Solutions for Lyophilization Process
and Formulation Development
What is lyophilization?
Lyophilization, or freeze-drying, is a technique used to render biologics and large molecule drugs stable for transport and long-term storage. The pharmaceutical lyophilization process is quite complex, with a series of precisely controlled temperature and pressure steps.
Process parameters and physio-chemical properties, such as freeze-dried cake moisture content, reconstitution time, integrity, homogeneity, uniformity and potency, are often employed to confirm drug product quality as well as its stability under storage. Despite decades of collective experience, the lyophilization process remains to be time-consuming and costly in both development and manufacturing scale-up phases due to the challenges in cycle development, process optimization, and cake characterization.
What is X-ray microscopy?
Current analytical approaches lack the sensitivity and resolution to analyze these microstructure associated properties without affecting the inherent cake structure. At DigiM, we apply non-invasive X-ray microscopy (XRM), AI analytics of critical quality parameters, and image-based simulation to evaluate cake quality and mass transport properties of lyophilized materials.
Non-destructive visualization of a lyophilized protein cake
microstructure with XRM imaging.
Application areas range from formulation and product quality assurance, lyophilization process development and inspection, and evaluation of new equipment and techniques such as spray-freeze drying.
With high-resolution, non-invasive XRM imaging, the thin walls and microporosity of lyophilzied cakes can be fully visualized in 3D. The microporosity quantified from XRM scans can be compared among samples prepared with different formulations and/or different process conditions. The spatial distribution of porosity can help assess both intra-cake and inter-cake uniformity. Image-based diffusion simulations can correlate the cake microstructure with sublimation rate, which provides a mechanistic insight to lyophilization process parameters.
Image-based characterization presents great potential in a number of areas of lyophilized drug product characterization. Unlike other techniques, XRM based analysis is able to both qualitatively and quantitatively assess cake integrity and purity non-invasively. In addition, parameters such as porosity that are challenging to be determined experimentally, can be assessed using image data. This approach can be used to assess inter-batch and intra-batch homogeneity as well as cake stability upon storage. The physio-chemical properties obtained can be used for fundamental understanding and correlation with process variation and optimization.
Resources
Non-invasive, quantitative characterization of lyophilized drug product using 3D XRM analytics
Drug Development and Delivery Paper in collaboration with BMS and Moderna
Non-invasive 3D X-Ray microscopy imaging technique for quantitative characterization of lyophilized drug product
IFPAC 2021 Presentation in collaboration with Dr. Maxwell Korang-Yeboah from the FDA
Assessing the risk of changes in container closure system of a freeze-dried product on primary drying efficiency and product quality
IFPAC 2021 Presentation by Dr. Maxwell Korang-Yeboah from the FDA featuring DigiM analysis
Root cause analysis of an inverse relationship between the ice nucleation temperature of a controlled ice nucleation process, process performance and product attributes
IFPAC 2021 Presentation by Dr. Maxwell Korang-Yeboah from the FDA featuring DigiM analysis