rapid/automated environmental monitoring on the ... environmental monitoring on the manufacturing...

Rapid/Automated Environmental

Monitoring on the Manufacturing Floor

Amy McDaniel, Ph.D.

IFPAC

Arlington, VA

January 2014

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

Introduction to Pfizer Biotech,

Sanford, NC

Sanford’s Role: • Commercial manufacturing for Prev(e)nar and Prev(e)nar13 conjugate

• Commercial manufacturing for CRM197 carrier protein

• Supply clinical trial materials for microbial / conjugate products

• Commercial launch and production site for microbial / conjugate products within the PGS

network

Why RMM for EM?

4

Get materials

Sample in

Manufacturing

Wait for

settle plates

Wait for

incubation

Return to lab

Read

Results

Identify samples

Get materials

Prepare on

mfg floor Collect samples

according to role

Load samples into automated

technology

Pre

sent

Futu

re?

Prepare in lab

Clean carts

Gown

Travel to manufacturing

Incubate plates

Clean up

Data entry

De Gown

QC Identifies samples

BioProcess Technicians

QC reviews 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

Reduced Time

to Results

QC micro analysts

5

Shift huddles utilize a short, routine meeting & white board to monitor/manage Micro lab operations

How are current EM sampling issues identified?

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 email alerts if a sample is missing.

Error proof and time saving!

RMM for EM: Standard Work Confirms

Advantage

Break

Equipment / Process Controlled Analyst Controlled

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


US Classification (2 carts) (8 Air sites)





Collecting Supplies

Break

Travel to Area

Gowning

Cart Cleaning


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

EM

0# # # # # #12 13 14 15 16 17

Hours Evening Night

Weekly Requ

Samples /Tests

TestTask

TypeTask

Day 1

8 9 10 11

Po

ten

tia

l E

M R

ole

(3

) H

oo

ds

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

Evaluating the Growth Direct II (GDII)

• Phase I: Evaluation of Consumables

• Phase II: Evaluation of Beta Unit

Growth Direct II: What is it?

9

User Interface Touch Screen

Interface to

Network or LIMS

Incubators 1 or 2 temperatures

300+ capacity/incubator

Interior

View

Input Queue

Cassette

Elevator

Slide graphics courtesy of Rapid Micro Biosystems

GDII: How does it work?

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


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)

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)


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

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 #1 9 11 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 #1 23 24 Active Air Site #2 13 14 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: 1 active air site, 1 settling plate, 2 analysts, two reps each 2 surface sites, 2 analysts, 2 reps each

Grade B: 2 active air locations, 1 settling plate, 2 analysts, 2 reps each 3 surface sites, 3 analysts, 2 reps each

Grade C/D 2 active air sites, 1 settling plate, 2 analysts, 2 reps each 5 surface sites, 3 analysts, 2 reps each

GDII: Evaluation of Consumables: Data

• Preparation for onsite evaluation in a GMP manufacturing

facility: – Project plan

– Change control

– Impact assessment

– Evaluation Protocol

• Install the unit

• Execute evaluation protocol

GDII: Beta Evaluation

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

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.


Stacked incubators showing location of plates (the

parking deck), touch screen and keyboard interface.


Installation nearing completion, right side imaging unit

installation, front components and loading stations

(input queues)

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 26-28 (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

√

√

√

√

• 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

GDII: Beta Evaluation - Project Plan

1133 C Air Site 2 3 6

1133 C Tank 120185 Top 0 0

1133 C Tank 120180 Top 2 0

1134 C Air Site 1 2 0

1134 C Air Site 2 2 2

1134 C Air Site 3 7 2

1134 C Tank 120110 Bottom 0 0

1134 C Wall 0 0

1134 C Counter 1 0

1134 C UP-1134 0 0

1135 C Air Site 1 4 1

1135 C Air Site 2 2 3

1135 C Air Site 3 8 1

1135 C Door to Rm 1131 0 0

1135 C Door to Rm 1145 11 0

1135 C Door to Rm 1153 0 0

1135 C Wall 0 0

1137 C Air Site 1 0 0

1137 C Air Site 2 0 1

Room Grade Sample Location

Growth

Dire/methodct

Result #CFU

Traditional EM

Result #CFU

GDII Beta Evaluation:

Potential Standard Work Efficiencies

Break

Equipment / Process Controlled Analyst Controlled

Collecting Supplies

Travel to Area

Gowning

Cart Cleaning






Collecting Supplies

Travel to Area

Gowning

Cart Cleaning


US Classification (2 carts) (8 Air sites)





Collecting Supplies

Break

Travel to Area

Gowning

Cart Cleaning


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

EM

0# # # # # #12 13 14 15 16 17

Hours Evening Night

Weekly Requ

Samples /Tests

TestTask

TypeTask

Day 1

8 9 10 11

Po

ten

tia

l E

M R

ole

(3

) H

oo

ds

X X

X

X X

X X

X

X X

*

*

*

*

*

*

* Timing/collection supplies (carts)

could be reduced

X Step could be eliminated

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

rapid/automated environmental monitoring on the ... environmental monitoring on the manufacturing...

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