Although no biopharmaceutical pills are yet on the horizon, formulation and delivery have advanced over the past 10 years. Formulators have new biophysical technologies and new product types (such as protein–drug conjugates) to work with. The most important issues haven’t changed much, though — from aggregation to stability, freezing to freeze-drying — although the FDA’s quality by design (QbD) initiative changes the strategies used to address them. Fragile proteins and other biologically sourced macromolecules need protection to achieve…
Formulation
Fight Cancer with Nanotechnology
Imagine a diagnostic test that sifts through millions of molecules in one drop of a patient’s blood to detect the tell-tale protein signature of a cancer subtype. Envision a drug “ferry†that doesn’t release its cytotoxic contents until it slips inside cancer cells — or a molecule or small panel of proteins that can reveal within days whether a cancer treatment is working. Bioprocess Applications of Nanoparticles () Researchers have created nanosized particles and devices that are…
Key Aspects of Enzyme Activity and Steady-State Kinetics
Living systems rely on enzymes to perform many essential functions for survival. One prime example is digestion, the conversion of food into energy. Each enzyme possesses specific requirements for the types of molecules that it can use as substrates or reactants to convert to products. Here, I provide some basic information about enzymes, explain their biochemical parameters (e.g., kinetic parameters) and significance for characterization, and review related assays currently available to the bioprocess industry. Lactose intolerance is a common enzyme…
Combination Products for Biotherapeutics
Combination products (see the “Definition†box) are experiencing steady growth in the pharmaceutical industry. According to one report, about 30% of products currently in development are combination products (1). Expanding interest in such products can be attributed to manufacturers’ need to generate new market value for current products that will soon lose patent, requirements for long-term patient care, pressure to reduce healthcare costs, and consumer interest in localized drug delivery with improved therapeutic effectiveness (2). During the 2008…
Stability Considerations for Biopharmaceuticals: Overview of Protein and Peptide Degradation Pathways
To ensure product safety and efficacy, protein therapeutics must meet defined quality characteristics immediately after manufacture as well at the end of their designated shelf lives. Many physical and chemical factors can affect the quality and stability of biopharmaceutical products, particularly after long-term storage in a container–closure system likely to be subject to variations in temperature, light, and agitation with shipping and handling. Compared with traditional chemical pharmaceuticals, proteins are considerably larger molecular entities with inherent physiochemical complexities, from their…
Formulation Effects on Opalescence of a High-Concentration MAb
Monoclonal antibodies (MAbs) are increasingly formulated at concentrations >100 mg/mL as a means to deliver a high dose in a low volume (1,2). Such high-concentration solutions are commonly opalescent (3,4), an undesirable characteristic of biopharmaceutical products for several reasons. Although it may be only aesthetic, opalescent products are not considered pharmaceutically “elegant.†Of more serious concern, opalescence may be a precursor to aggregation and indicate a propensity toward decreased product stability or quality. The term opalescent refers to…
A Formulation Strategy for Quickly Reaching Clinical Trials
The aim of any company making protein-based therapeutics is to get to the clinic quickly with a product formulation that has the best chance of success. Any number of specific formulation development and manufacturing issues can keep such drugs from advancing expeditiously to the clinic. To be successful organizations must balance the strengths and weaknesses of each individual molecule against timelines, budgets, and priorities. Ultimately, it’s not just about deploying the best methodologies and processes, but of applying them appropriately…
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 requires no…
The Human Network
Biotechnology is not simply about science or technology, process engineering or cell lines, corporations or regulations. It’s ultimately about the people involved in all these things — and about the people they hope to serve with their biotech aspirations. It’s about scientists and technicians, businessmen and medical professionals, patients and consumers, farmers and governments, all their lives touched in one way or another by the biotechnology industry — some admittedly more than others. Policy decisions made by…
Emerging Analytical Technologies for Biotherapeutics Development
A major goal of pharmaceutical development is to characterize pathways of chemical and physical instability and then to develop strategies to minimize them. Deamidation and oxidation are examples of the former, aggregation a result of the latter. The potential for the presence of multiple variants in protein-based pharmaceuticals highlights a need for analytical methods capable of reliably and accurately identifying and measuring those variants. The ideal analytical method would be sensitive, accurate, linear over a broad range, resistant to sample-matrix…