Downstream Development

Recent Advances in Endotoxin Removal: An Upgrade to a Traditional Method and a New Adsorption Chemistry

by

Endotoxin contamination has been the bane of the bioprocessing industry since its inception. Endotoxins are everywhere: They are toxic and/or interfere with every type of therapeutic, diagnostic, and research product; they are indestructible within the limits of product tolerance; and they are difficult to remove (1–4). Beyond that, they interact with various biological species in ways that prevent accurate measurement (5, 6). Managing these issues has been a focus of the industry for at least half a century, yet it…

October 19, 2017

Viral Vector Particle Integrity and Purity Analyses in Early Process Development

by , , and

Gene therapy is the transfer of genetic material to a patient’s cells to achieve a therapeutic effect. Therapeutic DNA typically is delivered using a viral vector system, and adenoviruses have been used for this purpose for over 20 years (1–3). Within the past 10 years or so, lentiviruses have shown promise in clinical trials (1–3), and adenoassociated viruses (AAVs) have been used in the first approved gene therapies in the Western world (4). The number of gene therapy applications based…

October 18, 2017

Moving DSC Downstream: Exploiting Differential Scanning Calorimetry As a Process Development Tool

by

The primary goal of biopharmaceutical process development is to determine what steps and conditions will maximize and optimize yields of purified product in the most reproducible, robust, and cost-efficient way. Characterized by high batch-to-batch comparability minimizing economic losses associated with batch failures, success relies on a thorough understanding of a given biological drug. Determining how its activity and stability are affected by processing and how to mitigate and control associated risks is advocated by a quality by design (QbD) approach.…

October 18, 2017

Development Approaches to Adenoassociated Virus Production

by , and

After many years of development, gene therapy is beginning to deliver on its promises in the clinic, in some cases with spectacular outputs. Those clinical successes also have led to an influx of funding and engagement from large pharmaceutical companies, thereby bringing the required financial support and expertise for late-stage clinical developments and product commercialization. Although many initial studies were confined to small patient groups and focused on a range of rare monogenetic diseases, new approaches to gene editing have…

September 19, 2017

Opportunities and Challenges in Biosimilar Development

by , and

A biosimilar biotherapeutic product is similar (but not identical) in terms of quality, safety, and efficacy to an already licensed reference product. Unlike generic small molecules, it is difficult to standardize such inherently complex products based on complicated manufacturing processes. Table 1 describes the main differences between biosimilar and generic drug molecules. The global biosimilar market is growing rapidly as patents on blockbuster biologic drugs expire (Table 2) and other healthcare sectors focus on reduction of costs. Biologics are among…

May 18, 2017

Implementing Quality By Design in Analytical Development: A Case Study on the Development of an Anion-Exchange HPLC Method

by , and

The concept of quality by design (QbD) initially was outlined in ICH Q8 guidance for drug-product development and later in Q11 for drug-substance development (1, 2). Since then, the QbD concept was further expanded to the development of analytical methods. FDA issued a 2015 guidance on analytical procedures and method validation for drugs and biologics (3). Although the agency did not explicitly state the requirement for implementation of QbD in analytical method development, the concept is embedded in its section…

May 18, 2017

Conditional/Inducible Gene-Expression Mouse Models Using Advanced Gene Editing

by , , , and

Transgenic mouse models have been an essential part of biomedical research for many decades. They have provided valuable insights in developmental biology, gene regulation, and our understanding of the genetic basis of human disease. And they play a critical role in drug discovery and development. Traditional methods to generate these mouse models entailed a milieu of disadvantages: e.g., low efficiency, high incidence of undesirable recombination outcomes, randomly and multiply inserted genes of interest, ectopic expression, gene silencing, and insertional mutations…

March 20, 2017

Accelerated Development Through Strategic Analytical Partnerships

by and

The analytical field for biologics has evolved greatly over the past 30 years, and the underlying growth has shifted from biopharmaceutical companies to contract research organizations (CROs). The global biopharmaceutical market is growing annually at >15%, making it the largest and consistently fastest growing segment of the healthcare industry with annual sales in excess of US$200 billion. Contract manufacturing organizations (CMOs) are expanding capacity by building new cost-efficient facilities, reflecting market demand. Many product sponsors are outsourcing, some even increasing…

March 14, 2017

Outsourcing Biosimilar Development

by and

As the debate continues over the high cost of pharmaceutical treatment options, the development of biosimilars continues to play a dominant role in that discussion and will be an important part of the solution. Biosimilar companies are working at a feverish pace to develop the next generation of follow-on products. Outsourcing to a growing group of contract development and manufacturing organizations (CDMOs) is a key strategy for savvy developers to accelerate their products’ launch. Finding the right CDMO isn’t an…

March 14, 2017

Introduction: Process Issues in Cell, Gene, and Tissue Therapies

by

It’s hard to believe that just six years ago, BioProcess International published its first cell therapy supplement, which included just one article on “cell therapy bioprocessing†(1). At the time, most such processing was conducted in special clinical laboratories and academic institutions. As BPI continued to cover this relatively new segment of the biopharmaceutical industry, we heard more about “the product is the process†and “scale out instead of scaling up.†After many trials, errors, and milestones, regenerative medicine has…

February 13, 2017