Manufacturing

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…

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…

Guide to Disposal of Single-Use Bioprocess Systems

Single-use bioprocess systems can provide a range of environmental benefits beyond those of stainless steel systems. Although single-use systems may generate additional solid waste, benefits include reduction in the amount of water, chemicals, and energy required for cleaning and sanitizing as well as avoiding the labor-intensive cleaning processes required with stainless steel systems (1, 2). One of BPSA’s core activities is to educate users and develop guides on issues pertaining to single-use systems. The organization’s disposals subcommittee was chartered to…

Secrets to a Successful Validation Project

Three major elements comprise validation projects in the biopharmaceutical industry: cost, schedule, and quality. If you can work within a budget, complete activities on time, and maintain regulatory-compliant documentation, then you significantly increase your chances for a successful validation project. Here we suggest ways you can improve these essential measurements with the help of a third-party validation team to achieve favorable outcomes. Team Selection The first key is building a validation team. Cohesion is critical for successful project management. All…

It’s Not Whether but Rather What and How to Implement

When considering integration of single-use technologies (SUTs or disposables) into a manufacturing process and facility, a number of criteria should be satisfied. These criteria govern both selection and implementation. Each criterion should be established by due diligence in which end-user requirements and the operation setting are considered carefully. Depending on a facility’s infrastructure and even a company’s business model, end users will define their criteria differently. Companies are driven to single-use technologies because of the simplicity and flexibility they impart…

Reconsidering the Supply Chain

An emerging challenge for biotech companies is understanding the bigger picture: How should manufacturing facilities be configured to link together process technologies? Should plants be highly flexible or focus on process standardization? How would a disruptive new technology affect current supply chains, and how could it be implemented? Meeting the challenge requires a complete and detailed understanding of supply chains. Much current focus in process development is on improving operations, with limited consideration to how improvements affect “big picture” variables.…

Validation of Adventitious Virus Removal By Virus Filtration

Regulatory bodies around the world expect downstream purification processes to demonstrate robust clearance of model adventitious viruses in time for execution of phase 3 clinical trials and product licensure (1,2,3). Model viruses selected for these studies should represent a diversity of viral physicochemical properties, and the clearance methods applied should include orthogonal mechanisms such as clearance based on size alongside chemical inactivation. Virus filtration is a critical unit operation used in numerous purification processes of monoclonal antibodies (MAbs), recombinant proteins,…

Delivery Technology Reenergizes DNA Drug Development

In vivo delivery of DNA-based biopharmaceutical agents encoding proteins of interest (“DNA drugs”) offers a means for the production of protein by target regions of tissue in a subject. This product class derives activity from an ability to induce sustained endogenous protein expression from recipients’ own cells. These unique characteristics are favorable for multiple applications, several of which are now in clinical testing. Therapeutic Proteins: DNA drugs encoding autologous therapeutic proteins could serve as an alternative to long-term therapy based…

Sharing Is What It’s All About

Recently in Washington, DC, two conferences were held on the topics of cell and gene therapy. The California Separation Science Society (CASSS, www.casss.org) hosted a Well-Characterized Biological Products (WCBP) Chemicals, Materials, and Controls (CMC) strategy forum on “Current Practices for Assessing the Comparability and Stability of Gene Therapy Products,” while blocks away, Phacilitate hosted the 2008 Cell and Gene Therapy forum. At the WCBP CMC strategy forum, participants heard the US FDA–CBER perspective on the importance of comparability studies for…

In the Therapeutics Zone

Small molecules are still not providing cures for many diseases, and this is why biological therapies continue to be developed. They often offer greater convenience to patients, as well as longer lasting therapies,” says William Prather, MD, senior vice president of corporate development at the Israeli stem cell company, Pluristem. The therapeutics area at this year’s BIO International Convention will play host to many interesting technologies for producing and improving protein therapeutics, vaccines, and stem cells. Protein Therapies Remain Top…