Biochemicals/Raw Materials

A Quick Guide for Sourcing Biopharmaceutical Raw Materials

Before the ratification of regulatory guidelines from The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q8–Q11 (1–4) — whose scope includes raw materials for biopharmaceutical production — many drug manufacturers chose the most cost-effective and readily available raw materials sourcing options without specifically considering the provenance of those materials. Depending on the chosen supply chain, such materials could be of widely varying quality and not necessarily suitable for a destined application. Raw-material…

Consistently Superior Cell Growth: Achieved with New Polyethylene Film Formulation

During the past decade, single-use bioprocessing bags and bioreactors have gained a significant foothold in the biopharmaceutical industry because they offer a number of advantages over traditional stainless steel equipment, especially for clinical production, multiproduct facilities, and emerging economies. At the same time, some companies are concerned that plastic materials might release potentially toxic substances that could affect cell growth and product titers (1). In a worst-case scenario, they could even compromise drug safety when a company uses disposable bags…

Tsunami - Japan 2011

Supply Chain Challenges in the Biopharmaceutical Industry: A Case Study Following the 2011 Tsunami in Japan

Global manufacturing of biopharmaceuticals for human use helps save the lives of millions of people and is a large commitment to public health. The industry operates in an environment with financial uncertainties and complex international supply chains, so the question of risk mitigation is paramount. There is an expectation that comprehensive risk mitigation programs should be in place to minimize the risk of supply chain interruptions that would negatively affect the manufacture of these vital therapeutics. Here we share how…

Activatable Immunoconjugates for Target Cancer-Cell–Specific Diagnosis and Therapy

In cancer treatment, early diagnosis and targeted therapies are assumed to yield the highest cure rates. However, most current methods are limited by their low sensitivity to early disease and a lack of specificity for targeted cell killing. Newly developed, activatable immunoconjugates assist in the accurate detection of cancer through in vivo imaging with high target-to-background contrast (1,2). They also provide for the possibility of highly specific, light-mediated treatment with minimal effects on healthy cells surrounding tumors (3). In fact,…

Powders and Bulk Liquids

    The two major bioprocess fluids — culture media for upstream production and buffers for downstream processing — are classic single-use products. They are used once and then disposed of. The two basic options for both differ by physical state: powdered media and buffers (“powders” for in-house preparation of liquids by end users) and bulk liquid culture media and buffers, which are fully prepared by their suppliers (“liquids”). We conducted market research studies comparing the benefits and risks (value…

Effective Cryopreservation and Recovery of Human Regulatory T Cells

The list of conditions being targeted by cell therapies is rapidly growing, but commercializing cells for widespread medical use will require standardized laboratory practices. Development processes must be adapted specifically for cell-based drug products. Regulatory T-cell therapy represents a promising new frontier in the immunotherapy of autoimmune disorders, especially for patients who have been refractory to available treatments. Because of intrinsic fragility, cell therapy products can be highly sensitive to variations in manufacturing procedures. Standardization of drug-product cryopreservation and storage…

IgM Purification with Hydroxyapatite

Hydroxyapatite (HA) has a long and successful history in the field of antibody purification, and it has worked well for immunoglobulin M (IgM) monoclonal antibodies (MAbs) (1,2,3,4,5,6,7,8). Applications range from initial capture to intermediate purification to final polishing. HA is best known for its superior ability to reduce antibody aggregates, but it also supports excellent reduction of DNA, viruses, and endotoxins. As IgM MAbs exhibit increasing potential in the fields of cancer and infectious disease and in stem-cell therapies, HA’s…

Accounting for the Donnan Effect in Diafiltration Optimization for High-Concentration UFDF Applications

The biopharmaceutical industry is targeting high-concentration protein formulations to enable subcutaneous administrations. Such administration can provide better patient convenience than intravenous administration. One challenge associated with high-concentration formulations is increased electrostatic interaction between proteins and excipients. That is a result of increased protein-charge density at high protein concentrations. Such interactions can create an offset between excipient levels in final products and diafiltration buffers in ultrafiltration processes. The effect of such electrostatic interactions in a membrane process is known as the…

Analysis By Size and Charge

An early BPI Lab article addressed the power of liquid chromatographic separations for biopharmaceutical laboratory use (1). Such techniques separate biomolecules based on a number of different properties: size, solubility, hydrophobicity/-philicity, binding affinity. The next most powerful means of separation — and thus high-resolution identification — of nucleic acids and proteins/peptides is based primarily on electrostatic properties: electrophoresis. Although it doesn’t really work in a process or preparative setting, it is a fundamental technique in modern biopharmaceutical laboratories, where it…

Impact of Process Interruption on Virus Retention of Small-Virus Filters

Manufacturers of biopharmaceuticals using mammalian cell culture must have processes in place to minimize the likelihood of virus contamination of their products. Regulatory agencies provide guidelines for testing strategies and best practices to assure raw-material safety and control of the manufacturing process. Safety assurance relies on an interdependent matrix of managed risks, including characterization and control of raw materials, extensive testing of process intermediates, and demonstration of the virus removal capabilities of purification unit operations Figure 1:  () A dedicated…