Both FDA and EMEA guidelines require integrity testing of filters used in processing sterile solutions such as large- and small-volume parenterals (LVPs and SVPs). The same regulatory agencies also require that corresponding test documentation be included with batch product records. PRODUCT FOCUS: PARENTERALSPROCESS FOCUS: DOWNSTREAM PROCESSING, SCALE-UPWHO SHOULD READ: QA/QC, PROCESS ENGINEERS, AND ANALYTICAL PERSONNELKEYWORDS: FILTRATION, INTEGRITY TESTING, VALIDATION, AUTOMATIONLEVEL: BASIC The function of integrity testing is to determine whether a particular filter is within or outside the validated specifications…
Analytical
Carbohydrates and Their Analysis, Part One
A mammalian cell exists, interacts, reproduces, and dies as a result of intricate biochemical and biophysical mechanisms — many of which remain unknown or not fully understood even today. Technological advances have allowed us to investigate the details of organelles and cell membranes, of the types of molecules synthesized within cells, and their distribution and trafficking and the effects they have in their environment. Among the main macromolecules that make up a living cell, DNA and protein structures were studied…
Demonstrating Comparability for Well-Characterized Biotechnology Products
Challenges and approaches in demonstrating comparability of a well-characterized biotechnology product after manufacturing changes can be as varied and complex as the products themselves. Participants at the January 2005 CMC Strategy Forum sought to discuss and agree on common implementation strategies for different manufacturing change scenarios. Development of flexible, comprehensive approaches in strategy development addressed evaluation of critical product characteristics, appropriate process steps to test, numbers of lots and levels of testing required, and assessment of product comparability (e.g., trending…
Process Monitoring in Suspension–Adapted CHO Cell Cultures
Suspension-adapted Chinese hamster ovary cell (CHO-S) cultures are widely used in biotechnological production of recombinant proteins. In fact, such special cell lines have become the standard for this type of biopharmaceutical production (1). The reasons for that include their fast reproduction, high protein expression rate compared with other eukaryotic cells and, above all, the glycosylation patterns generated by the cells (2, 3). PRODUCT FOCUS: Animal cell products (recombinant proteins)PROCESS FOCUS: Production and product developmentWHO SHOULD READ: Process and cell culture…
Integrated Strategies for Clone and Media Formulation Selection
Clone selection techniques used for development of stable, high-expressing recombinant cell lines suitable for robust fed-batch cell culture processes are critical for biopharmaceutical manufacturing. Basal media screening, feed development and addition strategies, and fed-batch bioreactor performance are all intimately tied to overall performance of the clones during scale-up. Serious issues can arise if a high-quality clone is not established, such as low or unstable protein yield and ineffective use of costly resources. PRODUCT FOCUS: Recombinant proteinsPROCESS FOCUS: ProductionWHO SHOULD READ:…
Proteomics Technology Applied to Upstream and Downstream Process Development of a Protein Vaccine
Development and manufacturing of recombinant-protein–based vaccines has in the past few years become very similar to that of other well-documented and well-characterized biological drugs. For investigational vaccines, chemistry, manufacturing, and controls (CMC) information is critical for a successful regulatory filing. The process development and CGMP manufacturing of a recombinant protein drug is on the critical path toward clinical phase 1 dosing and safety studies as well as proof-of-concept clinical studies (1, 2). However, resources invested in this process may be…