An Intercompany Perspective on Practical Experiences of Predicting, Optimizing and Analyzing High Concentration Biologic Therapeutic Formulations.

Developing high-dose biologic drugs for subcutaneous injection often requires high-concentration formulations and optimizing viscosity, solubility, and stability while overcoming analytical, manufacturing, and administration challenges. To understand industry approaches for developing high-concentration formulations, the Formulation Workstream of the BioPhorum Development Group, an industry-wide consortium, conducted an inter-company collaborative exercise which included several surveys. This collaboration provided an industry perspective, experience, and insight into the practicalities for developing high-concentration biologics.

An Intercompany Perspective on Compatibility and In-use Stability Studies to Enable Administration Of Biopharmaceutical Drug Products.

In-use stability and compatibility studies are often used in biotherapeutic development to assess stability and compatibility of biologic drugs with diluents and/or administration components at relevant conditions for the target route of administration (commonly intravenous, subcutaneous or intramuscular), to assure that patient safety and product efficacy are maintained during clinical use. To gain an understanding of current industry approaches for in-use stability and compatibility studies, the Formulation Workstream of the BioPhorum Development Group (BPDG), an industry-wide consortium, conducted an inter-company collaboration exercise, which included five bench-marking surveys around in-use stability and compatibility studies of biologic drugs. The results of this industry collaboration provide insights into the practicalities of these studies and how they are being used to support administration of biologics from early clinical programs to marketed products.

Development of Thermostable Lyophilized Sabin Inactivated Poliovirus Vaccine.

As oral poliovirus vaccine (OPV) causes vaccine-associated paralytic poliomyelitis, the polio endgame strategy introduced by the Global Polio Eradication Initiative calls for a phased withdrawal of OPV and an introduction of inactivated poliovirus vaccine (IPV). The introduction of IPV creates challenges in maintaining the cold chain for vaccine storage and distribution. Recent advances in lyophilization have helped in finding a temperature-stable formulation for multiple vaccines; however, poliovirus vaccines have yet to capture a stable, safe formula for lyophilization.

Clusterin glycopeptide variant characterization reveals significant site-specific glycan changes in the plasma of clear cell renal cell carcinoma.

Cancer-related alterations in protein glycosylation may serve as diagnostic or prognostic biomarkers or may be used for monitoring disease progression. Clusterin is a medium abundance, yet heavily glycosylated, glycoprotein that is upregulated in clear cell renal cell carcinoma (ccRCC) tumors. We recently reported that the N-glycan profile of clusterin is altered in the plasma of ccRCC patients.

Development of an improved fractionation of the human plasma proteome by a combination of abundant proteins depletion and multi-lectin affinity chromatography.

Aim: Current analytical tools lack the required capacity to reduce the complexity of the plasma proteome and identify low-level proteins of clinical interest. Hence, the need to develop a fractionation approach to provide adequate throughput for a clinical study and minimize the loss and improve the detection of low abundance proteins.

Materials & Methods: We present the development of an analytical platform that combines the depletion of 12 high abundance proteins and multi-lectin affinity chromatography (12P-M-LAC) fractionation.

Comparative studies of the proteome, glycoproteome, and N-glycome of clear cell renal cell carcinoma plasma before and after curative nephrectomy.

Clear cell renal cell carcinoma is the most prevalent of all reported kidney cancer cases, and currently there are no markers for early diagnosis. This has stimulated great research interest recently because early detection of the disease can significantly improve the low survival rate. Combining the proteome, glycoproteome, and N-glycome data from clear cell renal cell carcinoma plasma has the potential of identifying candidate markers for early diagnosis and prognosis and/or to monitor disease recurrence.

Characterization of glycoproteins in pancreatic cyst fluid using a high-performance multiple lectin affinity chromatography platform.

Currently, pancreatic cancer is the fourth cause of cancer death. In 2013, it is estimated that ∼38 460 people will die of pancreatic cancer. Early detection of malignant cyst (pancreatic cancer precursor) is necessary to help prevent late diagnosis of the tumor.