Biologic medicines have brought extraordinary clinical benefits to patients living with difficult conditions such as cancer and autoimmune and ophthalmic diseases. But such therapies are expensive, accounting for about 43% of pharmaceutical spending in the United States (1). The Biologics Price Competition and Innovation Act of 2009 (BPCIA) created a regulatory pathway for a class of biologics called biosimilars, which replicate branded biologic drugs at lower cost (2, 3). The BPCIA was designed to provide greater access to biologics by…
Manufacturing
High Precision: Automated Aseptic Filling of Small Volumes
Market experts recommend automated filling systems for drug developers seeking to reach the next level in drug-substance management. Many companies are starting automation initiatives, which suggests an overall trend towards automated filling. The stakes are high. Increased process deviation in fluid management can lead to increased loss of valuable biopharmaceutical products. Automated and standardized aliquoting of biopharmaceutical drug substances into single-use bioprocess containers simplifies the manufacturing process while improving throughput, speed, and filling accuracy. Fill out the form below to…
Purpose-Built Viral-Vector Facility Construction: Applying Quality and Engineering Controls
In this report, Avid shares its approach to producing high-quality, safe, and effective viral vectors for use in gene therapy and vaccine applications. The company is dedicated to minimizing the risks for, and associated high costs of cross-contamination and contamination during manufacture of viral-vector products. To this end, the contract development and manufacturing organization (CDMO) is establishing a rigorous quality control program as it completes its new facility. In 2021, Avid began building a 53,000-ft2 site in Costa Mesa, CA,…
Using Regulatory T Cells for Treatment of Type 1 Diabetes, Part 1
During the January 2023 Advanced Therapies Week in Miami, FL, Leonardo Ferreira, an assistant professor from the Medical University of South Carolina, spoke about his team’s work in developing chimeric antigen receptor (CAR) regulatory T cells (Tregs) as living therapeutics for type 1 diabetes. Ferreira has focused on type 1 diabetes since 2016, when he undertook postdoctoral work at the University of California at San Francisco under Qizhi Tang and Jeff Bluestone before continuing his research at his own laboratory…
Leveraging Material-Binding Recombinant Proteins: A Novel Approach to Tissue Regeneration
In March 2023, I took the opportunity to speak with Luis Alvarez about the founding of Theradaptive. The company specializes in engineering recombinant proteins, with an initial focus on developing therapeutics for regeneration of soft, vascular, and bone tissue. “Theradaptive grew out of my thinking about combat injuries,” Alvarez told me. Before earning a doctoral degree in biomedical engineering from the Massachusetts Institute of Technology and working as cofounding deputy director of the US Department of Defense’s regenerative medicine program,…
Overcoming the Digital Divide: Leveraging Intelligent Automation and Informatics Expertise
Shifting to a digital regulatory environment is forcing pharmaceutical companies to confront knowledge gaps across key research and development (R&D) functions. As health authorities streamline information exchange through data standardization, the separation between regulatory operations and other functions within the pharmaceutical industry begins to blur. By advancing implementation of ISO identification of medicinal product (IDMP) standards, companies are improving interoperability and information sharing among key clinical, pharmacovigilance, quality, manufacturing, and supply-chain–logistics teams. However, a company’s important regulatory and strategic planning…
Biopharma 4.0 — the Talent Evolution
Biopharma 4.0 refers to applications of data and digital technologies to biotherapeutic manufacturing. Technological advances now enable the internet and its embedded systems to serve as a nucleus through which biomanufacturers can integrate production lines and processes across organizational boundaries, thereby forming a networked and agile value chain. Solutions under the industry 4.0 umbrella include • platforms for “smart” manufacturing made possible by the internet of things (IoT) • artificial intelligence (AI) • systems for process automation • technologies for…
Quantitative Risk Assessment of Limits for Residual Host-Cell DNA: Ensuring Patient Safety for In Vitro Gene Therapies Produced Using Human-Derived Cell Lines
Viral-vector gene therapies (GTs) manufactured from cell-substrate production systems can contain residual amounts of host-cell DNA (hcDNA), which in a final product presents safety risks to treated patients. Therefore, drug manufacturers monitor and control residual hcDNA levels in purified products (1, 2). The US Food and Drug Administration (FDA) and other global regulatory agencies recommend tight, quantifiable limits for hcDNA levels: 10 ng/dose, with DNA fragments smaller than the functional gene size of 200 base pairs (bp) (3). However, because…
Going Big in Cold-Chain Management: Anticipating Challenges and Finding Solutions for Large Volumes
Bulk drug substances (BDS) often require frozen storage to preserve the integrity of biological material. Cold-chain management is particularly important given recent trends toward increasing globalization and decentralization and diversifying modalities. A secure cold chain is essential for maintaining a product’s critical quality attributes (CQAs) — such as drug product stability, integrity, and purity — and to prevent costly product losses. Scaling Up the Cold Chain Frozen storage at commercial scale presents its own challenges; facilities must be able to…
Strengthening Data Management and Integrity for CGT Applications
The specialized nature of cell and gene therapies (CGTs) requires that they be delivered to single patients or in low batch numbers. Manufacturing CGTs at scale is critical to industry success, but doing so at an economically viable cost is a key obstacle. Today’s therapies cost between US$400,000 and $3.5 million per patient, largely because of the need for highly skilled workers to deliver those innovative drugs. The CGT industry has innovated across all areas of production, from collection of…