APR March 2024 - 14

»
MICROBIOLOGY
»
Critical Behavioral Attributes and the Application of
COM-B Framework in Aseptic Processing
Satish Joshi
Founder
SHJ Consulting Services
Ajay Pazhayattil
Management Consultant
cGMP World
Marzena Ingram
Sr. Pharmaceutical Consultant
Validant
Mava Fakoori
Behavioral Counselor and Therapist
Introduction
The pivotal role of human behavior in aseptic operations cannot be
overstated, as it significantly influences the safety and efficacy of
sterile drug products. This article delves into the incorporation of
human factor principles as a proactive and strategic move, aiming to
navigate the complexities inherent in aseptic operations and, in turn,
ensure the steadfast safety and efficacy of sterile drug products. The
approach systematically addresses human factors that may impact
aseptic operations. First, organizations recognizing and accounting for
the human element in the aseptic manufacturing process go a long
way in initiating mitigation activities.
Recent regulatory scrutiny and the lessons drawn from FDA form 483s
and Warning Letters1,2
underscore the urgency for a paradigm shift
towards enhanced human factor risk management and intervention
strategies. Most behavioral observations pertained to violations of
first air principles, especially in Grade A areas during aseptic filling
operations. The cleanroom behaviors, such as slow and deliberate
movement in such a way that unidirectional airflow is not disrupted,
routine hand sanitization, sterile gown/glove management during
operation, going over vials, equipment open door/closed door setup,
vial loading/unloading, stopper replenishment process steps, handling
of broken vials, and interventions were all examples of areas where
the regulator was concerned for RABS systems. In some cases, the
CCTV video observed by the regulator proved that the documented
activities were indeed not performed, questioning employee integrity
and management effectiveness. The observations also emphasized the
importance of air visualization studies. The inspectors closely monitored
the interventions either live or via CCTV footage to ensure aseptic
product safety and to assess the effectiveness of aseptic processing
simulations. In many cases, organizations encountered shortcomings
here. The challenges encompass a spectrum of factors, ranging
from lapses in personnel training, personal integrity and awareness,
14 |
| March 2024
to equipment design and facility layout issues. The consequences
of overlooking these crucial aspects can be severe, with potential
ramifications for the quality and safety of sterile drug products and
the organization. These recent instances have cast a spotlight on the
imperative for the industry to fortify its human factor risk.
Cleanroom Behaviors
Impacting Patients
The sterility of a cleanroom component or the final product means the
complete absence of viable microorganisms, including viruses, which
pose a risk to the patient during administration. While achieving sterility
in parenteral manufacturing is important, it does not guarantee the
absence of non-viable pyrogens. To prevent pyrogenicity, it is essential
to avoid endotoxins, which are lipopolysaccharides that are shed into the
environment once a gram-negative bacterium dies and lyses. Endotoxin
levels are determined by the Limulus Amoebocyte Lysate (LAL) test
based on the clotting reaction of the hemolymph of the horseshoe
crab. Clinical cases3
have confirmed the serious risks associated with
endotoxins, which can lead to anaphylactic shock and death of patients.
Conducting smoke studies in cleanrooms is crucial to validate the effects
of operational interventions on unidirectional airflow. Swift movements
by operators can disrupt the airflow, leading to the generation of
airborne particles. Research indicates that the movement of operators
results in the formation of recirculation zones, causing localized
turbulence and the entrapment of contaminants.4
The establishment of
a low-pressure zone, either by the presence of personnel or an obstacle,
may lead to a reversal of airflow, detrimentally affecting the initial air
curtain designed to prevent the entry of contaminants.
The primary goal of utilizing sterile gloves in a cleanroom setting is
to prevent the introduction of human skin-associated microorganisms
and to prevent cross-contamination. The effectiveness of this

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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