Protein therapeutics have dramatically improved the lives of people with various forms of cancer, HIV, and other diseases. These life-saving biologic drugs can replace protein(s) in a patient that has a corresponding deficiency or abnormality, augment an existing pathway, or provide a new function entirely, and we continue to learn about their capabilities. Manufacturing protein-based therapeutics can be challenging because the protein molecules are inherently unstable and have a propensity to agglomerate together to form larger protein aggregate particles. This instability increases when molecules are exposed to stresses during manufacturing, shipping, storage, and even patient administration. Protein aggregation can have a negative impact on both drug efficacy and patient safety.
Detecting, identifying, and controlling unwanted sources of contamination in injectable protein drug products requires a multifaceted approach that focuses on the product, the manufacturing equipment and environment. SentrySciences has the expert knowledge, products, and personnel to help detect sub-visible particles (SbVP) in biologic drug products and to comply with USP<787> Sub-visible Particles in Protein Therapeutic Injections and USP<788> Particulate Matter in Injections. We can help you detect and identify protein aggregation, quantify the results and develop strategies to control protein aggregation in your drug products.
At SentrySciences, we understand the analytical challenges of compliance with USP<787> and USP<788> requirements for sub-visible particulates. Light Obscuration, the approved compendial method for subvisible particle testing for injectable drug lot release, is significantly challenged by inherent protein particles. The light obscuration method has known technical limitations when applied to protein drugs that result in under-counting and under-sizing translucent, low-contrast inherent protein aggregates and subvisible particles due to refractive index-matching issues. Orthogonal methods such as flow imaging microscopy (FIM), microfluidic imaging (MFI), and backgrounded membrane imaging (BMI) do not face the same refractive-index-matching limitations. Each of these methods is identified as an orthogonal method to light obscuration for drug lot release. These imaging-based methods provide information on particle size and count, but they lack robust algorithms capable of in-depth analysis of the unique textural and morphological features of the protein aggregates and subvisible particles embedded within their images.
ParticleSentryᴬᴵ software combines deep machine learning and computational statistics to deliver actionable, quantitative data from these orthogonal methods. For the first time, protein formulation development and chemistry, manufacturing, and controls (CMC) scientists have a robust supervised learning software able to quantitatively determine if a collection of protein aggregate images match a known stressor condition or represent a new outlier condition - all with statistical certainty!
Because they are injections, protein therapeutics are subject to the same GMP and related quality regulations that apply to small and large molecule parenteral products. Fortunately, providing and installing validated total particle, viable particle, rapid microbial detection and environmental monitoring systems in aseptic fill-finish environments has been a core solution from SentrySciences since our founding over 10 years ago.