APR March 2024 - 13

« BIOPHARMACEUTICALS
Opportunities for Small-Scale
Continuous Processing
Smart process development
At present, process development for continuous processes is performed
in batch mode with single operations at a time to generate a
fundamental understanding of each unit operation in order. However,
the mAb process is relatively well established and the unit operations
and order are essentially fixed, which presents another opportunity: To
perform process development directly using the continuous system.
Process knowledge combined with continuous experiments could enable
a rapid definition of not just each unit's operational parameters,
but also of the complete operation space and how changes upstream
impact the process.
Process intensification for other modalities
The process intensification path for mAbs is becoming well understood,
if not yet widely implemented. For other modalities that have emerged
in the last decade, the manufacturing platforms are not as clear or fully
defined. There will be opportunities to bring process intensification to
these platforms to help reduce cost and make difficult-to-manufacture
therapeutics accessible to more people.
The production of low-dose therapeutics, such as vaccines or
gene therapies, would extend the opportunity of such small-scale
manufacturing systems,11
particularly for in-country manufacturing.
3.
Miniaturization for portable/regional manufacturing
This could most easily be described as developing the current lab into
a small single-box solution. With the mass balancer and mass router
used currently in the lab, we can envisage how microfluidics could
be miniaturized into a single-box solution combining all the unit
operations into an automated mAb producing system in a box.
In addition to a reduced physical volume, future systems should also
offer flexibility and reconfigurability to enable multiple therapeutic
products to be created from the same common hardware. This should
be - to the greatest extent possible - via common hardware with
software-modified parameters.
While this could result in suboptimal biomanufacturing solutions
for each therapy, the overall ability to rapidly reconfigure a regional
biomanufacturing solution to address a local threat enables faster and
more agile regional responses.
This has utility in the developed world and especially in parts of the
developing world that lack biomanufacturing infrastructure.
Data management
Continuous processing offers the potential to capture orders of
magnitude more process data, during development and during
production. How can this data be organized, stored, and managed to
get the most insights on critical process parameters, in real time and as
4.
5.
part of ongoing continuous improvement strategies or development
of new products?
Many software tools are available. BioSolve Process software, used
for the project discussed here, offers an overview of the process
and its top-level inputs (recipes, workflow, operations, costs, labor,
energy, etc.) and outputs (product throughput, facility metrics,
cost of goods, capital intensity, etc). As a part of the project, this
top-level architecture is being integrated with normal process
development recipes, distributed control system (DCS) operational
inputs, and process outputs, with the aim of enabling technology
transfer from process development (PD) to clinical to commercial
scale-down manufacturing.
As the second UK government-funded project at CPI is set to complete,
plans are being made to extend the activities in the lab. Currently the
goal of a future project will be smart process development, perhaps
with a focus that goes beyond mAb modalities to viral vectors and
vaccine production.
References
1.
2.
American Pharmaceutical Review. Integrating Continuous
Technologies for
Rapid Delivery of Cost-Effective Biotherapeutics to Patients. 2022 https://www.
americanpharmaceuticalreview.com/featured-articles/589065-integrating-continuoustechnologies-for-rapid-delivery-of-cost-effective-biotherapeutics-to-patients/
Vanhoorne
V, Vervaet C. Recent progress in continuous manufacturing of oral solid dosage
forms. Int J Pharm. 2020;579:119194.
Varner C, Patil R, Godawat R, Warikoo V, Konstantinov K, Brower KP. Gamma
irradiating chromatography columns enables bioburden-free integrated continuous
biomanufacturing. Biotechnol J. 2021;16(4):e2000298. doi:10.1002/biot.202000298
USP 61 Microbiological examination of nonsterile products: Microbial enumeration tests,
https://www.usp.org/sites/default/files/usp/document/harmonization/gen-method/
q05b_pf_ira_34_6_2008.pdf
BioPhorum Group. Rapid detection of bacteria and viruses: justification, regulation,
requirements and technologies - how can industry achieve broad adoption? Published
October 2019. https://www.biophorum.com/wp-content/uploads/bp_downloads/TRMrapid-detection-of-bacteria-and-viruses-how-can-industry-achieve-broad-adoptionOctober-2019-1.pdf
6.
7.
8.
9.
10.
11.
Jagschies
G, Lindskog E, Łącki K, Galliher P, eds. Biopharmaceutical Processing:
Development, Design, and Implementation of Manufacturing Processes. Elsevier. 2017.
US Food and Drug Administration. Code of Federal Regulations Title 21, part 11: Electronic
Records, Electronic Signatures.
(ICH Q8[R2]) Pharmaceutical development - Scientific guideline https://www.ema.
europa.eu/en/ich-q8-r2-pharmaceutical-development-scientific-guideline
Kappeler SR, Nicholson G, Bohnenkamp HR, Bethke U. A plug-and-produce GMP plant for
cell and gene therapy - part 1: case study in modular facility design and deployment.
Bioprocess International. 2022 (Sep 28).
Ran T, Eichmüller SB, Schmidt P, Schlander M. Cost of decentralized CAR T-cell production in
an academic nonprofit setting. Int J Cancer. 2020;147(12):3438-3445.
Hamidi A, Yallop C, Drugmand J-C, Reniers A, Dubois S, Castillo J. A small-footprint,
integrated, and automated platform for viral production. GEN - Genetic Engineering and
Biotechnology News. 2020 (Feb 1). https://www.genengnews.com/resources/tutorial/asmall-footprint-integrated-and-automated-platform-for-viral-production/
www.americanpharmaceuticalreview.com
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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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