ENVIRONMENTAL MONITORING / TESTING TO CONFORM WITH ISO14644 & TGA GMP REQUIREMENTS

Transcription

1 ENVIRONMENTAL MONITORING / TESTING TO CONFORM WITH ISO14644 & TGA GMP REQUIREMENTS PRESENTATION TO RACI 20 TH APRIL 2016 PAUL MORGAN DIRECTOR CRITICAL CERTIFICATION PTY LTD

2 CHANGES TO ISO14644 PART 1 CHANGES TO ISO14644 PART 2 EXPECTED CHANGES TO ISO14644 PART 3 HOW WILL THIS LIKELY AFFECT EU / GMP PIC/S ISO29643 PARTICLE COUNTER REQUIREMENTS ISO21501 PART 4

3 CURRENT ISO STANDARDS: Part 1: Classification of air cleanliness Part 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration Part 3: Test methods Part 4: Design, construction and start-up Part 5: Operations Part 6: Vocabulary Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments) Part 8: Classification of airborne molecular contamination Part 9: Classification of surface cleanliness by particles (Under preparation) Part 10: Classification of air cleanliness by nanoparticles (Under preparation)

4 ISO14644 PART 1: 2015 MAJOR CHANGES: EQUIPMENT DESCRIPTION MOVED FROM PART 3 NUMBER OF LOCATIONS INCREASED SO THAT 95% UPPER CONFIDENCE LIMIT IS NO LONGER REQUIRED SOME REQUIREMENTS TO SAMPLE LARGER MICRON SIZE PARTICLES REMOVED

5 ISO Class number (N) ᶢ Maximum allowable concentrations (particles/m3) for particles equal to and greater than the considered sizes, shown belowᵃ 0.1µm 0.2µm 0.3µm 0.5µm 1.0µm 5.0µm 10ᵇ ᵈ ᵈ ᵈ ᵈ ᵉ ᵇ 10ᵇ ᵈ ᵈ ᵉ ᵇ ᵈ ᵉ ᵇ ᵉ ᵈᵉᶠ ᶜ ᶜ ᶜ ᶜ ᶜ ᶜ ᶜ ᶜ ᶜ ᵃ All concentrations in the table are cumulative, e.g. for ISO Class 5, the particles shown at 0,3 μm include all particles equal to and greater than this size. ᵇ These concentrations will lead to large air sample volumes for classification. Sequential sampling procedure may be applied; see Annex D. ᶜ Concentration limits are not applicable in this region of the table due to very high particle concentration. ᵈ Sampling and statistical limitations for particles in low concentrations make classification inappropriate. ᵉ Sample collection limitations for both particles in low concentrations and sizes greater than 1 μm make classification at this particle size inappropriate, due to potential particle losses in the sampling system. ᶠ In order to specify this particle size in association with ISO Class 5, the macroparticle descriptor M may be adapted and used in conjunction with at least one other particle size. (See C.7.) ᶢ This class is only applicable for the in-operation state.

6 THE EFFECT OF REMOVING THE REQUIREMENT FOR HIGHER PARTICLE SIZE: SECTION A.4.4: At each sampling location, sample a volume of air sufficient to detect a minimum of 20 particles if the particle concentration for the largest selected particle size were at the class limit for the designated ISO Class In effect, under the previous standard, when the largest particle size of 5.0µm was used for ISO Class 5, then determined that a cubic metre was to be sampled. However, this requirement for Class 5 has now been removed, however, the standard further states: If measurements are to be made at more than one considered particle size, each larger particle diameter (e.g. D2) shall be at least 1,5 times the next smaller particle diameter.

7 SAMPLING LOCATIONS: In the previous standard, the number of locations required to be sampled was determined as the square root of the floor area. i.e. for 100m² floor area, 10 locations were required. However, under this standard, that is no longer the case, for instance, in a 100m² room it is now required that 16 locations are sampled, see table on following slide. This is required to ensure that it provides at least 95 % confidence that at least 90 % of the cleanroom or clean zone area does not exceed the class limits. In order to position the sampling locations a) use the minimum number of sampling locations NL derived from Table A.1, b) then divide the whole cleanroom or clean zone into NL sections of equal area, c) select within each section a sampling location considered to be representative of the characteristics of the section, and d) at each location, position the particle counter probe in the plane of the work activity or anotherspecified point. Additional sampling locations may be selected for locations considered critical. Their number and positions shall also be agreed and specified.

8 AREA OF ROOM (m²) LESS THAN, OR EQUAL TO MINIMUM NUMBER OF SAMPLE LOCATIONS TO BE TESTED (Nᶫ)

9 Where the size of the room exceeds 100m², the following formula is to be applied: NL = 27x ( A ) (1000) where NL is the minimum number of sampling locations to be evaluated, rounded up to the next whole number; A is the area of the cleanroom in m². If the considered area falls between two values in the table, the greater of the two should be selected. I.e. If the floor area = 42m², then 10 positions are required

10 ISO PART 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration The previous version of this standard was titled Specifications for testing and monitoring to prove continued compliance with ISO This standard is now directed more towards Continuous Monitoring. However, this leaves a problem as the schedule for retesting has now been removed from this standard

11 ISO14644 Parts 1 & 2 have now been published. Part 3 was to have been published at the same time, however this did not occur. Major changes: Table for scheduled testing has been moved form Part 2 and will be included in Part 3. Determination of Room Recovery Rates has been amended.

12 ISO14644 PART Occupancy states as-built condition where the installation is complete with all services connected and functioning but with no production equipment, materials, or personnel present at-rest condition where the installation is complete with equipment installed and operating in a manner agreed upon by the customer and supplier, but with no personnel present operational condition where the installation is functioning in the specified manner, with the specified number of personnel present and working in the manner agreed upon

13 A3 Pre-test conditions: ISO14644 PART 3 Special care should be taken when determining the sequence for performing tests for cleanroom performance. The results of each cleanroom test may be dependent upon other pre-conditioning requirements being met. For example, some pre-conditions for the Pressure Difference Test are stated in B1.2.

14 ISO14644 PART 3 Table A2 Typical Test Frequency Type of selected test Pressure differentials Air supply volume in non-unidirectional airflow Air velocity in unidirectional airflow Installed filter system leakage - non-unidirectional airflow cleanroom Installed filter system leakage - unidirectional airflow cleanroom Air direction & visualisation Recovery rate Containment test Particle desposition rates Segregation tests Temperature & humidity Electrostatic & ion generator Typical period to retest 12 months 12 months 12 months 24 months 12 months 12 months

15 Revision to Room Recovery Rates Section B.4: For non-unidirectional cleanroom only This test now incorporates 100:1 and 10:1 tests. Test should be performed when the clean room is in the As Built or At Rest states, or after major modification to the cleanroom, or its operation. No requirement to retest every 2 years. It is not recommended that the 100:1 test be used for ISO 8 & 9

16 B4.3.4 Evaluation of Recovery rate: Recovery performance can be determined from the slope of particle concentration decreasing curve, as follows: a) Commence measurements and record time and concentration continuously. Sampling time should be as short as possible but sampling should be such that the count has statistical relevance. Time intervals between the samplings should be as short as possible. b) Plot the data of decreasing particle concentration on a semi-log chart (concentrations on the ordinate by the logarithmic scale, and the time values on the abscissa by the linear scale) c) Decide upper and lower concentration limits as to the decreasing curve measured is accepted as almost straight line. d) Cleanliness recovery rate is obtained from the slope of the line between the upper and lower concentrations. The cleanliness recovery rate between two measurements is calculated from the following equation: r = -2.3 x 1 log ( C1) t ( C0)

17 Where r is the cleanliness recovery rate; t1 is the time elapsed between measured concentration crosses C0 and C1 C0 is the upper concentration; C1 Is the lower concentration at t1 If it is possible to measure concentration at plural timing until the cleanliness is recovered, recovery rate can be evaluated using the least squares method. Average five to ten of recovery rate values obtained in a measurement. The recovery rate and 100:1 recovery time can be related as follows: r = -2.3 x 1 log¹º ( 1 ) = -2.3 x 1 (-2) = 4.6 x 1 t0.01 (100) t0.01 t0.01 where r is the cleanliness recovery rate; t0.01 is the time elapsed between measured concentration crosses initial and 0.01 of initial concentration.;

18 Annex C lists the Test apparatus required for each test. This annex describes the measuring apparatus that should be used for the recommended tests given in this part of ISO In this annex, data given in Tables C.1 to C.22 indicate the minimum necessary requirements for each item of apparatus. Items are listed and numbered to correspond with Annex B, e.g. the apparatus numbered C.1 is used in the test procedure given in B.1. Those responsible for planning tests may refer to Annex C for the selection of test apparatus and to Annex A for a checklist of recommended tests of an installation and the sequence in which to carry them out. Measuring apparatus should be chosen subject to agreement between the customer and supplier. This annex is informative, and should not prevent the use of improved apparatus as it becomes available. Alternative test apparatus may be appropriate and may be used subject to agreement between customer and supplier. Test apparatus should be selected with measurement limits and range that are appropriate for its application. The apparatus should also be calibrated with calibration points covering the range of its intended use. All test apparatus sensitivity should be 1.

19 Major differences when comparing ISO14644 Part 3 to testing performed by most Australian Testing Companies: Many different piece of test equipment can be utilised. Other test methods included in Part 3, not normally performed in Australia i.e. Sample testing of installed duct HEPA Filter installations. Testing of HEPA filters using DPC (Discrete Particle Counter). Air volume testing using Airflow Hoods / pitot tubes

20 ISO29643 ISO29643 High efficiency filters and filter media for removing particle in air is the new ISO Standard for HEPA Filters. It was published in October, It is broken into 5 parts, as follows: Part 1: Classification, performance testing & marking Part 2: Aerosol production, measuring equipment & particle counting statistics Part 3: Testing flat sheet filter media Part 4: Test method for determining leakage of filter elements Scan method Part 5: Test method for filter element

21 COMPARISON OF ISO29643 & EN1822 Efficiency (%) Penetration (%) E 10 > ISO 15 E E 11 > 95 5 ISO 20 E > 99 1 ISO 25 E E 12 > 99,5 0,5 ISO 30 E > 99,9 0,1 ISO 35 H H 13 > 99,95 0,05 ISO 40 H > 99,99 0,01 ISO 45 H H 14 > 99,995 0,005 ISO 50 U > 99,999 0,001 ISO 55 U U 15 > 99, ,000 5 ISO 60 U > 99, ,000 1 ISO 65 U U 16 > 99, , ISO 70 U > 99, , ISO 75 U U 17 > 99, ,

22 PARTICLE COUNTERS ISO21501 PART 4 The new released version ISO14644 Part 1 states: Not all instruments will be able to meet the requirements of this standard, in this case, the use of non compliant instruments will require an additional explanations

23 PARTICLE COUNTERS ISO21501 PART 4 ISO has the title Determination of particle size distribution Single particle light interaction methods. Included with ISO are four parts: Part 1: Light scattering aerosol spectrometer Part 2: Light scattering liquid-borne particle counter Part 3: Light extinction liquid-borne particle counter Part 4: Light scattering airborne particle counter for clean spaces The documentation and approval of ISO , -3, and -4 subsequently replaces and cancels ISO :2000. The ISO standard widens the scope of analysis to include methodology for airborne particle counting and liquid particle counting (both light scattering and extinction methods). Specifically, ISO provides a calibration procedure and verification method for airborne particle counters to minimize inaccurate measurements and reduce variations between different instruments. These new guidelines require pulse height analysis (PHA) for particle counter calibrations, which reduces inconsistencies.

24 Pulse Height Analyzer (PHA) Particle counters employ solid-state photodetectors that convert detected light energy into electrical signals. The particle signals, known as pulses, leave the detector with proportional amplitudes of energy that represent the particles or photons witnessed by the detectors. If these pulses are sorted according to their height or magnitude, we could equate the pulses to energy received from the particle or photon. Electronic systems that analyze particle pulses and categorize their respective intensities are called Pulse Height Analyzers (PHAs).

25 Single channel PHAs count only pulses of certain amplitudes, which are equivalent to a particle s or photon s perceived energy. Each pulse is placed into a counting bin, called a channel, and totaled with other pulses that are of the same amplitude. In effect, many smaller 0.1cfm DPC s, and those manufactured prior to say 2009 are no longer compliant with this standard.

26 THE END!!! THANK YOU

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