APR Sept/Oct 2023 - 39

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IT and OT should treat one another as hostile. It doesn't mean there's
hostility between the two teams. People can get along well, but
the networks shouldn't. There shouldn't be an opportunity for one
network to compromise another due to an entry point between them.
They should be entirely distinct from one another. No program should
be able to connect from one network to the other.
To achieve this, you'll have to set up a mechanism that stands between
the two networks. A network with a neutral territory zone for safety and
security is a common approach. Some people say, 'we only open one
port.' This has been said many times, and it really misses the point. It's
not firewall ports that are attacked during an attempted compromise
on a network. It's the software that runs on that port. It doesn't matter
who you are or what your development team is like, there is always an
exploit. The only way to protect yourself from exploitation through an
open firewall port is not to have an open firewall port.
Concepts, Principles and
Regulatory Expectations
Number and Frequency of APS
The number and type of APS should be based on a Risk Assessment of
the aseptic process and qualification/validation of a new facility or new
production process. APS is performed after facility, process, equipment,
facility decontamination, personnel training, room qualification and
EM program implementation is complete. APS is one of the last steps
in the qualification/validation process. Typically, a minimum of three
(3) APS are a regulatory expectation. Semi-annual APS are a regulatory
expectation for a qualified line/ process. If there are major changes to
facility or aseptic process - perform a Risk Assessment to determine if
APS is needed and how many.
Risk Assessment and Worst-Case Scenarios
Definition of Risk - combination of a hazard and its likelihood of
occurring and harming the patient. In aseptic processing this is loss
of sterility assurance. Risk assessment can be used to determine the
worst-case manufacturing scenarios using a holistic approach:
* Operating conditions-including personnel
*
Interventions
* Container closure - size and configuration
* Line speed
* Batch size
The Risk Assessment should be documented and used as the basis for
the design of the APS study.
Study Design
An APS study program should incorporate the contamination risk
factors that occur on a production line, and accurately assess the
state of process control. APS studies should closely simulate aseptic
manufacturing operations incorporating, as appropriate, worst-case
activities and conditions that provide a challenge to aseptic operations.
FDA recommends that the APS program address applicable issues
such as:1
Aseptic Compounding
* The entire aseptic compounding process should be simulated
including all aseptic additions. APS can be stand alone for the
compounding step or integrated with filling.
* Filling
* Longest duration of run on an aseptic processing line.
*
Interventions - inherent (routine) and corrective
(non-routine)
* Aseptic assembly-line set up
* Number of personnel - duration and activities, shift
changes, breaks
* Number of aseptic additions/transfers
* Connections/disconnections
* Processes such as Lyophilization
* Line speed and configuration
* Container closure types/systems
*
Inert gassing
* Number of units filled
* Frequency and number of runs
Documentation
Documentation of every step of the APS is very important. The
documentation will serve as record of the rationale for APS design
and its performance. Documentation should include step by step
instructions of the performance of the APS, acceptance criteria, all
results obtained, any deviation.
An aseptic simulation policy/procedure should be prepared which
gives an overall comprehensive list of requirements and rationale for
APS studies. The following documentation procedure is recommended.
Protocol
An approved APS protocol should be in place prior to starting the
study. Information/instructions in the protocol should include at
a minimum:
* Responsible groups for execution, testing
* Rationale for " worst case " scenarios
* Identification of room, filling line, equipment, process flow.
* Types of container closure to be used
* Fill volume
* Minimum number of units to be filled and rationale
* Line speed(s)
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APR Sept/Oct 2023

Table of Contents for the Digital Edition of APR Sept/Oct 2023
