Taking a biologic drug development program from discovery to commercialization is a lengthy and challenging endeavor that can often fail due to inadequate assessment during the discovery phase. It is essential to identify candidates as early as possible with attributes that will help commercialize safe and highly effective drug products to maximize speed and cost-effectiveness. The DEVELOPICK™ platform by Samsung Biologics revolutionizes the early phases of drug development by efficiently screening key attributes of biologic candidates with minimal resource use. This innovative platform streamlines the discovery process and leverages advanced analytical methods to identify the most promising candidates early, significantly reducing time and costs while enhancing the likelihood of commercializing safe and effective drug products.
Challenges in Biologic Drug Development
The biologics development process is long, cost-intensive, and fraught with risks. Pharmaceutical companies invest an average of $1.4 billion to bring each new drug to market, but nearly 90% of candidates that reach clinical trials fail to reach the market.1 These failures are often due to unsuitable physicochemical and structural properties, such as poor solubility, low stability, high viscosity, a tendency to aggregate, undesirable posttranscriptional modifications, and issues with manufacturability.
Despite the risks associated with the ever-increasing biomolecular complexity of biologic drug development, governments, payers, and patients are steadily increasing the pressure to deliver more effective products in less time with lower costs.
Strategic Importance of Early Developability Determination
Biologic candidates must demonstrate safety and efficacy in humans and possess favorable developability profiles to progress from preclinical phases to late-stage clinical trials, marketing approvals, and ultimately, product launches. Essential to this journey is the ability of a biologic to be manufactured robustly and consistently, ensuring the production of high-quality drug substances and drug products. These products must remain stable enough for packaging, storage, distribution, and patient use.
A pivotal strategy to curtail the time and expense involved in drug development is enhancing the ability to predict candidate performance right from the discovery phase. Effective early-stage candidate selection conserves resources to focus on molecules with promising developability profiles. This increases the likelihood of preventing expensive late-stage failures and achieving safety, efficacy, and manufacturability standards for successful commercialization.
Potency, specificity, immunogenicity, pharmacokinetics, and biophysical properties during in vivo activities and storage are critical considerations in assessing the developability of a biotherapeutic.2 Chemistry, manufacturing, and control (CMC) processes, along with regulatory requirements, also play significant roles in determining a candidate's suitability for development.
However, assessing developability poses challenges, largely due to the extensive material and time required for the myriad assays necessary for a thorough evaluation. These include physical experiments, such as characterization, stability, and forced degradation testing, alongside in silico or computational analyses. Using a streamlined candidate screening approach that minimizes the materials used while also effectively assessing multiple attributes can offer crucial early insights into each candidate, maximizing its potential for successful development.
Overview of the DEVELOPICK™ Platform
Samsung Biologics provides a spectrum of development services, from late discovery to investigational new drug application filing and beyond. These services encompass developability assessments using the DEVELOPICK™ platform, customized CMC solutions via SelecTailor™, as well as several proprietary platforms aimed at accelerating development timelines and minimizing risks.
Samsung Biologics engineered the DEVELOPICK™ platform to facilitate optimal candidate selection by evaluating the physicochemical properties of molecules using minimal starting material. The platform has evolved through several iterations: Version 1.0 focused on analyzing basic molecular characteristics and responses under heat stress and low pH conditions. Version 2.0 expanded to include primary structure determination, solubility assessments, and responses in high pH environments. The most recent iteration, DEVELOPICK™ 3.0, has been enhanced to assess hydrophobicity, a crucial molecular characteristic that aids in understanding a molecule’s binding affinity and specificity.
The aggregated data from various analyses within the DEVELOPICK™ platform provide a comprehensive developability profile for each candidate molecule. This information is pivotal in determining whether a candidate possesses the necessary attributes for clinical success, a robust and scalable manufacturing process, and stability during storage, distribution, and usage. Crucially, the toolbox features high-throughput solutions that allow for systematic, rapid, and simultaneous determination of multiple attributes using limited quantities of material
DEVELOPICK™ Workflow and Analytical Methods
The DEVELOPICK™ workflow (Figure 1) begins with material supply, which can be sourced from the client or produced using S-CHOsient™, Samsung Biologics’ transient expression platform which leverages our proprietary cell line S-CHOice®. The assessment process begins with primary structure determination using an internal in silico assessment tool, followed by a relative solubility check, basic characterization, heat stress treatment, and pH stability test (both low and high), culminating in hydrophobicity evaluation. Following these assessments, the data are collated, analyzed, and presented in a comprehensive report.
Figure 1. DEVELOPICK™ workflow
The assessment of the primary structure pinpoints potential risks or hotspots prone to degradation. Detailed biophysical characterization then scrutinizes structural integrity, thermal stability, aggregation tendencies, protein folding, and other critical properties. Exposing molecules to thermal stress and variable pH conditions helps identify likely degradation pathways and determine manufacturability. The simultaneous analysis of multiple candidates facilitates comparative behavior studies, and the resulting data helps develop risk-mitigated formulations and DSP processes for candidates poised to move beyond the discovery phase.
A diverse array of analytical methods is employed for biophysical characterization:
Differential scanning fluorimetry (DSF) and dynamic light scattering (DLS) measure protein stability and size.
Size-exclusion high-performance liquid chromatography (SE-HPLC) and capillary electrophoresis–sodium dodecyl sulphate (CE-SDS) offer insights into purity and degradation patterns.
Thermodynamic stability and aggregation, colloidal stability, hydrodynamic properties, and thermal unfolding data are gathered using HUNKY and UNCLE instruments (Unchained Labs). HUNKY provides chemical stability prediction results using guanidine hydrochloride or urea. In contrast, UNCLE measures thermal stability using fluorescence, static light scattering, and dynamic light scattering within a single instrument (Figure 2).
Figure 2. Biophysical characterization using UNCLE (left) and HUNKY (right)
Relative solubility assessments are conducted for multiple candidates under varied conditions using the polyethylene glycol (PEG) precipitation method. This technique requires minimal material, assists in comparing solubility properties across various molecular types, and is invaluable for selecting the most suitable molecules for further development (Figure 3).
Figure 3. Finding an optimal pH and buffer system to improve solubility
Hydrophobicity assessment is crucial as biomolecules with hydrophobic surfaces are more prone to aggregation, precipitation, and adhesion to surfaces (e.g., columns, vials, and tubing), leading to decreased solubility and as well as increased impurity levels and viscosities. Hydrophobic interaction chromatography (HIC) performed on standard HPLC systems allows for high-throughput analysis. Using Samsung Biologics’ HIC data set, a regression analysis of the retention times (normalized between 0 for the earliest and 1 for the latest retention time) enables a standardized comparison of relative hydrophobicity across candidates (Figure 4).
Figure 4. Regression analysis: Hydrophobicity of different molecules
When DEVELOPICK™ detects hydrophobic characteristics, Samsung Biologics immediately prepares for molecule purification prior to process development. This significantly reduces the risk of failure during process development.
Benefits of Using DEVELOPICK™ in Drug Development
Using the DEVELOPICK™ platform to comprehensively assess developability provides early and critical insights into the attributes of candidates, including safety, efficacy, and manufacturability. The systematic evaluation of multiple candidates through the platform identifies the most promising molecules to advance into preclinical testing. In addition, the unique array of analytical tools DEVELOPICK™ employs delivers extensive and valuable data quickly and efficiently, using only minimal material (80 milligrams). Most notably, these thorough assessments yield results within just one month.
Figure 5. DEVELOPICK™ benefits
Early access to such detailed information enables more informed decision-making about advancing to process development and minimizes risk through a comprehensive evaluation of the client’s sequence. The DEVELOPICK™ assessment offers insights to guide upstream and downstream process and formulation development strategies, enhancing overall project outcomes. DEVELOPICK™ substantially increases the likelihood of clinical and commercial success while preventing costly delays and potential project failure.
Accelerating Biologic Development with DEVELOPICK™
Navigating the complexities of biologic drug development, from discovery to commercialization, is an arduous and often unsuccessful journey. The early identification of candidates with attributes conducive to safe and successful product commercialization increases the speed and cost-effectiveness of this process.
The DEVELOPICK™ platform by Samsung Biologics exemplifies a tailored solution to this challenge. It facilitates efficient and simultaneous screening of multiple critical attributes of early-stage candidates using minimal sample quantities. This approach significantly reduces cost and length of early developability assessments. Samsung Biologics is continually innovating to the capabilities of this platform, with imminent enhancements planned for in silico aspects of the toolbox to further refine its predictive accuracy and utility.
Using a specialized in-house assessment platform like DEVELOPICK™ enables biologic drug developers to thoroughly understand candidate profiles at an early stage. This strategic methodology conserves financial resources and time by substantially reducing the risks associated with drug development through systematic, high-throughput screening and the selection of promising candidate molecules.
Reference
1. Burke, Ty. “Why New Drugs Are Worth Pursuing –– Even When They Fail.” Chicago Booth. 8 Nov. 2023.
2. Mieczkowski, Carl et al. “Blueprint for antibody biologics developability.” MAbs. 15: 2185924 (2023).
