities from early development through commercial supply.

Carniaux elaborates on the importance of aligning drug substance and drug product programs early in the development lifecycle. Piramal’s integrated model enables efficient transitions from API development into drug product manufacturing, supported by coordinated project management and cross-functional technical expertise. This approach helps maintain continuity as programs progress across development phases and global sites.

Carniaux also highlights Piramal’s capabilities in antibody-drug conjugates (ADCs), including its ADCelerator platform, which is designed to streamline development from early-stage work through fill-finish with accelerated timelines. Supporting these efforts, the company has invested approximately $400 million to expand its capabilities in bioconjugation, high-potency API (HPAPI) manufacturing, and sterile fill-finish services.

Videos

Rare Disease Approvals Are Becoming More Flexible

The first half of 2026 has been marked by a series of notable regulatory approvals and the introduction of a formal framework designed to accelerate the development of individualized therapies for rare and ultra-rare conditions.

 Taken together, these developments reflect a continued shift toward regulatory flexibility.

A representative example of this trend is the May 14, 2026 approval of Fasenra (benralizumab) for adult and pediatric patients with hypereosinophilic syndrome, a rare group of disorders characterized by persistently elevated eosinophil counts that can result in progressive and potentially fatal organ damage.

 The approval was supported by clinical data demonstrating a 65% reduction in the risk of disease flares relative to placebo. This approval illustrates an increasingly common lifecycle strategy, extending the clinical application of an established biologic into high-need orphan indications. Doing so requires manufacturing and supply chain teams to accommodate the distinct formulation, dosing, and distribution requirements of both adult and pediatric populations.

How Is the Regulatory Landscape Shifting for Ultra-Rare Therapies?

In February 2026, the Department of Health and Human Services and the FDA issued draft guidance specifically addressing individualized therapies, treatments designed to target unique genetic abnormalities in individual patients.

 The guidance covers modalities including genome editing and ribonucleic acid-based technologies, and introduces a Plausible Mechanism framework that permits approval on the basis of substantial evidence of effectiveness even when the conduct of traditional randomized controlled trials is not feasible due to extremely small patient populations.

Another core tenet of the guidance is the allowance for product variations targeting different mutations within the same gene to be evaluated under a single regulatory application.

 This rule has the potential to streamline clinical development programs and validation activities for sponsors working across a family of genetically related indications.

This regulatory flexibility is reflected in several recent approvals. 

On March 25, 2026, a therapy developed for the neurologic manifestations of Hunter syndrome received accelerated approval based on a surrogate endpoint

, specifically the reduction of heparan sulfate concentrations in cerebrospinal fluid.

 Similarly, a therapy for pediatric patients with achondroplasia, approved on March 4, 2026, was evaluated using annualized height growth velocity as a measure of effectiveness, with confirmatory studies required to establish impact on final adult height.

These cases highlight a consequential operational reality for pharmaceutical manufacturers, accelerated approval pathways compress the timeline to commercialization.

 These pathways often require that manufacturing scale-up and supply chain readiness proceed in parallel with, rather than following, the completion of confirmatory clinical data. For therapies targeting patient populations that may number in the hundreds globally, this necessitates manufacturing models that are both agile and capable of maintaining compliance under conditions of evolving clinical evidence.

What Role Do Observational Data Play in Modern Drug Approvals?

The FDA’s, March 10, 2026, labeling expansion for leucovorin calcium in cerebral folate transport deficiency offers a further illustration of how evidentiary standards are evolving.

 In this instance, the agency collaborated with the sponsor to update the product’s labeling based on a systematic review of published literature and case reports rather than prospectively collected randomized trial data. The determination was that existing real-world evidence, combined with a well-characterized natural history of the disease, provided a sufficient foundation to support the labeling update given the clear clinical benefit demonstrated across documented cases.

This case underscores the increasing evidentiary weight being assigned to rigorous natural history documentation and observational datasets, particularly in settings where prospective trial design is constrained by disease rarity.

 It also reinforces the value of systematic evidence synthesis as a regulatory tool, rather than a secondary consideration.

Collectively, the approvals and guidance documents issued in the first half of 2026 signal a sustained evolution in the regulatory environment for rare disease therapeutics.

 The focus is shifting toward precision manufacturing capable of producing highly specific treatments for patient populations that may be geographically dispersed and numerically small. Development timelines are compressing. Evidentiary standards are broadening. Teams that build adaptability into their clinical, regulatory, and manufacturing strategies will be better positioned to navigate these faster and more flexible pathways to market.

AstraZeneca. FASENRA approved in US for hypereosinophilic syndrome. AstraZeneca US. Press Release. May 14,2026. 

https://www.astrazeneca-us.com/content/az-us/media/articles/2026/FASENRA-approved-in-US-for-hypereosinophilic-syndrome.html

U.S. Food and Drug Administration. FDA launches framework for accelerating development of individualized therapies for ultra-rare diseases. U.S. Department of Health and Human Services. Press Release. February 22, 2026. 

https://www.hhs.gov/press-room/fda-launches-framework-accelerating-development-individualized-therapies-ultra-rare-diseases.html

U.S. Food and Drug Administration. FDA approves drug to treat neurologic manifestations of Hunter syndrome. Press Release. March 24, 2026. 

https://www.fda.gov/news-events/press-announcements/fda-approves-drug-treat-neurologic-manifestations-hunter-syndrome

U.S. Food and Drug Administration. FDA approves drug for pediatric patients with most common form of dwarfism. Press Release. March 4, 2026. 

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-pediatric-patients-most-common-form-dwarfism

U.S. Food and Drug Administration. FDA approves first treatment for patients with cerebral folate transport deficiency. Press Release. March 9, 2026. 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-cerebral-folate-transport-deficiency

Regulatory activity in early 2026 reflects accelerating flexibility for rare and ultra-rare therapeutics, spanning orphan lifecycle expansion, individualized therapy pathways, and broader evidentiary acceptance. Benralizumab’s approval in hypereosinophilic syndrome exemplifies repurposing established biologics into high-need, small-population indications with added pediatric operational complexity. New draft guidance introduces a Plausible Mechanism framework and permits mutation-level product variants under one application. Recent accelerated approvals leveraged surrogate endpoints, compressing CMC and supply-chain timelines. Labeling expansion based on systematic literature and case reports elevates natural history and observational data.

2026 regulatory shifts are accelerating rare disease drug approvals and reshaping clinical development, evidentiary standards, and pharmaceutical manufacturing strategies.

The Current State of Rare Disease Approvals

Strategic Advsor and Independent Board Director

sat down with Bryan Poltilove, strategic advisor and independent board director focused on bioprocessing and advanced therapy manufacturing, to discuss how just-in-time, point-of-care manufacturing is revolutionizing biopharma without compromising quality.

Watch the 2-part video interview with Poltilove:
Part 1: 

Bryan Poltilove on Evolving Bioprocessing Manufacturing Paradigms

Point-of-Use Media Manufacturing Could Cut Bioprocessing's Carbon Footprint by Two Thirds

What's Changing in Bioprocessing and Advanced Therapy Manufacturing and What Is Staying the Same?

The fundamentals aren't going anywhere, validation and GMP manufacturing. Nobody's willing to take risks there, nor should they be. The industry standard is well established and well understood.

What is changing is how and where manufacturing happens. We're seeing a significant shift toward point-of-care and place-of-care models, more distributed approaches to manufacturing, and supply chains that are becoming increasingly flexible in how reagents and other products are delivered to the industry. Cost has always mattered, but now environmental sustainability and supply chain resilience are becoming equally important drivers of that change.

It's a genuine paradigm change, a change in mentality and approach, not just a tweak to existing processes. The best analogy I can offer is the auto industry in the 1980s moving from large, inventory-heavy operations to just-in-time manufacturing. Biopharma is undergoing something very similar right now.

The key challenge is achieving that flexibility without compromising on the things that cannot be compromised. Reproducibility, availability, quality standards, those are non-negotiable. The goal is to find technologies and supply chain approaches that reduce inventory, make logistics more seamless, and give manufacturers more operational flexibility, all while keeping the product and the regulatory standards fully protected.

Where Are You Seeing this Play Out Most Concretely?

Cell therapy is probably the clearest example. We're seeing modular clean rooms, new cell processing technologies, and unit operations that can realistically be executed in a hospital setting. It's a remarkable development when you think about where cell therapy manufacturing stood even a decade ago.

I'm currently working with Nucleus Biologics, which has a particularly innovative approach to media manufacturing. The model is almost like a Nespresso or Keurig concept for cell culture media. Rather than producing a large, centralized batch and distributing it broadly, you're enabling on-demand, point-of-use manufacturing of the media itself. Their Krakatoa technology is built around that idea, storing powders on-site and only requiring water on-demand, rather than shipping and storing large volumes of liquid media.

What's the Practical Significance of that Powder-Based, On-Demand Approach?

The potential is substantial. Shipping requirements drop considerably because you're moving powder rather than liquid, and storage needs on-site shrink accordingly. Beyond the logistics, you gain the ability to manufacture exactly when and what you need, no excess, no waste.

What makes it compelling is that it combines the best of both existing formats: the ease of use and flexibility of liquid media with the logistical and cost advantages of powder. Bringing those two things together in a single workflow is genuinely innovative.

How Significant Is the Environmental Sustainability of this Shift?

It's increasingly central to how the industry evaluates these decisions. Best-in-class sustainability thinking now looks at total environmental impact from sourcing all the way through disposal, not just what comes out of a single step in the process.

Based on figures I've seen, moving to a distributed, point-of-use model for cell culture products can reduce end-to-end carbon footprint by roughly two-thirds compared to traditional centralized manufacturing. There's enormous promise here, or the industry and for the world more broadly.

It's just getting off the ground. A prototype system has been deployed in academic and industrial labs across multiple continents, used hundreds if not thousands of times, and has demonstrated strong reproducibility, consistency, and reliability at that scale. The commercial launch is happening now. Scaling that performance up to full bioprocessing scale is the next step, and I have every reason to believe the results will follow the same trajectory.

Validation and GMP rigor remain non-negotiable in bioprocessing, but manufacturing paradigms are shifting toward distributed, point-of-care/place-of-care models that prioritize flexibility, resilience, and sustainability alongside cost. This represents a just-in-time mindset change analogous to automotive manufacturing’s 1980s evolution, requiring inventory reduction without sacrificing reproducibility or quality. Cell therapy is the clearest near-term proving ground, enabled by modular clean rooms and hospital-executable unit operations. Powder-based, on-demand media manufacturing could materially reduce logistics burden, waste, and end-to-end carbon footprint.

Bryan Poltilove discusses how distributed, point-of-care manufacturing is reshaping biopharma supply chains and cutting carbon footprints.

Q&A: Bryan Poltilove on the Future of Bioprocessing

PharmTech Weekly Roundup-May 15, 2026

The pharmaceutical landscape is currently defined by three intersecting trends: rapid technological integration on the factory floor, a strategic shift toward globalized development networks, and significant leadership upheaval at the regulatory level. As manufacturing lines adopt advanced automation and AI to meet stricter sterility standards, the industry is simultaneously navigating a period of unprecedented volatility within the FDA. Furthermore, the ongoing challenge of supply chain resilience is forcing a move away from reactive inventory management toward data-driven, clinical-centric strategies.

 resigned following industry pressure, leaving the agency in a state of regulatory flux, underscoring a period of significant turnover and potentially impacting the stability of drug review initiatives. The resignation followed earlier reports that said the 

White House was planning to remove the commissioner.

entered into an agreement this week that highlights the strategic use of China's accelerated development timelines to generate early clinical data and de-risk global drug portfolios.

Manufacturing trends discussed this week include the use of 

, which are increasingly utilizing isolator technology, automation, and AI-driven analytics to enhance sterility assurance and meet stringent global regulatory standards like EU GMP Annex 1.

 by prioritizing proactive communication with health systems and implementing end-to-end inventory visibility tools compatible with hospital automation.

, implementing validated electronic master production records with structured governance is essential for strengthening data integrity and ensuring GMP inspection readiness throughout the manufacturing lifecycle.

focused on clinical criticality and cross-hospital collaboration is necessary to move past reactive hoarding and ensure medications reach the patients who need them most.

These shifts in technology, policy, and supply chain strategy require manufacturers to remain agile and data-focused. For in-depth analysis on any of these topics, please refer to the full reports on PharmTech.com.

This week, the industry saw rapid technological integration on the factory floor, a strategic shift toward globalized development networks, and leadership upheaval at the FDA. 

President 
     Concordia MCS, LLC
Scientific Advisor 
     SmartSkin Technologies

Senior Director
Education, Outreach, and Digital Experience
Open Biopharma Research and Training Institute

, co-hosts Chris Cole and Richard Jaenisch explore the emerging role of digital twins in pharmaceutical container systems with guests Mihaela Simianu, president of Concordia MCS and scientific advisor to SmartSkin Technologies, and Austin Caudle, vice president at SmartSkin Technologies.

To view the full fascinating, practical, engaging conversation, click here!

The discussion centers on how “smart” pharmaceutical container replicas—equipped with sensors and data-capture capabilities—can help manufacturers better understand how vials, syringes, cartridges, and other container closure systems interact with manufacturing equipment throughout the product lifecycle. Simianu explains that while today’s technology is not yet a fully virtualized digital twin, these physical smart replicas provide critical real-time data about seal forces, equipment interactions, and operational stresses that can impact product quality and patient safety.

The guests emphasize that container intelligence can play a significant role across development, clinical manufacturing, commercial scale-up, and tech transfer between manufacturing sites and CDMOs. By using sensor-enabled replicas to monitor equipment-container interactions, companies can reduce glass breakage, minimize downtime, optimize line setup, and better maintain container closure integrity throughout production and distribution.

A key theme throughout the conversation is risk reduction. Simianu and Caudle argue that integrating these tools early in development creates continuity as products move between facilities and scales, helping manufacturers preserve process understanding and reduce variability tied to changing equipment environments.

The episode also highlights broader industry trends toward data-driven manufacturing, predictive analytics, and digital transformation, positioning smart container technologies as foundational building blocks for the future of pharmaceutical digital twins and advanced manufacturing intelligence.

Mihaela Simianu and Austin Caudle join the show to discuss how digital container twins can improve pharma manufacturing, validation, and risk reduction.

George Kwiecinski, Global Key Solutions Corp

connected with George Kwiecinski, CEO and co-founder of Global Key Solutions Corp, to discuss FDA GMP inspection trends, supplier oversight gaps, and the rising regulatory scrutiny of AI in pharma compliance.

Watch the full video interview with George Kwiecinski:


George Kwiecinski on Why Now Is the Time to Reassess Your GMP Audit Strategy

PT: How Should Quality and Compliance Teams Prioritize Foreign Suppliers for Audit or Reinspection when Inspection Coverage Is Limited?

Kwiecinski: It comes down to resources and organizational capacity. Whether you're inspecting an internal facility or auditing a supplier, most organizations are working within real constraints. The question becomes: are you procuring the right tools and technology to make sound assessments? Are you selecting suppliers through a documented, demonstrable process? These aren't just best practices, they're expectations. With the QMSR changes affecting both medical devices and the FDA's ability to scrutinize internal audit documentation, this has become a hot-button issue. Organizations need to take a second look at how those processes are being handled and reprioritize accordingly. The good news is that tech stacks have improved significantly for most workflows, so there's really no excuse not to reassess.

What's Your Outlook on Compliance Risk in Global Supply Chains?

Honestly, I don't think the fundamental risk picture changes dramatically. The top citation areas will continue to revolve around the quality unit, drug efficacy and safety standards, and how those standards are being enforced across vendors. Those core pillars aren't going anywhere. What will shift is the context around them, especially as new technologies and practices become more common in the industry.

How can AI-powered Regulatory Intelligence Improve Oversight without Providing False Positives or Incomplete Data?

Yes, this is something we've been tracking closely. One trend that really made waves recently was that an AI citation appearing in an FDA warning letter. Essentially, a company had used AI to respond to the FDA and generate some of their documentation, and that usage was called out directly. Now, I think this kind of citation will become more frequent over time. It may not always be flagged explicitly, but AI use in regulatory processes is clearly on the FDA's radar.

We put together a white paper recently looking at how the FDA has used ‘AI’ as a keyword across its correspondence and documentation over the last 3-4 years. What we found was telling: there are now 5 distinct regulatory correspondences specifically referencing AI, and over 20 FDA guidance and documents that mention it, with the frequency increasing steadily over time. That trajectory tells us that AI is becoming a meaningful part of the agency's regulatory purview, and companies need to start thinking about what that means for them.

What Changes Do You Recommend to Strengthen Foreign Supplier Governance when API and Finished-dose Sourcing Is Heavily Concentrated Overseas?

The first step is just awareness, understanding that these changes are happening and that it's accelerating. From there, it's about looking at your own tech stack and honestly evaluating how your organization is managing AI-related risk. If your organization is using AI tools in any part of its regulatory or quality workflow, you need to be thoughtful about how those decisions are documented and defended.

As for whether companies should invest in new AI tools, I think that's a legitimate conversation to have, but the justification has to be grounded in business reality. If a tool can demonstrably save cost or drive profit, and you can implement it in a safe, controlled way, then pursuing it makes sense. What's going to matter most though, is the risk-based approach: how are you accounting for AI-assisted or AI-driven decisions within your processes? That's exactly the kind of thing that's subject to FDA scrutiny right now.

Global supplier oversight remains constrained by finite audit resources, elevating the importance of documented, defensible risk prioritization and fit-for-purpose technology. Persistent GMP citation drivers—quality unit effectiveness and enforcement of efficacy/safety standards across vendors—are expected to continue, but will be reframed by expanding use of AI in quality and regulatory workflows. FDA attention to AI is increasing, including explicit mention in warning-letter context and growing references across agency correspondences and guidances. Organizations should reassess audit strategies, strengthen governance of overseas sourcing, and formalize controls for AI-assisted decisions.

George Kwiecinski, Global Key Solutions Corp, breaks down GMP inspection risks, global supply chain compliance, and AI's growing role in FDA regulatory scrutiny.

Q&A: George Kwiecinski on How AI Is Reshaping FDA Regulatory Compliance

Valerie Bandy brings over 25 years of distinguished experience in healthcare leadership to her current role as Vice President Pharmacy Solutions at Tecsys. With a career marked by this steadfast leadership, she has consistently excelled in driving strategic initiatives and optimizing operational efficiency. In her present capacity, Valerie collaborates closely with sales, research and development, AI and marketing teams to refine pharmacy supply chain software solutions, leveraging her extensive expertise in healthcare operations, sales strategy, supply chain, consulting, and regulatory compliance. Prior to her tenure at Tecsys, Valerie held pivotal leadership roles at prominent healthcare institutions including Director of Pharmacy at Wellstar Atlanta Medical Center, System Director of Pharmacy operations at Trinity Health, and consulting firms including Deloitte Consulting where she was a Specialist Master, and PriceWaterhouse Coopers. Throughout her career, she has spearheaded initiatives that have significantly impacted pharmaceutical procurement, cost optimization, and operational excellence, managing multi-billion-dollar budgets with adept precision. Valerie's academic credentials include a Doctor of Pharmacy, an MBA, and a Bachelor of Science in Biology, underscoring her commitment to academic excellence and professional development. Driven by her passion for healthcare leadership, Valerie actively seeks opportunities that align with organizational missions and visions, embodying a steadfast dedication to advancing healthcare delivery and patient outcomes.


Valerie Bandy, Tecsys, discusses how pharmaceutical manufacturers and health systems can work together to build more strategic, resilient drug supply chains.

Watch the 2-part video interview with Bandy:
Part 1: 

Valerie Bandy on Building Smarter Pharma Supply Chains

Valerie Bandy on Reducing Drug Shortages Through Smarter Inventory Management

PT: How Should Manufacturers Think About Health System Roles in Supply Chain Strategy?

: Manufacturers must look at things from the health system's perspective. They're constantly balancing supply chain resilience against operational realities. Every new vendor relationship requires qualification, contract negotiation, and regulatory alignment specific to each drug and patient population.

The real lesson is that manufacturers are not invincible. Disruptions do happen, and how they support health systems through those moments matters enormously. Their goal should be building strong standing relationships with health system leaders and structuring contracts that genuinely reflect how those systems function.

What Should a Mid-Size Pharmaceutical Manufacturer Understand About Obligations to Health Systems?

Pharmaceutical manufacturers should design supply strategies around health system operational constraints, recognizing that qualification, contracting, and regulatory alignment make vendor changes burdensome. Manufacturer resilience is not guaranteed; proactive relationship-building and contracts reflecting real workflows are pivotal during disruptions. Company size matters less than drug criticality, making transparent, early communication on shortages essential. Health systems often default to manual workarounds and reactive behavior, underscoring the need for tiered critical-drug prioritization and contingency planning. Allocation should incorporate clinical demand and service-line realities, not procurement anxiety.

Valerie Bandy, Tecsys, explains how proactive vendor relationships, strategic drug allocation, and end-to-end visibility can prevent costly pharmaceutical supply disruptions.

Featured Content

Manufacturing Intelligence: Digital Twins Meet Pharma Containers

Behind the Headlines Episode 28

Ask the Expert

Drug Digest April 2026

A “Plan, Prevent, Prove” Approach