Downstream Processing

Outsourcing of Buffer Preparation Activity Is Increasing

The major fluid products used in bioprocessing — culture media and buffers — are classically prepared in-house by rehydrating (dissolving and mixing) powders purchased from suppliers. Most bioprocessing facilities consider in-house preparation of these fluids to be a core bioprocessing task. However, some companies are outsourcing the work either by purchasing preprepared materials from vendors or hiring contract manufacturing organizations (CMOs) to prepare them. Buffer fluid preparation is one area of downstream production operations that are seeing an increase in…

Special Report: A Strategy for Cost-Effective Capture Using Agarose-Based Protein A Resins

It is well recognized that the cost of Protein A resins is substantial. If a developmental monoclonal antibody (MAb) makes it to marketing approval and manufacturing, the high cost of purification using a Protein A resin is amortized over a large number of purification cycles, and the contribution to cost of goods is reduced to acceptable levels. However, a high percentage of clinical projects will fail, and the Protein A resin will be used only for a small number of…

Innovative Downstream Purification Solutions for Viral Vectors: Enabling Platform Approaches to Advance Gene Therapies

Over the past decade, gene therapy applications and their importance in the biopharmaceutical industry have been increasing. Gene therapies promise versatile treatment options that could revolutionize and transform medicine. As treatment modalities, they offer the possibility of long-term and potentially curative benefits to patients with genetic or acquired diseases. Gene therapies are designed to treat disease by delivering genetic material that encodes a protein with a therapeutic effect into a patient’s cells. It can be used to replace a missing…

Selective and Flexible Chromatography Media: Improving Biopharmaceutical Operational Efficiencies

Continuing development in protein and peptide engineering have produced a broad range of new biological products with improved therapeutic and diagnostic potential. In the development pipeline, more than 900 biologic products target more than 100 diseases (1). Increased manufacturing complexities caused by closely related impurities and requirements to improve process efficiencies and reduce operating costs highlight the need for new approaches in protein purification. Platform-based chromatographic approaches have been successfully applied in separating and purifying monoclonal antibody (MAb) products. But…

Viral Clearance in Antibody Purification Using Tentacle Ion Exchangers

Manufacturers strive toward cost-effective purification of target molecules and a high level of confidence that their biologics are safe and not compromised by the presence of endogenous retrovirus-like particles or adventitious viruses (1). Reliable reduction of viral particles throughout downstream purification processes must be ensured through different techniques such as chemical treatment, filtration, and chromatography. Common monoclonal antibody (MAb) purification schemes use both cation- and anion-exchange chromatography steps (CEX, AEX). Although CEX (to remove product- and process-related impurities) is not…

Continuous Chromatography Is Now Possible for Clinical Manufacturing

Intensified and integrated bioprocess technologies are creating a paradigm shift toward more efficient, higher flexibility facilities for biopharmaceutical manufacturing. Continuous technologies that are designed as single-use systems help to greatly facilitate process intensification, delivering further efficiencies with reduced set-up times and elimination of the need for cleaning and cleaning validation. Chromatography is often considered to be a challenging bioprocess step, which has caused great interest in a simplified, safer solution. Continuous multicolumn chromatography using a single-use flow path is an…

Development of a High-Performance, Integrated, and Disposable Clarification Solution for Continuous Bioprocessing

Current bioprocesses combine fed-batch cell culture with batch-wise downstream processing steps. To achieve integrated upstream and downstream continuous manufacturing, the industry has been in need of a continuous cell separation and clarification solution for bioprocess fluids from bioreactors. The Cadence Acoustic Separator from Pall Life Sciences provides this solution, with continuous first-stage clarification without the need for filter media in a scalable, single-use format with no negative impact on product attributes. The Cadence Acoustic Separator delivers cost and time savings…

Optimizing Continuous Monoclonal Antibody Polishing By Using Coupled Unit Operations

The biopharmaceutical industry is under a great deal of pressure to modernize manufacturing to meet the challenges of production at vastly different scales for niche drugs as well as for expected massive blockbusters, biosimilars, and regional manufacturing. To address these challenges, the biopharmaceutical industry is embracing process intensification through single-use and continuous processing technologies. Implementing these technologies offers increased productivity and manufacturing flexibility and reduces the footprint, capital outlay, and operating costs. Pall Life Sciences has developed several technologies designed…

Clearance of Persistent Small-Molecule Impurities: Alternative Strategies

Small-molecule impurities that bind to and copurify with protein biopharmaceuticals traditionally have been removed using bind-and-elute (BE) chromatography. However, that approach may be undesirable for a number of reasons. For instance, it may present a facility-fit challenge or provide a lower process yield than what is acceptable. A common scenario in which BE chromatography may be undesirable is in removal of unreacted conjugation reagents. Bioconjugates represent an important and growing class of pharmaceuticals that include PEGylated proteins, vaccines, and antibody–drug…

Best Practices for Critical Sterile Filter Operation: A Case Study

A number of regulatory guidelines recommend preuse integrity testing of critical sterilizing liquid filters for aseptic processing (1–3). Before sterilization, a preuse test will confirm that a filter is installed properly and was not damaged during shipment or handling. Performing a preuse test after sterilization detects damage that may have occurred during the sterilization cycle. Testing after sterilization limits risk, so it is a practice applied based on risk assessment. Because it is perceived to reduce business loss risk, preuse…