According to a 2017 industry report, 74% of biopharmaceuticals currently in development (phase 1–3) are possible first-in-class medicines. 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 patient care. Authors and experts in this Featured Report discuss how meeting and optimizing specific process needs for those products will be imperative to keep pace with innovation.
Introduction: Emerging Therapies Come of Age
A growing number of companies and research centers are working on next-generation biotherapies. Such products are just beginning to indicate their potential in clinical trials. The challenge now is to develop cost-effective and scalable manufacturing solutions to meet projected demands. The introduction provides an overview of the status of bispecific antibodies, antibody fragments, ADCs, and fusion proteins as reviewed by report authors.
Development Approaches to Adenoassociated Virus Production
Tony Hitchcock, Vera Lukashchuk, and Kevin Bowes
The clinical successes of gene therapies so far have led to further progress toward large-scale production. Efforts have focused on the potential use of adenoassociated virus medicated gene therapy for broader therapeutic applications, including immunotherapy. The authors discuss current approaches to transient AAV production (including transfection), vector design, and virus production.
Process Needs of Antibody Fragments and Bispecifics
Maribel Rios, with Jonathan Royce
This discussion covers the current progress of meeting the specific manufacturing needs of both antibody fragments and bispecific antibodies for therapeutic use. Both types offer advantages over full-length antibodies, but their preparation and achieving their unique structure can be challenging.
Controlling Glycosylation in Fusion Protein Manufacturing
to Generate Potent Biobetters
Stefan R. Schmidt
Some proteins can be engineered from fusion genes, developed by joining two different genes. Such proteins can be used in therapeutic applications that have extended half-lives, improved efficacies, reduced immunogenicity or toxicity, and enhanced pharmacokinectics. Several fusion proteins already have been marketed as biobetters. Schmidt discusses both N-linked and O-linked glycosylation to enhance circulation times and improve efficacy of therapeutic proteins. Both upstream and downstream processing approaches for controlling glycosylation are addressed.
Developments in Antibody-Drug Conjugates
Maribel Rios, with Thomas Ryall
As head of technical operations at ImmunoGen, Ryall discusses his company’s technologies and platform approaches in antibody-drug conjugate development, which already has been used in the development of approved ADC products. He addresses common complications with ensuring site-specific conjugation, off-target toxicity, and the need for increasing potency and homogeneity.