Aseptic process Validation, Simultation.doc

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Guidelines for Process Simulation Tests (PST) for Aseptic Dispensing Processes

Produced By

A Working Group of the Scottish Aseptic Services Specialist Interest Group and the

Scottish Quality Assurance Specialist Interest Group

Contents

Introduction

1. Process simulation test parameters

1.1. Approaches to PST

1.2. Frequency of PST

1.3.Number of containers filled in a PST

1.4. Scheduling of PST

1.5. PST controls

2. Materials for process simulation tests

2.1. Equipment/disposables

2.2. Growth media

3. Aseptic preparation processes

3.1. General procedure for performing process simulation tests

3.2. PST for an adult parenteral nutrition bag

3.3. PST for paediatric and neonatal TPN

3.3.1. PST for neonatal TPN using an Automix compounder

3.3.2. PST for neonatal TPN using syringes

3.4. PST for reconstitution of a powder with addition to an infusion bag3.5. PST for an IV bolus following reconstitution of a product in a vial

3.6. PST for an IV infusion using a reconstitution device

3.7. PST for a pump device (e.g. CADD pump)

3.8. PST for IV paediatric bolus syringes following reconstitution of a product in a vial

4. Incubation of completed tests

5. Analysis and interpretation of PST

6. Flow chart for action following PST fails

Definitions

References

Appendix I - Sample protocol for process simulation tests

Appendix II - Suppliers of growth media for process simulation tests

Appendix III - Sample worksheets/report forms for PST

INTRODUCTION

This document has been prepared in response to a requirement from the Scottish Aseptic Services Specialist

Interest Group (SASSIG) and the Scottish Quality Assurance Specialist Interest Group (SQASIG) for guidance

on process simulation tests for aseptic dispensing processes. The document aims to provide information on

various aspects relating to process simulation tests for generic aseptic dispensing processes. The information it
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ESSEShttp://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.1http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.2http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.3http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.3.1http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.3.2http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.4http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.5http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.6http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.7http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#3.8http://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#INCUBATION%20OF%20COMPLETED%20TESTShttp://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#ANALYSIS%20AND%20INTERPRETATION%20OF%20PSThttp://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#FLOW%20CHART%20FOR%20ACTION%20FOLLOWING%20PST%20FAILShttp://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#Definitionshttp://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#Referenceshttp://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#Appendix%20Ihttp://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#Appendix%20IIhttp://www.astcp.scot.nhs.uk/Old_site/Resources/ASTCP/Guidelines/guidelines/Process%20Simulation%20Tests.htm#Appendix%20III


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contains is intended to be used by both aseptic services managers and quality assurance professionals with

responsibilities for aseptic dispensing activities.

Much of the information contained in this guideline document has been obtained from reference documents [1,

2, 3]. If there is doubt about any aspect of process simulation tests, reference should be made to the original

documents. The information in this document is intended as guidelines only and must be adapted to individual

practices in each hospital.

Process simulation tests (PST) are techniques used to simulate an aseptic preparation process in combiningproduct or materials with product containers and closures, using microbiological growth medium in place of

product. The test is an overall assessment of the microbiological acceptability of an aseptic process and it allows

for evaluation of all steps in the process. PST are used to verify the acceptability of all aseptic preparation

processes and they should be considered as part of the overall validation activities. The PST devised should

mimic as closely as possible the aseptic preparation processes used in practice.

The results of PST should be considered along with other aspects of aseptic preparation such as:

environmental standards, monitoring and control - any monitoring of airborne and surface, viable and non-

viable particles, personnel monitoring including assessment of operator gloves/finger dabs.

operator training - trainee competence and assessment of competence, staff qualification to carry out

aseptic processes.

It must be stressed that in considering results of PST it is impossible to separate the operator from the process.

Any failure of a PST should consider not only the process, but the status of the operator completing the PST. It

is advised that completion of PST is carried out as part of operator training. Completion of PST by operators

allows the aseptic manager to assess the competence of personnel to complete aseptic processes and should

form part of the overall qualification of staff to operate in an aseptic facility.

Consideration should also be given to the preparation of a protocol for PST for aseptic dispensing processes

(Appendix I). The protocol should define the objective of PST, the methods to be used, including a description

of the work instructions or procedures to be operated when performing the PST, the test frequency, how theresults will be analysed/interpreted and what actions may be taken as a result.

1. PROCESS SIMULATION TEST PARAMETERS

The approach, frequency and number of containers filled in a PST are interconnected and should take into

consideration the number of operators working in an aseptic facility (dedicated or rotational staff), the total

number of containers filled per annum using each process and whether or not the operators are also completing

aseptic transfer tests (simple manipulations, unrelated to PST) for approval of aseptic technique. Some of the

possible permutations for the approach, frequency and number of containers filled in a PST are outlined below.

1.1. Approaches to PST

There are 2 approaches that may be taken when considering aseptic dispensing processes:

(a) treat every item prepared as a single lot

OR (b) consider all products prepared in the same dispensing session as a lot

The approach adopted will help to decide the frequency of performing PST and the number of containers filled.

1.2. Frequency of PST

The frequency of PST will depend on the approach adopted for performing PST and to a lesser extent on how

often the preparation process is used in practice.

Where the process is used often (e.g. daily) a PST may be carried out:
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(a) by every operator 3 monthly for each process

OR (b) by an operator at least 6 monthly or annually for each process if the

operator completes separate operator aseptic transfer tests to test aseptic

technique.

If the process is used infrequently then a PST should be carried out at least on an annual basis.

In addition, a PST should be carried out whenever there is any change to the process (however small it mayseem) e.g. modifications in equipment or modifications to immediate product containers or disposables.

1.3. Number of containers filled in a PST

The number of containers filled in a PST may be:

i.) a single container

ii.) the number normally filled in a given work session

iii.) the number filled in a pre-determined time period e.g. 1 hour

iv.) such that a sufficient number of containers are filled to properly determine the contamination rate (e.g.

3000 containers would need to be filled to be able to detect a contamination rate of 0.1% with

95% confidence)

i.), ii.) and iii.) above are capable of being carried out in the hospital environment.

The filling of 3000 containers is an unrealistic number of tests to perform for aseptic dispensing processes in the

hospital environment (based on the associated cost, number of processes to be considered and the number of

containers filled per annum by each process).

It is preferable if the total number of containers filled per annum for each PST reflects the overall workload of

the facility i.e. where large numbers of IV additives are filled a higher percentage of PST should be

performed for this process. A recommended figure for PST may be 1% of the total number of e.g. additives

prepared per annum.Where the process is used infrequently the number of containers filled in the PST should reflect the number of

containers filled per annum for that process, such that a minimum of 5 containers or 0.5% of the total number

are filled, whichever is the greater.

Analysis of the results of the PST (where small numbers of containers are filled) are considered later in section

5.

1.4. Scheduling of PST

The PST should be independent of normal work in the unit. They may be scheduled for various times during

normal working days/sessions. It is preferable, however, to schedule the PST at the end of a working session as

this generally represents worst case conditions where operators are tired (hence more liable to be careless or

make mistakes) and aseptic facilities are at their dirtiest.

1.5. PST controls

Prior to carrying out or implementing a system for PST it is essential that positive control tests are performed.

Positive control tests should not be carried out in aseptic facilities. Assistance or advice on carrying out such

tests should be sought from medical microbiology or the local quality control laboratory.

The control tests should demonstrate the growth promoting ability of the media in its final filled container using

filled control containers challenged with low levels of micro-organisms. The level of challenge should be 10 -

100 viable micro-organisms per container. The challenge should be carried out in duplicate for each type of

micro-organism and each type of container system.

The same incubation parameters for containers under test (i.e. without challenge micro-organisms) should be

used. The growth capability of the medium is considered acceptable if early and copious growth is observed in

at least one of the two test containers filled for each of the challenge micro-organisms.


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Where growth of a particular micro-organism is not observed then consideration should be given to using an

alternative media type which will support the growth under test conditions.

The recommended test micro-organisms are:

B. subtilis, C. albicans, C. sporogenes (Compendial test micro-organisms).

Alternatives may be used e.g.E. coli, P. aeruginosa, S. aureus, A. nigerprovided the range of micro-organismsused covers both bacterial (aerobic/anaerobic, sporing) and fungal species.

2. MATERIALS FOR PROCESS SIMULATION TESTS

2.1. Equipment/disposables

The equipment and disposables used are specified in the descriptions of generic aseptic processes. Individual

sites may have specific requirements and these should be adopted when implementing the PST at that site.

2.2. Growth media

The growth media used during the PST requires careful consideration. The following factors must be

considered:

i.) Selectivity - any growth media used should have low selectivity and be capable of supporting a wide

spectrum of micro-organisms. In addition the media should have good clarity and low levels of visible solids

(where filtration may be used during the PST).

ii.) Concentration - the concentration of the media should be such that it has proven growth capability. Use of

single or double strength media can be considered. Dilution of growth media e.g. by 10%, below normal single

strength should not affect the growth capability of media used. Where the dilution of media is greater than this

the growth capability of the media should be determined.

iii.) Media utilisation - it is preferable if the media used is pre-sterilised in order that the aseptic environment is

not put at risk from spillages or aerosol generation.

Media may be purchased from a variety of suppliers. A certificate of conformity/fertility/sterility should be

obtained for each batch/delivery of material.

Given the considerations above, the media type used may vary but a good general choice of media is Tryptone

Soya Broth which is available in a variety of presentations.

A list of suggested media types and recommended suppliers is included in Appendix II. It should be noted that

some materials are exclusive to a single manufacturer. The Appendix will be reviewed on a regular basis to

ensure that all manufacturers of appropriate materials are included.

3. ASEPTIC PREPARATION PROCESSES

In order to perform a PST the process must be well defined and documented by procedures or work instructions.

A simulation test can then be developed for that process. The PST should imitate as closely as possible all the

steps in the aseptic preparation process (compounding, filtration, filling and sealing) substituting growth media

for product.

The PST may be broad in its interpretation of the process in order to allow for minor variations betweendifferent sites, for instance the use of different types of filters or filling devices etc.

Included are recommendations for PST for generic aseptic processes as defined in the Aseptic Dispensing

Process Guidelines. Equipment and materials that would normally be used in specific preparation processes
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e.g. for cytotoxic products where vent needles/filters or mini-spikes (or equivalent) may be used, should be

incorporated into the PST.

3.1. General procedure for performing process simulation tests

1. Ensure that the PST is performed in an appropriate clean air device e.g. laminar air flow cabinet, safety

cabinet or isolator, and that the PST is preferably scheduled for the end of a work session.

2. Enter all necessary details on the worksheet e.g. hospital site, date of test, operator name, designation andclean air device to be used.

3. Collect together all necessary materials as specified on the worksheet and record manufacturer, batch number

and expiry date details. Do not use growth media which has expired.

4. Collect together all necessary equipment and final container(s) as specified on the worksheet. Do not

substitute alternative items of equipment from those listed.

5. Enter the area where the test is to be performed according to the appropriate standard operating procedure.

6. Prepare the clean air device following standard operating procedure.

7. Transfer worksheet, materials, equipment and final container(s) to the clean air device following standard

operating procedures.

8. Ensure that the necks of ampoules, vial tops and minibag access ports are swabbed with a sterile alcohol

impregnated swab e.g. Alcowipe. Allow the alcohol to evaporate before continuing.

9. Follow the method specified on the worksheet to prepare media filled unit(s). The use and assembly of

needles and syringes should be as per normal work practice. Withdrawal of liquid from vials, ampoules and

minibags and the subsequent transfer to other containers should be as per normal work practice or as described

in the PST.

10. Dispose of rubbish and used equipment in the clean air device following standard operating procedures.

11. Disinfect the clean air device after use following standard operating procedures.

12. Remove media filled unit(s) from the clean air device and label as specified on the worksheet.

13. Attach a sample label to the worksheet.

14. Enter initials of labeller and person despatching unit(s) to the laboratory on the worksheet.

15. If appropriate, seal unit(s) in a heavy duty polythene bag with the worksheet.

16. Despatch immediately to the incubation laboratory. Do not refrigerate unit(s) prior to despatch.

3.2. PST for an adult parenteral nutrition bag

3.2.1. Equipment and materials

Per test the following is required:

1 x 3litre 5-lead empty EVA bag

1 x 500ml Sterile TSB bottle3 x 100ml Sterile TSB minibag

3 x 10ml Sodium Chloride 0.9% ampoule

1 x 10ml Sterile Dried TSB vial

3 x 10ml syringe


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1 x air vent needle

Needles

Alcowipes

3.2.2. Procedure

1. Reconstitute the vial of dried TSB with 5ml sodium chloride 0.9%. Withdraw the contents of the vial and

inject into one of the 100ml TSB minibags.

2. Using a 10ml syringe transfer a further 10mls sodium chloride 0.9% into a second 100ml TSB minibag.

3. Using a 10ml syringe transfer a third 10ml aliquot of sodium chloride 0.9% into the third 100ml TSB

minibag.

4. Taking the empty EVA bag connect the lines to the constituents as follows:

Line 1 minibag prepared in step 1



Line 4 500ml TSB bottle (vented with air vent)Line 5 Clamped closed

5. Hang each of the infusion containers onto the hanging rail, and place the empty bag into the vacuum

chamber, ensuring that there are no kinks in the tubing.

6. Run the infusions in. On completion, remove from the vacuum chamber, gently mix the contents, and clamp

the line closed. Remove the additive lines and seal the end with a luer loc cap .

3.3. PST for paediatric and neonatal TPN

No two sites in Scotland prepare paediatric and neonatal TPN in exactly the same way. Therefore, considerationshould be given to the following:

1. If more than one bag is filled at once, what is the routine batch size prepared?

2. Are automated filling systems used?

3. What is the final container - bag, bottle, syringe?

4. Are filters or filter needles used? Are they reused?

5. Is a volume of liquid withdrawn from full bags prior to filling?

6. Are all volumes measured by syringe prior to filling bag?

7. How many additions are made?

Two PST are given:

3.3.1. PST for neonatal TPN using an Automix compounder


The principles outlined in these tests should be used and adapted to fit the local situation.

3.3.1. PST for neonatal TPN using an Automix compounder.

3.3.1.1. Equipment and Materials


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Per test the following is required :

6 x 100ml Sterile TSB minibag



1 x Automix compounder transfer set

1 x Automix connector set

1 x 10ml syringe

3 x 5ml syringeNeedles

3 x 500ml EVA bag

Alcowipes

3 x 0.22micron filter

3.3.1.2. Procedure

1. Set up Automix High Speed Compounder, spiking 3 x 100ml TSB minibags as supply containers.

2. Fill 3 empty EVA bags using 50ml from each supply container to fill each bag. Close filled bags and shake to

mix contents.

3. Reconstitute the vial of dried TSB with 10ml sodium chloride 0.9%.

4. Draw up approximately 3ml of the reconstituted TSB solution, attach filter and needle, adjust to 2ml and add

to a previously filled TSB bag.

5. Repeat for each bag.

6. Seal ports and shake to mix contents.


3.3.2.1. Equipment and Materials


1 x 100ml Sterile TSB vial



2 x 10ml syringe


Needles

1 x Minispike

1 x 50ml Luer loc syringe

1 x Luer loc syringe cap

Alcowipes

3.3.2.2. Procedure


2. Draw up 3ml of reconstituted TSB solution, attach filter and needle, adjust to 2ml and add to 100ml TSB vial.

3. Draw up 10ml of sodium chloride into a 10ml syringe, attach filter and needle, adjust volume to 9ml and addto 100ml TSB vial.

4. Shake filled TSB vial to mix.


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5. Using the minispike, withdraw 50ml of the TSB solution from the 100ml vial into the 50ml Luer loc syringe,

remove any air and cap syringe.

3.4. PST for reconstitution of a powder with addition to an infusion bag

3.4.1. Equipment and Materials





2 x 10ml syringe

1 x Additive cap

Needles

Alcowipes

3.4.2. Procedure


2. Withdraw 10ml of reconstituted TSB solution and transfer the contents of the syringe to the TSB minibag.

3. Shake to mix contents and seal additive port.

3.5. PST for an IV bolus following reconstitution of a product in a vial





1 x 10ml syringe

Needles

Alcowipes

1 x syringe cap

3.5.2. Procedure


2. Withdraw 10ml of reconstituted TSB solution into the 10ml syringe, remove any air and cap syringe.

3.6. PST for an IV infusion using a reconstitution device





1 x Reconstitution device

Alcowipes1 x Additive cap

3.6.2. Procedure
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1. Attach one end of the reconstitution device to the vial of dried TSB and the other into the additive port of the

TSB minibag.

2. Squeeze the minibag gently to transfer some of the liquid to the vial of dried TSB through the reconstitution

device.

3. Shake to dissolve the contents of the vial.

4. When the contents of the vial have dissolved, invert and push the air from the bag back into the vial. Release

the pressure and allow the reconstituted TSB to flow from the vial to the minibag.

5. Repeat to ensure all powder in the vial has been dissolved and the resulting solution has transferred to the

minibag.

6. Remove reconstitution device from minibag.

7. Shake the minibag to mix the contents and seal additive port.

3.7. PST for a pump device (e.g. CADD pump)


Per test the following is required



1 x Pump Set

1 x 2ml syringe

1 x 10ml syringe


Alcowipes

3.7.2. Procedure

1. Withdraw 35ml of TSB from one of the vials and inject into the empty pump set.

2. Withdraw 2ml of TSB from a 10ml TSB vial, and add to the pump set.

3. From the second 10ml TSB vial withdraw 5ml and add this to the pump set.

4. Mix contents of the set and remove any excess air before clamping the line closed and sealing the end withthe luer loc cap.

3.8. PST for IV paediatric bolus syringes following reconstitution of a product in a vial





1 x 10ml Luer loc syringe1 x 0.22m filter

4 x 1ml syringe

Needles
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4 x Syringe cap

Alcowipes

3.8.2. Procedure


2. Fill 4 x 1ml syringes with 1ml of reconstituted TSB solution through a 0.22m filter and needle.

3. Remove any air and attach syringe caps.

4. INCUBATION OF COMPLETED TESTS

The incubation conditions should be strictly controlled. A minimum incubation period of 14 days is

recommended. The 14 day incubation period will allow stressed or partially damaged micro-organisms the

chance to repair and replicate. Steps should be taken to ensure that all parts of the filled container come into

contact with growth media by rotating or inverting the containers as necessary. The temperature used for

incubation will depend largely on the growth medium used and the type of micro-organisms that are likely to be

present. The incubation temperature range with Tryptone Soya Broth is between 30 and 35C. Where alternate

media types are used suitable incubation conditions should be used. Incubation conditions should be monitoredand recorded to ensure that the appropriate incubation temperature is maintained throughout the incubation

phase.

It is advisable to examine containers for evidence of growth throughout the 14 day incubation period e.g. at days

3 or 4, day 7 and day 14. Examination of containers throughout the incubation period will allow early

identification of PST failures.

5. ANALYSIS AND INTERPRETATION OF PST

Following incubation of the test containers they should be examined for damage which might compromise the

integrity of the packaging system. Exclude any damaged containers when evaluating the test results. An

investigation into the cause of the damage should be carried out.

A PASS result is where no growth is present in any of the media filled containers. Where the result is a PASS

no action is required other than completion of the appropriate report form.

A FAIL is where growth is present in any of the media filled containers. For the levels of PST proposed (i.e.

very low number of containers filled) the presence ofanymicrobial contamination must be regarded as an action

limit.

Where the result is a FAIL the Responsible Pharmacist or QA Pharmacist should be contacted immediately and

action/investigation taken as suggested on the accompanying flow chart. Growth occurring in any container

should be identified (colony and cellular morphology, Gram stain as a minimum). This should assist in theinvestigation of the cause and route of the contamination. Record any action taken on the report form. Use the

reverse of the report form to record all investigations and outcomes following a fail result.


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6. FLOW CHART FOR ACTION FOLLOWING PST FAILS
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Definitions

Process simulation - a technique used to test the ability of an entire preparation process to combine product or

materials, product containers and closures, using microbiological growth medium in place of normal product.

Media fill - that part of a process simulation concerned with the filling of a microbiological growth medium

into product containers and sealing those containers to give an indication of the suitability of the filling process.

Sterility - the complete absence of living micro-organisms

References

[1] Technical Monograph No. 2 - Validation of aseptic filling for solution drug products. Parenteral Drug

Association Inc., Philadelphia PA. 1980.

[2] Parenteral Society Technical Monograph No. 4 - The use of process simulation tests in the evaluation of

processes for the manufacture of sterile products. The Parenteral Society, Swindon. 1993.

[3] Aseptic Dispensing Process Guidelines. The Scottish Aseptic Services Specialist Interest Group. 1996.

Appendix I

SAMPLE PROTOCOL FOR PROCESS SIMULATION TESTS

1. OBJECTIVE

To demonstrate that the procedures used in aseptic dispensing and the operators undertaking those procedures

are capable of maintaining the sterility of the products.

2. METHOD

Routine aseptic procedures will be performed by all operators, substituting microbiological media for usual

ingredients to produce broth-filled units which can then be tested for contamination.

These process simulation tests will be performed according to master worksheets to simulate the dispensing

procedure for each type of product routinely prepared in the aseptic unit.

Each test will be carried out using the clean air device and disposable equipment which would normally be used

to dispense the product.

3. TEST FREQUENCY

Each operator will complete one process simulation test for each process type at three monthly intervals to

remain approved to dispense that particular type of product.

Any operator may be tested more frequently at the discretion of the Responsible Pharmacist.

4. RESULTS

Media-filled units will be forwarded immediately to the incubation laboratory.

For a pass test result, media-filled units will show no bacterial growth after incubation for 14 days. A fail test

will be investigated with appropriate corrective action carried out and recorded.

Test failures will be reported immediately to the Responsible Pharmacist for the aseptic unit, and a full

investigation will be carried out.


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Appendix II - Suppliers of growth media for process simulation tests

Supplier: Unipath (Oxoid). Tel: 01256-816566. Fax: 01256-479525

Cat No. Media/Description Volume No./Pack

B0369M Tryptone Soya Broth in vial 100ml 10

B0369M Tryptone Soya Broth in vial 500ml 1

B0412V Tryptone Soya Broth (DS) in vial 500ml 1

Supplier: BioMrieux. Tel: 01256-461881. Fax: 01256-816863


44011 Tryptone Soya Broth (Inj cap) 100ml 12

Supplier: Cherwell Labs Ltd. Tel: 01869-355500. Fax: 01869-355545


225010 Tryptone Soya Broth vial CTE 100ml 25

125280 Tryptone Soya Broth (DS) vial CTE 100ml 25

226273 Tryptone Soya Broth DIN SC 100ml 25

226263 Tryptone Soya Broth (DS) DIN SC 100ml 25

227183 Tryptone Soya Broth DIN SC 500ml 12

227193 Tryptone Soya Broth (DS) DIN SC 500ml 12

Supplier: Area QC Laboratory, Western Infirmary, Glasgow. Tel: 0141-211-2811. Fax: 0141-211-2879

Media/Description Volume No./Pack

Tryptone Soya Broth vial 10ml Any size

Dried TSB vial 10ml Any size

Tryptone Soya Broth vial 50ml Any size

Tryptone Soya Broth vial 100ml Any sizeTryptone Soya Broth minibag 100ml Any size

Supplier: Southern Laboratories, Corby, Northants. Tel: 01536-403815. Fax: 01536-403814

Media/Description Volume No./Pack

Tryptone Soya Broth vial 10ml 144/25

Tryptone Soya Broth vial 20ml 144/25

Tryptone Soya Broth vial 50ml 48



Tryptone Soya Broth vial 900ml 12Tryptone Soya Broth (DS) vial 10ml 144/25

Tryptone Soya Broth (DS) vial 900ml 12

Key: DS = double strength

vial CTE = vial with centre tear off cap

DIN SC = DIN bottle with snap cap


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Appendix III - Sample worksheets/report forms for PST

Site: Written by

Address: Approved by

Date

Supersedes

PST WORKSHEET AND REPORT FORM Review date

PST FOR AN ADULT PARENTERAL NUTRITION BAG

HOSPITAL SITE DATE OF TEST

NAME OF OPERATOR DESIGNATION CABINET USED

INGREDIENTS QUANTITY MANUFACTURER AND

BATCH NO

EXPIRY DATE

500ml STERILE TSB BOTTLE

100ml STERILE TSB MINIBAG10ml SODIUM CHLORIDE 0.9% AMPOULE

10ml STERILE DRIED TSB VIAL

1

33

1

TYPE AND SIZE OF CONTAINER

1 x 3litre 5-lead empty EVA bag

EQUIPMENT

3x 10ml Syringe

1 x air vent needleNeedlesAlcowipes

METHOD

1. Swab top of vials and ports on all bags

2. Reconstitute the vial of dried TSB with 5ml sodium chloride 0.9%. Withdraw the contents of the vial and inject into one

of the 100ml TSB minibags.3. Using a 10ml syringe transfer a further 10mls sodium chloride 0.9% into a second 100ml TSB minibag.

4. Using a 10ml syringe transfer a third 10ml aliquot of sodium chloride 0.9% into the third 100ml TSB minibag.

5. Taking the empty EVA bag connect the lines to the constituents as follows:Line 1 minibag prepared in step 2

Line 2 minibag prepared in step 3Line 3 minibag prepared in step 4

Line 4 500ml TSB bottle (vented with air vent)Line 5 Clamped closed

6. Hang each of the infusion containers onto the hanging rail, and place the empty bag into the vacuum chamber, ensuringthat there no kinks in the tubing.

7. Run the infusions in. On completion, remove from the vacuum chamber, gently mix the contents, and clamp the lineclosed. Remove the additive lines and seal the end with a luer loc cap .

8. Label bags, seal in heavy duty polythene bag and send to incubation laboratory.

STORAGE Room temperature DESPATCH DEADLINE Must arrive at laboratory before 4.30 pm on same dayas test

AFFIX SAMPLE LABEL

825ml TSB EVA Bag

PROCESS SIMULATION TESTADULT TPN

LABELLED

BY

Hospital site: Date of Test: / /

Operator Name: Cabinet used:

DESPATCH BY

DATE TEST RECEIVED IN LABORATORY INCUBATION 30-35C for 14 days

TEST RESULT

(PASS/FAIL)

IMMEDIATE ACTION TAKEN ON RESULT

ORGANISMS ISOLATED

BACTERIOLOGIST DATE

RESPONSIBLE/QA PHARMACIST DATE


15/17

Site: Written by


Date

Supersedes


PST FOR NEONATAL TPN USING AN AUTOMIXCOMPOUNDER



INGREDIENTS MANUFACTURER

AND BATCH NO

EXPIRY

DATE

VOLUME

PER BAG

SPECIFIC

GRAVITY

6 x 100ml STERILE TSB MINIBAG

1 x 10ml STERILE DRIED TSB VIAL1 x 10ml SODIUM CHLORIDE 0.9% AMPOULE

150ml

} 2ml

1.18


3 x 500ml EVA BAG

EQUIPMENT

1 x Automix compounder transfer set

1 x Automix connector set1 x 10ml syringe3 x 5ml syringe

NeedlesAlcowipes


METHOD

1. Swab top of TSB vial and ports on TSB 100ml minibags2. Set up Automix High Speed Compounder, spiking 3 x 100ml TSB minibags as supply containers.

3. Fill 3 empty EVA bags using 50ml from each supply container to fill each bag. Close filled bags and shake to mixcontents.

4. Reconstitute the vial of dried TSB with 10ml sodium chloride 0.9%.5. Draw up approximately 3ml of the reconstituted TSB solution, attach filter and needle, adjust to 2ml and add to a

previously filled TSB bag.6. Repeat for each bag.

7. Seal ports and shake to mix contents.8. Label bags, seal in heavy duty polythene bag and send to incubation laboratory.


3x

AFFIX SAMPLE LABEL

3x 152ml TSB EVA Bag

PROCESS SIMULATION TESTNEONATAL TPN

LABELLED

BY



DESPATCH BY


TEST RESULT

(PASS/FAIL)


ORGANISMS ISOLATED 1ST BAG 2ND BAG 3RD BAG

BACTERIOLOGIST DATE



16/17

Site: Written by


DateSupersedes


PST FOR AN IV INFUSION USING A

RECONSTITUTION DEVICE




BATCH NO

EXPIRY DATE

10ml STERILE DRIEDTSB VIAL100ml STERILE TSB MINIBAG

11

TYPE AND SIZE OF CONTAINER100ml STERILE TSB MINIBAG

EQUIPMENT1 x Reconstitution device

Alcowipes

1 x Additive cap

METHOD

1. Swab top of vial and additive port on minibag2. Attach one end of the reconstitution device to the vial of dried TSB and the other into the additive port of the TSB

minibag.3. Squeeze the minibag gently to transfer some of the liquid to the vial of dried TSB through the reconstitution device.

4. Shake to dissolve the contents of the vial.5. When the contents of the vial have dissolved, invert and push the air from the bag back into the vial. Release the pressure

and allow the reconstituted TSB to flow from the vial to the minibag.6. Repeat to ensure all powder in the vial has been dissolved and the resulting solution has transferred to the minibag.

7. Remove reconstitution device from minibag.8. Shake the minibag to mix the contents and seal additive port.

9. Label minibag, seal in heavy duty polythene bag and send to incubation laboratory.

STORAGE Room temperature DESPATCH DEADLINE Must arrive at laboratory before 4.30 pm on same day

as test

AFFIX SAMPLE LABEL

100ml TSB Minibag

PROCESS SIMULATION TESTIV ADDITIVE

LABELLED

BY



DESPATCH BY


TEST RESULT

(PASS/FAIL)


ORGANISMS ISOLATED

BACTERIOLOGIST DATE



17/17

Site: Written by


Date

Supersedes


PST FOR IV PAEDIATRIC BOLUS SYRINGES




BATCH NO

EXPIRY DATE

10ml STERILE DRIED TSB VIAL

10ml SODIUM CHLORIDE 0.9% AMPOULE

1

1


4 x 1ml SYRINGE

EQUIPMENT1 x 10ml Luer loc syringe

1 x 0.22m filter


4 x Syringe cap

Alcowipes

METHOD

1. Swab top of vial and neck of ampoule


3. Fill 4 x 1ml syringes with 1ml of reconstituted TSB solution through a 0.22m filter and needle.

4. Remove any air and attach syringe caps.5. Seal syringes in heavy duty polythene bag.

6. Label bag and send to incubation laboratory.


AFFIX SAMPLE LABEL

4 x 1ml TSB Syringes

PROCESS SIMULATION TEST

LABELLEDBY

PAEDIATRIC BOLUS SYRINGES



DESPATCH BY


TEST RESULT

(PASS/FAIL)


ORGANISMS ISOLATED

1ST SYRINGE 3RD SYRINGE

2ND SYRINGE 4TH SYRINGE

BACTERIOLOGIST DATE


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