Achieving a good stability profile is integral to the developability of a biopharmaceutical, and incorporates Critical Quality Attributes which must be monitored throughout development and into manufacture. Advances in stability profiling and stability prediction methods, along with the industry’s desire to ‘fail fast and fail cheap’, have driven the desire for reliable assessment of a candidate molecule’s or formulation’s stability ever earlier in the development pipeline, and the increase in novel molecule types as biotherapeutics brings new analytical challenges and complexity.
Understanding the complex behavior of biomolecules and therapeutic candidates under a broad set of solution conditions requires multivariate datasets, to enable researchers to make informed decisions on the identification and progression of viable drug candidates. Malvern Panalytical provides a portfolio of information-rich analytical techniques that delivers the measurement attributes and complementary datasets for reliable stability profiling throughout development workflows.
Stability screening and aggregation propensity
Getting an early indication of adverse molecular interactions, such as those that lead to the formation of aggregates, is vital for streamlining the development pipeline to ensure that critical resources are targeted at candidates with viable developability profiles.?
- Low volume, low concentration stability screening solutions deliver multivariate data sets for stability metrics, and provide analytical capabilities to meet emerging challenges associated with novel molecule types
Quantifying monomer and aggregate populations
Instability pathways in development of biologics are highlighted by the oligomerization of proteins, resulting in loss of the desired target molecule population to aggregates (e.g. dimers, trimers and higher order oligomers). Quantification of the change in target molecule population to aggregate population is a key stability profile metric.?
- Applying multi-detector solutions to industry-standard SEC analysis delivers both the required molecular identification and population resolution for robust oligomeric purity assessment
Extended submicron and subvisible particle characterization
Control of subvisible particle populations in biotherapeutics is a regulatory requirement, as their presence can impact efficacy and increase immunogenic risk. Quantifying the submicron particle population (0.1 - 1mm) provides a more complete aggregation profile of bioformulations, and this size range is attracting more regulatory attention.
- Extended characterization methods provide information on subvisible particle populations down into the nanoparticle-scale range – including differentiation between proteinaceous and non-proteinaceous particles
Formulation viscosity profiling
With most biological drugs being delivered as intravenous or subcutaneous liquid preparations, the viscosity of their formulation is a key attribute which must be monitored to ensure both manufacturability and deliverability.
- Utilizing relative viscosity data from early low concentration stability screens to determine abnormal solution behavior, to measuring absolute viscosity as a drug product release specification
Comparability and biosimilarity
Stability indicating assays play a key role in assessing product consistency between batches of the same product, and also in the development of biosimilars to assure equivalent product characteristics to innovator biological drugs and meet regulatory requirements.
- Applying a range of complementary and first principle techniques with structured analytical processes enables more informed development and delivers fingerprint stability profiles of biologics and biosimilars