Engineering a Flawless Scale-Up: How CDMOs De-Risk the Path to Commercial Supply

Today’s advanced therapies, biologics and high-value products, require high-level infrastructure, technology, and manufacturing strategy. Scaling up from clinical trials to full commercial supply demands exceptional operational agility and risk management. 

Grand River Aseptic Manufacturing (GRAM) addresses this challenge by providing a flexible, deeply collaborative approach as opposed to short-term campaign planning. By aligning manufacturing capacity with long-term client goals, proactively mitigating facility risks through robust redundancy systems, and streamlining the technology transfer process, GRAM secures operational continuity for its partners. This strategic focus ensures that client products transition smoothly and maintain consistent performance at commercial volumes.

Nick Bykerk, Chief Financial Officer at GRAM shares insight on the company’s approach to  capacity and expansion, facility design and risk mitigation, reducing bottlenecks for clients as products scale up, and improving yield.

Contract Pharma: How does GRAM approach manufacturing capacity and expansion strategies for clients?

Nick Bykerk: At GRAM, capacity planning begins with the client’s long-term commercialization strategy rather than simply the next campaign. We work closely with clients to understand forecast assumptions, launch timelines, market growth expectations, and inventory strategies so that capacity can be aligned with both current and future demand.

Our approach emphasizes flexibility and scalability. We leverage multiple filling technologies and manufacturing platforms to support programs from clinical development through commercial supply. By evaluating forecast scenarios early, we can identify capacity constraints before they become limiting factors and implement expansion plans, equipment investments, or manufacturing strategies that support sustainable growth. This proactive approach reduces supply risk and provides clients with greater confidence as products advance toward commercialization.

Contract Pharma: When it comes to facility design and risk mitigation, what are some common redundancies of utilities, equipment, and technology?

Nick Bykerk: In sterile manufacturing, risk mitigation starts with facility design. Redundancy is often incorporated into critical utilities such as power distribution, HVAC systems, compressed gases, water-for-injection generation and distribution, and environmental monitoring systems.

From an equipment perspective, redundant or alternative manufacturing pathways can provide operational resilience when maintenance events or unexpected downtime occur. Facilities also increasingly utilize digital manufacturing technologies and automated monitoring systems to improve visibility and detect potential issues before they affect product quality. GRAM’s investments in integrated production monitoring support operational continuity while improving compliance and manufacturing reliability. 

The goal is not simply duplication of assets. Effective redundancy ensures that a single point of failure does not compromise product quality, supply continuity, or regulatory compliance.

Contract Pharma: In what key areas can CDMOs reduce bottlenecks for clients as products scale up?

Nick Bykerk: One of the most significant bottlenecks during scale-up is technology transfer. Processes that perform well in development settings often require refinement to achieve consistent performance at commercial volumes. CDMOs can reduce this risk through early process characterization, robust transfer protocols, and close collaboration between development, manufacturing, engineering, and quality teams.

Supply chain readiness is another critical area. Component qualification, raw material sourcing, and inventory planning become increasingly important as demand grows. CDMOs can also reduce bottlenecks through automation and review-by-exception capabilities that accelerate batch release activities. 

Ultimately, successful scale-up depends on identifying constraints before they impact production and addressing them through a combination of technical, operational, and quality-focused solutions.

Contract Pharma: How does GRAM’s process development approach transition from clinical-scale equipment to commercial manufacturing scales?

Nick Bykerk: GRAM focuses on developing processes that are scalable from the outset. During development, we seek to understand the critical process parameters and product quality attributes that drive performance. This knowledge enables us to establish a strong foundation for future commercial manufacturing.

As programs advance, our teams evaluate equipment differences, mixing characteristics, filling performance, container closure systems, and process controls to ensure that product quality remains consistent across manufacturing scales. The transition is supported by structured technology transfer activities, engineering studies, risk assessments, and validation planning.

Rather than viewing commercial scale as a separate process, we view scale-up as a continuum where scientific understanding, process knowledge, and manufacturing experience are progressively expanded to support reliable commercial execution.

Contract Pharma: How can CDMOs reduce waste and improve yield for client products?

Nick Bykerk: Reducing waste begins with process understanding. The more thoroughly a process is characterized, the better manufacturers can predict performance, minimize variability, and reduce losses. For high-value biologics and advanced therapies, even small yield improvements can translate into meaningful economic value.

Automation also plays an important role. Automated process controls and real-time monitoring help reduce human error, improve execution consistency, and identify deviations earlier in the manufacturing process. GRAM’s digital manufacturing initiatives are designed to strengthen process compliance while reducing non-conformances, corrections, waste, and scrap. 

In addition, investment in robust equipment design, preventative maintenance programs, operator training, and continuous improvement initiatives can drive sustained gains in yield and overall equipment effectiveness.

Contract Pharma: What is your approach to executing Installation, Operational, and Performance Qualifications for new equipment and automated processes?

Nick Bykerk: Successful qualification starts well before equipment arrives on the manufacturing floor. At GRAM, qualification activities begin during the design phase through user requirements, risk assessments, and quality planning. This ensures that qualification efforts are focused on the functions and controls that are most critical to product quality and patient safety.

Installation Qualification verifies that systems are installed according to approved specifications. Operational Qualification confirms that equipment and automated processes operate as intended across defined operating ranges. Performance Qualification demonstrates that the process consistently performs under routine manufacturing conditions.

For automated systems, qualification efforts are integrated with computerized system validation principles, data integrity requirements, and risk-based testing methodologies. Consistent with industry best practices, testing efforts focus on configured functionality, integrations, recipes, and system extensions while leveraging supplier qualification packages where appropriate. 

The ultimate objective is to establish a scientifically sound, documented state of control that supports reliable operations, regulatory compliance, and long-term manufacturing success.

Visit www.grandriverasepticmfg.com to learn more.