Biologics, which are drugs and treatments derived from natural products, undergo a long development process before they reach the clinic. When you invest a lot of time and money in the process to ensure the success of your candidate, catching issues early on makes your efforts worthwhile. Biologics is a growing market worth over $300 billion in 2020 (and a predicted worth of over $500 billion dollars by 2025), so that extra attention at the beginning will pay off.
At the earliest parts of protein biologic development, the stability of a candidate is assessed to rule out any long-term stability issues. One method that gives a wealth of information that can ultimately improve outcomes is DLS, or dynamic light scattering. Learn about some of the specific sub-focuses of biologics and how DLS can help optimize your biologics for the market.
Antibody development
Antibodies (Abs) offer immense potential as drugs thanks to their targeting and specificity. In order to increase go-to-market efficiency, researchers are looking into how rationally-designed mutations to the structural core of an Ab systematically affect their stability. However, artificial intelligence (AI) and other computational approaches are still not able to reliably predict how mutations will affect stability or antigen binding.
DLS measures how mutations affect the size and propensity to aggregate in derived antibodies. This information can be input into AI programs with the goal of developing better systematic approaches to these engineered changes. Antibody researchers want to know if the Abs developed from screening libraries will be stable, and thus more likely to be successful as therapeutics.
Formulation
The goal of the formulation process is to find a safe, efficient and convenient form of a biologic that will be used downstream for assays, therapeutics, or bioengineered processes. This work involves monitoring how a protein behaves in a given environment. Biologics often have complex structures, and are very sensitive to their environment, which must be optimised to prevent aggregation or denaturation.
DLS measures the unfolding of a protein or the existence of several protein species, which are important indications that your formulation needs work. Changes in buffer salt concentration, pH, temperature, or protein concentration all affect a protein’s stability.
Drug conjugates
Antibody Drug Conjugates (ADCs) deliver a small molecule drug of interest to a very specific target in the cells. The small molecule drug is covalently linked to an antibody, which has the desired specificity for a given antigen. Researchers developing ADCs need to understand how covalent attachment of a small molecule drug affects the overall stability and behaviour of their Abs. The conjugation process can destabilize the antibody; furthermore, once that Ab is carrying the drug, its long term formulation and storage might be affected.
DLS allows researchers to monitor how conjugation affects their antibody stability.
Bispecifics
The latest trend in building better biologics is developing bi-specific Abs and Ab-derived molecules that act as targeted carriers of a drug or treatment. This allows these Ab-derived molecules to specifically target an antigen while “carrying” a more complex treatment such as another protein or nucleic acid. These biologics are usually derived from the variable chains of the Fab region of the antibody, and they must target both the drug that they carry and the cell-specific receptor they are delivering to.
DLS not only gives information about how these engineered fragments behave long term, but also help researchers determine whether or not the drug or target is binding the bispecific.
Quality Control
During the course of clinical trials, as well as during scale-up and mass marketing, it is crucial to maintain uniformity across batches. Changes to the production process or even the environment the biologic is produced in can affect the stability and therefore impact the quality of different batches. This will have a negative effect on the efficacy and safety of a biologic, and is considered unacceptable for government body approval.
DLS can help predict long-term storage stability by using it to do accelerated stress tests. These tests allow researchers to extrapolate denaturing conditions for biologics stored in freezers for long periods of time. By determining the dispersity and aggregation profile of a biologic prior to scaling up production, researchers determine the ideal parameters to prevent loss of quality when changes are introduced in their production methodology.
Biologics are a growing market with a lot of potential for better patient outcomes in the clinic. The first step in their development requires thorough understanding of their dispersity and aggregation in order to optimize them for long-term development and scale-up. Together, this demonstrates the value DLS adds throughout the biologics development process.
The Prometheus Panta now integrates DLS information into its already trusted and reliable information on thermal and chemical stability via nanoDSF. Learn how Prometheus Panta can improve your biologics workflows.
