Biopharmaceutical Manufacturing: Creating a Robust and Productive Process

Samsung BioLogics was established in 2011, since then, the company has firmly positioned itself as a leader within the biopharmaceutical manufacturing industry, producing high-quality products, benefiting patients worldwide. The company has been the recipient of numerous awards, including the 2018 Asia-Pacific Bioprocessing Excellence Award based on its competitiveness in speed, cost, and quality.

We recently spoke to Alice S. Chuck, Ph.D. Manufacturing Sciences & Technology Team Leader at Samsung BioLogics to learn more about the company’s values and day-to-day operation. Alice discusses the key stages of biomanufacturing, highlights the importance of regulatory compliance and explains how the completion of their newest facility, 'Songdo Plant No.3' has enhanced their current manufacturing capabilities and overall operation.

Laura Mason (LM): Could you tell us more about Samsung BioLogics, your company mission and key values?

Alice S. Chuck (AC): Samsung BioLogics is a Contract Development and Manufacturing Organization (CDMO) headquartered in Songdo, South Korea. Over the past 7 years, we have established ourselves as the world’s largest CDMO reaching 362,000 liters of total manufacturing capacity with two fill and finish lines. This makes us the fastest growing company in the bioindustry in terms of capacity and innovation.

We believe that CDMOs can operate more efficiently and cost-effectively than internal biopharmaceutical manufacturing organizations. By leveraging Samsung’s expertise in plant construction and operation, Samsung BioLogics saved almost 40 percent of CAPEX in plant No.2. Since initially we did not have any experience in the biopharma industry, Samsung BioLogics hired global experts from the very beginning. As a result, Samsung BioLogics now produces high-quality biologics drugs while reducing cost dramatically. We believe this cost competitiveness ultimately benefits the patients who are depending on the quality and efficacy of the products.

LM: The biomanufacturing process is comprised of several key stages, could you elaborate on these stages? What considerations should be made during process scale-up?

AC: To initiate clinical trials, the small-scale laboratory process used to produce the drug for research purposes should be adapted and developed to produce the product for human use. This means the process should define how to reliably achieve the required product quality profile, i.e. product purity, safety, and efficacy. Process variability should be understood to determine process robustness: process performance should be represented from multiple independent runs using multiple lots of key raw materials. Limits should be determined for cell age, solution hold times, and product pool hold times. The process must be developed with scale-independent parameters defined, in order to be scalable for production in a Current Good Manufacturing Practice (cGMP) facility – at Samsung BioLogics, 1 kL, 5 kL, 15 kL scale fed-batch productions are possible.

As a product goes through its clinical phases, process development may continue; to refine the target product quality profile, to improve process yields, to reduce process variability, and to increase manufacturability. The process should be ‘locked’ prior to process characterization so that it is ready for process validation. Process characterization is performed at laboratory scale, and is comprised of evaluations of all process parameters, and demonstrates which parameters contribute to product purity, safety, and efficacy, and which parameters impact process yield. This allows you to define acceptable ranges, within which a process must operate. This process knowledge is a basic requirement of process validation. Process validation is demonstrated at commercial scale in a series of process performance qualification (PPQ) batches, where control of the acceptable process ranges are highlighted.

After PPQ and successful health authority inspections where process validation, product characterization, and clinical efficacy are evaluated, the commercial phase of the product lifecycle begins. In this stage, the process is monitored closely to ensure the process and product purity, potency, and safety are all maintained in a state of control. During process monitoring, manufacturing efficiencies and detailed opportunities to reduce cost of goods may be further identified.

LM: Your facilities are custom designed for mammalian-cell therapeutic monoclonal antibody production, during the designing phase, were there any specific features incorporated in to the design, to enable you to achieve maximum processing efficiency and to prevent cross-contamination?

AC: Samsung BioLogics established a differentiated position from other manufacturers by successfully building and validating its state-of-the-art multi product biologics facility in record time. We utilized new and innovative technologies which enabled Samsung to improve product quality, while reducing the costs of producing high-quality medicines.

All construction activities were executed concurrently. Concurrent processing is difficult because scheduling is extremely tricky. However, our in-house engineers collectively have extensive experience in a multitude of industries, including semiconductor and petrochemical, and thus were able to finish it successfully.

In addition to concurrent processing, Samsung BioLogics applied a 3D modeling method. It was mainly used when installing plant/clean utilities and manufacturing process equipment, to prevent any duplicated work that would impact the overall construction time and budget.

Our newest plant No.3 is the largest single plant and has state-of-the-art facilities as it is currently the newest one in the world. It was completed in November 2017 and is expected to be validated by Q4 of this year. Samsung BioLogics has added N-1 perfusion which has been applied to a mega facility for the first time in the industry. It will minimize the period of annual shutdown as well as product change over and run the facility by eliminating inefficiencies in operation.

LM: Could you touch on the importance of regulatory compliance?

AC: Samsung BioLogics has received 11 approvals from global regulatory agencies such as the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA). Samsung BioLogics has set the record for the shortest time to get an approval in the industry. Plant No.1 achieved FDA approvals in 25 months after the plant started operation. The company broke its own world record with plant No.2, which achieved its first approval in 19 months – 6 months faster than plant No.1, despite it being five times larger.

Regulatory compliance is the foremost important factor for a Contract Manufacturing Organization (CMO) like us. If a CMO fails to comply with the regulatory agencies’ guideline, clients and patients can be negatively affected.

Internal quality systems should be stringently managed and monitored to fulfill both client and regulatory agency requirements. Samsung BioLogics’ quality system ensures all equipment and systems are maintained throughout cGMP production and our dedicated quality and compliance department provides the proper oversight of release and/ or rejection of raw materials, intermediates, products, packaging, and labeling materials. Samsung BioLogics has secured manufacturing contracts for 16 products from 11 pharmaceutical companies including Bristol-Myers Squibb (BMS) and Roche.

LM: Samsung BioLogics’ newest facility, Songdo Plant No.3 was mechanically completed in November 2017, how has the addition of this third plant enhanced your current operation?

AC: Plant No.3, one of the world’s largest biological drug production facilities, was completed at the end of 2017. Once it becomes cGMP ready in Q4 of this year, Samsung BioLogics will have a total production capacity of 362,000 liters and will be the world’s largest biopharmaceutical CDMO. With the completion of the third bio manufacturing facility, we are able to reliably supply large volumes of biologics to the global biopharmaceutical market as it continues to grow.

In addition to its large capacity, Plant No.3 is competitively designed, and has the ability to become a multiproduct facility at sophisticated agile operation. Samsung BioLogics has also integrated technologies that will deal with emerging issues in biopharmaceutical manufacturing including high cell density culture or high titer process.

Alice S. Chuck, Ph.D. was speaking to Laura Elizabeth Mason, Science Writer for Technology Networks.