Production of biologics is expensive. To optimize capacity use, bulk protein solution produced in manufacturing campaigns is often converted into drug product based on market demand, so it may be stored for relatively long periods. To decouple production of bulk solution from that of a final drug product, the bulk is often stored frozen. Transport of frozen bulk between sites offers several practical advantages over bulk transport in the liquid state (2–8 °C). Maintaining 2–8 °C requires accurate…
Pre-Formulation
Large-Scale Freezing of Biologics
Production of biologics is an expensive process, and to optimize capacity use, bulk protein solution is often produced in manufacturing campaigns. It is converted into drug product based on market demand and therefore may have to be stored for relatively long periods. To decouple the bulk solution production from that of the final drug product, bulk is often stored frozen. Transport of frozen bulk product between sites offers several practical advantages over its transport in the liquid state (2–8 °C).…
A Practical Method for Resolving the Nucleation Problem in Lyophilization
Given the prevalence of lyophilization and the growing pipeline of sensitive biological drugs requiring stabilization, pharmaceutical development and manufacturing personnel need complete, reproducible control over the operation, scale-up, and transfer of their lyophilization processes. To address the nucleation problem, Praxair has developed a step-change technology that adds consistent control to the freezing step of lyophilization. This low-capital, plug-and-play option can be readily implemented on most existing freeze-dryers with minor equipment additions and controls integration. Adoption of the technology…
Applying Intelligent Flow Microscopy to Biotechnology
Ongoing requirements for additional insight and CGMP-compliant measurement have led to interest in new technologies that can be applied to the analysis of many different types of particle-containing fluids. Micro-Flow imaging (MFI) is a robust, versatile, and intelligent vision technology that is increasingly used for evaluating populations of microparticles encountered during bioformulation development (1). It is also being accepted in fill–finish processes and many other biotechnology applications. Features of MFI technology that have contributed to its rising popularity include the…
Maximizing Data Collection and Analysis During Preformulation of Biotherapeutic Proteins
Preformulation research, a critical component in the development of biotherapeutics, explores the effects of variables such as pH, ionic strength, and excipients on the solution behavior of a protein. This activity can greatly assist in guiding downstream formulation development, and it provides valuable information concerning protein stability, solubility, and structure. Successful preformulation research leads to identification of potential protein degradation pathways and development of robust formulations with acceptable product shelf-lives. PRODUCT FOCUS: PROTEINSPROCESS FOCUS: DOWNSTREAM PROCESSING, FORMULATIONWHO SHOULD READ: FORMULATIONS,…
Novel Excipients Prevent Aggregation in Manufacturing and Formulation of Protein and Peptide Therapeutics
Protein and peptide therapeutics may undergo numerous physical and chemical changes during manufacturing, shipping, storage, and administration that can adversely alter drug potency and safety. Earlier concerns focused upon denaturation (unfolding), oxidation, and deamidation of certain key aminoacyl residues. Recently, aggregation has emerged as a key issue underlying multiple deleterious effects for peptide- or protein-based therapeutics, including loss of efficacy, altered pharmacokinetics, reduced stability and product shelf life, and induction of unwanted immunogenicity. As a result, the US FDA and…
Probing Thermal Stability of MAbs By Intrinsic Tryptophan Fluorescence
In the arsenal of biophysical techniques available for rapidly monitoring the stability of protein formulations, spectroscopic techniques have some convincing advantages over others (1, 2). The main advantages to using methods such as circular dichroism (CD), infrared spectroscopy (IR) and fluorescence spectroscopy are their extremely high sensitivity (favorable signal-to-noise ratios), freedom from sample interactions with column resins or extrinsic probes (noninvasive techniques), and coverage of an extremely broad protein concentration range — from pM to mM (3, 4). To reduce…