APR March 2024 - 38

» BIOPHARMACEUTICALS
»
Comparative Assessment
The superiority of isolation technology to cRABS as outlined in the
table is evident. The opinion stated above are derived from numerous
publications comparing the technologies (see the accompanying
bibliography). RABS designs evolved from substantially older staffed
cleanroom facilities as something that would avoid the then prevalent
negative concerns of adopting isolation technology to an existing
facility. These concerns related to difficulties with leak detection,
decontamination, and the uncertainties that these might present in
project execution. Given the limited sophistication of many early RABS
designs, that simplicity had a certain appeal to those uncertain of the
new obstacles that isolators might entail. Contemporary cRABS designs
now incorporate operation in a fully closed mode, with no operator
access during aseptic operations and automated decontamination,
making them more isolator-like.
The presence of leaks in isolators, which were an obsession decades
ago, has largely disappeared. Recognition that the alternative systems,
whether staffed cleanrooms or RABS, rely on air flowing from the
critical zone towards the operators meant that leaks were not strictly
an isolator problem. In fact, given the sustainable pressure differential
between the isolator interior and the surrounding environment leaks
are far less significant with isolators.
The concerns
voiced by some regulators
regarding
enclosure
decontamination uncertainty extends to their use with both cRABS
and isolators. Thus, any perceived faults in the use of H2
O2 for enclosure
decontamination are shared by both technologies.
The first RABS were designed to provide the operational performance
of isolators at lower cost with simpler execution. Industry experience
has shown that while the performance of cRABS can approach that
of isolators, the cost of operating a cRABS is higher. One could argue
that the increasing desire to reliably decontaminate cRABS systems
after set-up (a premise of the above comparison) has resulted in
more challenges than in a comparably sized isolator (where design
standardization and independent HVAC systems makes for simpler
execution of the decontamination process).
Isolation technology has been successfully implemented worldwide
many times and regulatory authorities have indicated a preference for
its use over all other aseptic technologies. Industry surveys indicate
that more isolators have been installed than RABS. Several multinational
firms have made isolation technology their default choice
for new installations as they have recognized their superiority in most
applications. The introduction of gloveless isolators relying upon
robotics and automation takes the separation of personnel from sterile
materials to levels far beyond that of prior technologies.
RABS technologies can provide a means for the gradual upgrade of
ordinary staffed cleanrooms as the ancillary classified environments
needed for both are identical. Gowning, sterilization / depyrogenation,
material airlocks, corridors and other classified areas would be virtually
unchanged by the replacement of a conventional staffed line by
a RABS. Introducing an isolator into a pre-existing facility would
ordinarily require more extensive modifications.
38 |
| March 2024
6.
7.
8.
9.
The real-world experience gained with both RABS and isolators
makes the selection of suitable technology simpler than it once was.
There's little reason to choose a cRABS system in any new installation
given the numerous advantages of isolation technology. Isolators
are clearly the best available technology for aseptic processing and
containment application.
References
1.
2.
Agalloco, J., Akers, J., Madsen, R., " Choosing Technologies for Aseptic Filling - Back to the
Future? " Pharmaceutical Engineering, Vol. 27, No. 1, p 8-16, 2007.
Akers, J., Agalloco, J., Madsen, R., " What is Advanced Aseptic Processing? " Pharmaceutical
Manufacturing, Vol.4, No.2, pp 25-27, 2006.
Bibliography
1.
2.
3.
4.
5.
Agalloco, J., Akers, J., Madsen, R., " Choosing Technologies for Aseptic Filling - Back to the
Future? " , Pharmaceutical Engineering, Vol. 27, No. 1, p 8-16, 2007.
PDA. " Technical Report No. 34, Design and Validation of Isolator Systems for the
Manufacturing and Testing of Health Care Products. " PDA J. Pharmaceutical Science &
Technology. 55(5, Supplement). 2001.
Akers, J., Agalloco, J., Madsen, R., " What is Advanced Aseptic Processing? " , Pharmaceutical
Manufacturing, Vol.4, No.2, pp 25-27, 2006.
ISPE, Restricted Access Barrier Systems (RABS) for Aseptic Processing Definition, 2005.
FDA. Guidance for Industry. Sterile Products Produced by Aseptic Processing - Current Good
Manufacturing Practice. 2004.
Lysford, J. and Farguharson . " Barrier Isolation History and Trends " , International Society
for Pharmaceutical Engineering Washington Conference: Barrier Isolation Technology, June
2004.
Lysford, J., " Current Aseptic Processing Trends with the Use of Isolators and RABS (Restricted
Access Barrier Systems " . ISPE Barrier Isolator Conference, Tampa, March 2008.
Nieuwenhuizen, P., " Aseptic Considerations in Formulation, Fill and Finish - Choosing
Between Barrier and Isolator Technologies " , Bioprocess International, Vol. 19, No.9, pp 1-6,
2021
National Academies of Sciences, Engineering, and Medicine 2021. Innovations in
Pharmaceutical Manufacturing on the Horizon: Technical Challenges, Regulatory Issues,
and Recommendations. Washington, DC: The National Academies Press. https://doi.
org/10.17226/26009. 2021.
10. Weston, F., " Debating the Role of RABS and Isolators in Aseptic Manufacturing " .
Pharmaceutical Technology, Outsourcing Resources Supplement, August 2016.
11.
Bozenhardt, H. and Bozenhardt E. " What, You Call That A RABS? " 7 (Real-Life) Aseptic
Filling Blunders To Avoid " , Pharmaceutical On-line, 2019
12. Drinkwater, J., " RABS in Operation with Isolators " . www,cleanroomtechnologies.com
13.
Lavarreda, C., " RABS vs, Isolators - Technology & Operations " , Pharmaceutical On-Line ,
2017.
14. Williamson, J., " Barrier and Isolation Systems: Technology in Transition " , Cleanrooms, Vol.
21, No. 04, 2007.
15.
16.
17.
Mackler, S., " Barrier Isolation Technology Can Improve Life Sciences Cleanroom
Applications " , Journal of Advancing Applications in Contamination Control, October 2001.
Kline, S., " Current Trends in Sterile Manufacturing " , IPS, 2014.
Fruergaard, C., " Trends in Sterile Manufacturing Technologies " , ISPE Thailand Annual
Meeting, July 2013.
18. Anonymous, " Open RABS, Closed RABS And Isolators: Focus On Energy Savings " . IMALife,
2013.

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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