Manufacturing

Certified Reference Mixtures in Extractables Screening of Polymeric Materials: For Container–Closure Systems and Single-Use Equipment

Plastics have been used for decades in container–closure systems (CCS) for drugs and in single-use (SU) manufacturing equipment for biopharmaceutical processing. Biomanufacturers must comply with national and international laws and regulations that require proof that use of such polymeric materials is safe (1, 2). That necessitates testing for potential biological responses and interactions with drug substances. Comprehensive extractables and leachables (E&L) studies also are required for potential release of undesired compounds from polymers. Extractables tests are performed on materials under…

Regulatory Testing for Cell and Gene Therapies: Meeting the Challenges

Compared with small molecules and other biopharmaceuticals, advanced therapies typically have more complex mechanisms of action and therefore more complex testing requirements. These requirements also change over time as innovators, testing organizations, and regulators apply recent learnings to current projects. When developing a novel cell or gene therapy it is therefore crucial to have a robust, flexible plan for testing your drug. This plan must be sufficient for proving that your drug meets safety standards and other benchmarks, and ultimately,…

The Evolution of Predictive Toxicology: Improving Predictivity Using New-Approach Methodologies

A pharmaceutical’s approval for commercial distribution is contingent on submission of pharmacological and toxicological safety data as defined by regulatory agencies such as the US FDA and ICH. Guidances state that such data can come from in vivo or in vitro studies. The current paradigm works well for collecting critical data about, e.g., a drug’s pharmacological effects and mechanism of action (MoA). However, increasing evidence points to current methods’ inadequacy for predicting a drug’s risks to human patients. Such limitations…

Cold Chain Excellence: Getting Control Over Freezing of Biologics

HOW CONTROLLED FREEZING ENABLES SCALABILITY: Controlling the freezing behavior of drug substance is the ultimate goal in pharmaceutical manufacturing. It opens doors to process reproducibility, consistent quality of the final drug product by maintaining uniform conditions for the biopharmaceuticals during freezing and consequently for frozen storage and shipment. As one of the most essential parameters to achieve control over freezing & thawing bulk, the freezing rate has been considered and evaluated in different tests. The leverage of the ice front…

eBook: Intensifying Processes for Monoclonal Antibodies

The commercial manufacturing success of monoclonal antibodies (MAbs) has become a touchstone of the biopharmaceutical industry. MAbs are so well established that they often are referred to as “traditional” biologics, and well-known MAb processing methods have become a model for processing of other “advanced” or “emerging” therapies. But MAb processing continues to advance as biomanufacturers seek ways to improve efficiencies, lower costs, and (most recently) increase sustainability of facilities. Drug makers are particularly interested in strategies for MAb process intensification.…

Hurdles Ahead for Cell and Gene Therapy Makers

Significant growth of the cell and gene therapy (CGT) pipeline in recent years demonstrates the enormous potential of these modalities to treat or even cure otherwise intractable diseases. Several CGT products have been approved for clinical use over the past five years. More than 75 such products have come to the market around the world so far. They include chimeric antigen receptor (CAR) T-cell therapies that involve genetic engineering of patient cells ex vivo as well as in vivo gene therapies…

Scalability in Cell and Gene Therapy Facilities: How Today’s Developers Are Preparing for Tomorrow’s Commercial Success

Propelled by year after year of record-setting investments and regulatory approvals, cell and gene therapy (CGT) innovators are on track to revolutionize medicine by providing potential cures for many conditions. Now, CGT manufacturers must plan for a future beyond the production constraints of laboratories. What needs to happen now to prepare for a sustainable, commercially viable scale-up process in years to come? To answer that and other important questions about CGT production, my company, the CRB Group, surveyed more than…

Novel Technologies for Advancing Allogeneic Cell Therapies

In many ways, cells are the ultimate therapeutic product. They can integrate and participate in different biologic processes and replace missing biological functions. Cell therapies are dynamic, versatile, and with the appropriate engineering, capable of influencing and correcting disease processes robustly. Cell therapies essentially are living medicines, and their adaptability contrasts with conventional drug modalities that generally have only a single specific target or effect. Because cell therapies are highly complex modalities, their scientific and R&D challenges are different from…

Process Intelligence: Gene Therapy Case Study Shows That the Journey to Improved Capabilities Starts with One Step

The product development team at a gene therapy contract development and manufacturing organization (CDMO) was working on a high-priority drug-substance project for a key client. The material was crucial to that client’s early stage clinical trial, with an immediate value over US$500,000 to both the client and the CDMO. Unfortunately, the bioreactor used in the upstream process — a transfection unit operation for an adenoassociated virus (AAV) vector — had developed an intermittent problem that could force it to shut…

The CRISPR Saga (So Far)

Since January 2016 (with a brief interlude as described below), the Patent Trial and Appeal Board has been attempting to adjudicate the proper inventorship of CRISPR technology in (to date) six separate patent-interference proceedings. (Scientific “priority has been decided, for now, by the awarding of the Nobel Prize in Chemistry to Jennifer Doudna and Emmanuelle Charpentier in 2020; see the “Priority Claims” box). CRISPR-based gene editing was hailed as the “Breakthrough of the Year” in 2015 (1), and the scientific…