Process characterization (PC) studies are experiments performed primarily at laboratory scale to demonstrate process robustness and provide data necessary for planning, risk mitigation, and successful execution of process validation (1, 2). These typically involve extensive, multifactorial testing designed to determine the effects of operational parameter perturbations and raw materials on process performance and product quality (1, 2). Product-specific information from development studies may be used to help guide PC study design; however, such information may be limited or…
Monday, October 1, 2012 Daily Archives
Regenerative Medicine
The year 2011 may be seen as one in which regenerative medicine entered its adolescence. Public attention — from investors to desperate patients — finally turned toward this nascent industry with something other than skepticism or unrealistic expectations. The FDA’s approval of Dendreon’s Provenge cellular immunotherapy switched on the spotlight, and cell therapy companies suddenly faced a barrage of questions about cost, manufacturing issues, product development, and patient access. US Policy: In May 2011, US representatives Brian Bilbray…
A New Kinetic Structured Model for Cell Cultivation in a Chemostat
Mathematically modeling the kinetics of batch and continuous cultivation allows you to not only calculate and evaluate the effects of process parameters, but also to forecast those parameters and duration of cultivation to develop a cost-effective production process. Mathematical modeling microorganism cultivation was intensively developed in the second half of the last century. Equations 1–6: () Monod proposed Equation 1 for batch processes in 1942 (1). In that equation, µ and µmax are the specific and maximum…
A Host Cell Protein Assay for Biologics Expressed in Plants
Host cell proteins (HCPs) can be present in significant amounts in biological products through copurification with a recombinant protein-drug substance. Purified active ingredients developed for human use must be free of all contaminants — including residual HCPs — to minimize the incidence of immunogenicity against a drug product or its trace contaminants (1). HCP assays allow for monitoring host-related impurities during product development and process development. Most are in the enzyme-linked immunosorbent assay (ELISA) format for detecting…
Integrity Testing of Ultrafiltration Systems for Biopharmaceutical Applications
Ultrafiltration (UF) is a membrane-based separation technology commonly used in the biopharmaceutical industry for concentration or diafiltration of protein solutions to remove low–molecular-weight (LMW) impurities or exchange buffers. The nominal MW limit of UF membranes ranges from 1,000 Da (1 kDa) to 1,000,000 Da (1,000 kDa). A target product is retained by the membrane while lower-MW solutes or impurities pass through (1). For a target product with a smaller MW than the impurities, separation is accomplished by allowing…
Enhancing Data Quality with a Partly Controllable System at Shake Flask Scale
In bioprocess development, small-scale systems are used to identify appropriate cell lines, media, and feeds before applying more expensive, controlled cultivation systems at larger scales. Process development relies on data generated in such uncontrolled small-scale cultivation systems, so comparability is an issue. Shake flasks are commonly used for small-scale culture of mammalian suspensions. Incubators provide a suitable environment with carbon dioxide (CO2) supply and humidity control and ensure sufficient oxygen transfer and homogenization of cell suspension by appropriate…
Global Marketplace
3D Bioreactor Product: InBreath whole-organ bioreactor Applications: Tissue engineering and regenerative medicine for trachea, esophagus, intestines, blood vessels, and other hollow, tubular organs Features: The autoclavable, GLP-compatible InBreath bioreactor is designed for cell seeding and culturing on intraluminal and extraluminal surfaces of a tubular matrix. A polymer culture chamber houses the scaffold and culture medium for the entire duration of organ generation. Secondary “paddle” elements move with the scaffold holder to mix the culture medium continuously for mass transport and…
IBC’s Inaugural Drug Product Quality Summit
The vast majority of drug shortages — 82% of the 168 products in short supply — are sterile injectables. According to an IMS Institute for Healthcare Informatics report from November 2011, many are linked to fill– finish deficiencies. In addition to supply shortages, medicines can be delayed in reaching patients due to contaminated raw materials, findings of particulates, extractables and leachables, vial stopper and glass problems or interactions with product, and even cross contamination. IBC’s Drug Product Quality Summit is…
Listening to Patients’ Voices
The role of patients in changing the pharmaceutical industry’s research agenda is evolving. Patients are greatly affected by drug R&D, with its potential to provide cures or treatments for a wide range of different medical conditions. But new product development does not always meet all patients’ needs. For example, drugs for Parkinson’s disease most often aim to treat movement disorders, whereas patients are also concerned about pain, sleep problems, lack of bowel and bladder control, and sexual dysfunction…