Air flows (1) UNIDIRECTIONAL

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Different Airflows

Air flows (1) UNIDIRECTIONAL Air inlet HEPA Filter Unidirectional Flow (also called Laminar Flow): 0.45 m/s ±20% air speed Fastest ambient class recovery time Excellent with powder (in that case a top-down flow must be adopted The huge amount of air to be handled must be taken into consideration Air inlet HEPA Filter HEPA Filter Air outlet HEPA Filter Side views Water Drain www.comecer.com/isolation

Turbulent flow: 20 40 air changes per hour Higher ambient class recovery time than with the Unidirectional Flow, due to the lowest volume of air used Excellent for transportable or small size Isolators Excellent when an inert gas (Nitrogen, Argon ) must be used in alternative to the normal Air Some areas can remain dirty (non reached by the air flow) Air flows (2) TURBULENT Air inlet HEPA Filter Front view HEPA Filter Air outlet www.comecer.com/isolation

HEPA and ULPA Filters Absolute ULPA Classification CEN EN 1822 Class Efficiency % with MPPS method Global Efficiency Minimum value of localized efficiency Absolute HEPA Semi Absolute High efficiency Media efficiency Low efficiency High Medium Low www.comecer.com/isolation

HEPA and ULPA Filters (2) Different shapes and sizes available: squared, rectangular and cylindrical Different flow capacity expressed in m 3 /hour www.comecer.com/isolation

Internal cartridge filter (HEPA) for turbulent air flow Internal rectangular panel filter (HEPA) for unidirectional air flow

External HEPA Filter with stainless steel case (Bag In / Bag Out replacement system)

2 1 (Bag In / Bag Out Filter Replacement System)

External Rectangular Filter bag-in/bag-out

External Rectangular Filter Replacement (Bag In / Out System) External Canister Safe Filter Removal with containment bag Positioning of a new filter Door closing

Replacement Scheme (Bag In / Out System)

Dwyer pressure gauges to constantly check filter status / obstruction

UNIDIRECTIONAL (Laminar) Air Flow UNIDIRECTIONAL air Flow allows a constant cleaning of the working area; it creates a barrier between different environments protecting the critical operation in sterile condition; allows to work in negative pressure to protect the operator and the surrounding environment or positive pressure to protect the product inside the glove box keeping the ambient cassified, avoiding contact with contaminated airborne particles. can handle bigger air volumes and allows quick class recovery.

Visual Verification of the Unidirectional flow (Smoke test) Verification of the critical working zone constantly cleaned by the unidirectional flow. This test is made to verify the unidirectional flow

Verification of unidirectional air flow rate This test is made to check the compliance of the unidirectional air flow wich has to respect a velocity included between 0,36 and 0,54 m/s near the working zone. Air flow rate for isolators can be even lower (EC-GMP Annex1-2003)

Smoke test (for Turbulent air flow) Smoke introduction inside the isolator box with ventilation interruption. The test begins activating the ventilation. Visual Inspection of the time necessary for the complete smoke extraction.

Glove Breach test This test is made to verify that in the worst case (accidental glove removal) isolator is able to guarantee a correct air flow (originating outside the box and coming inside it in case of underpressure) with a mininum rate of 0,5 m/s (reference value according to ISO 14644-7:2004).

Verification of Filter Integrity Scheme of test execution Fotometer Filter Canister Areosol Generator Filter Sensor for filter Scan

Verification of Filter Integrity Potential filter leackage is tested. The filter is scanned on its complete surface. Also the filter gaskets are tested. Defective Filter with punctual leackage on the surface.

Classification of a clean area Clean-room or clean area: is a special room or area where the concentration of air-borne particles is controlled. It is constructed in such a way as to reduce the introduction, generation and retention of particles within the area. Classification: Level (or the process of specifying or determining the level) of air-borne particulate cleanliness applicable to a clean-room or clean zone, expressed in terms of an ISO Class N, which represents maximum allowable concentrations (in particles per cubic meter of air) for considered size of particles Example: the concentration limit for ISO class 5 is 3520 particles/m 3 air, considering particles with a size of Ø 0.5 μm. www.comecer.com/isolation

LIMITS OF PARTICLE CONCENTRATION (0.5 μm) ISO class ISO 14644-1 FS 209E FS 209E CLASS 1 == == == 2 4 == == 3 35 35,3 1 4 352 353 10 5 3 520 3 530 100 6 35 200 35 300 1 000 7 352 000 353 000 10 000 8 3 520 000 3 530 000 100 000 9 35 200 000 == == GMP particle correspondence: Grade A and B correspond to class 100, M 3.5, ISO 5 Grade C corresponds to class 10000, M 5.5, ISO 7 Grade D corresponds to class 100000, M 6.5, ISO 8 Note: the GMP classification does not only refer to the particle contamination, but also to microbiological contamination, which can be achieved by sanitization and/or sterilization. www.comecer.com/isolation

Verification of air particle concentration Particle Counting Test Test report