June 19, 2023 PAO-05-23-CL-07
Daniel Buckley (DB): The regulatory environment is unquestionably one of the top challenges facing drug developers today. Regulators make evolving requirements to keep up with the rapid technological advances taking place in the biopharmaceutical industry, particularly when it comes to next-generation therapies. The regulatory framework is consequently growing more complex, making it difficult for drug manufacturers to not only maintain compliance but also to bring new molecules into the clinical stage and forward to commercialization.
Simultaneously, there is growing pressure to reduce drug prices from many fronts. Regulatory authorities and government legislators seek to find ways to increase patient access to both novel and traditional drug products. Biopharmaceutical companies, meanwhile, are facing both higher R&D costs and higher risk of failure, especially as it has become even more important than in the past to be first to market or introduce a new best-in-class molecule.
DB: In a very real sense, the leading CDMOs today are innovators themselves. They develop and implement novel manufacturing solutions that address some of the most pressing problems facing drug developers. They have developed the specialized skills and expertise that are key to the successful development of complex molecules in the accelerated timelines required today, but are not practical for every drug developer to establish in-house.
In addition, because the top CDMOs have vast experience with a wide diversity of molecule types and regulatory submissions — Investigational New Drug (IND) applications, Novel Drug Approval (NDA) applications, and Biologic License Applications (BLAs) — they have a deep understanding of the regulatory requirements and the ways in which the development process can be effectively accelerated. Their ongoing involvement in regulatory audits also prepares and positions them to meet the changing requirements of multiple agencies while achieving those accelerated timelines.
DB: Since the overall goal of any biopharmaceutical company is to develop and commercialize quality biomedicines that meet unmet patient needs, when looking for an outsourcing partner, drug developers should seek CDMOs that have the expertise, technical capability, capacity, and personnel to support client projects across the full development spectrum from discovery to post-market approval.
DB: To get the most out of an outsourcing relationship, biopharmaceutical companies are considering many different aspects of CDMO performance, including their audit histories, quality assurance controls, interactions with various regulatory agencies, and compliance track records. Those CDMOs that pass the first evaluation are then leveraged for their experience, technical and regulatory knowledge and specialized skills, expertise, and technologies to streamline development activities while maintaining regulatory compliance and reducing risk.
DB: There are two types of assessments that should be completed: an assessment of a CDMO’s performance (capabilities, track record, recent expansion) and face-to-face meetings to gain an impression of some of the softer but still critical attributes, including flexibility, transparency, and the ability to retain talent.
The best CDMOs have a long track record of successful project completions involving many different types of molecules and technologies. That includes regulatory approvals from multiple authorities around the world, as it is a strong indicator of their experience with those regulatory agencies. They have established platform processes to accelerate timelines while simultaneously increasing the likelihood of success. The site’s team and the facility’s capabilities and capacity should be expanding as well, as that indicates they are attracting more clients and building a greater degree of trust in their capabilities. The continuous mentality of expansion and improvement of capabilities to meet market demand is also a powerful indicator of success, as well as the ability to meet future clinical and commercial demands as projects advance from early development stages.
Face-to-face meetings are important because you can learn a lot from direct, personal interactions. It is also possible to see in person the actual technical equipment and evaluate on an individual basis the skills and expertise of the key personnel that will be involved. Also importantly, being onsite provides a means for assessing a CDMO’s flexibility in terms of nimbleness and the ability to respond and overcome challenges. Audits also allow for assessment of the company culture and employees’ commitment, which is very important but difficult to evaluate on paper or from afar.
DB: There are six key factors that must be addressed: regulatory, sustainability, confidentiality, quality, speed, and cost. Samsung believes that a “right the first time” approach results in higher quality, which in turn enables faster development timelines and reduced costs while ensuring sustainability, confidentiality, and regulatory compliance. Because we have a flexible development approach built into our operations, we are able to execute the right studies at the right time and using the right analytical methods to ensure that we identify and address any development challenges that may arise as early as possible.
DB: First, it is important to understand what co-location means, since that's a term that may be used differently person to person. For Samsung Biologics, it means truly having all of the required expertise, technologies, and facilities at a single site organized under an overarching strategy that takes into account the full development life cycle and therefore minimizes the potential for problems to arise when moving from one development phase to the next.
Drug development and manufacturing has many hurdles that need to be overcome and continues to become even more challenging as new candidate molecules become more complex. Problems will arise even in the face of the most comprehensive planning, and decisions will need to be made quickly. The best decisions are made in consideration of input from manufacturing, analytical, engineering, quality assurance, regulatory, and so on, so that all aspects of the drug substance and/or drug product are considered — that can only happen quickly if all of those people are fully informed and easily accessible. Co-location makes that possible. It also helps ensure that any need for redevelopment in later stages, which is always accompanied by costly capital investments, is minimized. Having all development and manufacturing activities located at one site enables seamless integration between development, tox production, clinical manufacturing, and large-scale commercialization, which is invaluable.
DB: We have developed several platform processes and technologies to facilitate development and manufacturing of a wide range of different types of molecules. Our S-CHOice® platform is our proprietary cell line technology launched in August 2020. S-CHOice® builds on glutamine synthase (GS) knock-out Chinese hamster ovary (CHO) cell line technology and exhibits titers up to two-fold above the industry average, reaching above 7 g/L for standard monoclonal antibodies in many cases. The cell line also shows enhanced cell viability with over 90% at day 21 in a fed-batch study, demonstrating its effectiveness in producing high-quality cell lines. The cells also divide rapidly (18–20 hours). This property, when combined with the Berkeley Lights Beacon® technology, enables Samsung Biologics to reduce average development timelines by one month.
Our two newest development platforms — S-DUAL™ and DEVELOPICK™ — were introduced in September 2022 and also streamline the antibody development process. S-DUAL™ is a high-yield bispecific antibody platform with a 99% chain-pairing success rate. Process efficiency is maximized through extensive process control. The unique asymmetrical structure afforded by the S-DUAL™ technology reduces the risks associated with chemistry, manufacturing, and control (CMC) requirements and ensures high binding affinity among chains to produce high titer and purity for optimized manufacturability. Currently, Samsung Biologics is developing a platform purification process to pair with the S-DUAL™ upstream platform.
DEVELOPICK™ is a rapid developability assessment platform that systematically screens molecules at an early development stage to identify the candidates with the best potential for advancement to IND and BLA filing. Requiring as little as 20 milligrams of material, the assessment platform enables clients to conduct a robust risk assessment for unsorted drug candidates within a month, guiding them to the path of biotherapeutic development success. The flexible modular platform consists of a wide range of analytical methods that can be deployed in a high-throughput manner as needed for a given molecule (and selected upfront with the client). Results are compared to those of commercial molecules, and — using a proprietary scoring technique — each molecule is placed on the developability scale. More importantly, the assessment is performed by highly experienced scientists, which gives the clients confidence in the results.
DB: Tremendous growth is anticipated for the ADC market, and Samsung Biologics will be ready to support clients advancing their promising ADC candidates. We plan to add an ADC facility nearby but completely isolated from our Sondgo headquarters. The new ADC facility to deliver client pipelines will be cGMP ready within 2024. Construction of the lab has already been initiated, and we will be prepared for the massive growth to come.
DB: While many companies are still looking at traditional mAbs and the development of biosimilars and biobetters for mAbs that are soon to come off patent, many are also looking at next-generation antibody formats, such as bispecifics, mRNA therapeutics, and vaccines, to improve efficacy and specificity.
All of this novel molecule development is increasing costs at a time when downward pricing pressure is growing and regulatory expectations are growing. The focus for the industry is thus on intensifying processes, improving yields and purity, and leveraging advanced and innovative technologies and facilities that help reduce costs. Successful CDMOs are developing multimodal capabilities designed to enable support of traditional and next-generation drug substances and drug products. Samsung Biologics, however, has taken this proactive approach from the start.
DB: Samsung Biologics is taking the same strategy to mRNA outsourcing services as it has for other biologics: offering end-to-end support across the entire spectrum, from sourcing raw materials, reagents, and single-use equipment to implementing and monitoring temperature controls across each phase of development and distribution to seamlessly connecting drug substance (mRNA) and drug product (mRNA–LNP) production at one site. Being an integrated CDMO supporting the complete mRNA workflow with pre- and post-mRNA manufacturing co-located allows us to overcome supply chain limitations and reduced development timelines. End-to-end support also facilitates scale-up of mRNA drug substance and drug product manufacturing for our clients. The ability to perform all activities from lab to commercial scale at one facility eliminates the time, costs, and risks associated with the transfer of material from one site to another.
DB: Samsung Biologics’ latest, fourth manufacturing plant is fully completed this year as committed adding 240,000 liters to the company’s three existing facilities, making a total of 604,000 liters up and running. Continuing on this expansion, we are also commencing the first phase of our second Bio Campus with Plant 5, which will provide additional capacity of 180,000 liters, making a total of 784,000 liters. The new plant will be operational by April 2025. We are also fostering biomanufacturing talent, localizing the supply chain, and providing tech support to biotechs with the goal of creating a local biocluster and ecosystem for greater supply independence. There are also plans to expand our global operational presence in the United States beyond our San Francisco lab and New Jersey sales office and eventually also into Europe so that Samsung can provide this high level of support in a local manner to our customers from around the world.
DB: Regardless of the current state of the market, the future is always uncertain. No drug developer or CDMO is able to predict with 100% accuracy what the market will look like five or 10 years from now. However, Samsung Biologics has established concrete strategies for managing that uncertainty. First, we have built-in flexibility and agility, enabling rapid responses to changing market dynamics that influence both the supply of key raw materials and the demand for final drug products. We are also pursuing a localized supply approach, establishing a strong ecosystem nearby that is better equipped to respond to sudden crises. Integration of typically segmented production operations into consistent processes all at one site not only streamlines development activities; it also allows for greater control. Finally, our extensive experience and expertise with mAb development and manufacturing is being leveraged where appropriate to address the challenges presented by new modalities, including those on our radar today and those likely to emerge in the future.
Daniel Buckley is Associate Director of CDO Downstream Development at Samsung Biologics. He has an extensive background in the biotech industry, with more than 17 years of experience in new product introductions, purification scale-up, biotech facility design, biotech facility commissioning and qualification (C&Q), process validation, commercial manufacturing, audit readiness, and regulatory inspections. Prior to joining Samsung Biologics, Daniel served as manager for two downstream purification facilities at Eli Lilly.
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