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Media Fill

This document discusses media fills/process simulation which are used to evaluate an aseptic process' ability to produce sterile products. It describes using a risk-based approach to design media fills that incorporate worst case conditions. Critical factors like run duration, line speed, and personnel are addressed. Guidelines are provided around media fill assessment criteria, unit accountability and reconciliation, and acceptance criteria. The conclusion emphasizes that media fills are just one part of ensuring sterility and that even negative results do not guarantee no contamination occurred.

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raghu
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924 views13 pages

Media Fill

This document discusses media fills/process simulation which are used to evaluate an aseptic process' ability to produce sterile products. It describes using a risk-based approach to design media fills that incorporate worst case conditions. Critical factors like run duration, line speed, and personnel are addressed. Guidelines are provided around media fill assessment criteria, unit accountability and reconciliation, and acceptance criteria. The conclusion emphasizes that media fills are just one part of ensuring sterility and that even negative results do not guarantee no contamination occurred.

Uploaded by

raghu
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPT, PDF, TXT or read online on Scribd
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Media Fills / Process

Simulation
Process Simulation: Media Fill
Objective of media fill
 To evaluate the capability of the aseptic process to produce
sterile drug product
 To learn how failures have to be evaluated and what
consequences they have

Use of risk-based approach in media fill design


 Incorporate the same risk factors for contamination that
occur in production runs
 Incorporate the worst case conditions that can occur in the
operation:
 the process
 the manufacturing environment, and
 the operators
Critical Factors
Study Design - Accuracy of Simulation
simulate actual process as closely as possible, and
address worst-case conditions

Critical risk factors for contamination


duration and size of run
line speed: filling speeds
manual manipulations
personnel (number, shift changes,
fatigue)
routine and non-routine interventions
Size and Duration of Media Fill Run
 Size: number of units filled should be sufficient to
reflect the effect of potential operator fatigue, and
adequately represent the maximum number of
interventions.
 Duration: long enough to challenge or stress the
process, the environment, and the operators
 Stressesfull duration media fills for manually
intensive processes
Personnel

 Number of personnel and their activities

 shift changes and breaks


Media Fill Assessment
Concept paper provides guidance for:

 Criteria for removal of media fill units:


 The interventions in media fill should simulate what
occurs in a commercial production run.
 Where units can be removed as part of an intervention,
SOPs should include sufficient detail with respect to type
of intervention and number of units removed
 Media fill records should document all interventions
performed and the number of units removed.
 Unit accountability and reconciliation: integral and non-
integral units. Incubation of all integral units.
Unit Accountability and Reconciliation
 Unit reconciliation, e.g.
 # units filled = # units incubated + # units rejected for cause + # units for growth
promotion

 Accountability for all units removed


 during manual interventions
 at final inspection, non-integral units with container-closure defects

 All integral units (including units with cosmetic defects) should be incubated and
counted as part of media fill evaluation
Unit Inspection (container/closure defects)
 Pre-incubation inspection: When a firm performs a
final production inspection of units immediately after
the media fill run, only those units found to be
defective in container/closure integrity can be
removed. Units with cosmetic defects should be
incubated and included as part of the media fill run.

 Post-incubation inspection: Units found to be


damaged after the pre-incubation inspection should
be included as part of the media fill batch because
such units would also likely to have escaped
detection during normal production and be released
to the market.
Acceptance Criteria
 When filling fewer than 5000 units, no contaminated units should
be detected. –
 One (1) contaminated unit is considered cause for revalidation,
following an investigation. •
 When filling from 5,000 to 10,000 units: --
 One (1) contaminated unit should result in an investigation,
including consideration of a repeat media fill.
 -- Two (2) contaminated units are considered cause for
revalidation, following investigation. • When filling more than
10,000 units: --
 One (1) contaminated unit should result in an investigation. –
 Two (2) contaminated units are considered cause for revalidation,
following investigation. acceptance limit of < 0.1% contaminated
units at 95% confidence level (approx. 1 in 5000).
 FDA agrees with PDA that the target should be zero
contaminated units regardless of size of run.
Media and incubation temp

 Temperature and media chosen should bases


on its ability to recover microorganism
normally found environmentally or in the
product bioburden.
 Temp: 20-35oC
2 temp: 20-25oC for 7 days, followed by 30-35oC for 7 days
 media: TSB aerobic organisms, FTM for anaerobic
organisms
Guide lines

 Pharmaceutical regulations:
- Regulations: FDA “guidance for industry, sterile drug
products produced by aseptic processing – cGMP” -
- EU GMP Part I annex 1 –
- PIC/S PI 007-2 “recommendations on the validation of
aseptic process”
CONCLUSION
 Even if all media fills are negative in a Company, it does
not necessarily indicate that no products were ever
possibly contaminated because the frequency
requirement of media fill testing is so minimal that it is
not statistically significant

 A robust media fill programme is a necessary step to


validate process

 Media fill testing is just one part of a necessary overall


quality assurance program (HVAC qualification, cleaning
procedure, sanitization, personnel training, …)

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