This blog series will address regulatory problem-solving. Our expertise spans preclinical to market, supporting regulatory submissions, application reviews, and post-approval changes (PAC). Our senior experts have over 200 years of combined experience, including service with the USP, FDA Scientific Advisory Committees, and as FDA Special Government Employees. We have also provided FDA educational courses and collaborated with the agency to deliver the first FDA course in Africa

For over 30 years, Improved Pharma and its predecessor, SSCI, have addressed critical challenges, contributing to market approval for numerous products including NCEs with breakthrough and fast track designations and high-profile pharmaceuticals like atorvastatin calcium and lenalidomide. Our state-of-the-art laboratories are equipped for chemical and physical analysis including X-ray diffraction, thermal analysis, spectroscopy, microscopy, and moisture absorption studies. We also offer advanced analytical capabilities like chromatography (UPLC, HPLC) and mass spectrometry (MS), and facilities for troubleshooting crystallization, drug products, and processes, including stability and dissolution testing.

Located in the Purdue Research Park, a leading university-affiliated research park, we are near Argonne National Laboratory (ANL). Improved Pharma scientists are registered users of the Advanced Photon Source (APS), enabling detailed examination of complex materials using high-energy X-ray beams. We deliver high-quality data, accurate reporting and robust documentation.

Regulatory Problem-Solving

Improved Pharma’s regulatory expertise encompasses CMC with a foundation in solid-state and analytical chemistry (including method development and validation), formulation design, and manufacturing. We emphasize establishing critical performance attributes for robust specifications, enabling rapid root-cause diagnosis for specification failures and variabilities, often linked to unanticipated solid-form transformations of APIs. These are common challenges in navigating regulatory approval.

Solid-State Chemistry Expertise

Our solid-state chemistry specialization, as detailed in Solid-State Properties of Pharmaceutical Materials by Byrn et al., includes:

  • Polymorphism and Solid-State Form Consistency: Using advanced tools like synchrotron X-ray diffraction, we verify solid-state form consistency throughout manufacturing, storage, scale-ups/scale-downs, and PACs, ensuring consistent product quality.
  • Crystal Form Optimization: We identify stable crystal forms and guide form selection through robust screening and characterization. This mitigates risks of polymorphic transformations during formulation and processing, preventing costly delays, clinical data variability, and protracted regulatory reviews.

Stability and Impurity Studies

We excel in identifying chemical and solid form impurities at low detection limits, which can cause unwanted changes and specification failures. Our capabilities include:

  • Impurity Detection: At APS, Beamline 11-BM allows highly sensitive detection of low-level solid form impurities
  • Solid-State Transformations: Synchrotron-based techniques and PDF analysis determine the structure and behavior of complex materials at the atomic level
  • Thermal and Kinetic Analysis: Techniques like DSC, modulated DSC, TGA, and hot-stage microscopy characterize thermal properties and enable robust formulations, such as amorphous solid dispersions
  • Microscopy Techniques: Light microscopy, Raman microscopy, and SEM provide insights into particle attributes, impurity/contaminant particles, and formulation compatibility. Raman mapping visualizes component distribution, blend/content uniformity, and potential incompatibilities, including at coating interfaces, impacting product performance and stability

Process Development and Scalability

Applying QbD principles to crystallization, formulation, and co-processing, we ensure scalability and product quality:

  • Target Product Profiles: We establish API and product attributes, including process and testing methods, aligning with clinical trial design and therapeutic use. These evolving tools enhance stakeholder understanding and sponsor-regulatory interactions.
  • Product and Process Design: We establish processing conditions for desired API solid form quality, ensuring consistent drug product performance
  • Co-processing: We are leaders in co-processed materials, an approach gaining industry and regulatory interest for simplifying processes, and achieving robust APIs with desired properties for streamlined drug product processing

Methods and Documentation

We use calibrated, modern instruments meeting ICH Q2 and Q14 guidelines. Reference materials ensure data traceability and reliability. Our scientists provide quality data and interpretation, translating complex findings into actionable steps. We support clients with comprehensive documentation, including development reports and QOS. Our experts advise on PACs, particularly those impacted by polymorphic transitions.

Innovative Collaborations

Collaborations with ANL and Excelsus Structural Solutions (accessing the Swiss Light Source) enhance our ability to address complex materials questions. By leveraging advanced technologies, we deliver robust solutions to critical regulatory challenges.

Improved Pharma advances understanding of solid-state properties and regulatory compliance, providing clients with insights and a strategic advantage. Future blogs will explore specific challenges like stability studies, analytical method development, thermodynamic evaluations, complex regulatory issues, and innovative solutions.