APR Sept/Oct 2023 - 52

»
MICROBIOLOGY
»
Standardized, Scalable
And Efficient: Producing
Recombinant Factor C to
Quality Standards
Tim Sandle
Head of GxP Compliance and Quality Risk Management
Bio Products Laboratory Limited
Introduction
The shift in the endotoxin reagent industry away from reagents
sourced from the horseshoe crab towards reagents produced using
recombinant technology has been occurring along a rapid and, most
probably, inescapable trajectory. This is in the form of recombinant
factor C (rFC) based on the gene sequence of the horseshoe crab and
fluorimetric detection (or, in the case of one manufacturer, replicating
the entire cascade through the use of recombinant protein technology
with the exclusion of the glucan-triggered factor). Concerns over the
variability of animal derived lysate (influenced by the age, sex, location
and season of horseshoe crab harvest)1
mortality2,3
as well as boosting sustainability,4
and reducing the risk of animal
have been the leading
drivers propelling this change.5 The basis for the use of recombinant
reagent is to provide a reagent that reacts in the same way as the
natural cascade within the North American (Limulus) and Asian
(Tachypleus) horseshoe crabs.
By way of a marker, in 2020 this author wrote in American Pharmaceutical
Review: " This somewhat gradual process is attributable to a clash
between drivers (seeking to conserve horseshoe crabs, albeit with the
mortality rate an imprecise and sometimes underreported figure) and
points of hesitancy (regulatory uncertainty, lack of standardization,
imprecise validation requirements and so on). " 6
The text was written
upon publication of the European Pharmacopeia monograph
describing the use of recombinant factor C. Further progress has now
been made with each of the main endotoxin reagent manufacturers
(as well as some emergent entrants) now offering a recombinant factor
C product. To serve the needs of the pharmaceutical and healthcare
sectors, the factor C needs to be standardized, produced to scale,
purified, characterized, and be of the appropriate quality. This article
looks at the variables that affect these criteria.
Evolution of Recombinant Factors as
Test Reagents
This path towards a recombinant product has its origins in advances
with our understanding of the LAL test reaction. In 1986 researchers
52 |
| September/October 2023

APR Sept/Oct 2023

Table of Contents for the Digital Edition of APR Sept/Oct 2023

INSIDER INSIGHT - From Guidelines to Standards: Why Comprehensive AI Regulation is Essential to Spurring Innovation
BIOPHARMACEUTICAL - Aseptic Process Simulation: Cell and Gene Therapy Manufacture
FORMULATION & DEVELOPMENT - Challenges of Analytical Validation for ATMPs
QC Corner - The Intricacies of Testing for Mycoplasmas in Cell Culture Systems
MICROBIOLOGY - Standardized, Scalable And Efficient: Producing Recombinant Factor C to Quality Standards
FORMULATION AND DEVELOPMENT - R Code to Estimate Probability of Passing USP Dissolution Test
FORMULATION AND DEVELOPMENT - Cloud Computing for Drug Discovery: The Time is Now
CGT CIRCUIT - Navigating the Complex Testing Strategies for Viral Vector-based Gene Therapies
MANUFACTURING - Simplifying Finished Product Manufacturer Site Transfer Variations
FORMULATION AND DEVELOPMENT - Advancing Regulatory Compliance with Natural Language Processing
DRUG DELIVERY - Finding a Greater Vantage Point for Creating Green Therapies
WHITEPAPER - Microbial Testing for the Pharmaceutical Industry
Facility Tour - Eurofins BioPharma Product Testing
ROUNDTABLE - Drug Delivery
MANUFACTURING - Accelerating Biologics R&D with Unified Software and Data Flows
An Interview with Jason Downing, Senior Product Manager, TriLink BioTechnologies®
FORMULATION AND DEVELOPMENT - The Role of Data in the Pharmaceutical Lifecycle
BIOPHARMACEUTICAL - Uniting Quality Expectations on Reinvigorated Biopharma Campuses
WHITEPAPER - VITAMIN C – Tableting with LUBRITAB® RBW Lubricant
WHITEPAPER - Leveraging Analytical Technology Process for CMC
BIOPHARMACEUTICAL - Maximizing the Commercialization Potential of Cell and Gene Therapies
MICROBIOLOGY - Comments on Aseptic Process Simulation (APS) in the New EU GMP Annex 1
VENDOR VIEWPOINT - Continuous & Intervention-Free Microbial Monitoring
APR Sept/Oct 2023 - Cover1
APR Sept/Oct 2023 - Cover2
APR Sept/Oct 2023 - 1
APR Sept/Oct 2023 - 2
APR Sept/Oct 2023 - 3
APR Sept/Oct 2023 - 4
APR Sept/Oct 2023 - 5
APR Sept/Oct 2023 - 6
APR Sept/Oct 2023 - 7
APR Sept/Oct 2023 - 8
APR Sept/Oct 2023 - 9
APR Sept/Oct 2023 - 10
APR Sept/Oct 2023 - 11
APR Sept/Oct 2023 - 12
APR Sept/Oct 2023 - 13
APR Sept/Oct 2023 - 14
APR Sept/Oct 2023 - 15
APR Sept/Oct 2023 - 16
APR Sept/Oct 2023 - 17
APR Sept/Oct 2023 - 18
APR Sept/Oct 2023 - 19
APR Sept/Oct 2023 - 20
APR Sept/Oct 2023 - 21
APR Sept/Oct 2023 - 22
APR Sept/Oct 2023 - 23
APR Sept/Oct 2023 - 24
APR Sept/Oct 2023 - 25
APR Sept/Oct 2023 - 26
APR Sept/Oct 2023 - 27
APR Sept/Oct 2023 - 28
APR Sept/Oct 2023 - 29
APR Sept/Oct 2023 - 30
APR Sept/Oct 2023 - INSIDER INSIGHT - From Guidelines to Standards: Why Comprehensive AI Regulation is Essential to Spurring Innovation
APR Sept/Oct 2023 - 32
APR Sept/Oct 2023 - 33
APR Sept/Oct 2023 - BIOPHARMACEUTICAL - Aseptic Process Simulation: Cell and Gene Therapy Manufacture
APR Sept/Oct 2023 - 35
APR Sept/Oct 2023 - 36
APR Sept/Oct 2023 - 37
APR Sept/Oct 2023 - 38
APR Sept/Oct 2023 - 39
APR Sept/Oct 2023 - 40
APR Sept/Oct 2023 - 41
APR Sept/Oct 2023 - 42
APR Sept/Oct 2023 - 43
APR Sept/Oct 2023 - FORMULATION & DEVELOPMENT - Challenges of Analytical Validation for ATMPs
APR Sept/Oct 2023 - 45
APR Sept/Oct 2023 - 46
APR Sept/Oct 2023 - 47
APR Sept/Oct 2023 - 48
APR Sept/Oct 2023 - 49
APR Sept/Oct 2023 - QC Corner - The Intricacies of Testing for Mycoplasmas in Cell Culture Systems
APR Sept/Oct 2023 - 51
APR Sept/Oct 2023 - MICROBIOLOGY - Standardized, Scalable And Efficient: Producing Recombinant Factor C to Quality Standards
APR Sept/Oct 2023 - 53
APR Sept/Oct 2023 - 54
APR Sept/Oct 2023 - 55
APR Sept/Oct 2023 - FORMULATION AND DEVELOPMENT - R Code to Estimate Probability of Passing USP Dissolution Test
APR Sept/Oct 2023 - 57
APR Sept/Oct 2023 - 58
APR Sept/Oct 2023 - 59
APR Sept/Oct 2023 - 60
APR Sept/Oct 2023 - 61
APR Sept/Oct 2023 - FORMULATION AND DEVELOPMENT - Cloud Computing for Drug Discovery: The Time is Now
APR Sept/Oct 2023 - 63
APR Sept/Oct 2023 - 64
APR Sept/Oct 2023 - 65
APR Sept/Oct 2023 - 66
APR Sept/Oct 2023 - 67
APR Sept/Oct 2023 - CGT CIRCUIT - Navigating the Complex Testing Strategies for Viral Vector-based Gene Therapies
APR Sept/Oct 2023 - 69
APR Sept/Oct 2023 - MANUFACTURING - Simplifying Finished Product Manufacturer Site Transfer Variations
APR Sept/Oct 2023 - 71
APR Sept/Oct 2023 - 72
APR Sept/Oct 2023 - 73
APR Sept/Oct 2023 - FORMULATION AND DEVELOPMENT - Advancing Regulatory Compliance with Natural Language Processing
APR Sept/Oct 2023 - 75
APR Sept/Oct 2023 - 76
APR Sept/Oct 2023 - 77
APR Sept/Oct 2023 - DRUG DELIVERY - Finding a Greater Vantage Point for Creating Green Therapies
APR Sept/Oct 2023 - 79
APR Sept/Oct 2023 - 80
APR Sept/Oct 2023 - 81
APR Sept/Oct 2023 - WHITEPAPER - Microbial Testing for the Pharmaceutical Industry
APR Sept/Oct 2023 - 83
APR Sept/Oct 2023 - 84
APR Sept/Oct 2023 - 85
APR Sept/Oct 2023 - Facility Tour - Eurofins BioPharma Product Testing
APR Sept/Oct 2023 - 87
APR Sept/Oct 2023 - 88
APR Sept/Oct 2023 - ROUNDTABLE - Drug Delivery
APR Sept/Oct 2023 - 90
APR Sept/Oct 2023 - 91
APR Sept/Oct 2023 - MANUFACTURING - Accelerating Biologics R&D with Unified Software and Data Flows
APR Sept/Oct 2023 - 93
APR Sept/Oct 2023 - An Interview with Jason Downing, Senior Product Manager, TriLink BioTechnologies®
APR Sept/Oct 2023 - 95
APR Sept/Oct 2023 - FORMULATION AND DEVELOPMENT - The Role of Data in the Pharmaceutical Lifecycle
APR Sept/Oct 2023 - 97
APR Sept/Oct 2023 - 98
APR Sept/Oct 2023 - BIOPHARMACEUTICAL - Uniting Quality Expectations on Reinvigorated Biopharma Campuses
APR Sept/Oct 2023 - 100
APR Sept/Oct 2023 - 101
APR Sept/Oct 2023 - WHITEPAPER - VITAMIN C – Tableting with LUBRITAB® RBW Lubricant
APR Sept/Oct 2023 - 103
APR Sept/Oct 2023 - WHITEPAPER - Leveraging Analytical Technology Process for CMC
APR Sept/Oct 2023 - 105
APR Sept/Oct 2023 - 106
APR Sept/Oct 2023 - BIOPHARMACEUTICAL - Maximizing the Commercialization Potential of Cell and Gene Therapies
APR Sept/Oct 2023 - 108
APR Sept/Oct 2023 - 109
APR Sept/Oct 2023 - MICROBIOLOGY - Comments on Aseptic Process Simulation (APS) in the New EU GMP Annex 1
APR Sept/Oct 2023 - 111
APR Sept/Oct 2023 - 112
APR Sept/Oct 2023 - 113
APR Sept/Oct 2023 - VENDOR VIEWPOINT - Continuous & Intervention-Free Microbial Monitoring
APR Sept/Oct 2023 - 115
APR Sept/Oct 2023 - 116
APR Sept/Oct 2023 - 117
APR Sept/Oct 2023 - 118
APR Sept/Oct 2023 - 119
APR Sept/Oct 2023 - 120
APR Sept/Oct 2023 - Cover3
APR Sept/Oct 2023 - Cover4
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