SVP Aseptic Media Fill Simulation Testing Protocol (Aseptically Filled Products)

Title: SVP Aseptic Media Fill Simulation Testing Protocol (Aseptically Filled Products)
Number: Val 01-4 Copies to: Distributed upon request, as

Supercedes: Val 01-3 Date: June 1999 per procedure Val 01-4
Compiled by: Checked by: Approved by:
Original: Kept as a working copy in the
validation file
Issue Date: 4 February 2002
Brief details amendment/update: Inclusion of Media Fill Rationale and Processing
Changes
Validation Interval: Bi-annual Appendices: 5
Confidential Document
MEDIA FILL PROTOCOL
Equipment/system name: 6000/hr SVP Ampoule Filling Machine
Protocol number : Val 01-4
Asset number: As per finance
Model: F97/22-K-TDB Liquid filling machine
Serial number: Filler: RA3051
Department: Multi product filling suite
Addendum: N/A
Effective Date:
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Contents Page
1. OBJECTIVE 3
2. SCOPE 3
3. INTRODUCTION 3
4. PROTOCOL CHANGES 4
5. REFERENCES 4
6. DEFINITIONS 4
7. SPECIAL PRECAUTIONS 5
RESPONSIBILITIES
Validation Department
8. QA Manager / QA Release Pharmacists 5
Microbiological Laboratory
S.V.P Department
WORST CASE RATIONALE
Environmental Exposure & Filling Room Complement
9. 6
Container Size and Line Speed
Filling Medium & Interventions
10. FILLING METHODOLOGY 8
MEDIA FILL TEMPERATURE AND MEDIA SELECTION
11. 12
RATIONALE
12. ACCEPTANCE CRITERIA 14
13. NUMBER OF RUNS REQUIRED 15
14. REPORT 16
15. INVESTIGATION OF FAILURES 16
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Completion of the above signature block signifies that the appropriate parties have
reviewed this protocol and agree with the methodology and acceptance criteria. A
complete report will be issued for separate approval.
1. OBJECTIVE
The objective of this SVP Aseptic Media Fill Process Simulation Testing Protocol is:
To demonstrate the capability of the aseptic process to produce sterile drug

products;
To contribute to confidence in the sterile status of product manufactured by the
specific operator since last media fill the operator was involved with;
To promote sterility assurance of future products manufactured employing
aseptic technique;
To comply with current Good Manufacturing Practice requirements;
To provide a measure of aseptic technique of each operator involved in the media
fill
Note: This study is supplemented by Val 133 - Aseptic Fill Challenge for Vial Filling
Operators, which is intended as a certification tool for operators assigned to
filling aseptic product, on either an Ampoule or a Vial filling line.
In cases where an operator is not available to take part in a media fill, such
exposure may be used to qualify the operator in absence of Media Fill. However,
each operator shall be exposed to at least one run of a conventional media fill
per year.
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2. SCOPE
This study addresses the validation of the aseptic processing during:
compounding and
filling activities.
It describes methods and procedures for the conduct of the process simulation tests,
as described below.
The scope of this protocol relates to the filling equipment currently used for filling of
all Vials as well as all Aseptically filled Ampoules within the current SVP Filling Suite.
A special section deals with Aseptic Compounding.
3. INTRODUCTION
The aseptic fill validation is based on the fill of bacterial culture medium as a
substitute for product and in this respect it is essential that validation be conducted
as a normal production run.
All equipment should be cleaned, sanitized, sterilized, handled and assembled as per
standard operating procedure with all conditions prevailing as normal.
Similarly all compounding and filling operations must also be carried out as per
standard operating procedure, while introducing interventions as experienced
during day-to-day filling operations.
4. PROTOCOL CHANGES
Inclusion of Incubation Temperature selection rationale
Inclusion of Media Selection rationale
Inclusion of the Aseptic Compounding process (XXXXXXX manufacture)
5. REFERENCES
PDA Journal of Pharmaceutical Science and Technology
Technical Report 22: Process Simulation Testing for aseptically Filled Products
(1997)
Journal of Parenteral Science and Technology 1987
Current Practices in the Use of media Fills for the Validation of Aseptic
Processing
Journal of Parenteral Science and Technology 1990
Validation and Environmental Monitoring of Aseptic Processing
Practical Aspects of Pharmaceutical Validation David Begg
Lecture 12: Validation of Aseptic Processing using Sterile medium Simulations
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Validation of Aseptic Pharmaceutical Processes (Carelton & Agallaco)

Chapter 24: Validation of Aseptic Filling Operations
The Validation Dictionary Institute of Validation Technology
SA GMP Guide
EU GMP Guide
6. DEFINITIONS
Growth Sustaining Media:A substance, which contains low levels of
micronutrients, and satisfy the minimum requirements for
sustaining microbial life.
Growth Promoting Media: A substance which contains optimal levels of the correct
nutrients, maintained at ideal pH and osmolality in order
to actively promote proliferation of the specific
microorganisms it was designed to support.
Aseptic Filling: Part of aseptic processing where a pre-sterilized product

is filled and/or packaged into sterile containers and
closed.
Aseptic Processing: Handling sterile materials in a controlled environment, in

which the air supply, materials, equipment and personnel
are regulated to control microbial and particulate
contamination to acceptable levels.
This term encompasses aseptic compounding and filling
activities.
Aseptic Compounding: A process whereby two or more materials are brought

together and mixed in an aseptic environment. The
finished product is not subject to sterilization by any
means, either prior or post filling.
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7. SPECIAL PRECAUTIONS
As indicated above the validation activity must mimic production as closely as
possible.
The only extraordinary attention that must be paid, is in containing and attending to
spillages or breakages, since media so introduced into the clean room is by design
intended to promote proliferative microbial growth, which is totally contradictory to
clean room principles.
8. RESPONSIBILITIES
Undertaking of a Protocol of this nature requires the participation and assistance of:
Validation Department
8..1. To guide and co-ordinate the execution of this protocol.
8..2. Acquisition of raw material and componentry.
8..3. To confirm that the HVAC System is functioning within specifications.
8..4. Perform monitoring of non-viable particulates using either remote scanning or a
handheld scanner.
8..5. Control and report on incubation conditions of the Media Fill.
8..6. Issuing of a report at completion of the Media Fill.
QA Manager / QA Release Pharmacists

8..1. To ensure that conditions simulated had been a true reflection of production
conditions
8..2. Official Approval of the Media Fill Challenge Results
Microbiological Laboratory
8..1. To assist in planning of Media Fill, and acquisition of materials required.
8..2. To demonstrate that the media and the incubation period and temperatures
employed are effective for the promotion of growth of low levels of normal
microbial contaminants as encountered in microbiological monitoring as well as
standard challenge microorganisms. In addition, special attention should be
given to growth promotion of media post homogenization and filling as
performed in the Aseptic Compounding Challenge.
8..3. To monitor and control the fill process in conjunction with Production.
8..4. To evaluate the filled containers.
8..5. To conduct routine microbial monitoring of the filling and media introduction
areas during the validation run.
8..6. To assist in compilation of the final report, inclusive of environmental results.
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S.V.P Department
8..1. To plan for provision of equipment and personnel at times convenient to
Production, microbiology and Validation departments.
8..2. To carry out filling under control and supervision of a technically competent
person who must be responsible for ensuring that all components and equipment
are correctly treated and handled and that all assembly and process operations
are correctly carried out.
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9. WORST CASE RATIONALE
As per standard Validation approach, worst case conditions should be used when
performing a Media Fill.
However, care must be taken that this is not overdone; i.e. inadvertently moving from
Worst Case to Ridiculous Case.
Standard operations should be performed (e.g. standard machine setup, volume
adjustments, etc.)
The following criteria Worst Case criteria should be considered:

Environmental Exposure
In the course of normal operation, equipment is routinely sterilized prior to use. In
other words, equipment may be exposed to the Clean Room environment for some
time prior to usage.
This exposure is normally restricted to 72 hours; however standing time normally
does not exceed 24 to 48hours. In addition, although a truly sterile Clean Room
Environment is pursued, it must be demonstrated (by validation) that the
environment does not contribute to loss of sterility of any stored product contact
equipment.
In order to justify the maximum allowable window though, a standing time in the
vicinity of 24 to 48hours should be pursued for a media fill, in order to demonstrate
the maintenance of equipment sterility. If a standing time of longer than the norm can
be demonstrated, it may be accepted that the product contact equipment is not at risk
during normal staging activities. Standing time should therefore be made as long as
is practically possible.
However, as it is neither practical nor possible to stage equipment for each run three
days prior to filling, this requirement is only enforced for the first run of the Media
Fill, on each machine. The completion time for the initial Staging Time Validation
study will therefore be three Media Fills (1.5 years).
Filling Room Complement

Standard staff complement in the SVP Filling Room is as follows:
Four Filling Machine Operators (1 per machine)
One additional operator (support)
One Technician (enters when required)
One Cleaner
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One representative from the Microbiological Laboratory (sampling; enters when

required)
XXXXXXX Compounder (enters only when aforementioned product is being
compounded)
Once again, worst case conditions must apply, therefore, the following is
recommended:
Filling Machine Operators as per norm (four)
One additional Operator
Technician / representative to be present in the area during the filling process
(exits thereafter, but re-enters upon starting the next run)
One Cleaner (permanently present)
One representative from the Microbiology Laboratory (to be permanently present)
XXXXXXX Compounder (to be present when the aforementioned is being filled)
One representative from the Validation Department (to be present for entire
duration of filling)
Container Size and Line Speed

Container selection has a two-fold impact: Exposed Aperture and Filling Line Speed.
Therefore two different size containers are to be filled:
Smallest Size filled on each specific machine
This increases the filling rate (which should be set to maximum used for the
specific size container), while causing handling difficulty (risk).
Largest Size filled on each specific machine
This represents the slowest operational (filling) speed (and should be set to the
minimum speed normally used for the specific size container). This also
represents the worst-case contamination risk, as these containers tend to have
the largest filling aperture, which increase the risk of aerial contamination
entering.
Filling Medium
Normal product (which may be growth inhibiting, sustaining or promoting) is
substituted with a medium, which is ideal for maximal proliferation of microorganisms.
Interventions
As per normal filling operation, interventions must take place. This is to include (but
may not be limited to):
At least one needle change per run
At least one simulated (or actual) machine breakdown per run
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10. FILLING METHODOLOGY

Below describes the methods for both products sterilized by filtration and aseptically
compounded product.
General
10..1. For process as well as filling machine details, refer to the attached Batch
Documentation (Appendices 1 5).
10..2. The entire process (from compounding through filling) is to be videotaped for
review and problem resolution. Ensure moving of the Video Camera as to
capture operations of all compounding and filling lines, as far as practical.
10..3. All containers must comply to the following:
10..3.1. Must be of clear glass, of the quality as per in-house specification.
10..3.2. As a cost-saving measure, non-approved containers may be used in a
media fill, provided that such use does not compromise the integrity of
the Media Fill (i.e. units rejected on the basis of dimensional non-
conformity) may be used.
10..3.3. Bungs must comply to all quality requirements and must be approved
by Quality Assurance
10..3.4. All vessel types used during standard production must be used in the
Media Fill, e.g. direct filling will not be allowed if transfer and collecting
vessels are used as norm, and visa versa.
10..3.5. No deviation from standard operations will be allowed during the Media
Fill operation.
10..3.6. Target is 3000units per run. At least 3200 units must be filled and
incubated in order to allow for any breakages that may occur.
10..3.7. Media Fill Volume and Media Batch Sizes have been specified in the
attached Batch Books (Appendix 1 5). This must be strictly adhered
to.
10..3.8. Environmental Monitoring shall be performed as per standard
operation, although additional monitoring may be indicated. This shall
include Settle Plates, Contact Plates, Air counts (both viable and non-
viable), Finger Dabs, etc.
Aseptically Filled Product, Sterilized by Filtration

10..1. Identify the largest, as well as the smallest, routinely filled container for each
filling machine/process.
10..2. Prepare components and equipment as per control document and procedural
instruction (refer attached Media Fill Batch Books).
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10..3. Prepare sufficient media (refer to point 11.2 for selection criteria) as per
manufacturers instructions (refer attached Media Fill Batch Books as well as
point 10.2 Aseptic Compounding).
10..4. Carry out standard machine set up, observing all necessary precautions and
aseptic technique.
10..5. All compounding and filling operations must be carried out as per standard
operating procedure (Refer SVP9209157 SVP Mixing Room Operations;
SVP9209159#9809405 Filter Integrity Testing; SVP9609336 Bulk Product
Transfer of SVP Product from Mixing to Filling; SVP9209151 General Rules
and Precautions for working in the SVP Filling Room).
10..6. Each Batch of Media shall be continuously sparged with Nitrogen throughout
the filling process.
10..7. Included in the Media Fill Challenge, for each machine, must be at least one
needle change intervention (Refer procedure SVP9208126 Filling Needle
Change) as well as one stoppage per run to simulate production breaks. All
media filled containers specific to and around these interventions must be
clearly identified.
10..8. Sufficient volume of media is to be filled into each container as to be able to
coat the entire internal surface upon being swirled. A minimum volume of half
the volume of the container is recommended.
10..9. Fill a minimum of 3000 (target of 3200 to 3500) ampoule/vials of the required
size to standard fill volume, and submit the containers (in suitable packaging)
to the Validation Department for incubation.
10..10. An additional two runs will be required, however refer to point 13 for
rules guiding the reduction of number of runs required.
10..11. Incubate all containers, as specified under point 11.3 & 11.4. At the end
of the incubation period, all containers are inspected for growth by the
Microbiology Laboratory. Staff from other areas may be used to assist in the
inspection process, however this will only be allowed once the Microbiology
Laboratory Manager is satisfied with such staffs ability of distinguish sterile and
compromised containers.
10..12. Any ampoules showing growth shall be crack detected to rule out
process damage. Any vials showing growth shall be visually checked for any
signs of damage.
Aseptically Compounded Product

10..1. XXXXXXX is only filled into one vial size, which is 2ml. As the purpose of this
challenge is only to demonstrate method suitability, the run is only to be
executed once.
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10..2. Prepare components and equipment as per control document and procedural
instruction (refer attached Media Fill Batch Book Appendix 5).
10..3. All compounding and filling operations must be carried out as per standard
operating procedure (Refer SVP9209157 SVP Mixing Room Operations;
SVP9209159#9809405 Filter Integrity Testing; SVP9609336 Bulk Product
Transfer of SVP Product from Mixing to Filling; SVP9209151 General Rules
and Precautions for working in the SVP Filling Room; SVP9305193
XXXXXXX Aseptic Compounding).
10..4. Media (refer to point 11.2 for selection criteria) is prepared using Water-for-
Injection, as per standard media fill practice, and is transferred to the
XXXXXXX Compounding Area. Sterilization is by filtration.
10..5. In the XXXXXXX Compounding Area, pre-sterilized (by Gamma-irradiation)
Cake Flour is used to mimic the normal compounding procedure. In other
words, the XXXXXXX compounding method is used, substituting
Medroxyprogesterone for Cake Flour (in a ratio of 1:4.5; Flour :
Medroxyprogesterone Acetate). For compounding instructions, refer to
procedure SVP9305193 XXXXXXX Aseptic Compounding).
10..6. Carry out standard machine set up, observing all necessary precautions and
aseptic technique.
10..7. As the challenge is only for actual Compounding step, needle changes and
breakdowns need not be simulated.
10..8. As the filling operation is independently challenged, actual fill into final dosage
form is not required as part of this study. All aseptic compounding and sampling
procedures are however carried out as per normal.
10..9. Fill a minimum of 3 x 5L, pre-sterilized containers (Schott Bottles are suitable)
aseptically, and submit the containers (in suitable packaging) to the Validation
Department for incubation.
10..10. An additional two runs will be required, however refer to point 13 for
rules guiding the reduction of number of runs required.
10..11. Incubate all containers, as specified under point 11.3 & 11.4. At the end
of the incubation period, all containers are inspected for growth by the
Microbiology Laboratory. Staff from other areas may be used to assist in the
inspection process, however this will only be allowed once the Microbiology
Laboratory Manager is satisfied with such staffs ability of distinguish sterile and
compromised containers.
NOTE a A Control Report document must be drawn up for each validation

: . and appropriately completed with all necessary details.
a. b. Each validation run requires the protocol (Media Fill Batch Book)
to be completed in its entirety. All equipment must be re-
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prepared, sterilized and the process started afresh for next

validation run. A minimum of three runs of both smallest and
largest unit routinely filled on each specific machine must be
carried out on that machine.
c. c. Details of any problems experienced during runs must be
recorded in the Control Report document.
d. d It is critical that careful attention be given to post validation
. cleaning and sanitization of equipment and area. It is
recommended that a Fumigation of the filling area be carried out
at completion of the Media Fill (Refer procedure VAL 0107538).
11. MEDIA FILL TEMPERATURE AND MEDIA SELECTION RATIONALE

GENERAL
In the case of Aseptic Challenges / Media Fills, intent is to establish the presence of
viable organisms in the finished product. As the organisms may be damaged or
weakened by the preparatory steps, conditions optimum for bacterial proliferations
should be pursued within the container to be challenged. Not only will this speed up
bacterial multiplication, making it easier to detect the presence of the organisms with
the naked eye, but also serves to speed up organism recovery and regeneration post
preparation and filling activities. Although this would generally appear to be over
compensating or excessive/unrealistic worst-case, it must be considered the
organism may have two years (or even longer) to recover from the trauma should it be
present in finished product destined for the market place.
These optimum conditions are supplied by:

1. Providing a suitable, nutritious medium at the optimum pH, etc. for the organisms
to proliferate
2. Ensuring that the containers are maintained at the optimum temperature required
to ensure ideal growth rates
NUTRIENT PROVISION
Tryptone Soy Broth (TSB) is used as medium for various reasons:
1. It is versatile, all-purpose medium, that supports growth of many fastidious
organisms
2. Supports growth of aerobes, facultative anaerobes, certain fungi
3. No serum addition required
4. Has a high nutrient value
5. Maintained with a pH of 7.2 by inclusion of a phosphate buffer (which
mimics human physiological pH)
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Main shortcoming is lack of support for strict anaerobes
NOTE a. Growth promotion studies are to be performed on each lot of

: media used in the media fill.
e. b. In the case of Aseptic Compounding, growth study should be
performed after the media has been sterilized.
f. c. In addition, it must be demonstrated that the sterilized Cake Flour
does not negatively influence bacterial proliferation.
TEMPERATURE SELECTION
Temperature is one of the most important environmental factors influencing the growth
and survival of microorganisms. It can affect living organisms in either of two opposing
ways. As temperature rises, chemical and enzymatic reactions in the cell proceed at
more rapid rates and growth becomes faster. However, above a certain temperature,
proteins, nucleic acids, and other cellular components are sensitive to high
temperatures and may be irreversibly denatured. Usually, therefore, as the
temperature is increased within a given range, growth and metabolic function is
increased to a certain point where inactivation reactions set in. Above this point cell
functions fall sharply to zero.
Microorganisms are usually divided into five groups according to their optimum growth
temperatures:
Organism Type Growth

Range
Psychrophiles <0C - <20C
Psychrotroph 0C - >25C
Mesophiles 15C - 45C
Thermophiles 50C - 70C
Extreme 70C - >100C
Thermophiles
Historically, the bacteria encountered in the clean room have been identified as
mesophiles (15C - 45C) and facultative psychrophiles (0 - 20C) and are usually
grown at temperatures from 20C - 37C.
Various recommendations and requirements are available as to incubation
temperature selection. According to USP24 (<71> - Sterility Testing) incubation time
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for microbial recovery are given as 32.5C2.5C for bacteria (with an incubation time
of 7 days) and at 22.5C2.5C for Yeasts and Molds (with an incubation time of 7
days). Therefore, assessment is to be performed after a minimum of 14 days. The SA
GMP Guide supports this requirement.
As it is impractical to duplicate aseptic challenge trials (in addition to the introduction

of an additional variable) the same containers shall be incubated at both temperature
ranges.
Note a Incubation temperature is given as a target. Although it is recommended

: that above temperatures be followed, some degree of variation will be
acceptable.
b Because of the risk of bacterial protein denaturation, temperatures above
37C should be avoided, even for brief periods of time.
INCUBATION METHOD
Incubation is to take place in the Media Fill Incubation Chamber, located in the
Warehouse. As discussed under point 11.3, a two-tier incubation method is used. Total
incubation period not less than 14 days (as per standard practice for all aseptically
filled products).
Week 1: 25C (22.5C2.5C; i.e. 20-25 C) (Room Temperature)

Incubation at 25C for 7days will allow for optimal cultivation of molds and
yeasts, while supporting growth of bacterial contaminants
Week 2: 35C (32.5C2.5C; i.e. 30-35C)

Incubation at 35C for 7days will allow for optimal cultivation of bacterial
contaminants, while supporting growth of mold or yeast contaminating
organisms.
Upon loading of the filled containers into the Incubation Chamber, each package is to
be gently inverted, as to assure coating of all internal surfaces of the container with
media.
11.5 USE OF CAKE FLOUR IN ASEPTIC COMPOUNDING CHALLENGE

Cake Flour is used in this instance due to its characteristics of:
1. Similar consistency and particle size to Medroxyprogesterone
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2. Difficult wetability
3. Clumping
4. Insolubility
12. ACCEPTANCE CRITERIA

Less than 0.1% contamination rate.
A minimum of three runs for each Line / process in both largest and smallest
container size normally process on each specific machine. For details on
reduction of the number of runs, refer to point 13.
All environmental results must comply with standard specification. For non-viable
particulate limits, refer to the Bodene Airclass Monitoring Policy and Federal
Standard 209E / ISO14644.
NOTE: a In the event of any unsatisfactory results a full

. investigation must be carried out, assignable causes
determined and necessary corrective action taken before
attempting validation repeat.
b In addition, all operators and equipment involved in the
. affected run shall be restricted to the filling of Terminally
Sterilized product until such investigation has been
completed and ratified by the QA Manager.
NOTE c. Any containers showing growth must be further cultured to
: identify the contaminant microorganism.
d The growth promoting ability of the medium must be
. demonstrated by means of controlled challenge with low
levels of suitable microorganisms.
13. NUMBER OF RUNS REQUIRED

Although practice is to perform trials in triplicate, under certain conditions, the
number of runs for a Media Fill may be reduced.
In order for such reduction, the following criteria must be satisfied:
13..1. No process failures for the previous three consecutive media fills.
13..2. Failures may only by classed as assignable and non-process related
when:
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13..2.1. They have been demonstrated to be personnel related (operator

to be removed from Filling Room immediately and only re-
admitted upon successful qualification Refer Val 133);
13..2.2. Process deviation from normal practice (to be corrected
immediately and reported on. Refer point 14.2);
13..2.3. Filter Failures, total equipment failure or other type on
compromise of the area;
13..2.4. Sterilization failure of componentry (full autoclave investigation
and requalification required).
Where so indicated, number of runs required may be reduced to two.

Upon completion of two consecutive Media Fills, without any process failures
(barring assignable failures as discussed under point 13.2.2), the Media Fill
requirement may be reduced to one run per line, for both largest and smallest
containers filled on that line.
Should a process failure be recorded at any time, revert back to three runs per
line, for both smallest and largest containers filled.
14. REPORT
Ensure timeous recovery of data, record sheets and signatures for report
compilation and presentation.
The report is to include Investigations into run failures (if any), which are to be
signed off by the Production Manager, QA Manager and Managing Director. Such
investigation is to include assignable cause, as corrective action taken, as well as
the date of the repeat Media Fill. In addition, the endorsement is to include the
timeframe of the moratorium on Aseptic Processing on the affected lines /
processes as well as status of product already filled.
Incubation Temperature Report is to be issued and attached to the final document.
Results for each Filling Line to be kept on file by the Validation Department and
records are to be readily available to the Department, Production and the
Inspectorate.
Report all results to the Validation and Production Departments.
15. INVESTIGATION OF FAILURES

In the event of any unsatisfactory results a full investigation must be carried out,
assignable causes determined and necessary corrective action taken before
attempting validation repeat.
Such investigation shall include:
15..1. Container integrity verification
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15..2. Contaminant identification (to at least genus level)

15..3. Identification of possible source of the organism (wherever possible)
15..4. Batch Documentation review
15..5. Review of environmental results
15..6. Review of the Media Fill Video record
15..7. Review of any breakdowns, interventions or deviations
Issue a Failure Investigation Report, containing at least the following:
15..1. A summary of the occurrence
15..2. A listing of all systems investigated, including outcome, regardless whether
positive or negative
15..3. A conclusion as to cause of the failure
15..4. Any corrective action taken
15..5. List of recommendations
15..6. Outcome of the repeat study
15..7. This document is to be signed by the Validation committee
The Investigation report is to be kept on file with the Media Fill results.
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Title: SVP Aseptic Media Fill Simulation Testing Protocol (Aseptically Filled Products)

Number: Val 01-4 Copies to: Distributed upon request, as

MEDIA FILL PROTOCOL

Equipment/system name: 6000/hr SVP Ampoule Filling Machine

Protocol number : Val 01-4

Asset number: As per finance

Model: F97/22-K-TDB Liquid filling machine

Serial number: Filler: RA3051

Department: Multi product filling suite

13. NUMBER OF RUNS REQUIRED 15

15. INVESTIGATION OF FAILURES 16

To demonstrate the capability of the aseptic process to produce sterile drug

Validation of Aseptic Pharmaceutical Processes (Carelton & Agallaco)

Aseptic Filling: Part of aseptic processing where a pre-sterilized product

Aseptic Processing: Handling sterile materials in a controlled environment, in

Aseptic Compounding: A process whereby two or more materials are brought

QA Manager / QA Release Pharmacists

9. WORST CASE RATIONALE

The following criteria Worst Case criteria should be considered:

Filling Room Complement

One representative from the Microbiological Laboratory (sampling; enters when

Container Size and Line Speed

10. FILLING METHODOLOGY

Aseptically Filled Product, Sterilized by Filtration

Aseptically Compounded Product

NOTE a A Control Report document must be drawn up for each validation

prepared, sterilized and the process started afresh for next

11. MEDIA FILL TEMPERATURE AND MEDIA SELECTION RATIONALE

These optimum conditions are supplied by:

Main shortcoming is lack of support for strict anaerobes

NOTE a. Growth promotion studies are to be performed on each lot of

Organism Type Growth

As it is impractical to duplicate aseptic challenge trials (in addition to the introduction

Note a Incubation temperature is given as a target. Although it is recommended

Week 1: 25C (22.5C2.5C; i.e. 20-25 C) (Room Temperature)

Week 2: 35C (32.5C2.5C; i.e. 30-35C)

11.5 USE OF CAKE FLOUR IN ASEPTIC COMPOUNDING CHALLENGE

12. ACCEPTANCE CRITERIA

NOTE: a In the event of any unsatisfactory results a full

13. NUMBER OF RUNS REQUIRED

13..2.1. They have been demonstrated to be personnel related (operator

Where so indicated, number of runs required may be reduced to two.

15. INVESTIGATION OF FAILURES

15..2. Contaminant identification (to at least genus level)

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