APR March 2024 - 8

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BIOPHARMACEUTICALS
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Getting to GMP-Quality Biotherapeutics From Today's
Bench-Scale Continuous Manufacturing Systems:
A Gap Analysis
Simon Hawdon,1
Allan Watkinson,2
CPI
Sean Ruane,1
Rob Noel,5 Martin Glenz,6
2Labcorp
3AMAT
4BiologIC
5Biopharm Services
6Cytiva
Introduction
CPI Biologics, in collaboration with Cytiva, SCIEX, BiologIC
Technologies, and Biopharm Services, have developed a benchscale
demonstration of continuous processing that operates from
the perfusion bioreactor through the downstream processing steps,
to finish with a formulated high-concentration mAb product.1
The
potential for this development system to be adapted to GMP readiness
has been analyzed and gaps identified. This report summarizes the
gap analysis in the hope of provoking wider discussion in the industry,
leading to further developments to capitalize on the potential of
intensified manufacturing technologies and improve the availability
of biotherapeutics to patients.
CPI Continuous Processing Lab
The continuous processing lab at CPI consists of a series of
interconnected unit operations. These are, in order, perfusion
bioreactor, alternating tangential flow filtration (ATF) for cell
retention, Protein A capture operated via periodic counter current
chromatography, low pH virus inactivation, depth and sterile filtration,
flow-through anion exchange chromatography (AEX), and bind and
elute cation exchange chromatography (CEX) polishing steps (both
operated in alternating mode without interconnection of columns),
virus filtration, inline diafiltration, and inline concentration.
Biologic Technologies have developed a novel mass balancer and
mass router to manage the flow between unit operations. The mass
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| March 2024
Residence Time Distribution
The mass balancer adds a degree of complexity to the process but
also simplifies the challenge of monitoring product residence time
distribution. Residence time distribution is not an issue in batch
processing, where the product is processed through one operation
and captured in a single tank before the next unit operation begins.
The material in the hold tanks between unit operations is considered
homogenous. However, in continuous processing, product flows
directly to the next unit operation before the previous one has
processed all the material.
router enables the switching of input and output feed streams for
priming and cleaning of flow paths, as well as diversion of material to
waste or to quarantine material. The mass balancer enables a direct
connection between unit operations with minimal holdup volume,
resulting in the ideal scenario of near " one piece flow " . Normally this
is a challenge, as unit operations are driven by their own system
pumps. Slight differences in the flow rates when directing flow from
one pump to another can cause pressure build-up if the first pump is
operating faster than the second. Alternatively, if the second pump is
operating at a faster flow rate than the first, low pressure can induce
cavitation. To overcome this, the mass balancer can operate " on the fly "
to instantaneously add buffer if the downstream pump is demanding
a higher flow rate than the upstream pump. Where the downstream
pump is operating more slowly than the upstream pump, a fraction
of the flow can be diverted to waste to balance the volumetric
throughput of the two pumps.
Matt McEwan,3
Liam Nattrass,1
Nick Rollings,4
John Welsh, 6
Ruth de la Fuente Sanz,6 and Mark Schofield6
1

APR March 2024

Table of Contents for the Digital Edition of APR March 2024

Message from the Editor
Editorial Advisory Board
BIOPHARMACEUTICALS - Getting to GMP-Quality Biotherapeutics From Today’s Bench-Scale Continuous Manufacturing Systems: A Gap Analysis
MICROBIOLOGY - Critical Behavioral Attributes and the Application of COM-B Framework in Aseptic Processing
FORMULATION AND DEVELOPMENT - Use of AUC in AAV Analysis in a GMP Setting
FORMULATION AND DEVELOPMENT - Precision Medicine in Clinical Trials: A Statistical Perspective
An Interview with Dan Smithey, PhD President & CEO, Serán
FORMULATION AND DEVELOPMENT - Still Early Days for AI in Drug Discovery...Says Who?
QC Corner - Enhancing Material and Equipment Availability in Production Isolators
BIOPHARMACEUTICALS - Technologies for Aseptic Filling: The Choice is Clear
Vendor Viewpoint - Data Integrity and Rapid Micro Methods: Transforming to a Modern Microbiology Lab
MICROBIOLOGY - Bacterial Spore Formers in Disinfectant Efficacy Testing
Partner Perspective - Nanoparticle Technologies: Enablers for Ocular Drug Delivery
DRUG DELIVERY - Your Nails and You
DRUG DEVELOPMENT - Battling Exorbitance: High Costs in Sickle Cell Gene Therapies and the Imperative of Global Patient Registries for Equity
FORMULATION AND DEVELOPMENT - How Pharma Companies Are Solving Regulatory Challenges with AI-based Technology
Event Preview - CPHI North America
Event Preview - Excipient World 2024
P.I.N. Points
Advertiser's Index
APR March 2024 - CoverTip01
APR March 2024 - CoverTip02
APR March 2024 - Cover1
APR March 2024 - Cover2
APR March 2024 - 1
APR March 2024 - 2
APR March 2024 - 3
APR March 2024 - 4
APR March 2024 - 5
APR March 2024 - Message from the Editor
APR March 2024 - Editorial Advisory Board
APR March 2024 - BIOPHARMACEUTICALS - Getting to GMP-Quality Biotherapeutics From Today’s Bench-Scale Continuous Manufacturing Systems: A Gap Analysis
APR March 2024 - 9
APR March 2024 - 10
APR March 2024 - 11
APR March 2024 - 12
APR March 2024 - 13
APR March 2024 - MICROBIOLOGY - Critical Behavioral Attributes and the Application of COM-B Framework in Aseptic Processing
APR March 2024 - 15
APR March 2024 - 16
APR March 2024 - 17
APR March 2024 - 18
APR March 2024 - FORMULATION AND DEVELOPMENT - Use of AUC in AAV Analysis in a GMP Setting
APR March 2024 - 20
APR March 2024 - 21
APR March 2024 - 22
APR March 2024 - 23
APR March 2024 - FORMULATION AND DEVELOPMENT - Precision Medicine in Clinical Trials: A Statistical Perspective
APR March 2024 - 25
APR March 2024 - 26
APR March 2024 - 27
APR March 2024 - An Interview with Dan Smithey, PhD President & CEO, Serán
APR March 2024 - 29
APR March 2024 - 30
APR March 2024 - FORMULATION AND DEVELOPMENT - Still Early Days for AI in Drug Discovery...Says Who?
APR March 2024 - 32
APR March 2024 - 33
APR March 2024 - QC Corner - Enhancing Material and Equipment Availability in Production Isolators
APR March 2024 - 35
APR March 2024 - BIOPHARMACEUTICALS - Technologies for Aseptic Filling: The Choice is Clear
APR March 2024 - 37
APR March 2024 - 38
APR March 2024 - 39
APR March 2024 - Vendor Viewpoint - Data Integrity and Rapid Micro Methods: Transforming to a Modern Microbiology Lab
APR March 2024 - 41
APR March 2024 - MICROBIOLOGY - Bacterial Spore Formers in Disinfectant Efficacy Testing
APR March 2024 - 43
APR March 2024 - Partner Perspective - Nanoparticle Technologies: Enablers for Ocular Drug Delivery
APR March 2024 - 45
APR March 2024 - 46
APR March 2024 - 47
APR March 2024 - DRUG DELIVERY - Your Nails and You
APR March 2024 - 49
APR March 2024 - 50
APR March 2024 - 51
APR March 2024 - DRUG DEVELOPMENT - Battling Exorbitance: High Costs in Sickle Cell Gene Therapies and the Imperative of Global Patient Registries for Equity
APR March 2024 - 53
APR March 2024 - 54
APR March 2024 - 55
APR March 2024 - FORMULATION AND DEVELOPMENT - How Pharma Companies Are Solving Regulatory Challenges with AI-based Technology
APR March 2024 - 57
APR March 2024 - Event Preview - CPHI North America
APR March 2024 - 59
APR March 2024 - Event Preview - Excipient World 2024
APR March 2024 - 61
APR March 2024 - P.I.N. Points
APR March 2024 - 63
APR March 2024 - Advertiser's Index
APR March 2024 - Cover3
APR March 2024 - Cover4
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