Manufacturing

Determining Control Chart Limits for Continued Process Verification with Autocorrelated Data

Control charts are used to assist in process monitoring activities. They use an estimate of central tendency (the overall mean) and variation (the standard deviation). Sample standard deviations (S) tend to underestimate process standard deviations (σ) when they are calculated using limited sample sizes of independent results (1). For this reason, the unbiasing constant c4 is used as a divisor when calculating Shewhart control-chart limits. If data used for control charting are positively autocorrelated, that tends to underestimate σ further…

Antibody Derivatives: Deconstructing MAbs for the Next Wave of Biotherapies

Although they make up the largest and most successful category of biopharmaceuticals so far, monoclonal antibodies (MAbs) suffer from certain disadvantages. Some companies are addressing those limitations by deconstructing MAb molecules to create new emergent therapeutics. These antibody derivatives include: antibody fusions and fragments, bispecifics, trifunctional antibodies, and more. This eBook combines market analysis from consultant David Orchard-Webb with technical discussion from BPI cofounder and senior technical editor Cheryl Scott. It also includes commentary from editorial advisor Michiel Ultee and…

The Role of Single-Use Polymeric Solutions in Enabling Cell and Gene Therapy Production: Part 1: Introduction and Manufacturing Process

by Bio-Process Systems Alliance Cell and Gene Therapy Committee The Bio-Process Systems Alliance (BPSA) was formed in 2005 as an industry-led international industry association dedicated to encouraging and accelerating the adoption of single-use manufacturing technologies used in the production of biopharmaceuticals and vaccines. Corporate members include plastic-equipment suppliers, service providers, and users in the biopharmaceutical industry who share this mission. A key focus of BPSA’s core activities is to educate its members and others through sharing of information and development…

A Perspective on GMPs for Cellular Therapy Commercialization

Cellular therapies can be classified by therapeutic indication, by cell types, and by whether cells are taken from and administered to the same individual (autologous) or derived from healthy donors (allogeneic). Regulatory classification of cellular therapies differentiates among minimally manipulated cells for homologous use, transplants or transfusions, and cells that are more than minimally manipulated and regulated as medicines. Medical cellular therapies must meet quality, safety, and efficacy standards to obtain marketing authorization (1–8). Such therapies can be subdivided into…

Scientific and Technological Advancements in Applications of Single-Use Technology: A Conference Report

Single-use technology (SUT) has been used increasingly both in clinical and commercial biomanufacturing (1). Proven major advantages include relatively low capital investment, elimination of batch-to-batch cross contamination and reuse cleaning validation efforts, flexibility in manufacturing, and shortened product lifecycles. However, some challenges and barriers to implementation remain: Consumables costs are increasing. Specific regulatory guidance is lacking, as is component interchangeability and standardization. And few if any leak-proof components/systems are available. International groups and associations focused on setting best practices and…

Cell and Gene Therapy Data Management: Solutions to Address Complex Challenges

At the Phacilitate Leaders World and World Stem Cell Summit 2019, held 22–25 January, Steve Goodman (head of drug product manufacturing at bluebird bio) and Robert Di Scipio (CEO of Skyland Analytics) shared the podium to address what the product and process data-management ecosystem looks like for cell and gene therapy (CGT) development and manufacturing. A starting point for their presentation was that CGT development presents significant data challenges: capturing and analyzing product development and manufacturing data, tracking the collection,…

Is the QbD Toolbox Ready for Cell and Gene Therapies? Integrating Patient Outcomes into Manufacturing Cell and Gene Therapy Bioproducts

In their lifecycle development and manufacturing models, biotechnology products and the biopharmaceutical industry have been founded on principles originating from the pharmaceutical small-molecule industry. Such principles define clinical programs that establish risk benefits of a dosage and its delivery system on healthy individuals and patients. A company then develops a process to manufacture that product consistently over several years. Product quality attributes set through manufacturing controls are expected to ensure patient outcomes in terms of safety and efficacy and deliver…

Introduction: Drug Product Discussions

Quality by design (QbD), risk management, and new technologies are shaping biologics formulation work in the 21st century. We saw much evidence of this at the BioProcess International Conference and Exhibition in Boston last fall, where a wide range of talks filled the Drug Product, Fill–Finish, and Formulations track during the week after Labor Day. Dingjiang Liu (Regeneron) offered a high-level discussion from the BioPhorum Development Group (BPDG) on “An Intercompany Perspective on Biopharmaceutical Product Robustness Studies.” Such studies ensure…

Early Stage Development of Advanced Formulations in the Drug Development Process Provides Competitive Advantages: Survey Predicts That Drug Product Formulation Recognition and Budgets Will Increase Significantly

New antibody formats and aggregate-prone, subcutaneously administered protein therapeutics present biopharmaceutical companies with major challenges regarding protein stability and aggregation. At the same time, protein stability often is not given enough attention in early stages of development. Protein aggregation reduces drug activity so that increasing doses are needed to achieve the same desired effect. Even worse, protein aggregates can induce immunogenecity that endangers patients and compromises product approval. A market study presented for the first time at the Bio-Europe 2018…

Manufacturing Insights: Interviews from BWB 2018 Highlight Perspectives on Streamlining Manufacturing Timelines

Addressing manufacturing and technologies strategies to accelerate market entry is one of BPI’s highlighted themes for 2019. In partnership with our conference colleagues in Informa’s KNect365 division, this already has been a shared theme, reflecting the general goals of the industry and related advice from its regulators. BPI’s summer 2018 preconference ebook included interviews by Dan Stanton (editor, BioProcess Insider) with speakers previewing their talks for the BPI Conference in Boston on 7 September 2018. Two of those conversations focused…