Pharmaceutical manufacturing steps are often isolated in space and time. The synthesis, isolation and purification of the drug substance (DS) and the formulation of the drug product (DP) may be located in different regions across the globe. Unsurprisingly, this elongates supply chains and significantly increases the time and costs of drug production while detrimentally impacting quality (Domokos et al., 2021).
For this reason, many pharmaceutical and biotechnology companies partner with contract development and manufacturing organizations (CDMOs) that provide integrated end-to-end manufacturing solutions for biopharmaceutical products (King, 2023).
Key benefits of integrated manufacturing
Integrated end-to-end manufacturing solutions ensure efficient, consistent, flexible and high-quality production of drug substances and drug products. These solutions minimize bottlenecks, accelerate time to market and reduce costs, while standardized procedures and comprehensive management systems reinforce the consistency of every product batch. Furthermore, adaptive manufacturing processes provide the flexibility to tailor solutions to specific client requirements.
However, end-to-end manufacturing solutions are useful in particular, if every stage is rigorously controlled to meet the highest quality standards. A commitment to quality and adherence to good manufacturing practice (GMP) guidelines is crucial for the safe and effective use of the drug product.
Threading quality into every step: One-stop manufacturing at Samsung Biologics
Samsung Biologics, a fully integrated CDMO, is dedicated to ensuring high-quality production through its comprehensive end-to-end solutions, which span from cell line development to aseptic fill/finish and laboratory testing. The company continuously invests in advanced technologies, such as an antibody-drug conjugate (ADC) facility, an mRNA manufacturing facility and additional aseptic filling sites.
With an extensive production capacity of 604,000 liters across multiple state-of-the-art plants, Samsung Biologics is well-equipped to handle DS/DP manufacturing while maintaining the highest quality standards. Their facilities are designed to support both large-scale commercial production and smaller-scale clinical manufacturing, ensuring flexibility and reliability across different scales.
To maintain product integrity and quality during distribution, Samsung Biologics employs advanced packaging solutions, for example shrink-wrapping techniques, which minimize transport damage and reduce cosmetic defects and false rejection rates. Furthermore, automatic labeling systems ensure precise and compliant product labeling following regulatory standards.
Samsung Biologics aligns its infrastructure with client-specific quality requirements. Through thorough facility fit/gap assessments and by using a network of local vendors, the company optimizes its operations to meet the unique demands of each project. Samsung Biologics ensures that every aspect of the manufacturing environment is tailored to support high-quality outcomes.
Critical quality attributes (CQAs) and critical process parameters (CPPs) are fundamental aspects of process control strategies and scale-down model studies. Samsung Biologics uses advanced technologies, such as continuous monitoring and real-time data adjustments, to optimize manufacturing efficiency and achieve right-first-time results.
Samsung Biologics’ commitment to quality is further demonstrated in its approach to analytical technology transfer. Through comprehensive training and robust documentation, the company equips quality control (QC) personnel with the necessary expertise to ensure the safety, integrity, strength, purity and quality (SISPQ) of the final products.
To prepare for commercial production, engineering runs that test critical factors such as product shear, temperature sensitivity and uniformity are conducted. The insights gained from these runs are used to further refine the manufacturing process.
Samsung Biologics works closely with clients to ensure their Process Performance Qualification (PPQ) batches are completed with precision. Interim PPQ reports accelerate regulatory inspections and approvals.
In-process control (IPC) monitoring ensures that manufacturing processes meet predefined parameters and that final products comply with safety, efficacy, and quality standards. The combination of automatic and manual inspection strategies reduces false rejection rates and improves overall yield. Furthermore, Samsung Biologics offers comprehensive regulatory filing support, reinforced by a robust quality management system (QMS).
By integrating quality into every step of their end-to-end manufacturing process, Samsung Biologics ensures that new therapies reach the market efficiently and are safe to use for patients.
Case study 1: Optimizing tech transfer to accelerate time to market
A typical tech transfer for PPQ takes nine months. By working closely with their client and local vendors, Samsung Biologics modified the filtration process, thawing system and automatic labeling system for the vials. Furthermore, they streamlined external testing by providing a QC member of their own team. These measures helped cut the time for the tech transfer to five months.
In the transportation of mRNA drug products, precise monitoring of the differential pressure across the sterile filter is crucial, as required by filter validation studies. Initially, during the tech transfer phase, real-time monitoring of this differential pressure was not possible. To ensure compliance and quality, pressure readings before and after the sterile filter were recorded every 30 minutes based on the Manufacturing Batch Record, with calculations performed to confirm the differential pressure stayed within acceptable limits. After the process, an audit trail review validated that there were no differential pressure issues.
To enhance capabilities, Samsung Biologics subsequently upgraded the Manufacturing Control System (MCS) to include automation and real-time alarm settings. This advancement enables to continuously calculate and monitor the differential pressure across the sterile filter throughout the manufacturing process, demonstrating the company’s commitment to maintaining high standards and ensuring the reliability of drug product manufacturing services.
Case study 2: Reducing an amplified false rejection rate
Due to cosmetic characteristics, a particular automatic inspection process produced an abnormally high false rejection rate of about 34%. Samsung Biologics coordinated with vendors to implement shrink-wrapping. Additionally, a HEPA-filtered air supplier was added to reduce dust particles on the outside of the vial. These measures reduced false rejection rates by 6% and ensured yields above 95% through secondary inspections.
References
Domokos, A., Nagy, B., Szilágyi, B., Marosi, G., & Nagy, Z. K. (2021). Integrated Continuous Pharmaceutical Technologies-A Review. Organic Process Research & Development, 25(4), 721-739. https://doi.org/https://doi.org/10.1021/acs.oprd.0c00504
King, D. (2023). LEVERAGING CDMO EXPERTISE: A CASE STUDY IN ACHIEVING ASEPTIC FILL/FINISH SUCCESS.
Samsung Biologics. Highest-Quality, On-Time Tech Transfer of Drug Product.