Rapid/Automated Environmental Monitoring on the Manufacturing Floor. Amy McDaniel, Ph.D. IFPAC Arlington, VA January 2014

Transcription

1 Rapid/Automated Environmental Monitoring on the Manufacturing Floor Amy McDaniel, Ph.D. IFPAC Arlington, VA January 2014

2 Outline Introduction to Pfizer Biotech, Sanford Introduction to Rapid Microbial Methods (RMM) for Environmental Monitoring (EM) Evaluation of the Growth Direct II in a manufacturing facility Evaluation of Consumables Beta Instrument Evaluation Conclusions

3 Introduction to Pfizer Biotech, Sanford, NC Sanford s Role: Commercial manufacturing for Prev(e)nar and Prev(e)nar13 conjugate Commercial manufacturing for CRM 197 carrier protein Supply clinical trial materials for microbial / conjugate products Commercial launch and production site for microbial / conjugate products within the PGS network

4 Future? Present Why RMM for EM? Gown Travel to manufacturing Clean carts De Gown Return to lab Prepare in lab QC micro analysts Clean up Identify samples Get materials Sample in Manufacturing Wait for settle plates Data entry Incubate plates Wait for incubation Read Results Prepare on mfg floor BioProcess Technicians Collect samples according to role Reduced Time to Results Growth Direct communicates with LIMS to download results, sends alerts electronically as programmed Growth Direct segregates positive plates for identification (in QC lab), discards negative plates QC Identifies samples Get materials Load samples into automated technology QC reviews results 4

5 How are current EM sampling issues identified? Shift huddles utilize a short, routine meeting & white board to monitor/manage Micro lab operations Relies on analyst knowledge and memory to communicate any missed samples. The ideal technology should be programmed to automatically read bar-coded labels, know what samples to expect, and send alerts if a sample is missing. Error proof and time saving! 5

6 RMM for EM: Standard Work Confirms Advantage EM Weekly Requ Samples /Tests Test Task Type Task Collecting Supplies Travel to Area Gowning Cart Cleaning Prep Equip and Materials in Manuf. European Grade (4 carts) (20 Air sites) Prepping Cart/Clean Up/Data Entry Degowning/Travel to Lab Data Download/Incubation Break Equipment / Process Controlled Analyst Contro Day 1 Hours Evening N # # # # # # 0 Potential EM Role (3) Hoods Collecting Supplies Travel to Area Gowning Cart Cleaning Prep Equip and Materials in Manuf. US Classification (2 carts) (8 Air sites) European Grade (2 carts) (9 Air sites) Prepping Cart/Clean Up/Data Entry Degowning/Travel to Lab Data Download/Incubation Collecting Supplies Break Travel to Area Gowning Cart Cleaning Prep Equip and Materials in Manuf. Hood Monitoring Settle Plates (Room) B Room C Rooms (27 VA) Clean Up/Data Entry/Data Download Degown/Travel to Lab/Clean Up/Incubate Lunch

7 What technologies are available for Rapid/Automated EM? Active Air Sampling IMD (Instant Microbial Detection) PMS (Particle Measuring Systems) TSI (BioLaz) Growth Direct II (Rapid Micro Biosystems) Surface Sampling Swabbing & preparation with: ScanRDI (BioMerieux) ATP systems (e.g., Celsis, PallCheck, MilliFlex Rapid) Growth Direct II RODACS: Growth Direct II Passive Air: Growth Direct II

8 Evaluating the Growth Direct II (GDII) Phase I: Evaluation of Consumables Phase II: Evaluation of Beta Unit

9 Growth Direct II: What is it? User Interface Touch Screen Cassette Elevator Interface to Network or LIMS Interior View Input Queue Slide graphics courtesy of Rapid Micro Biosystems Incubators 1 or 2 temperatures 300+ capacity/incubator 9

10 GDII: How does it work?

11 GDII: Evaluation of Consumables Why? The intention was to train manufacturing technicians to take EM samples Designed the study to compare an experienced analyst (QC Micro) with a new technician Assess handling of plates, switching lids, general equivalence of results with offline incubation

12 GDII: Evaluation of Consumables Active air sampling Same sampling apparatus able to be used for GDII and traditional testing Media accommodated within the sampler with an adaptor (made by manufacturer of the sampling device)

13 GDII: Evaluation of Consumables Passive Air sampling: No difference in testing set up for GDII and traditional Traditional plates are slightly larger diameter than GDII (evaluation of impact ongoing)

14 GDII: Evaluation of Consumables Surface Sampling with RODACs: Currently the only technology capable of automating this element of EM Same convex surface of the plate with black membrane overlayed on agar Diameter of the test surface is the same, GDII plates have a wider base

15 GDII: Evaluation of Consumables: Data Grade Sample Type Results (Avg CFU/plate) Growth Direct Traditional A Active Air 0 0 Settle Plates 0 0 Surface #1 0 0 Surface #2 0 0 B Active Air 3 3 Settle Plates 1 1 Surface #1 0 0 Surface #2 1 1 C Active Air Site # Active Air Site #2 7 8 Settle Plates 3 1 Surface #1 0 0 Surface #2 5 1 Surface #3 0 0 Surface #4 2 1 Surface #5 0 0 D Active Air Site # Active Air Site # Settle Plates 1 2 Surface #1 5 5 Surface #2 0 0 Surface #3 1 1 Surface #4 0 0 Surface #5 0 0 Grade A: Grade B: Grade C/D 1 active air site, 1 settling plate, 2 analysts, two reps each 2 surface sites, 2 analysts, 2 reps each 2 active air locations, 1 settling plate, 2 analysts, 2 reps each 3 surface sites, 3 analysts, 2 reps each 2 active air sites, 1 settling plate, 2 analysts, 2 reps each 5 surface sites, 3 analysts, 2 reps each 15

16 GDII: Beta Evaluation Preparation for onsite evaluation in a GMP manufacturing facility: Project plan Change control Impact assessment Evaluation Protocol Install the unit Execute evaluation protocol

17 GDII: Beta Evaluation - Planning Proposal was to locate it within the classified area in manufacturing To gain the full benefit of efficiency, plates not moving out of the area, carts not moving in Equipment pass through (Grade D) Evaluated options with project manager System requires water (to humidify incubators), air (to power the robotics), 230V power, gives off 4200BTU/hr of heat (all assessed for impact and accommodated) Evaluated Risk of microbial growth in controlled area Closed incubators Plates are individually closed (lids lock to the base) Disposal chamber is contained within the instrument Increased monitoring around the instrument performed during evaluation 17

18 GDII: Beta Evaluation Site Installation Equipment pass through to manufacturing. Uncontrolled corridor looking into the pass through. Modular installation of unit was preceded by vendor assessment of area.

19 GDII: Beta Evaluation Site Installation Stacked incubators showing location of plates (the parking deck), touch screen and keyboard interface.

20 GDII: Beta Evaluation Site Installation Installation nearing completion, right side imaging unit installation, front components and loading stations (input queues)

21 GDII: Beta Evaluation - Project Plan Month 1: System install Train technicians on EM Program the test methods (two tiered incubation, load sampling sites, load trend rules, load response to growth output queue) Evaluate LIMS interface capability, network interface capability Success criteria Successful install (operational without rework) June (sample ran successfully) Successful test method input (methods are accepted without rework or computer issues, or with successful & timely resolution) Integration with LIMS is assessed as feasible Integration with network is assessed as feasible ( Pfizerized PC on 7/2, connected to network) 21

22 GDII: Beta Evaluation - Project Plan Months 2/3: 156 samples completed Inconsistencies evaluated (no discrepancies in action limits reached by one system and not the other) Results indicated acceptability of the technology Growth Traditional EM Room Grade Sample Location Dire/methodct Result #CFU Result #CFU 1133 C Air Site C Tank Top C Tank Top C Air Site C Air Site C Air Site C Tank Bottom C Wall C Counter C UP C Air Site C Air Site C Air Site C Door to Rm C Door to Rm C Door to Rm C Wall C Air Site C Air Site 2 0 1

23 GDII Beta Evaluation: Potential Standard Work Efficiencies EM Weekly Requ Samples /Tests Test Potential EM Role (3) Hoods Task Type Task Collecting Supplies Travel to Area Gowning Cart Cleaning Prep Equip and Materials in Manuf. European Grade (4 carts) (20 Air sites) Prepping Cart/Clean Up/Data Entry Degowning/Travel to Lab Data Download/Incubation Collecting Supplies Travel to Area Gowning Cart Cleaning Prep Equip and Materials in Manuf. US Classification (2 carts) (8 Air sites) European Grade (2 carts) (9 Air sites) Prepping Cart/Clean Up/Data Entry Degowning/Travel to Lab Data Download/Incubation Collecting Supplies Break Travel to Area Gowning Cart Cleaning Prep Equip and Materials in Manuf. Hood Monitoring Settle Plates (Room) B Room C Rooms (27 VA) Clean Up/Data Entry/Data Download Degown/Travel to Lab/Clean Up/Incubate Lunch * * Break Equipment / Process Controlled Analyst Contro Day 1 Hours Evening N # # # # # # 0 X X X X X X * * X X * * X X * Timing/collection supplies (carts) could be reduced X Step could be eliminated

24 Conclusions Rapid/Automated methods for EM can add value: Standard work efficiencies Environmental control (with faster results and notifications of trends or events) Right First time (by automating receipt of expected samples and counting errors) Moving EM technology and sampling to the manufacturing area: Increases efficiencies mentioned above Decreases movement of materials in and out of controlled area Improves awareness of technicians to EM Ownership of the EM program resides with QC, Manufacturing is a sampling resource The Growth Direct II is a feasible technology for implementation in a GMP facility