Off Script: A Pharma Manufacturing Podcast

Delivering Pharma’s Mega-Projects in a Resource-Constrained World: Part One

Rising capital investment in pharmaceutical manufacturing is pushing projects to unprecedented scale, but execution strategies haven’t fully kept pace. As companies commit billions to new facilities they’re encountering a new set of challenges around planning, coordination, and risk management. What worked for smaller, site-based upgrades is insufficient for multibillion-dollar builds involving thousands of stakeholders, constrained resources, and increasingly complex regional dynamics.

In this episode of Off Script, we spoke with Pathfinder President Steve Cabano and Mark Christopher, vice president and head of the company's pharmaceutical division, about what it takes to successfully deliver mega-scale capital projects in today’s environment. Pathfinder is a project management consulting firm. The conversation explores how the industry’s shift back toward large-scale North American manufacturing is exposing gaps in project controls, contracting strategies, and organizational readiness. They discuss the growing importance of early-stage planning, clearer decision ownership, and construction-driven execution models, as well as how labor competition, permitting hurdles, utility constraints, and global procurement risks are reshaping timelines and cost structures.

Annex 1 and the Shift to Proactive Sterile Manufacturing

Ever since the revised Annex 1 was published, drug makers have been navigating a broader transformation of sterile manufacturing that extends beyond compliance. Contamination control, in turn, is becoming a more proactive, data-driven, and highly collaborative model, one that emphasizes continuous improvement, global alignment, and deeper integration across the supply chain. While the regulation itself builds on decades of precedent, its latest iteration is accelerating expectations around risk management, documentation, and end-to-end control strategies.

In this episode of Off Script, we spoke with Haley Johnson, senior manager of product management, and Bill Matakas, vice president of business transformation at West Pharmaceutical Services, about how Annex 1 is reshaping sterile manufacturing operations and supplier relationships. The conversation explores the industry’s shift from reactive remediation to proactive risk prevention, the growing importance of contamination control strategies as living systems, and how inspectors are increasingly focused on measurable, year-over-year improvement. 

How U.S. Policy Is Reshaping Pharma Outsourcing

As the U.S. government pushes to reshore pharmaceutical manufacturing and rein in drug pricing, the implications for CDMOs and the broader outsourcing ecosystem are coming into sharper focus. While large-scale onshoring investments dominate headlines, questions remain around how policy will account for outsourced manufacturing and whether incentives align with the realities of global supply chains.

In this episode of Off Script, we spoke with Gil Roth, founder and president of the Pharma & Biopharma Outsourcing Association (PBOA), about how recent policy developments are impacting CDMOs and their customers. The conversation explores the role of CDMOs in onshoring efforts, the economic and structural barriers to reshoring API and generic drug manufacturing, and what current tariff frameworks signal about policy priorities. Roth also discusses FDA staffing challenges, potential impacts on drug review timelines, and the broader uncertainty shaping R&D, sourcing, and investment decisions across the industry.

Building the Foundation for Autonomous Bioprocessing

While fully autonomous bioprocessing is within reach, adoption remains gradual as manufacturers navigate challenges around data maturity, regulatory expectations, and operational readiness. As companies modernize, the focus is shifting toward building the digital and organizational foundations needed to enable more intelligent, scalable process control, particularly through connected systems, stronger data infrastructure, and more explainable AI models that can support real-time decision-making.

In this episode of Off Script, we spoke with Mel Radford, director, life sciences global accounts at Rockwell Automation, about the key barriers to autonomy and how companies can move from reactive operations toward predictive and closed-loop process control. The conversation explores how hybrid models combining first-principles engineering with AI can improve control performance, stability, and yield while remaining transparent and easier to validate, as well as the importance of embedding compliance, governance, and human-centered change management into next-generation control strategies.

Reshoring APIs and Scaling Continuous Manufacturing for Generic Drug Supply

Generic medicines account for the vast majority of prescriptions in the U.S., yet much of their underlying supply chain remains heavily dependent on foreign-sourced active pharmaceutical ingredients (APIs). As concerns around drug shortages and supply chain resilience intensify, attention is shifting upstream toward how APIs are manufactured, where they are sourced, and what it will take to rebuild domestic production capacity. At the same time, advanced manufacturing approaches like continuous flow are gaining traction as a way to improve efficiency, safety, and cost competitiveness in a traditionally low-margin market.

In this episode of Off Script, we spoke with Brian Doty, vice president of R&D and programs at the API Innovation Center (APIIC), about the structural challenges facing generic drug manufacturing and the role advanced technologies could play in addressing them. The conversation explores why API supply is often the cause of downstream drug shortages, the technical and economic limitations of traditional batch processing, and how continuous manufacturing can reduce process steps, improve control, and enable safer production. Doty also discusses the practical barriers to adoption as well as the growing role of FDA engagement programs and policy incentives in accelerating change.

Engineering the Next Generation of ADCs

Antibody–drug conjugates (ADCs) are rapidly evolving from experimental hybrid molecules into mature, platform-driven therapeutics, with the global market projected to reach $36 billion by 2029. As pipelines expand and molecular designs grow more complex, developers are rethinking how ADCs are designed, characterized, and manufactured. In this episode of Off Script, we spoke with Lonza's Sandro Holzer, PhD, director and head of development bioconjugates, and Anette Sommer, PhD, head of bioconjugates research, about how the ADC field has changed over the last several years and what is driving the next wave of innovation.

The conversation explores the industry’s shift toward standardized linker–payload platforms, site-specific conjugation, higher drug-to-antibody ratios, and emerging dual-payload ADCs aimed at overcoming tumor heterogeneity and drug resistance. Holzer and Sommer discuss how rising molecular complexity is reshaping CMC strategy, analytics, and downstream processing, and why early integration of biology, chemistry, and manufacturability is essential to de-risk development and enable scale-up. The episode also examines how ADC manufacturing paradigms are now informing adjacent bioconjugate modalities signaling a broader move toward integrated, multi-component therapeutics beyond oncology.

Automating Cell and Gene Therapy Manufacturing for Scale

Cell and gene therapies (CGTs) have demonstrated transformative clinical potential, but manufacturing remains a major barrier to broader patient access. Highly manual, labor-intensive production processes limit throughput, introduce variability, and drive up costs, making it difficult to scale these therapies to meet growing demand. As the industry looks to expand access, there is increasing focus on how automation, robotics, and digitalization can enable more consistent, efficient, and scalable manufacturing without compromising the underlying biology.

In this episode of Off Script, we spoke with Edwin Stone, PhD, CEO of Cellular Origins, about the core bottlenecks constraining CGT manufacturing and how automation is beginning to address them. The conversation explores why labor remains a dominant cost driver, how process variability extends beyond patient starting material into everyday manual operations, and what it takes to transition from fragmented workflows to fully integrated, robotic production environments. Stone also discusses the importance of preserving biological integrity during automation, the role of digital data capture in improving consistency and regulatory confidence, and more.

Bridging Precision and Scale in Microparticle Drug Delivery Manufacturing

Producing uniform drug delivery particles at scale has long presented a challenge for pharmaceutical manufacturers. Techniques that offer tight control over particle size and structure often struggle with throughput, while traditional industrial methods deliver volume but less consistency. As advanced drug delivery systems become more important for long-acting therapies and targeted treatments, manufacturers are increasingly seeking production methods that can balance precision, scalability, and reproducibility.

In this episode of Off Script, we spoke with Nathalie Pinkerton, PhD, assistant professor of the chemical and biomolecular engineering department at the NYU Tandon School of Engineering, about Sequential NanoPrecipitation (SNaP), a continuous flow technique designed to bring greater control to polymeric particle manufacturing. The conversation explores how separating particle formation into sequential mixing stages enables more predictable control over particle size and composition, the role of micromixer design in achieving consistent mixing and scale-up, and why encapsulation efficiency plays a critical role in manufacturing economics. Pinkerton also discusses the remaining steps needed to translate emerging particle manufacturing technologies from the lab into commercially viable pharmaceutical production platforms.

Fixing the Structural Weaknesses in the Global Drug Supply Chain: Part Two

In this episode of Off Script, we continue our conversation on the structural vulnerabilities in the global pharmaceutical supply chain with Ronald T. Piervincenzi, CEO, USP, turning the focus toward practical strategies for strengthening the resilience of the global medicine supply chain.

Piervincenzi discusses the economic and structural barriers to rebuilding domestic capacity for APIs and key starting materials, and explains why resilience will require coordinated incentives that reward supply security rather than simply the lowest price. He also explores how advanced manufacturing approaches could help make domestic production more viable by improving efficiency and reducing environmental impact.

The conversation also examines how global quality standards can enable trusted international manufacturing networks among allied countries, and how USP’s new Resilience Center aims to bring together data, benchmarking frameworks, and stakeholder collaboration to help industry and policymakers better measure supply chain resilience.

Fixing the Structural Weaknesses in the Global Drug Supply Chain: Part One

The global medicine supply chain faces mounting strain from chronic generic drug shortages, geopolitical tensions, and heavy reliance on geographically concentrated manufacturing. Quality failures, pricing pressures, and opaque sourcing of key starting materials have exposed structural vulnerabilities that extend beyond routine disruptions to broader national security and public health risks. This episode is part one of a two-part series examining the root causes of these vulnerabilities and the structural changes needed to address them.

In this series, we spoke with Ronald T. Piervincenzi, Ph.D., CEO of the U.S. Pharmacopeia, about how these risks emerged and what it will take to build a more resilient pharmaceutical supply chain. In part one, Piervincenzi explains why generic drug shortages and national security concerns are often conflated, how extreme price erosion is driving manufacturers out of the market, and what USP’s data reveals about supply concentration, including the critical role of key starting materials sourced from countries like China and India. The conversation also dives into USP’s new Resilience Center and the strategic role it will serve in improving supply chain security.