Pre-Formulation

Outsourcing Stability Testing: Discussions with Contract Laboratories

Stability testing is required for all biopharmaceutical drug products to detect all changes in identity, purity, and potency as a result of a number of environmental and processing factors. Whether testing is conducted in-house or through contact laboratories, it involves the development and performance of comprehensive and specific stability protocols for all stages of a product’s life cycle (1). Testing product stability in-house requires signficant time and resources, and carries challenges associated with commercialization market, time, and capacity. Market: The…

Compatibility Assessment of a Model Monoclonal Antibody Formulation in Glass and Blow–Fill–Seal Plastic Vials

Blow–fill–seal (BFS) technology has been recognized by the industry as an advanced aseptic solution (1–3). Catalent Pharma Solutions has been commercially supplying sterile BFS products to the pharmaceutical industry for decades, primarily in the respiratory and topical ophthalmic markets. Such product formulations range from simple solutions to emulsions with drug substances from classical small molecules to large complex proteins such as biologics. The company also has optimized BFS processes and its Advasept plastic container system for the manufacture of sterile…

Biophysical Analysis: A Paradigm Shift in the Characterization of Protein-Based Biological Products

Generating a stable environment for a biopharmaceutical drug substance is a critical step for ensuring a long drug-product shelf life (1–6). This process begins early in development with preformulation screening. Some of the most critical parameters to maintaining potency and activity are protein conformation (tertiary or three-dimensional (3-D) structure), folding (secondary structure), and proper subunit association (quaternary structure). Collectively, those are known as higher-order structure (HOS) and can be highly influenced by the formulation environment of a protein drug product.…

Development of a High-Throughput Formulation Screening Platform for Monoclonal Antibodies

The goal of formulation development for therapeutic proteins is to find conditions under which a protein remains stable during storage, transport, and delivery to patients. Both chemical and physical stability must be considered. Chemical stability is related to the rates of chemical modification to a protein molecule such as deamidation of aspargine residues and oxidation of methionine residues (1, 2). Particularly important to control if they affect biological function, those modifications could also lead to changes in conformation or half-life…

Evaluation of a Variable-Pathlength Spectrophotometer: A Comparable Instrument for Determining Protein Concentration

Protein concentrations in bioprocessing are determined by multiplying the measured absorbance of UV light as it passes through a sample by the protein extinction coefficient. Conventional spectrophotometer measurements are based on a fixed pathlength depending on the cuvette used to hold the sample (typically 10 mm). Only a small portion of the UV curve is linear at that pathlength. As a result, conventional spectrophotometers have a limited linear range and are unable to measure a large range of protein concentrations…

Highly Concentrated Protein Formulations: Finding Solutions for the Next Generation of Parenteral Biologics

Therapeutic protein formulation is no easy task. Biological drugs may be destined for prefilled syringes or glass vials, or they may be made into lyophilized powders that will be reconstituted in a clinical setting. No matter what their final state will be, recombinant proteins must remain potent and efficacious during storage. In recent years, pharmaceutical companies have turned increasingly to high-concentration protein formulations. Such drug formulations can offer patients the convenience of self-injection — instead of a trip to the…

Development of Protein Capsular Matrix Vaccine Platform Technology

Polysaccharide vaccines account for about 30% of the total >$20-billion/year vaccine market. Despite efficacious vaccines in the field, diseases such as invasive Streptococcus pneumoniae and typhoid fever persist. Development of multivalent polysaccharide conjugate vaccines requires complex chemistries and multiple, expensive good manufacturing practice (GMP) process steps. Matrivax Research and Development Corporation is developing a protein capsular matrix vaccine (PCMV) technology that simplifies synthesis of polysaccharide vaccines with fewer process steps than are required by typical conjugation vaccine processes. Polysaccharide Vaccine…

“Transformation By Infection”

Every bioprocess begins with an expression system, and every expression system begins with DNA transfection. Derived from transformation and infection, the word paradoxically has come to be applied mainly to nonviral methods of genetically engineering cells; viral-vector–mediated DNA transfer is often called transduction. There are chemical, particulate, physical/mechanical, and viral means of getting new genetic material into a cell, and that DNA may take a number of different forms. Even the cloning method (pictured right) using a microscopic needle to…

Drug Products for Biological Medicines

Traditionally, the CaSSS CMC Strategy Forum meetings have provided a scientific focus on the development of biotech drug substances and their manufacture and characterization, leaving the development of drug product formulation and filling, understanding primary containers, and considering novel delivery systems somewhat out of scope. Over recent years, however, the importance of investing more science and technology into drug product development has become evident as different product types, higher protein concentrations, and doses and requirements for improved delivery of biological…

Tunable Half-Life Technology

While a constantly developing market puts increasing pressure on pharmaceutical companies to provide advanced and personalized therapies, the industry is investing heavily in the development of targeted biologics. The aim is often to take new therapeutics through clinical trials and to market as quickly as possible and to develop more novel, tailored drugs. One common challenge for many biologics is their short plasma half-life. That often leads to reduced bioavailability, meaning that an administered drug will clear from a patient’s…