Manufacturing

The 2017 World Biological Forum: Successes and Future Trends in Continuous Biomanufacturing

Continuous biomanufacturing was a central topic at the fourth annual World Biological Forum in Oxford, UK, on 26–28 June 2017. A well-rounded lineup of presenters appeared at this forum held in Oxford University’s Lady Margaret Hall, an eclectic location that well captured the historic charm of the university. Delegates were well supported throughout the meeting with generous meals, refreshments, and assistance provided by helpful staff. Papers were presented in Talbot Hall in the center of the college. The stately main…

Introduction: Emerging Therapies Come of Age

According to a 2017 industry report, 74% of biopharmaceuticals currently in development (phase 1–3) are possible first-in-class medicines (those that use a unique mechanism of action), thus representing a potential new pharmacological class of treatment (1). They include regenerative medicines, conjugated monoclonal antibodies (MAbs), and DNA and RNA therapeutics. Some emerging therapies — such as antibody–drug conjugates (ADCs) and biobetters — have been more at the forefront of discussions than others, but all are poised to bring exciting changes to…

Process Needs of Antibody Fragments and Bispecifics: A Discussion with Jonathan Royce of GE Healthcare

Although the number of bispecific antibodies approved so far (two) and antibody fragments either approved or with an investigational new drug (IND) filed (∼20, both antigen-binding and variable) are far below the number of approved and candidate monoclonal antibodies (MAbs), research in both fragments and bispecifics continues to look promising. And as Jonathan Royce, business leader for chromatography resins at GE Healthcare, discusses here, both offer specific therapeutic advantages over MAbs. But manufacturers should be aware that their diverse structures…

Controlling Glycosylation in Fusion Protein Manufacturing to Generate Potent Biobetters

The pipelines of pharmaceutical companies are full of biological drugs. Many of them are innovative therapeutic proteins, but a growing number represent biosimilars and biobetters (Figure 1) (1). Biobetters typically are defined as being “based on innovative biologics but with improved properties” (2). Their development benefits from known therapeutic approaches and mechanisms of action resulting in low risk, fast paths to the clinic and thus lower costs. Superiority is achieved through extended half-life (t1/2), improved efficacy, and reduced immunogenicity or…

Developments in Antibody–Drug Conjugates: A Discussion with Thomas Ryll of ImmunoGen

As a major class of emerging therapies, antibody-drug conjugates (ADCs) already have gained the attention of biopharmaceutical researchers and manufacturers because they combine both the precision of monoclonal antibodies and the potency of highly potent drug compounds. A few ADCs already have entered the market, but many more candidates are progressing through industry pipelines. Platform processes are not yet universal (and it remains to be seen whether they ever will be), but major ADC developers are establishing their own with…

Change Happens: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management (CMC Forum)

In the current global regulatory environment, management and implementation of postapproval CMC changes often can be unpredictable and inefficient. Timelines for change approval can vary from months to years, depending on regional regulatory procedures. Therefore, the challenge in postapproval lifecycle management is to maintain a constant supply of high-quality product while supporting innovation and continual improvement. This was the premise of the CASSS Chemistry, Manufacturing, and Controls (CMC) Strategy Forum held in Gaithersburg, MD, on 20–21 July 2016. The forum…

Polysorbates, Biotherapeutics, and Anaphylaxis: A Review

Rapidly increasing use of monoclonal antibodies (MAbs) in the treatment of neoplastic, autoimmune, and inflammatory diseases has led to a dramatic increase in hypersensitivity reactions worldwide, complicating the use of MAbs as first-line therapies and limiting patient survival and quality of life (1). The origins of anaphylaxis are not well understood, though its mechanism is fairly straightforward (Figure 1). It is usually attributed to some undefined intrinsic property or properties of a biotherapeutic — despite the fact that biotherapeutic formulations…

Continuous Processes: Disposables Enable the Integration of Upstream and Downstream Processing

Despite decades of advancement in characterization analytics, biotherapeutics still are largely defined by the manufacturing processes used to make them. This linking of process to clinical results (and thus to commercial success) has made the biopharmaceutical industry somewhat risk-averse when it comes to the adoption of new technologies. That desire to “derisk” biomanufacturing through better process understanding — as well as the need to adapt to uncertainties in patient population size through process flexibility — in turn drives the need…

The Value of Single-Use and Other Flexible Technologies

The biopharmaceutical industry is adding mammalian cell culture capacity at rates that we haven’t seen in over a decade. Over the past five years (2012–2016), we estimate that industry-wide capacity has increased from 3.4 ML to 4.0 ML, an increase of 18% (1). We estimate that industry-wide capacity will increase over the coming five years (2016–2020) to 5.7 ML, an increase of >40%. Clearly, this growth is a response to the continued increase in demand for biopharmaceutical products and to…

Difficult-to-Express Proteins: Resolving Bioprocessing Challenges with a Scalable Perfusion Bioreactor

Recent advances in protein engineering have identified new classes of complex biotherapeutics that challenge existing manufacturing platforms. These products have unique cell culture requirements that make them difficult to manufacture cost effectively. Industry standard bioprocessing platforms include large-scale (1,000–5,000 L) batch and fed-batch stirred-tank bioreactors. Historically, the powerhouse molecule of the biologics industry has been human IgG, which necessitates those large-scale platforms. Difficult-to-express proteins and other new modalities (including precision medicine and orphan drugs) have increased pressure on manufacturers to…