Environmental Monitoring

Transcription

1 Chapter 10 Environmental Monitoring By the end of this chapter, you will be able to: l List the types of environmental testing l Name three types of checks that are carried out to ensure the isolator is working correctly Introduction This chapter examines the ways in which we monitor the cleanroom environments in which we work and also the operators performing aseptic manipulations. Why do we need to monitor the environment? Regular monitoring of the environment, process and finished product must occur according to a written procedure and in line with the published written standards and guidelines. All areas associated with the aseptic preparation process should be assessed for compliance with the standards on commissioning, after routine maintenance and routinely at a defined frequency. Written reports should be completed and assessed so that appropriate action can be taken if abnormal results are obtained. Techniques used for monitoring should be easy to perform, produce meaningful results and must not contribute to contamination. Chapter 10: Environmental Monitoring 1

2 Aseptic Processing What is environmental monitoring? Environmental monitoring is testing of the equipment, cleanrooms and people to: l check that the cleanrooms, laminar flow cabinets and isolators are performing as expected; l ensure that the facilities and equipment are controlling the environment within the correct limits; and l ensure that the SOPs are being followed to maintain the cleanroom environment. Types of environmental testing: l Physical Tests l Microbiological Tests l Chemical Tests l Integrity of the filters l Particle count l Room air change rates l LAFC/Isolator velocities These tests are usually carried out by quality control (QC) Microbiological tests include: Physical tests include: l Gauge checking for pressure and filter status of rooms l Pressure and filter status of Laminar Air Flow Cabinet (LAFC) l Glove leak test in isolator l Isolator leak test These tests are usually carried out by operators l Settle Plates l Contact Plates l Swabs l Finger Dabs (touch plates) l Active Air samples Chemical tests include: l Surface swabs for chemical residues e.g. cytotoxics l Surface wipes for chemical residues 2 Chapter 10: Environmental Monitoring

3 Chapter 10 Environmental Monitoring Test Yourself Complete the following sentence: Environmental monitoring is testing of the Write down three reasons why we carry out environmental testing Chapter 10: Environmental Monitoring 3

4 Aseptic Processing What methods and equipment do we use to test the environment? Passive Air Sampling Microbiological Testing Active Air Sampling Biotest RSC Plus Air Samplers Active air sampling machines are used to test the air. There are several types available. Bacterial counts are monitored when a sample of the air is drawn over a media on which microbes will grow. Tests are carried out in the manned (operational) state and results compared to standards set for the appropriate grade of environment. Settle Plates Settle plates are used to detect any bacteria that may be present in the environment that fall onto the plates whilst they are exposed, usually for 4 hours. The plates contain a medium that is ideal for most bacteria to grow on. Plates are exposed during each working session in the work zone. Plates are usually also exposed at least weekly in the clean room and hatches. Plates are incubated at a specific temperature and then checked for growth after a set period of incubation. The number of colonies grown is recorded and the levels compared against standards in the Orange Guide. 4 Chapter 10: Environmental Monitoring

5 Chapter 10 Environmental Monitoring Surface Sampling Operator Sampling Surface Swabs Swabs are taken from areas where dirt and bacteria are most likely to be present to check that the cleaning is being carried out effectively. Finger Dabs Contact Plates Image supplied by BiotestUK Contact plates have a raised agar surface. They are placed lightly onto the surface for 15 seconds and then incubated. They also check that cleaning has been carried out properly. Finger dabs are carried out by all operators after a working session. Sometimes an un-gloved before dab is used to assess hand washing techniques to ensure all dirt and bacteria are removed when scrubbing up. Finger dabs assess operator technique and the efficiency of item transfer techniques. If bacteria are present, this could be due to poor operator technique or poor spraying and wiping technique when bacteria are still present on the outer surface of bottles and containers or components which may have been passed into the LFC or Isolator. Chapter 10: Environmental Monitoring 5

6 Aseptic Processing Physical Testing Particle Testing Room Pressure Testing Gauges (Manometers) The differential pressure between the cleanrooms and the outer environment should be measured regularly. A schedule is provided in the Yellow Guide. Biotest APC handheld Airborne Particle Counter. At a suitable frequency, the Quality Control Department will visit to carry out non-viable airborne particulate counting. This assesses the number of particles which are present in the air to check on the level of contamination present at that time, both in the manned and unmanned states. Results are compared to standards. If the results are higher than the limit, investigations must be carried out to determine the cause of the problem. This may be due to problems with the air filtration systems. DOP (Dispersed Oil Particulates) Test This test is carried out to determine the filter integrity to ensure the filter has not been damaged. It also checks the filter housing to ensure there is no air by-pass due to poor seals. DOP is introduced as a 0.3 micron sized aerosol into the duct, upstream of the filter and a sample of the downstream air is passed across a light source and photometer. A photometer analyses the penetration and gives a pass/fail result. All operators should check the room pressure before using a cleanroom. Temperature and Humidity Thermometer The temperature of cleanrooms should be 20 o C ± 2 o C This should be checked regularly together with the relative humidity. 6 Chapter 10: Environmental Monitoring

7 Chapter 10 Environmental Monitoring Air Flow and Room Air Change Rate Anenometer Image supplied by Envair Laminar flow cabinets should provide airflow at 0.45 meters per second on average over the whole filter face. Airflow into a cleanroom is also measured so that the air change rate can be calculated. Other Testing In addition, lighting and noise levels should also be tested periodically. Isolator Leak Testing and Glove Leak Testing Isolators are leak tested on a weekly basis. Pressure decay (Isolator leak) tests are also carried out to ensure the integrity of the internal environment is maintained. Glove leak tests are carried out to check for holes that may not be visible and that the glove has been fitted correctly. Glove leak tests also check the sleeves for holes. Chapter 10: Environmental Monitoring 7

8 Aseptic Processing Environmental Monitoring In every manufacturing facility there is a schedule for testing which contributes to validation of cleaning and disinfection. All results of testing are recorded and results need to be within acceptable levels. Below is an example of a schedule of monitoring Type Frequency Where Manometer readings (gauges) Dailly Room Sessional LAFC/Isolator Settle Plates Weekly Room Surface Samples (contact plates, swabs) Sessional Weekly LAFC/Isolator Room Finger Dabs Sessional Workzone Below are the acceptable levels for all the different types of environmental monitoring. Grade of room Finger dabs /cfu/hand Settle plates 90mm cfu/4 hrs Contact plates 55mm cfu/m 3 Active air sample cfu/m 3 A <1 <1 <1 <1 B C N/A D N/A Reference: Orange Guide 2007 Any results which are out of limits i.e. outside the acceptable levels, must be reported immediately to the clean room supervisor or person in charge. It must also be documented as laid down in your SOP. Further actions or remedies must also be recorded. This is very important to help maintain the quality of the environment. Validation Tests Staff are expected to undertake evaluation tests both initially and at a designated frequency to check their aseptic technique to ensure their working practices do not contaminate the products. Further Reading: See Chapter 8 Quality Systems for Operators for detailed information on staff validation tests. 8 Chapter 10: Environmental Monitoring

9 Chapter 10 Environmental Monitoring Control of Air Flow: Cleanroom Monitoring Positive Air Flow In order to prevent dirty air entering the facility when doors or transfer devices are opened, the facility is maintained at positive pressure. This means that air will always flow out of the facility and dirty air cannot enter and contaminate the environment. Pressure gauges (manometers) between rooms should be checked in accordance with the SOP to ensure that the pressure is correct and that air is flowing in the right direction. Gauges are present that display the pressure differences between the areas in the facility. The gauges record values, which are between limits marked on the gauges or laid down in standard operating procedures (SOPs). Limits are 10Pa difference between cleanto-clean areas and 15Pa difference between clean-to-dirty areas. If the limits are not achieved, then no work is to take place until the correct pressure is established. This decision will be made by the Unit Manager. If the agreed values are not met/exceeded, then there may be a problem with the filters and so work should be suspended until this can be investigated. Calibration checks are carried out on manometers by Quality Control to assess the accuracy of the gauges. Pa = Pascals: This is the international unit of pressure. Control of Airflow: Workstation Monitoring HEPA Filter Gauges The HEPA gauge on workstation cabinets should be checked to monitor the blocking of the HEPA filter. The Laminar Air Flow Cabinet (LAFC) gauge should be checked to ensure: l The cabinet is switched on and functioning within acceptable limits l The HEPA filter is functioning within limits Isolator gauges should be checked to ensure: l The isolator is switched on and operating to protect the operator and product l The HEPA filter is functioning within limits l The total air change rate is operating within acceptable limits. The Laminar Air Flow Cabinets and isolators are specially designed workstations with super clean air in which the products should be prepared. Laminar Air Flow Cabinets should be left running at all times. Clean up times after interruptions, i.e. power failures, should be validated. Chapter 10: Environmental Monitoring 9

10 Aseptic Processing Environmental Monitoring Systems In this example we will look at a computer system which monitors the particles and pressures using monitors placed throughout an aseptic unit. Overview screen This screen shows a graph of the differential pressures of the unit for one day. Peaks and troughs show when the unit is occupied and operators move from one area to another. A Particle Monitoring System This screen display shows the full plan of an aseptic unit. Green symbols indicate that these zones are within limits. In an alarm state the symbols change to red, indicating increased levels of particles or pressures. Differential Pressure displays The software allows a number of ways of viewing the displays. Here is a close up of one of the particle monitors in the unit. This one is situated on a wall in the assembly room. They are also fitted into the ceilings. This unit has 24 ports situated throughout the entire unit. This screen shows the pressure differentials between rooms. Positive pressure must be maintained throughout. The green squares will change to red if the pressure falls below 10 Pascals (minimum standard between cleanrooms). 10 Chapter 10: Environmental Monitoring

11 Chapter 10 Environmental Monitoring This image shows a particle monitor within a LAFC. It is connected via tubing to an outlet in the wall. The pump in the plant room draws the air sample into the machine which then counts the particles in the area. (The other device is a CCTV camera used for checking see Chapter 8: Aseptic Services CCTV Checking Systems for further information). A screen displays the values received by the particle monitors around the unit. The system can count particles ranging is size from 0.3 micron to 25 micron. The air samples are pulled into the main controls which are situated in the pharmacy plant room by a system of ultra clean Bevaline tubing. Chapter 10: Environmental Monitoring 11

12 Aseptic Processing Questions Q1 Complete the table to show examples of each type of environmental test. Physical Microbiological Chemical Q2 Air: What methods do we use to test the quality of the following? Surfaces: People: 12 Chapter 10: Environmental Monitoring

13 Chapter 10 Environmental Monitoring 1. Q3 Give 2 examples of tests that we use to monitor HEPA filters. 2. Q4 How often are isolators leak tested? Name the types of leak tests for Isolators? (4) Chapter 10: Environmental Monitoring 13

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