Manufacturing of Biodrugs

Abstract

Biodrugs (biologics) are much more complex than chemically synthesized drugs because of their structural heterogeneity and interactions within a given biologic system. The manufacturing process in the biodrug industry varies with each type of molecule and is far more elaborate and stringent due to the use of living organisms and complex substrates. Product purity and altered structural characteristics leading to potential immunogenicity have often been of concern when establishing quality and safety in the use of biodrugs. Regulatory compliance in manufacturing and commercialization of biodrugs involves quality control, quality assurance, and batch documentation. Many factors such as host cell development, cell bank establishment, cell culture, protein production, purification, analysis, formulation, storage, and handling are critical for ensuring the purity, activity, and safety of the finished product. Good Manufacturing Practice (GMP) for biodrugs has been developed in certain regions such as the EU, US, and Japan. Due to differences in manufacturing methods and systems, product-specific GMP guidelines are evolving. In general, there are variations in GMP guidelines between countries, which lead to difficulty for the manufacturers in conforming to different standards, thus entailing delays in the commercialization of biodrugs. There is a need to develop a unified regulatory guideline for biodrug manufacturing across various countries, which would be helpful in the marketing of products and trade. This review deals with the comparative framework and analysis of GMP regulation of biodrugs.

A Brief Reminder of Systems of Production and Chromatography-Based Recovery of Recombinant Protein Biopharmaceuticals

“…According to the established requirements, biologics produced by different expression systems must be tested for toxicity potential or viral presence (viral clearance processes). The detailed processes of manufacturing and validating biodrugs with regard to host cell type, protein drug type, and acceptable levels of different residual molecules are discussed in an excellent review by Sahoo et al (2009) [48].…”

Regulatory Perspectives on Biopharmaceuticals for Chronic Inflammatory Diseases in North Africa: A Narrative Review

“…Biologic agents are large molecules derived from living cells, usually manufactured using recombinant DNA or other biotechnologies. These agents (i.e., reference, originator, or innovator products) have greater complexity than chemically synthesized drugs because of their structural heterogeneity and specific activity within biologic systems, and their cost is usually higher [5,14,15]. Biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) such as anti-TNFα agents are very effective in the treatment of chronic immunoinflammatory diseases [4,16,17], but access is limited in many regions, including North Africa, partly because of cost constraints [18,19].…”

Manufacturing DTaP-based combination vaccines: industrial challenges around essential public health tools

“…As well as the Good Manufacturing Practices (GMP) and Quality Assurance requirements applicable to all biodrugs and more specifically to vaccines (15)(16)(17)(18)(19), there are numerous manufacturing and quality control specificities and challenges associated with these complex products (20-25, 101,102) compared to traditional pharma products (26) or even to some biological products such as humanized monoclonal antibodies obtained from recombinant technology (27) or ribonucleic acids (28).…”