Agenda

What's in the Package? How Component Quality Impacts the Product and the Bottom Line

Regulatory expectations and product quality pressures are intensifying for pharmaceutical manufacturers. Updates to EU GMP Annex 1 and global requirements for Contamination Control Strategies (CCS) emphasize tighter control of contamination risks throughout the aseptic process, including packaging components. At the same time, market data from FDA recalls between 2011 and 2021 show that impurities and contaminants were the leading cause of drug recalls (37%).
In response to these challenges, Grand River Aseptic Manufacturing (GRAM), West Pharmaceutical Services, and Corning conducted a joint study to evaluate how premium components, specifically coated vials and high-quality stoppers, impact final drug product quality, yield, and operational performance. The study measured four key outcomes:

1.Reduced rejected vials and improved COGS
2.Higher yield of saleable product
3.Operational efficiencies via reduced inspections and investigations
4.Improved total cost of ownership despite higher component costs

This presentation will share study design, data findings, and insights to help biopharma companies assess the cost-benefit of adopting higher-quality packaging components as part of their manufacturing partners' contamination control and operational excellence strategy.

The Andelyn Biosciences facility produces life-saving advanced therapies for patients with rare and ultra-rare diseases. Born from Nationwide Children's Hospital's pioneering work in cell and gene therapy development, where several of the first FDA-approved therapies were clinically trialed, Andelyn represents a unique transition from academic research to commercial manufacturing.
 
This case study will examine Andelyn's journey from concept through production, including:

   
• Organizational structure and therapeutic focus areas
   
• Design decisions for multi-product ATMP manufacturing
   
• Alternative approaches considered and lessons from path not taken
   
• Critical success factors and improvement opportunities encountered

Attendees will gain practical insights into establishing a commercial ATMP facility and achieving operational readiness on a patient driven timeline.

The presentation guides pharmaceutical manufacturers through implementing the revised Annex 1.  It combines regulatory insights with resilient quality systems for compliance.  The session covers a risk-informed roadmap to enhance market readiness and patient safety.

It includes:

 
• GAP Analysis: Identifying compliance gaps in legacy aseptic facilities through a methodical, risk-based framework.
 
• QMS Integration: Integrating quality management systems to enhance operational resilience and regulatory alignment.
 
• Contamination Control Strategy (CCS): Demonstrating integrated and effective contamination control mechanisms, from environmental monitoring to operator training.
 
• Regulatory Navigation: Detailing execution strategies for quality systems, such as GMP and data integrity, to streamline product approvals and accelerate market access.

This session translates complex requirements into actionable strategies for implementation.

At Pharmascience’s Candiac site in Canada, a new aseptic formulation/fill-finish and  lyophilization facility was designed to meet today’s patient health and regulatory needs.  Specific product challenges include potent compounds (OEB 4/5) and flammable solvents  (e.g., 100% ethanol fills). The risk-based approach targets full compliance with EU Annex 1,  FDA, and Health Canada requirements (among others).

1) Product mix and process control:
For a multiproduct operation, product mix and process control along with regulatory expectations  (including Annex 1) are focal points for the discussions today. Pharmascience operates both as a  CDMO and produces their own products. Discussion includes manufacturing, product classifications/ attributes, and design trade-offs. Process and plant efficiencies, line changeover, and cleaning  strategies for managing potential cross-contamination are discussed.

2) The Pharmascience site and process design strategy:
Central to the approach was a contamination control strategy (CCS), risk assessments, and an  integration plan that aligns with the site’s master plan. Production workflows, internal testing,  airflow (CFD/smoke studies), and cleaning studies were integral to the design. Other process topics  include flexible formulation design approaches, VPHP cycle optimization studies for aseptic/potency  management, kill tank design and washdown approach, and explosion-resistant ATEX-aligned equipment  designs.

Determining optimal filling parameters for parenteral drug products presents a significant challenge  due to the unique properties of each product, target dosing volumes, and the wide range of filling  line configurations across different manufacturing sites. Establishing appropriate parameters for  new processes or adapting existing ones often requires extensive trial-and-error, which can disrupt  production schedules and consume substantial resources.

Computational Fluid Dynamics (CFD) offers a promising solution by enabling the prediction and  validation of filling parameters through detailed simulations. This approach allows for efficient  exploration of the design space with minimal experimental effort, accelerating process development  at any stage. When combined with validated CFD data across various configurations, artificial  intelligence (AI) can further enhance this process by developing predictive models that enable rapid  identification of optimal parameters.

This presentation aims to provide an overview of the process development for parenteral drug  products, emphasizing the creation of digital twins of filling operations. It will explore how CFD  and AI-driven modeling can be integrated to streamline the development process and improve control  over fill accuracy, ultimately leading to more robust and efficient manufacturing processes.

The presentation picks up Annex 1’s multiple requests for airflow visualization in grade A environments.

Airflow studies—commonly called “smoke studies”—must be performed during (re-)qualification of equipment under dynamic conditions and video-taped to prove unidirectionality of airflow and the capability of effectively removing particles from the space above openly exposed parenteral product. The significance of the study depends very much on visualization technique, which is a combination of tracer delivery and illumination. ASTM has recently published a new “Standard Guide for Critical Airflow Visualization,” which explains the different types of tracer, the devices for distribution without adversely impacting the airflow, and the videotaping technique including illumination to optimize visibility of aerodynamics.

This talk shows state-of-the-art techniques for performing smoke studies—including distributor innovations, tracer discussion (glycol versus WFI vapor), and laser sheet techniques for high-contrast visibility of airflow.

This presentation offers a detailed case study of a collaborative initiative between Integrated Containment Systems (ICS) and University of Iowa Pharmaceuticals (UIP) to design and implement a next-generation aseptic and toxic fill-finish system. The project was driven by the need for a flexible, high-throughput solution capable of handling potent compounds while maintaining strict aseptic conditions and regulatory compliance.

The system integrates isolator-based technology with advanced automation, including ISO 5 environments, guillotine doors, RTPs, and conveyor systems. It features cascading pressure zones and HEPA filtration to ensure both product sterility and operator safety. The presentation will walk attendees through the full lifecycle of the project—from concept and design to qualification and operation—highlighting key innovations and lessons learned.

Attendees will gain practical insights into:

 
• Customizing isolator systems for multi-product aseptic fill-finish operations
 
• Implementing automated material handling and transfer systems
 
• Maintaining chain of custody and environmental control in toxic fill scenarios
 
• Navigating facility constraints and real-estate limitations with modular design

This session is ideal for professionals seeking actionable strategies to modernize aseptic manufacturing facilities and meet the demands of increasingly complex pharmaceutical production environments.

The fill-finish industry is facing a pivotal moment. Can sterile product drug manufacturers continue relying on risk-based approaches to aseptic processing, or is a shift toward truly sterile processing inevitable? Barrier isolator-based filling lines are under increasing regulatory scrutiny, with recent inspections focusing on sterilized part setup, adherence to first air principles, and glove use near critical zones. Long-standing procedures and validated solutions are now being re-evaluated. What are the impacts on cost of goods and reliable supply of medicines?

This three-part program will:

 
1. Review how barrier isolator systems have historically ensured product sterility through validated VPHP bio-decontamination and preparatory procedures for aseptic environments.
 
2. Share real-world experiences from three CDMOs, including inspection outcomes and operational challenges.
 
3. Conclude with a dynamic panel discussion where industry experts and attendees debate the future of aseptic processing.

The revision of Annex 1 (2022) has emphasized stricter requirements for aseptic processing, particularly regarding freeze-dryer loading and unloading operations. Section 8.123 was granted a two-year implementation period, compared to one year for most other requirements, reflecting regulators’ awareness of the complexity of applying these provisions in existing manufacturing environments.

In response, a redesign of the loading system was evaluated and successfully implemented at a Sanofi Italy site. A line previously based on manual loading was transformed into a semi-automatic configuration, while preserving cleanroom constraints and the original filling and capping systems. The new solution introduced semi-automatic trolleys with electronically adjustable loading plates and a unidirectional Grade A airflow, ensuring aseptic continuity and eliminating operator-related contamination risks.

In parallel, the handling of lyophilizer loading frames sterilized in autoclaves was re-engineered: frames are now managed through dedicated sterilized storage and automated support, maintaining Grade A continuity throughout their lifecycle. This integrated approach enabled compliance with regulatory expectations while strengthening process robustness.

The case study illustrates how targeted technological upgrades, focused on the critical loading step, can align legacy equipment with Annex 1 requirements, achieving regulatory compliance without disrupting overall manufacturing workflow.

Join us to hear how one company implemented, qualified, and validated a closed, gloveless SA25 aseptic filling workcell—using a rigorous, standardized approach to earn GMP certification in just 18 months. Explore the advantages of real-time monitoring using biofluorescent particle counters (BFPC). And discover how to use BFPC for Grade A monitoring, from setting baselines to handling interference and getting ready for inspections. This approach can greatly reduce the extra validation work that otherwise would fall on the end users. Leave with practical tips for using gloveless isolators and BFPC to protect your product, improve environmental monitoring, stay compliant, and speed up your path to market.

Controlled nucleation is a deliberate strategy to trigger and homogenize the liquid-to-solid phase transition during product freezing in lyophilization. In conventional freezing, ice nucleation is stochastic and spatially non-uniform: small thermal gradients and the intrinsic instability of the phenomenon cause vials to nucleate over broad supercooling ranges and extended times, propagating variability and lengthening production cycles.

The presentation covers an innovative “ice-fog” approach that diffuses micron-scale ice crystals, generated from ultra-cooled vapor, throughout the freeze-dryer chamber to seed nucleation nearly simultaneously across all vials. This controlled seeding reduces inter-vial heterogeneity, elevates nucleation temperature, and yields larger initial ice crystal conditions known to lower dry-layer resistance and accelerate primary drying while preserving critical quality attributes.

Data from pilot and production installations show robust batch-wide nucleation uniformity, shorter primary-drying durations, and more stable, transferable recipes; recent scale-up case studies further demonstrate successful implementation on GMP equipment. Collectively, these results support ice-fog controlled nucleation as a practical, scalable route to faster, more predictable freeze-drying with improved process consistency.

This proposal directly supports the field of aseptic processing and contamination control by providing a long-term analysis of glove use in RABS environments. Glove integrity is a critical control point in barrier systems, and failures can compromise product sterility. By presenting real-world data over a 15-year period—including heatmap-based failure analysis, glove lifecycle management, and traceability processes—this presentation contributes to practical contamination control strategies.

It also addresses barrier technology by examining how glove materials, designs, and handling procedures have impacted performance and durability. Through process improvements and risk mitigation approaches, the presentation offers valuable insight for professionals seeking to enhance RABS reliability and reduce glove-related interventions in critical areas.

Annex 1 mandates automation of lyophilizer loading and unloading as much as possible. However, very few projects for retrofits have been presented so far.

The presentation will show such a case study of retrofitting an existing cleanroom for lyo vial unloading from manual to automated unloading in just 1 year in 2024.

First, the former cleanroom layout and material flows will be displayed. Current Annex 1 requirements will then be discussed to show Vetter's decision path to retrofit this cleanroom.

Subsequently, the challenges as well as our corresponding solutions of the project phase will be discussed in detail, among other things:

 
• Concept of automation
 
• Concept of construction while commercial production
 
• Reduction of timeline to reduce impact on supply chain
 
• Impact on aseptic process simulation concept, etc.

The successful implementation in just one year was mainly driven by setting up a technical twin next to use proven technology. Key learnings of the success of this project will be discussed.