Digital Transformation in Pharma Manufacturing

Patent Cliff Deals, Tariff Pressures, and the In Vivo Cell Therapy Bet

Behind the Headlines, Episode 23

ICH Q12 and Post-Approval Changes

Speed, Flexibility Top Large-Molecule Manufacturing Trends

Drug Digest July 2025

Key Insights from Industry Survey Results

Bio/Pharma's Tariff Response

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

Silver Spring, MD, USA - June 25, 2022: The FDA White Oak Campus, headquarters of the United States Food and Drug Administration, a federal agency of the Department of Health and Human Services (HHS). | Image Credit: © Tada Images - stock.adobe.com

Two months after saying it would embrace “radical transparency” by 

 (CRLs) issued in response to drug approval applications, FDA said on Sept. 4, 2025 that it was furthering that policy by releasing future CRLs “promptly” after being issued to sponsors (1,2). The agency immediately released 89 previously unpublished CRLs, issued from 2024 to the present, dealing with pending or withdrawn applications (2).

“This is a milestone day for the agency,” FDA Commissioner Marty Makary, MD, MPH, said in an agency press release (2). “By embracing radical transparency—one of the guiding principles of this administration—we’re giving invaluable insights to help speed therapies and cures to market, providing complete context to investors and shareholders, and above all, restoring public trust.”

One newly published CRL that attracted immediate attention was addressed to 

, for an 3,4-Methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of post-traumatic stress disorder (PTSD). The nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS) commended FDA for its transparency, but dissented with the decision expressed in 

“Let’s be clear: the CRL reveals a devastating truth—FDA moved the goalposts,” 

, PhD, MAPS founder and president, said in a statement (3). “Thirteen million Americans live with PTSD today. Every year of delay means more will die by suicide and more remain trapped in cycles of trauma and despair. They deserve better ... Lykos will continue negotiations with FDA.”

Following FDA’s initial disclosure of transparency regarding CRLs, 

, for an experimental treatment (deramiocel) for cardiomyopathy associated with Duchenne muscular dystrophy, and 

, for RP1 (vusolimogene oderparepvec) in combination with nivolumab for the treatment of advanced melanoma (4).

“I wonder if part of the problem is that many biotechs do not have sufficient experience in-house, and rely on contract organizations,” 

, said at the time, speaking from his perspective as a consultant for various industry companies (4). “However, the contract staff may not be sufficiently familiar with the details of the project they are working on. Thus, things fall between the cracks, so to speak.”

What does this mean for drug discovery, development, and manufacturing?

This policy shift ostensibly gives developers, including those in discovery, preclinical, and clinical domains, much earlier access to FDA feedback on safety and effectiveness issues detailed in CRLs (2). Access to these real-time communications enables sponsors to detect recurring deficiencies and better align their study design and regulatory strategies with the agency’s expectations.

Also, CRLs often cite detailed chemistry, manufacturing, and controls (CMC) deficiencies. With immediate public access to these letters—albeit redacted for trade secrets and proprietary information—developers gain indirect insight into the most common CMC pitfalls flagged by FDA. This heightened awareness may allow for more proactive quality assurance and process control planning.

On the other hand, although FDA has committed to “prompt” publication and redaction of confidential information such as trade secrets and personal identifiers, precise timing as it relates to CRL issuance remains unspecified (2). Additionally, the policy currently covers human drug and biologic applications; direction on other application types has not been clarified.

FDA’s searchable database of CRLs can be accessed 

FDA Embraces Radical Transparency by Publishing Complete Response Letters. Press Release.

FDA Announces Real-Time Release of Complete Response Letters, Posts Previously Unpublished Batch of 89.

MAPS Statement on FDA’s Public Release of Complete Response Letter for MDMA-Assisted Therapy.

 Press Release. Sept. 4, 2025.
4. Cole, C. 

CMC and Analytical Gaps in CRLs: Why They Persist Despite FDA Guidance and How You Can Position Yourself for Success.

Articles

The FDA has committed to publishing complete response letters (CRLs) promptly after issuance, enhancing transparency and providing insights into drug approval processes. This move aims to accelerate therapy development, offer context to investors, and restore public trust. The release of 89 previously unpublished CRLs has sparked varied responses from companies, with some expressing concerns over shifting regulatory expectations. The policy allows developers to access FDA feedback earlier, potentially improving study design and regulatory alignment. However, the timing of CRL publication and coverage of application types remain unspecified.

The agency says it will now publish complete response letters promptly, offering developers early insight into regulatory deficiencies to improve development planning.

FDA Initiates Real-Time CRL Publication: What It Means for Drug Developers

In this new PharmTech video feature, we highlight the week’s industry news in an easy-to-consume, fun format

PharmTech Weekly News Roundup - Week of September 1, 2025

In this new PharmTech video feature, we’ll highlight the week’s industry news in an easy-to-consume, fun format. New roundups will drop every Friday, so be sure to come back each week. And be sure to check the links below for more in-depth coverage of each story.

Cytokinetics' Aficamten, a cardiac myosin inhibitor, 

significantly outperformed metoprolol in a Phase III trial

 (MAPLE-HCM) for obstructive hypertrophic cardiomyopathy, demonstrating superior efficacy in improving exercise capacity, symptoms, and left ventricular outflow tract gradients.


The European Medicines Agency and the World Health Organization are 

celebrating a decade of successful collaboration

 aimed at enhancing global regulatory capacity and public health.


The University of Oxford and the Ellison Institute of Technology launched the 

Correlates of Immunity—Artificial Intelligence program

, a £118 million (US$158 million) initiative focused on understanding immune responses and vaccine protection against antibiotic-resistant pathogens.


Concerns are rising in the US over the removal of key advisory figures, including 

Paul Offit, from FDA vaccine advisory committee

 under HHS Secretary Robert F. Kennedy Jr.


Finally, the Pistoia Alliance announced an 

 to establish standards and protocols for the safe and responsible adoption of "agentic AI" in the life sciences.

Videos

Aficamten beat metoprolol for oHCM, EMA/WHO hit 10 yrs, Oxford and EIT collaborated on AI vaccine, Offit's FDA exit stirred policy, and Pistoia set agentic AI rule.

PharmTech Weekly Roundup – Week of September 1, 2025

Doctor technology AI integrates big data analytics with clinical research, enabling precise treatment plans tailored to individual patient needs and genetic profiles. | Image Credit: © Suriyo - stock.adobe.com

, a global nonprofit, early in 2025, a theme emerged: that agentic artificial intelligence (AI) is viewed by life sciences professionals as potentially being among the most disruptive emerging technologies over the next two to three years (1). Agentic AI has the potential, according to the Pistoia Alliance, to accelerate multi-step processes, such as target prioritization and compound optimization, by joining together reasoning, tool use, and execution.

However, the Pistoia Alliance said in a Sept. 4, 2025 press release that surrendering full autonomy to AI creates a sort of “black box” that may undermine trust, capacity for reproducibility, and regulatory compliance (1). It is for those reasons—with the overarching mission of safely adopting agentic AI—that the nonprofit is establishing a new initiative bringing together experts from the pharmaceutical, technology, and biotech industries to help shape certain standards and protocols under which AI agents will be allowed to perform.

How will the initiative encourage responsible AI use?

With Genentech providing the initial seed funding for the project, the Pistoia Alliance said it is currently seeking both additional partners and funds (1). The nonprofit has stated strategic priorities to harness AI and expedite R&D and is calling upon an AI and machine learning (ML) community of experts to continue building support for the industry-wide responsible adoption of AI.

“Our members see agentic AI as one of the most impactful technologies set to change how they work and innovate, but they also recognize the risks if adoption happens without the right guardrails,” said 

, PhD, president of the Pistoia Alliance, in the press release (1). “The Alliance is uniquely positioned to lead this work, drawing on more than eight years’ experience in pre-competitive collaboration around AI, from benchmarking frameworks for large language models to a pharmacovigilance community focused on responsible AI deployment. We know that more expert minds focused on the same topic will advance the safe and successful use of AI technologies.”

As part of a recent webinar, the Pistoia Alliance said it polled more than 100 pharma professionals, and the consensus top priority for pre-competitive collaboration was the creation of shared validation frameworks and metrics, for model robustness and bias (1). Shared frameworks urgently need to be established, according to the Pistoia Alliance, for the safe adoption of AI because when evidence must be validated, auditable agent workflows that are shaped by subject matter experts and reputable data sources are necessary for the production of reliable results.

“This initiative will address the common issues we all face in integrating AI developments into a cohesive ecosystem that improves output quality,” said 

, the Agentic AI program lead at the Pistoia Alliance, in the press release (1). “It will enable members to link standalone AI applications into a dynamic network and build workflows where multiple agents can reason, plan and act together. By becoming sponsors, organizations can act as first movers—shaping the standards, gaining early access to outputs, and ensuring they are at the forefront of the next wave of AI innovation in healthcare.”

 within the bio/pharmaceutical industry to share their experiences in a survey that seeks perspectives on new and rapidly evolving technologies as automation, advanced analytics, digital twins, and AI (2). The survey can be accessed directly 

Pistoia Alliance Unveils Agentic AI Initiative and Seeks Industry Funding to Drive Safe Adoption.

 Press Release. Sept. 4, 2025.
2. Cole, C. 

Digital Transformation in Pharma Manufacturing: Industry Perspectives Survey.

Agentic AI is anticipated to be a disruptive technology in life sciences, with potential to enhance processes like target prioritization and compound optimization. However, concerns about trust, reproducibility, and regulatory compliance arise when AI is given full autonomy. The Pistoia Alliance is launching an initiative to establish standards for AI use, supported by Genentech's initial funding. Priorities include creating shared validation frameworks for model robustness and bias. The initiative aims to integrate AI into a cohesive ecosystem, enabling collaboration and innovation in healthcare.

The nonprofit is calling upon its community of experts in both artificial intelligence and machine learning to continue building support for responsible adoption of AI in the bio/pharmaceutical industry.

Pistoia Alliance Announces Agentic AI Collaboration Initiative

Famous Radcliffe Camera in the Oxford University - aerial view | Image Credit: © 4kclips - stock.adobe.com

Led by the Oxford Vaccine Group, the University of Oxford (Oxford) said it is lending its expertise in human challenge studies, immune science, and vaccine development to a strategic partnership with the Ellison Institute of Technology (EIT), whose cutting-edge artificial intelligence (AI) innovation technology will be used for an ambitious new program of vaccine research (1).

In a press release, Oxford said the Correlates of Immunity—Artificial Intelligence (CoI-AI) program, which has received research funding of £118 million (US$158 million), will endeavor to better understand how the body fights infection, and how vaccines protect humans (1). Specifically, it will study how the immune system responds to certain germs causing serious infections and contributing to antibiotic resistance—

Oxford says germs such as these have tended to resist traditional vaccine approaches, but in the design of this program, human challenge models who are exposed to bacteria safely and under controlled conditions will be used to apply modern immunology and AI tools to identify immune responses that are adequate predictors of protection (1).

What is the strategic context for pharma?

Oxford’s program is set in the broader backdrop of declining or uncertain vaccine R&D investment in some regions—namely, the United States—underscoring a possible shift in global leadership toward academic–technology collaborations that span discovery to application (2). The integration of AI into immunological studies exemplifies a strategic direction where pharmaceutical companies could gain from partnering with such initiatives—or risk being disrupted if they do not adapt.

However, at this time, no data were provided demonstrating how immunological insights from human challenge studies might be converted into scalable vaccine platforms or market-ready products (2). This absence reflects a broader uncertainty: While such studies may yield valuable information about protective immune responses, there is no assurance that these findings will translate directly into manufacturing processes or commercially viable interventions—so while the program’s ambition is clear, its downstream application to the pharmaceutical industry remains speculative until supported by peer-reviewed results and evidence of successful product development.

“Researchers in the CoI-AI program will use artificial intelligence models developed at EIT to identify and better understand the immune responses that predict protection,” 

, EIT chairman, said in the press release (1). “This vaccine development program combines Oxford’s leadership in immunology and human challenge models with cutting-edge AI, laying the groundwork for a new era of vaccine discovery—one that is faster, smarter, and better able to respond to infectious disease outbreaks throughout the world.”

“This program will give us completely new tools to study how vaccines work at both a cellular and system-wide level, by studying infections in real time, in people, and using smart immunology tools and data to find the answers,” 

, professor and deputy director of the Oxford Vaccine Group, said (1). “This will open up whole new avenues to vaccine design as we improve our understanding of infection and immunity.”

, professor and director of the Oxford Vaccine Group, said the program addresses one of the most urgent problems in infectious disease: a lack of deep understanding of immunity in order to develop innovative vaccines against deadly diseases that are so far evasive to prevention.

“By combining advanced immunology with artificial intelligence, and using human challenge models to study diseases, CoI-AI will provide the tools we need to tackle serious infections and reduce the growing threat of antibiotic resistance,” Pollard said (1). “This is a new frontier in vaccine science.”

Oxford Launches Major New AI Vaccine Research Programme with the Ellison Institute of Technology.

 Press Release. Sept. 1, 2025.
2. Kuchler, H. 

Oracle Billionaire’s Institute Gives Oxford Major Grant for AI Vaccine Research.

The University of Oxford, in collaboration with the Ellison Institute of Technology, is launching the Correlates of Immunity—Artificial Intelligence (CoI-AI) program, funded with £118 million. This initiative aims to enhance understanding of immune responses to infections and vaccine protection using AI and human challenge models. The program addresses the challenge of antibiotic-resistant pathogens like Streptococcus pneumoniae, Staphylococcus aureus, and E. coli. While promising, the translation of these insights into scalable vaccine platforms remains uncertain, highlighting the need for further evidence and peer-reviewed results.

The partnership, which has received £118 million (US$158 million) in research funding, aims to establish a better understanding not only of how the body fights infection, but also how vaccines protect it.

Oxford, EIT Address Urgent Problem with AI Vaccine Research

Silver Spring, MD, USA - June 25, 2022: Closeup of the FDA sign seen at its headquarters campus in Silver Spring, Maryland. FDA is a federal agency of the Department of Health and Human Services | Image Credit: © Tada Images - stock.adobe.com.

Major shifts in federal vaccine policy under Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. are reshaping the advisory landscape that underpins US vaccine approvals and immunization strategy (1). These developments could signal a more unpredictable regulatory environment with direct implications for vaccine development, manufacturing, and commercialization.

Paul Offit, pediatrician and co-inventor of the rotavirus vaccine, was recently removed from the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC)—a panel central to evaluating vaccine safety and efficacy data for approval (1). Although Offit had previously agreed to a two-year term extension at the agency’s request, his position was abruptly terminated. HHS stated that approximately a dozen advisory members across eight FDA panels were removed after their service terms expired, but no clarity was provided on renewals.

Offit’s removal follows a series of high-profile exits driven by policy changes:

CDC Director Susan Monarez was dismissed last week after pressure from Kennedy (2).

Three senior CDC officials resigned in protest of Monarez being forced out, warning that systematic dismantling of scientific advisory structures jeopardizes evidence-based policymaking (3).

Vinay Prasad exited his position as head of the FDA

’s Center for Biologics Evaluation and Research amid tumult in biologics oversight, and then 

All 17 members of CDC’s Advisory Committee on Immunization Practices were fired

 in June, eliminating the independent body that sets national vaccination recommendations.

 in March, citing interference and misinformation.

For vaccine developers, these shifts raise several critical issues:

Regulatory Uncertainty: The removal of independent scientific advisors creates ambiguity around how future vaccine candidates will be assessed. Developers may face greater unpredictability in approval timelines, safety evaluations, and market authorization pathways.

Market Dynamics: Offit and others have argued that Kennedy’s approach could restrict vaccine availability and affordability (1). If this leads to reduced public uptake or changes in reimbursement structures, it could directly impact revenue models for manufacturers.

Erosion of Scientific Oversight: The sidelining of established experts could weaken confidence among investors, healthcare professionals, and international stakeholders in the rigor of the US vaccine regulatory system—a reputation that has historically underpinned global trust in pharmaceutical innovation.

Policy Misalignment: Offit’s willingness to critique certain broad immunization strategies (such as universal annual coronavirus vaccination) highlights that expert debate has been suppressed alongside anti-vaccine policymaking (1). Industry stakeholders may face a regulatory body less receptive to evidence-based nuance, which is typically critical for guiding clinical trial design and targeted rollout strategies.

Kennedy is set to appear before the Senate Finance Committee this week, where lawmakers are expected to question his vaccine policy decisions (1). The outcome may provide early signals on whether Congress could intervene or push back against the erosion of traditional scientific advisory mechanisms.

As the regulatory climate continues to shift, bio/pharma companies should prepare for greater political volatility in vaccine policy, with implications for development pipelines, regulatory strategy, and long-term commercial planning.

Offit’s VRBPAC Departure Raises Questions About Another HHS Panel Revamp

CDC Director Susan Monarez fired by Trump administration after refusing to resign, citing 'reckless directives'

CDC leaders fight back in wake of attack on agency, public health

Recent changes in federal vaccine policy under HHS Secretary Robert F. Kennedy Jr. are altering the advisory framework for US vaccine approvals and immunization strategies. The removal of key figures like Paul Offit from the FDA’s VRBPAC and other advisory bodies has led to concerns about regulatory uncertainty, market dynamics, and the erosion of scientific oversight. These shifts could impact vaccine development, manufacturing, and commercialization. As Kennedy faces scrutiny from the Senate Finance Committee, the bio/pharma industry must brace for increased political volatility in vaccine policy.

Paul Offit removed from FDA vaccine panel as RFK Jr. reshapes US immunization policy, raising concerns for bio/pharma and regulation.

Pharma Implications of Paul Offit’s Removal from Vaccine Advisory Committee

Blockchain for transparent supply chain tracking | Image Credit: ©Andrey -stock.adobe.com

The pharmaceutical supply chain is a complex ecosystem consisting of procurement, ingredients suppliers, contract manufacturers, regional regulations, temperature controls, and track and trace technologies. This ecosystem is highly impacted by facility quality deficiencies, which can delay manufacturing and create drug shortages (1). The threat of anticounterfeit drugs is also a spoke in the wheel, with technologies and regulations working together to safeguard patients (2).

“The pharmaceutical supply chain is like a global relay race involving suppliers, manufacturers, distributors, pharmacies, and regulators,” explains Dr Damodharan Muniyandi, chief quality officer–Global Quality & Regulatory Affairs at Sai Life Sciences. “Complexity tends to arise from sourcing APIs and excipients worldwide, meeting diverse regulatory requirements, managing cold chain logistics for biologics, and tackling counterfeit risks. To navigate this complexity, companies are turning to digital supply chain platforms, predictive analytics, and multi-tier supplier networks for resilience. Quality-by-design and continuous manufacturing help maintain consistency, while cross-border regulatory harmonization builds transparency and agility. It’s about blending smart technology with robust partnerships to keep medicines moving safely and efficiently across the globe.”

Integrated digital systems offer real-time visibility and ensure compliance, according to John DiPalo, chief strategy officer for ACSIS, part of Antares Vision Group. “Technologies like serialization and centralized data platforms help manufacturers track product movement, spot irregularities, and quickly respond to issues, protecting patients and preserving brand reputation,” he says.

“Digital technologies—RFID [radio frequency identification], IoT [Internet of Things], and AI [artificial intelligence]—transform fragmented processes into a transparent, resilient, and responsive network, enabling accurate demand planning, reduced waste, and better service levels,” concurs Grethe Bonde, marketing communications specialist at Murata.

Pharmaceutical companies establish quality control departments to manage supply chain issues, according to Sundar Narsimhan, chief procurement officer, Neuland Laboratories Limited. These departments follow guidelines, such as those established by the International Council for Harmonisation (ICH) and local regulatory agencies.

Differing political and regulatory climates can make managing a drug supply chain even more complex. “In the current context, the volatile geopolitical situation coupled with unprecedented tariff escalations and new drug price prospecting have elevated this to a new level,” says Narsimhan.“We are witnessing a real fragile supply chain situation as we speak.”

Sticking to the basics and a commitment to enduring relationships with supply chain stakeholders is key to navigating this ever-changing situation, according to Narsimhan. “Given the scale of damage that loss of business or customers can cause, keep your calm and a watchful eye on the daily developments, such as tariffs, customer and supplier voices, and demand and inventory data,” he advises. “Take very well-thought-out positions on price, concessions, cost-sharing, and commitments for the short-term, keeping in mind that this situation will not last forever. Finally, be very agile and alert to make changes in response to emerging situations—on shipment routing, inventories, and so on.”

The country-to-country variety in regulations from government and standard-setting organizations adds to the complexity of the supply chain. “Fragmented regulations can lead to unexpected compliance issues, product recalls, or halted shipments,” Sade Mokuolu, PhD, regional business development manager, life sciences, Watson Marlow Fluid Technology Solutions, states.

A common regulatory language and standardized regulations enhance supply chain security, says Bonde. “Global standards, like GS1 for product identification and serialization, reduce errors and fraud. In the EU, the Falsified Medicines Directive (FMD) is a prime example: it mandates unique identifiers, tamper-evident features, and verification through the European Medicines Verification System (EMVS). This harmonized framework prevents counterfeit medicines from entering the legal supply chain, strengthens traceability, and ensures consistent product authenticity and quality across markets,” she says.

“Standardized rules foster clearer communication between manufacturers, suppliers, regulators, and consumers,” Mokuolu agrees. “This transparency strengthens relationships across the supply chain and supports responsible product stewardship.”

“Organizations such as ICH, PIC/S [Pharmaceutical Inspection Co-operation Scheme], and WHO [World Health Organization] are driving this harmonization of GMP [good manufacturing practice] standards, making audits easier and compliance less costly. The result is a supply chain that’s more transparent, more trusted, and far better equipped to keep medicines moving quickly and safely from manufacturer to patient, no matter where they’re made,” agrees Muniyandi.

A shared framework for complying with different global supply chain regulations that includes data exchange, product serialization, and traceability is necessary, according to DiPalo. “This consistency allows smooth interoperability among global partners, simplifying compliance and improving visibility and accountability throughout the supply chain,” he explains.

Regulators have been making headway on securing the drug supply chain in recent years. In August 2025, FDA created a new program to decrease US reliance on foreign manufacturers. The FDA PreCheck Program will have a two-phase approach to the development of new manufacturing facilities in the US, allowing manufacturers to communicate more directly with the agency on things like facility design, construction, and pre-production. It will also streamline the development of the chemistry, manufacturing, and controls section of a drug application through pre-application meetings and feedback (3).

The European Medicines Agency (EMA) is dealing with drug shortages by focusing on specific areas. In July 2025, the agency issued recommendations for securing the supply of anti-D immunoglobulins used to prevent RhD immunization during pregnancy in the European Union (4). And in April 2025, EMA published recommendations to strengthen the supply chain of radiopharmaceuticals (5).

Recent political impacts have also added to the complexity of the drug supply chain. The Trump administration’s changing tariff policies in the US have forced companies to reassess their supply chains and operations (6), and the flow of APIs and raw materials has been disrupted.

Jason Waite, an international trade expert at Alston & Bird, stressed that pharmaceutical companies should build cross-functional trade compliance teams in response to rising global trade tensions—particularly potential Section 232 tariffs. Compliance regarding product origin, classification, and valuation, must occur early in R&D and manufacturing to avoid downstream disruptions, he said in an interview with Pharmaceutical Technology®. He also emphasized proactive communication between R&D, finance, logistics, tax, and trade departments to help successfully navigate trade policy changes (7).

Best practices to secure the supply chain

Performing best practices can help minimize disruptions brought about in the manufacturing process. Strict GMP adherence on the shop floor can ensure quality, says Muniyandi, as can using process analytical technology to perform real-time monitoring, validating equipment, and properly training staff. “Machine learning can spot potential quality issues early, optimize processes, and keep batch cycle times under control. IoT sensors enable predictive maintenance to prevent breakdowns, while IoT-enabled logistics track environmental conditions and location once products leave the plant,” he says. “Together, these measures create a clear chain of custody.”

Strong in-line quality controls are key, says DiPalo, specifically machine vision inspection, leak detection, and material verification. “These systems lay the groundwork for the simultaneous use of unique serial numbers and aggregation management, which enables unit-level tracking with serial numbers and aggregation codes,” he says. “Combining this with data from a reliable serialization platform provides complete traceability from manufacturing to the patient, allowing quick responses to recalls, theft, or diversion. These steps together ensure both quality assurance and complete visibility.”

“In manufacturing, quality is ensured through in-process controls, environmental monitoring, and process validation, while traceability is achieved via unique serialization and aggregation,” Bonde says. “RFID and IoT sensors create digital product passports, tracking each unit’s journey and monitoring critical parameters, such as temperature and humidity, in real time. This enables rapid recalls, minimizes waste, and ensures compliance up to the point of care.”

When it comes to using automated inspection systems in the pharma industry, Eran Sinbar, CEO of Yoran Imaging, stresses that they be performed non-invasively and in a way that links inspection data to unique product identification, “two key reasons that thermal imaging-based inspection is beginning to make inroads.”

Utilizing supplier quality management provides a structured approach for ensuring materials, components, and services received by third-party suppliers meet quality and regulatory standards, says Mokuolu. “For drug products that utilize single-use technologies, establishing a consistent set of compliance information across all single-use suppliers enables drug manufacturers to make more accurate comparisons and ensures confidence in dual sourcing strategies,” she continues. “When compliance criteria are open to interpretation, it becomes difficult to assess supplier equivalency.”

Technologies used in the protection of the small-molecule supply chain include tamper-evident packaging and integrated track-and-trace systems that are connected to such platforms as enterprise resource planning and warehouse management systems, according to Bonde. Additional measures are required for biologics, she stresses, such as IoT-based cold chain monitoring, cloud-connected data loggers and blockchain/distributed ledger technology.

Antares Vision Group Life Science uses serialization, aggregation, and automated machine vision inspection in its operations to ensure a secure supply chain for small molecule drugs. For temperature-sensitive large molecules, the company uses real-time cold chain monitoring and RFID-based tracking for reusable assets.

Regarding packaging technologies, Sinbar is seeing increased interest in thermal imaging-based inspection, which Sinbar says gives verifiable, reportable proof of seal integrity and valuable production performance data.

“For small molecules, supply chain security often relies on scale and future-proofing strategies, such as flow chemistry, enzymatic synthesis, short cycle (including greener) synthesis using breakthrough reactions, and derisking strategies, such as supply base and geographic diversification, along with prioritizing reliable partners over mercurial ones,” says Narsimhan.“For large-scale molecules, backward integration is key: adopting novel synthesis methods alongside traditional synthesis, securing raw material supplies despite the geographic concentration, and—if outsourcing—choosing the right supply partner after due diligence for long-term cooperation, since de-risking is often expensive and switching suppliers carries high costs.”

AI is increasingly being utilized in the pharmaceutical industry for supply chain security including automating quality control processes, tracking changing global regulations, predictive analysis for risk detection, counterfeit identification, optimizing logistics, and anomaly detection. According to Sinbar, Yoran Imaging uses AI for big data analysis, root cause investigation, and predictive maintenance. “AI adoption should continue to expand to improve responsiveness, reduce human error, and support real-time decision making,” Sinbar says.

“However, [AI’s] broader adoption is limited by fragmented datasets, lack of interoperability, and regulatory constraints,” Bonde advises.“When integrated with IoT and RFID, AI can proactively reroute shipments, optimize inventory, and identify threats before they cause disruptions.”

AI offers quicker and more accurate detection of problems within the supply chain ecosystem, according to DiPalo, and can drive predictive analytics for managing found risks. “For example,” offers DiPalo, “Antares Vision Group’s AI-GO platform uses deep learning for precise defect detection and adaptive process control, helping to enhance safety, quality, and efficiency throughout the supply chain.”

“By leveraging supplier management tools, organizations can collect and analyze performance data from each supplier,” says Mokuolu. “Integrating machine learning and artificial intelligence enables deeper insights into supplier reliability and operational trends. These technologies help proactively identify potential risks and disruptions, effectively future proofing the supply chain.”

“Challenges [to AI adoption] include high implementation costs, a shortage of skilled talent, data silos, and regulatory uncertainty,” says Muniyandi. “Even so, AI should play a bigger role. It can dramatically boost resilience, efficiency, and security—critical in a post-COVID world in which supply chains must be faster, smarter, and more adaptable than ever.”

A variety of AI tools have entered the chat. In April 2025, SkyCell partnered with Microsoft to integrate SkyMind, SkyCell’s AI-powered supply chain solution, with Microsoft Teams and Copilot based on Azure OpenAI Service. The collaboration will enable those working in the pharmaceutical supply chain to access real-time shipment data, predictive insights, and automated alerts within a Microsoft system, according to SkyCell (8).

The drug supply chain’s many facets allow for multiple avenues for a negative impact on the patients who need medications to live a quality life. Disruptions in the supply chain can stem from such regional problems as natural disasters, quality problems at manufacturing facilities, and political discourse. These disruptions are often out of a drug company’s control. Drug manufacturers should control what they can to minimize these problems by following GMPs and employing the best tools for ensuring quality.

FDA. Drug Supply Chain Security Act (DSCSA). 

FDA. FDA Announces New FDA PreCheck Program to Boost US Drug Manufacturing. Press Release. Aug. 7, 2025.

EMA. Strengthening Supply Chain of Anti-D Immunoglobulins. Press Release. July 4, 2025.

Barton, C. EMA Is Tackling Vulnerabilities in the Supply Chain of Radiopharmaceuticals. 

Cole, C. Survey: Impacts of Tariffs and Trade Policy on the Bio/Pharmaceutical Industry. 

Cole, C. How Pharma Can Build Resilient Supply Chains Amid Trade and Tariff Shifts. 

SkyCell. SkyCell and Microsoft Announce Collaboration to Bring Copilot into Pharma Supply Chains. Press Release. April 7, 2025.

®
Vol. 49, No. 7
September 2025
Pages: 22–25

When referring to this article, please cite it as Haigney, S. Keys to Navigating the Complex Drug Supply Chain. 

The pharmaceutical supply chain is a multifaceted ecosystem involving procurement, manufacturing, and distribution, heavily influenced by regulatory and geopolitical factors. Quality deficiencies and counterfeit threats pose significant challenges, necessitating robust digital technologies and regulatory harmonization for resilience. Integrated digital systems, AI, and IoT enhance transparency, compliance, and predictive capabilities, while standardized regulations improve security and traceability. Political and regulatory complexities further complicate supply chain management, requiring agile strategies and strong partnerships. Ultimately, ensuring supply chain integrity is crucial for patient safety and maintaining drug availability.

Digital solutions help pharmaceutical manufacturers navigate the complex supply chain.

Keys to Navigating the Complex Drug Supply Chain

Evonne Brennan, evonne@evonnebrennan.com, is an experienced educator and consultant delivering tailored tuition and courses in pharmaceutical formulation and processing. Evonne is a member of 

Chemistry professor wearing a lab coat and gloves, demonstrating a vibrant chemical solution in a beaker to engaged students during an interactive experiment in a university laboratory | Image Credit: ©DusanJelicic - stock.adobe.com

It is important to learn and continue learning.

While context is essential, hearing different perspectives enhances clarity. It strengthens validation of what is known and supports learning if it’s not. Information flows at us in many forms of printed, digital, or in-person meetings. However, with this information overload, there still exists a unique challenge: time; it continues its angst, causing a gap in fundamental knowledge. This can impact negatively in reasoning and even more so if questioning does not feel encouraged. Retention is another consideration. Memory can lapse from not utilizing knowledge; there are times when you are only as good as your last project, and sometimes one needs to reactivate the neural pathways.

In response to the perceived need for continued learning in the industry, 

Editorial Advisory Board (EAB), along with the editorial team, decided to help keep our readers activated by selecting central topics, all within the construct of the magazine’s focus, to assist with learning while perusing the monthly print issue and digital content available on 

. I am happy to lead the topics of development and manufacturing in this task (stay tuned, its coming soon), and with such diverse expertise within the EAB, we are happy to take this journey with you.

While a broad subject area, the development segment will encompass five key topics: pre-formulation, formulation, scale-up, and post-formulation. Initially, with pre-formulation, such subtopics as drug discovery will be explored as we look at its process and where the industry is today. The well-known image showing the stages of the drug discovery process carrying its hefty price tag of approximately $1 billion along with the time taken to market will resonate well here. Considering the wider audience, this article series will visit the alternate stages in bringing a generic drug to the market. The complexity of a drug can impact time and cost, as more R&D work is needed to meet bioequivalence.

Pharmacokinetics (ADME [absorption, distribution, metabolism, and excretion]) grips efficacy and safety of medicines. It is the way one understands how a drug will behave in the body, its complexities and mechanisms of delivery, and where underlying illness and stubborn gastrointestinal challenges can impact performance.

Clinical trials are a significant cost in the development process; therefore, this series will cover its growing complexity, the dreaded placebo effect, and running trials in today’s climate, especially with the shift to decentralized trials. While medicine prices remain questionable, and in a variable state, the cost of bringing a drug to market is high. The specific cost of trials is challenged with potential losses and the realization that, unfortunately, not all will be successful.

Drug delivery and experimental design are significant fields in drug formulation, given the multifaceted subtopics and typical approaches. While newer technologies exist and there have been updates in design and function, standard technologies and their relevance to the industry today will be evaluated. As drug solubility is challenged, complexity arises, but there is support, with shared information, through research, and an added foresight of success when a drug is already marketed.

The quality-by-design pathway will be discussed, including considerations on API, excipient, and process characteristics, and ultimately, developing a robust dosage form delivering its target product profile. Moving from batch to continuous manufacturing, developing a new dosage form, or switching manufacturing processes requires a good design. Decisions, such as choice of excipient, could impact success. Patient centricity has been advancing in the industry, and while other factors exist, developing a suitable dosage form can influence continued patient uptake and adherence.

Following on from formulation development and success at the bench, scale-up is a challenging phase in development and manufacturing. The fundamentals series will cover considerations in scale up and possible change protocols as one moves from pilot stage to manufacturing and troubleshooting.

While cost features heavily in all earlier sections, it can significantly show its effect in the segment on post-formulation, where we will discuss topics covering improvements, stability, Phase IV, and lean manufacturing. Sometimes these learnings will resonate with that wonderful term “hindsight” and could aid in future decision making. Time and speed to market continue to challenge excellence and cost.

Regulatory topics will feature prominently in this series. Decision making can be impacted due to the regulatory route and delays. Also, quality, particularly as analytical testing has advanced, has its consequential impact on a risk-averse landscape.

As we take this journey, we would also like to hear from you! If there are any topics you find challenging or any experiences you would like to share, we welcome your thoughts/comments. Send comments and questions to 

®
Vol. 49, No. 7
September 2025
Pages: 20–21

When referring to this article, please cite it as Brennan, E. Focusing on the Fundamentals of Formulation. 

This article previews some formulation topics discussed in the Pharma Fundamentals series, which aims to enhance learning for professionals in pharmaceutical drug development and manufacturing.

Focusing on the Fundamentals of Formulation

Michelle Heiter is laboratory and quality control specialist at Regulatory Compliance Associates, a Nelson Labs Company.

Susan J. Schniepp is a fellow at Regulatory Compliance Associates, Inc. and a member of Pharmaceutical Technology's Editorial Advisory Board.

Q. What is a contamination control strategy (CCS) and how does it support sustainable compliance and continuous improvement?

 A CCS is required in pharmaceutical manufacturing to ensure product safety, regulatory compliance, and efficient operations. The updated EudraLex, Volume 4, Annex 1 (1) mandates a CCS for sterile manufacturing in the European Union, aligning with similar FDA requirements
(2, 3) in the United States, as well as International Council for Harmonisation (ICH) Q9 Quality Risk Management (4) and ICH Q10 Pharmaceutical Quality System (5) guidelines.

A review of FDA 483s and FDA Complete Response Letters (CRLs) highlights areas for improvement in pharmaceutical manufacturing. Citations have been issued for deficiencies related to microbial contamination, environmental monitoring, and aseptic practices. Addressing these observations is required for drug approvals and to strengthen a CCS.

A CCS is a holistic approach to minimizing contamination by evaluating good manufacturing practices (GMPs). A CCS provides a proactive method for identifying, controlling, and scientifically evaluating quality risks designed to reduce contamination and enhance product safety and quality.

Elements of a CCS include the following (6):

Monitoring controls—personnel, in-process, materials, environmental, utilities, and pest controls

Validation controls—qualification/requalification of personnel, process, analytical methods, facility, utilities, and equipment

Contamination controls—personnel training, hygiene and gowning, process design, vendor material, consumable containers, equipment design, cleaning and sanitization

Quality risk management and risk assessment identify potential contamination sources and assess their impact on product quality and safety

Scientific and technical knowledge to prevent contamination

Personnel management to empower personnel through training. Staff education, awareness, and skills play a crucial role in maintaining contamination control.

A strong CCS serves as an invaluable quality tool, ensuring regulatory compliance while safeguarding product quality, safety, and enhancing the company’s reputation. Let’s embrace its power!

Q. Why is a risk assessment required for a CCS?

Conducting a risk assessment is critical for a successful CCS. It helps to proactively identify contamination sources and their effects, enabling implementation of targeted preventative measures that safeguard both products and the well-being of patients.

Identify hazards and risks before they turn into real problems.

Prioritize control measures based on the severity and likelihood of each risk to enable the allocation of resources to the areas vulnerable to contamination.

A contamination control strategy (CCS) is essential in pharmaceutical manufacturing to ensure product safety, regulatory compliance, and operational efficiency. It aligns with EU and US regulations and ICH guidelines, focusing on minimizing contamination through good manufacturing practices. Key elements include monitoring, validation, contamination controls, and personnel management. A risk assessment is crucial for identifying and prioritizing contamination risks, fostering continuous improvement, and maintaining regulatory compliance. A robust CCS enhances product quality, patient safety, and company reputation by proactively addressing contamination risks.

Michelle Heiter, laboratory and quality control specialist, and Susan J. Schniepp, distinguished fellow, Regulatory Compliance Associates, a Nelson Labs Company, discuss how to effectively use contamination control strategies in your operations.

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