Performance Verification of AEC Downflow Booth via Surrogate Air Monitoring with Lactose Monohydrate Presented by: John

1. Performance Verification of AEC Downflow Booth via Surrogate Air Monitoring with Lactose Monohydrate Presented by: John Kremer of AEC Hari Floura of Floura LLC ISPE NJ Chapter Day 2009

2. Introduction • AEC has established performance verification testing program for selected containment systems in their portfolio. improvement. • AEC has conducted testing to access the airborne particulate containment performance the AEC Downflow Booth. • The purpose of the testing was to record the containment performance of the Downflow Booth when the recommended operator work practices are followed, and to access the improvements gained through the use of supplemental engineered controls.

3. Floura LLC is a multi-disciplined consulting company providing services to the pharmaceutical industry with a core specialty in potent material handling/containment technology and capabilities for front end facility design studies and project management. Through their network of consulting associates, Floura LLC is also able to provide a broad range of pharmaceutical expertise in areas such as, architectural, process, commissioning, qualification, validation and rationalization. Third Party Contributors AEC retained an independent 3rd party expert (SafeBridge Consultants Inc) to conduct the performance verification testing to ensure the samples and results were valid. Floura LLC provided consultation to ensure that the testing was carried out in accordance with industry standards and the ISPE Good Practice Guide: Assessing the Particulate Containment Performance of Pharmaceutical Equipment (President Hari Floura – contributed to the guides development)

4. Testing Protocol • Performance verification testing the Downflow Booth was conducted by surrogate air monitoring with lactose as suggested in the ISPE Good Practice Guide. • The testing simulated bulk material transfer through the manual transfer of 25 kg of lactose from a bulk product drum to a receiving drum. • One trained operator carried out all the powder handling tasks. The operators PPE consisted of a Tyvek® disposable suit and several pairs of nitrile gloves.

5. Testing Protocol • The testing was conducted under three operating conditions: • Downflow Booth alone • Downflow Booth with drum handler and a ventilated charging collar. • Downflow Booth with ventilation off • A total of three process iterations per test condition were conducted. The duration of each iteration was 20 minutes, with a 15 minute extension to ensure a sample representative of all dust emitted was collected. The operator remained in the Downflow Booth during the extension period. • Only one iteration was conducted with the Downflow Booth off, followed by a shortened extension period (5 minutes). This was done to limit cross contamination into the test area.

6. Testing Protocol • Air sampling pumps were stopped and the filter cassettes removed changed at the end of each iteration

7. Sample collection device (25 mm, 1.0 µm PTFE filter in 2-piece blank, conductive cassette) Test Equipment SKC Air Monitoring Pumps Model 224-PCXR4, were operated at a flow rate of approximately 2.0 liters per minute. These pumps were calibrated before and after sampling by an airflow meter, Mini-Buck Calibrator Model M-5, calibrated to the National Bureau of Standards (NBS).

8. 8” 8” = = 5’ 8” Safe Work Zone Limit = = 8” 8” Air Sampling Locations Downflow Booth (Plan View) = Sampling Locations (Consistent with the recommendations of the ISPE guideline for assessing particulate containment performance)

9. Laboratory Analysis • All air samples were submitted to ESA Laboratories, Inc. (ESA), for sample analysis for lactose. • Each sample was number and stored to minimize potential for degradation • Field blanks included for every ten air samples collected to assess potential contamination during sampling, shipping, storage and/or analysis. • Blanks handled in the same manner as the other air samples, except that no air was drawn through the filter cassettes. • The analytical method for lactose at ESA utilizes High Performance Liquid Chromatography (HPLC) with Pulsed Amperometric Detection (PAD). • The sample was extracted from each PTFE filter utilizing in situ methodology with a suitable solvent. • The analytical detection limit reported for lactose was 2 nanograms.

10. Background Area Air Samples Testing was conducted over two consecutive days. Two background area air samples were performed prior to operations each day. Samples collected both inside and outside the Downflow Booth, at locations used during the operational testing. One field blank generated for every ten air samples collected. Background ranged from <0.01 µg/m3 to <0.05 µg/m3 over the two days. The one high background reading found inside booth just after bulk containers were moved in. Field blanks all reported less than 2ng/filter

11. Testing – No Additional Controls AEC Downflow Booth testing with no additional engineering controls utilized

12. Results – No Additional Controls • Total of 21 air samples collected • Operator exposure assessed by 3 OBZ samples, one pre iteration. Sample time ranged between 37 and 39 minutes to complete (including the 15 minute extension period) • Range: 0.64 to 1.54 µg/m3 • Mean: 1.01 µg/m3 • 18 area air samples – area air samples were collected at 3 locations within and 3 locations outside the booth • Inside - Range: <0.02 to 0.06 µg/m3 • Inside - Mean: 0.03 µg/m3 • Outside - Range: <0.02 to 0.05 µg/m3 • Outside - Mean: 0.02 µg/m3

13. Testing – Additional Controls AEC Downflow Booth testing with additional engineering controls utilized

14. Additional Controls • A Ventilation Sleeve Containment System and Drum Handler as Manufactured by EHS solutions was utilized as a additional engineering control. This system has the following features: • Provides high capture velocity around the perimeter of the collar. • Liner or funnel of the discharging drum is positioned below the slotted exhaust plane of the collar during the discharging process. Airborne dust contaminates rising up through the collar are captured in this exhaust plane, significantly reducing airborne particle levels. • Collar supported by portable HEPA filtered air handling unit, with approximately 425 cfm airflow.

15. Results –Booth With Additional Controls • Total of 21 air samples collected • OBZ air samples for 3 iterations; each iteration took between 32 and 35 minutes to complete (including the 15 minute extension period)- • Range: <0.03 to 0.04 µg/m3 • Mean: 0.03 µg/m3 • 18 area air samples – • Inside - Range: <0.03 to <0.03TR µg/m3 • Inside - Mean: 0.03 µg/m3 • Outside - Range: <0.02 to 0.05 µg/m3 • Outside - Mean: 0.03 µg/m3 • TR = trace amount detected on sample, although still below the analytical detection limit for the air volume collected.

16. No Controls (Downflow Off) Repeated manual transfer without additional controls with booth turned off. The purpose of this test was to determine the protection factor offered by the Downflow booth. Since there was a concern that lactose dust would contaminate the surfaces in the booth and the testing area, only one iteration of this test was performed, followed by a limited, 5 minute, extension period.

17. Results – No Controls (Downflow Off) • Total of 7 air samples collected • 1 OBZ air samples was collected, for one iteration. 24 minute sample to complete (including a 5 minute extension period) • Result: 2,250 µg/m3 • 6 area air samples – • Inside - Range: 51.6 to 177.0 µg/m3 • Inside - Mean: 123.5 µg/m3 • Outside - Range: 10.0 to 32.3 µg/m3 • Outside - Mean: 20.0 µg/m3

18. Results – Summary Results not time weighted – concentrations reported per task duration Downflow Booth Protection factor = 2000

19. Conclusions from Testing Results • Without the Downflow Booth the test results confirm that the airborne dust concentrations are substantial. • Results for the 4 background area air samples collected and the 5 field blanks submitted for analysis, indicate that the sampling and analytical results obtained in this study are valid. • The test results clearly demonstrate the effectiveness of the Downflow Booth to contain and control high airborne concentrations of contaminant. • While Downflow Booths are generally considered to control operator exposures to less than 50 µg/m3 of airborne dust, the results of this study indicate that even greater control can be achieved through supplemental controls and good operating technique.

20. Conclusions from Testing Results • The Downflow Booth alone demonstrated exposure control at 1 µg/m3 for the period of operation. The static area air samples collected inside and outside were extremely low, with only two samples producing low but detectable readings. • The combination of ventilated collar and AEC Downflow Booth successfully demonstrated exposure control well below 1 µg/m3 for the period of operation. There was only two samples above the low range of detection among all the static area air samples collected (0.05 µg/m3).

21. Conclusions from Testing Results Material handling in a Downflow Booth can greatly reduce potential operator exposure to airborne contaminates. Good operator technique is necessary to control airborne levels. The use of supplemental engineered controls further decrease airborne concentrations. Effectiveness of any engineered control is dependent upon material properties (electrostatic, dustiness) and process