APR March 2024 - 16

» MICROBIOLOGY
»
during the entire aseptic operation. The operator should conduct the
aseptic removal of the final wrap only during the introduction stage.
The component preparation teams' wrapping skills often come into
play for seamless unwrapping and installation. Sterile tools associated
with sterile supports, hangers and their adequate placements are
required to minimize contact between the toll and surfaces. The
sampling step should be performed in such a way that it does not
pose any contaminating risks. Where possible, best practices highlight
that significant assembly is avoided by using sterilized pre-assembled
items. Overall, the long-established industry best practices in aseptic
operations are highly influenced by the operator's level of training and
the resulting behavioral patterns displayed.
COM-B Framework for
Behavioral Change
The Capability, Opportunity, Motivation-Behavior (COM-B) model is
a systematic theoretical framework of behavior change developed
by Susan Michie, Maartje van Stralen, and Robert West in 2011.16
The human behavior model identifies capability (C), opportunity (O),
and motivation (M) as the three key factors capable of influencing
behaviors. The theory identifies that behavioral changes can be
induced by modifying one of the components. A recent study17
identified that opportunity and motivation directly affected hand
hygiene behavior. While capability and opportunity were indirectly
linked to hand hygiene behavior through motivation (Figure 3). The
study substantiates the direct applicability of the COM-B Model in
enhancing aseptic behaviors, which include hand hygiene practices.
Opportunity
Table 1. Factors Impacting Positive Aseptic Behaviors
Capability
* Adequate time for execution
*
Sufficient tools & resources
* Peer-observation & prompt
* Physical capability
* Dexterity & training
* Adequate eyesight
Motivation
*
Existence of a reward system
* Pre-batch team meeting
* Developing specialists
behavioral requirements need to be identified and controlled upfront as
part of process development itself. The sources of variability addressed
during development include- material (ex., raw materials, components),
machine (ex., manufacturing equipment), method (ex., manufacturing
process, cleaning process, analytical
process), measurement (ex.,
Figure 3. COM-B Model for Hand Hygiene Behavior17
Factors such as those in Table 1 can induce positive behaviors during
aseptic processing.
Introducing Critical Behavioral
Attributes (CBAs)
Based on the above discussions, it is evident that aseptic behavior
requirements and human behavior improvement traits are well
understood and characterized; the limitation now becomes establishing
a product/process-specific model to ensure consistent adoption of
these behavioral requirements. The repeated aseptic behavior failure
during regulatory inspection necessitates a renewed look at how
16 |
| March 2024
analytical instrument), mother nature (ex., temperature, humidity
conditions), and man (ex. operators, analysts). An ICH Q8 (QbD)18
based process development (Stage 1 of the process validation lifecycle)
identifies the Critical Material Attributes (CMAs) and Critical Process
Parameters (CPPs) and determines their degree of impact on Critical
Quality Attributes (CQAs) through the planned Design of Experiments
(DoEs). The equipment, instrument, facility- temperature, and humidity
variability are well understood and controlled as part of qualification
efforts (Stage 2A of the process validation lifecycle). Raw material
attributes are established and controlled as part of development.
While components are qualified for aseptic operations, their sterility
maintenance is also ensured. The process control strategy should
encompass the controls related to minimizing potential sources of
variability that impact CQAs. In addition to the above parameters and
attributes affecting product Safety, Identity, Strength, Purity and Quality
(SISPQ), an aseptic process needs to also focus on personal aseptic
behavioral controls. The reason is that personal behavioral variability can
result in loss of product sterility and cross-contamination, both patient
critical. For this reason, we propose a new set of behavioral criteria,
namely- Critical Behavioral Attributes (CBAs) similar to CMAs and CPPs
in the case of aseptic manufacturing processes. The CBAs need to be
identified, and the additional controls in place need to be enumerated
since these human behavioral attributes are difficult to qualify. Table 2
displays one such example.
The purpose of identifying CBAs per operation and applying riskbased
controls as part of Stage 1 (of the process validation lifecycle) is
to reduce the variability associated with patient-impacting behaviors.
The consistency of the CBAs needs to be confirmed during PPQ
(Stage 2B ), and CBAs need to be monitored as part of the CPV (Stage
3) program.19
When adequate electronic or automation technology
becomes available, organizations should switch to those solutions to
reduce behavioral bias as much as possible. Switching from manual
Tyvek lid removal and inner liner removal of the Pre-Filled Syringe
(PFS) tub to automatic removal by robotic arms is one example. Tools
such as the Post Approval Change Management Protocol (PACMP),
as stipulated in ICH Q12,20
may be utilized to implement the change,
thereby minimizing the impact of a CBA, i.e., tub loading technique.
Conclusion
Aseptic best practices have been in place in the industry for
decades. However, the Quality by Design (QbD) concepts to process

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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