Anda di halaman 1dari 17

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 bag 3.5. 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

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 combining product 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 nonviable 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 the results 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:

(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 may seem) 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.) ii.) iii.) iv.) a single container the number normally filled in a given work session the number filled in a pre-determined time period e.g. 1 hour 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.

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. niger provided the range of micro-organisms used 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 between different 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

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 and clean 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 bottle 3 x 100ml Sterile TSB minibag 3 x 10ml Sodium Chloride 0.9% ampoule 1 x 10ml Sterile Dried TSB vial 3 x 10ml syringe

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 2 minibag prepared in step 2 Line 3 minibag prepared in step 3 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, consideration should 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. 3.3.2. PST for neonatal TPN using an Automix compounder PST for neonatal TPN using syringes

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

Per test the following is required : 6 x 100ml Sterile TSB minibag 1 x 10ml Sterile Dried TSB vial 1 x 10ml Sodium Chloride 0.9% ampoule 1 x Automix compounder transfer set 1 x Automix connector set 1 x 10ml syringe 3 x 5ml syringe Needles 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. PST for neonatal TPN using syringes 3.3.2.1. Equipment and Materials Per test the following is required : 1 x 100ml Sterile TSB vial 1 x 10ml Sterile Dried TSB vial 2 x 10ml Sodium Chloride 0.9% ampoule 2 x 10ml syringe 2 x 0.22micron filter Needles 1 x Minispike 1 x 50ml Luer loc syringe 1 x Luer loc syringe cap Alcowipes 3.3.2.2. Procedure 1. Reconstitute the vial of dried TSB with 10ml sodium chloride 0.9%. 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 add to 100ml TSB vial. 4. Shake filled TSB vial to mix.

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 Per test the following is required : 1 x 100ml Sterile TSB minibag 1 x 10ml Sterile Dried TSB vial 1 x 10ml Sodium Chloride 0.9% ampoule 2 x 10ml syringe 1 x Additive cap Needles Alcowipes 3.4.2. Procedure 1. Reconstitute the vial of dried TSB with 10ml sodium chloride 0.9%. 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 3.5.1. Equipment and Materials Per test the following is required: 1 x 10ml Sterile Dried TSB vial 1 x 10ml Sodium Chloride 0.9% ampoule 1 x 10ml syringe Needles Alcowipes 1 x syringe cap 3.5.2. Procedure 1. Reconstitute the vial of dried TSB with 10ml sodium chloride 0.9%. 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 3.6.1. Equipment and Materials Per test the following is required: 1 x 10ml Sterile Dried TSB vial 1 x 100ml Sterile TSB minibag 1 x Reconstitution device Alcowipes 1 x Additive cap 3.6.2. Procedure

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) 3.7.1. Equipment and Materials Per test the following is required 1 x 100ml Sterile TSB vial 2 x 10ml Sterile TSB vial 1 x Pump Set 1 x 2ml syringe 1 x 10ml syringe 1 x 50ml syringe Needles 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 with the luer loc cap. 3.8. PST for IV paediatric bolus syringes following reconstitution of a product in a vial 3.8.1. Equipment and Materials Per test the following is required: 1 x 10ml Sterile Dried TSB vial 1 x 10ml Sodium Chloride 0.9% ampoule 1 x 10ml Luer loc syringe 1 x 0.22m filter 4 x 1ml syringe Needles

4 x Syringe cap Alcowipes 3.8.2. Procedure 1. Reconstitute the vial of dried TSB with 10ml sodium chloride 0.9%. 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 monitored and 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 of anymicrobial 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 the investigation 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.

6. FLOW CHART FOR ACTION FOLLOWING PST FAILS

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.

Appendix II - Suppliers of growth media for process simulation tests Supplier: Unipath (Oxoid). Tel: 01256-816566. Fax: 01256-479525 Cat No. B0369M B0369M B0412V Media/Description Tryptone Soya Broth in vial Tryptone Soya Broth in vial Tryptone Soya Broth (DS) in vial Volume 100ml 500ml 500ml No./Pack 10 1 1

Supplier: BioMrieux. Tel: 01256-461881. Fax: 01256-816863 Cat No. 44011 Media/Description Tryptone Soya Broth (Inj cap) Volume 100ml No./Pack 12

Supplier: Cherwell Labs Ltd. Tel: 01869-355500. Fax: 01869-355545 Cat No. 225010 125280 226273 226263 227183 227193 Media/Description Tryptone Soya Broth vial CTE Tryptone Soya Broth (DS) vial CTE Tryptone Soya Broth DIN SC Tryptone Soya Broth (DS) DIN SC Tryptone Soya Broth DIN SC Tryptone Soya Broth (DS) DIN SC Volume 100ml 100ml 100ml 100ml 500ml 500ml No./Pack 25 25 25 25 12 12

Supplier: Area QC Laboratory, Western Infirmary, Glasgow. Tel: 0141-211-2811. Fax: 0141-211-2879 Media/Description Tryptone Soya Broth vial Dried TSB vial Tryptone Soya Broth vial Tryptone Soya Broth vial Tryptone Soya Broth minibag Volume 10ml 10ml 50ml 100ml 100ml No./Pack Any size Any size Any size Any size Any size

Supplier: Southern Laboratories, Corby, Northants. Tel: 01536-403815. Fax: 01536-403814 Media/Description Tryptone Soya Broth vial Tryptone Soya Broth vial Tryptone Soya Broth vial Tryptone Soya Broth vial Tryptone Soya Broth vial Tryptone Soya Broth vial Tryptone Soya Broth (DS) vial Tryptone Soya Broth (DS) vial Key: DS = double strength vial CTE = vial with centre tear off cap DIN SC = DIN bottle with snap cap Volume 10ml 20ml 50ml 100ml 500ml 900ml 10ml 900ml No./Pack 144/25 144/25 48 48 12 12 144/25 12

Appendix III - Sample worksheets/report forms for PST


Site: Address: Written by Approved by Date Supersedes Review date DATE OF TEST CABINET USED MANUFACTURER AND EXPIRY DATE BATCH NO

PST WORKSHEET AND REPORT FORM PST FOR AN ADULT PARENTERAL NUTRITION BAG HOSPITAL SITE NAME OF OPERATOR INGREDIENTS 500ml STERILE TSB BOTTLE 100ml STERILE TSB MINIBAG 10ml SODIUM CHLORIDE 0.9% AMPOULE 10ml STERILE DRIED TSB VIAL TYPE AND SIZE OF CONTAINER 1 x 3litre 5-lead empty EVA bag

DESIGNATION QUANTITY

1 3 3 1 EQUIPMENT 3x 10ml Syringe 1 x air vent needle Needles Alcowipes

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 3 Line 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, ensuring that 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 line closed. 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. DESPATCH DEADLINE Must arrive at laboratory before 4.30 pm on same day STORAGE Room temperature as test 825ml TSB EVA Bag LABELLED BY PROCESS SIMULATION TEST AFFIX SAMPLE LABEL ADULT TPN DESPATCH BY Hospital site: Date of Test: / / Operator Name: DATE TEST RECEIVED IN LABORATORY Cabinet used: INCUBATION 30-35C for 14 days

TEST RESULT IMMEDIATE ACTION TAKEN ON RESULT (PASS/FAIL) ORGANISMS ISOLATED BACTERIOLOGIST DATE RESPONSIBLE/QA PHARMACIST DATE

Site: Address:

PST WORKSHEET AND REPORT FORM PST FOR NEONATAL TPN USING AN AUTOMIX COMPOUNDER HOSPITAL SITE NAME OF OPERATOR INGREDIENTS 6 x 100ml STERILE TSB MINIBAG 1 x 10ml STERILE DRIED TSB VIAL 1 x 10ml SODIUM CHLORIDE 0.9% AMPOULE TYPE AND SIZE OF CONTAINER 3 x 500ml EVA BAG

Written by Approved by Date Supersedes Review date

DATE OF TEST CABINET USED EXPIRY DATE VOLUME PER BAG 150ml } 2ml SPECIFIC GRAVITY 1.18

DESIGNATION MANUFACTURER AND BATCH NO

EQUIPMENT 1 x Automix compounder transfer set 1 x Automix connector set 1 x 10ml syringe 3 x 5ml syringe Needles Alcowipes 3 x 0.22micron filter

METHOD 1. Swab top of TSB vial and ports on TSB 100ml minibags 2. 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 mix contents. 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. DESPATCH DEADLINE Must arrive at laboratory before 4.30 pm on same day STORAGE Room temperature as test 3x 3x 152ml TSB EVA Bag LABELLED BY PROCESS SIMULATION TEST AFFIX SAMPLE LABEL NEONATAL TPN Hospital site: Date of Test: / / DESPATCH BY DATE TEST RECEIVED IN LABORATORY Operator Name: Cabinet used: INCUBATION 30-35C for 14 days

TEST RESULT IMMEDIATE ACTION TAKEN ON RESULT (PASS/FAIL) ORGANISMS ISOLATED 1ST BAG 2ND BAG 3RD BAG BACTERIOLOGIST DATE RESPONSIBLE/QA PHARMACIST DATE

Site: Address:

PST WORKSHEET AND REPORT FORM PST FOR AN IV INFUSION USING A RECONSTITUTION DEVICE HOSPITAL SITE NAME OF OPERATOR INGREDIENTS 10ml STERILE DRIED TSB VIAL 100ml STERILE TSB MINIBAG TYPE AND SIZE OF CONTAINER 100ml STERILE TSB MINIBAG

Written by Approved by Date Supersedes Review date

DATE OF TEST DESIGNATION QUANTITY CABINET USED MANUFACTURER AND EXPIRY DATE BATCH NO

1 1 EQUIPMENT 1 x Reconstitution device Alcowipes 1 x Additive cap

METHOD 1. Swab top of vial and additive port on minibag 2. 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. DESPATCH DEADLINE Must arrive at laboratory before 4.30 pm on same day STORAGE Room temperature as test 100ml TSB Minibag LABELLED BY PROCESS SIMULATION TEST AFFIX SAMPLE LABEL IV ADDITIVE DESPATCH BY Hospital site: Date of Test: / / Operator Name: DATE TEST RECEIVED IN LABORATORY Cabinet used: INCUBATION 30-35C for 14 days

TEST RESULT IMMEDIATE ACTION TAKEN ON RESULT (PASS/FAIL) ORGANISMS ISOLATED BACTERIOLOGIST DATE RESPONSIBLE/QA PHARMACIST DATE

Site: Address:

PST WORKSHEET AND REPORT FORM PST FOR IV PAEDIATRIC BOLUS SYRINGES HOSPITAL SITE NAME OF OPERATOR INGREDIENTS 10ml STERILE DRIED TSB VIAL 10ml SODIUM CHLORIDE 0.9% AMPOULE TYPE AND SIZE OF CONTAINER 4 x 1ml SYRINGE

Written by Approved by Date Supersedes Review date DATE OF TEST CABINET USED MANUFACTURER AND EXPIRY DATE BATCH NO

DESIGNATION QUANTITY

1 1 EQUIPMENT 1 x 10ml Luer loc syringe 1 x 0.22m filter 4 x 1ml syringe Needles 4 x Syringe cap Alcowipes

METHOD 1. Swab top of vial and neck of ampoule 2. Reconstitute the vial of dried TSB with 10ml sodium chloride 0.9%. 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. DESPATCH DEADLINE Must arrive at laboratory before 4.30 pm on same day STORAGE Room temperature as test 4 x 1ml TSB Syringes LABELLED BY PROCESS SIMULATION TEST AFFIX SAMPLE LABEL PAEDIATRIC BOLUS SYRINGES DESPATCH BY Hospital site: DATE TEST RECEIVED IN LABORATORY Date of Test: / /

Operator Name: Cabinet used: INCUBATION 30-35C for 14 days

TEST RESULT IMMEDIATE ACTION TAKEN ON RESULT (PASS/FAIL) ORGANISMS ISOLATED 1ST SYRINGE 3RD SYRINGE 2ND SYRINGE 4TH SYRINGE BACTERIOLOGIST DATE RESPONSIBLE/QA PHARMACIST DATE