Impact of operators and pharmaceutical operations upon air quality of controlled atmosphere areas

Transcription

1 Impact of operators and pharmaceutical operations upon air quality of controlled atmosphere areas S. Filali ; B. Darricau ; C. Bretagnolle ; EH. Diouf ; D. Salmon ; ML. Tall ; C. Pivot ; F. Pirot Groupement Hospitalier Edouard Herriot - Service Pharmaceutique - Préparation et contrôles des médicaments samira.filali@chu-lyon.fr 1

2 1. I n t r o d u c t i o n Particle control NF S norm Microbiological control BPP 2007 A B C 2

3 2. O b j e c t i v e s Main: To monitor the air quality of controlled atmosphere areas during pharmaceutical operations in the presence or the absence of operators Specific: To characterize the impact of human presence on the air quality 3

4 3. M a t e r i a l s & M e t h o d s Monitoring A Monitoring B Human presence and pharmaceutical operations Production : Preparation of parenteral nutrition mixtures Human presence only No production Immobile or moving body Period : 5 h 3 operators in class A (surface 7m²) + 1 operator in class B (2 m²) Sampling in the worst cases Volume: 15 m 3 of air Period : sequence of 20 min 1 operator in class A Sampling at different distances and at different body levels Volume: 1 m 3 of air 4

5 3. M a t e r i a l s & M e t h o d s Particle control Monitoring A Microbiological control Period : 5 h Alternating between 2 points 1: transfert of materials from ZAC B to ZAC A 2: transfert of preparation from mixture zone to filtration zone Volume: 15 m 3 of air A B A Aerobiocollection: 4 samples Period: 10 min Volume: 1 m 3 of air Sedimentation: - ZAC A : samples systematically performed at each preparation Sous le plafond soufflant Paillasse A l extérieur du plafond soufflant Point Sampling de prélèvement point (mixture + filtration) - ZAC B : same sampling point than aerobiocollection Kinetics of controls point in ZAC during and after activity Laminar flow system turn on Laminar flow system on standby Preparation material + mixture Filtration At rest Preparation of parenteral nutrition No activity 5

6 3. M a t e r i a l s & M e t h o d s Monitoring B Particle control Particle counting: - Period: 20 min - Volume: 1 m 3 of air Microbiological control Aerobiocollection: - Period: 10 min - Volume: 1 m 3 of air 35 cm 50 cm 20 cm Sampling probe of counter 6 particle and aerobiocollector

7 3. M a t e r i a l s & M e t h o d s Metering conditions 1 st day 2 d day 3 d day 4 th day 5 th day 6 th day 7 th day Air velocities [m.s -1 ] 0,46 m.s -1 0,46 m.s -1 0,46 m.s -1 0,46 m.s -1 0,46 m.s -1 0,46 m.s -1 0,46 m.s -1 Differential Pressures [Pa] Unrealized Leak containment Leak on mounting filters Metrology Maintenance report : No Maintenance report : No Particle counter Aerobiocollector Mark Lange Air Ideal Model 3423 Air Test Oméga Serial number Date of last calibration October 2013 October 2013 Background noise of counter 0 Sampling rate 50 L/min 100 L/min Measurement uncertainties 5% à particles/m 3 ( particles/ft3) 7

8 4. R e s u l t s Monitoring A : Particle counting of air in ZAC A MAX 3520 Particle count of air/m MAX H 2H - 3H 3H - 5H 0,5 µm ,0 µm

9 4. R e s u l t s Monitoring A : Particle counting of air in ZAC B MAX Particle count of air/m MAX H 2H - 3H 3H - 5H 0,5 µm ,0 µm

10 C o lo n y F o rm in g U n it (C F U ) C o lo n y F o rm in g U n it (C F U ) 4. R e s u l t s Monitoring A : Microbiological control of air in ZAC A and ZAC B 4 Aerobiocollection S e d im e n ta tio n Z A C A 1.5 Z A C A 3 Z A C B Z A C B h 0-2 h 2-3 h 3-5 h h 2-3 h In activity At rest In activity 10

11 4. R e s u l t s Monitoring B : Particle control of air in ZAC A 72/m 3 10/m 3 75/m 3 5/m 3 1/m 3 3/m 3 217/m 3 59/m 3 774/m 3 93m 3 15/m 3 46/m 3 268/m 3 839/m /m 3 526/m 3 160/m 3 56/m 3 0,5 µm 5 µm

12 4. R e s u l t s Monitoring B : Microbiological control of air in ZAC A 0 UFC 0 UFC 0 UFC 0 UFC 0 UFC 0 UFC 0 UFC 0 UFC 2 UFC 0 UFC 0 UFC 0 UFC 0 UFC 2 UFC 0 UFC 0 UFC 0 UFC 0 UFC Bacteria Fungal

13 5. D i s c u s s i o n - Rationalization of operator number under laminar flow system - Establishment of a safe distance between pharmaceutical raw materials and operator 13

14 6. C o n c l u s i o n - Identify the steps and critical areas to eventually change practices or limit certain steps in time - Monitoring of air quality during activity are recommended in the Good Manufacturing Practices, but not in Good Preparation Practice - Risk factors: (1) human presence (2) bottles at open neck (3) pharmaceutical operations 14