Temperature MappingEquipment, Procedures and Compliance

-Kevin Loomis

Sr Validation EngineerPanasonic Healthcare Corporation of NA

Temperature Mapping 101

Equipment and facilities are temperature mapped to verify that they have the ability to meet specified performance characteristics. Specifications are established using URS, DS, FS, regulatory compliance criteria and established specifications for the products of the application.

Planning

Step 1 – Determine Critical Mapping Points

Step 2 – Determine Sample Rate

Step 3 – Establish Data Logger Criteria

Step 4 – Place Loggers at Pre Determined Points

Step 5 – Capture, Retrieve and Evaluate Logged Data

Step 6 – Document Processes (and Repeat?)

Regulatory References and Guidesfor Temperature Mapping

PIC/S GMP Guide Part I: Basic

Requirements for Medicinal

Program Sections 3.19 and 4.9

ISPE Good Practice Guide –Cold Chain Management (2011)

ISPE Controlled Temperature Chamber Mapping (2012)

ICH Q10 Pharmaceutical Quality

System (2009)

PIC/S GMP Guide Part II: Basic

Requirements for Active

Pharmaceutical Ingredients

Sections 7.42 and 10.1

21 CFR Part 820 cGMPs for Medical Devices

21 CFR Part 820.150 Storage

PDA Technical Report No. 52 –

Guidance for Good Distribution

Practices for the Pharmaceutical

Supply Chain (2011)

21 CFR Part 211 cGMPs for Finished Pharmaceuticals

USP Chapter 1079 Monitoring

Devices – Good Storage and

Shipping Practices (under revision

2011)

21 CFR Part 210 cGMPs for Manufacturing, Processing or Holding of Drugs

Many guides tell you why to map, but don’t tell you how to map!

Reference ISPE doc above & IEC 60068-3-11 for methodology.

Temperature Mapping - Basic Equipment

Sensors & Systems

PRTDs, Thermocouples or Thermistersconnected to a recording device.

(NIST/ISO17025 Calibrated)

Softwarefor Data, Graphs and Analysis

(21 CFR Part 11 Compliant)

Differences in Equipment

• Wired and Wireless

• Loggers and Live

• Sensors

• Software

Equipment Advantages and Disadvantages

• Wireless “loggers” are easy to set up, but can’t be monitored live.

• Wireless “transmitters” can be monitored live, but signal loss is a concern.

• Wired systems are robust, but often create gaps in chamber seals. Limited to sensor wire length.

• Integrated software may be easy to use, but may not be regulatory compliant.

Sensors

Sensor types should be acceptable for the accuracy and range of the device/system being mapped.

Good for incubators, refrigerators, and freezers.

1.0C or 0.75%

1.0C or 1.5%

>0 to 350C

-200 to 0C

T

OK for refrigerators and freezers, unacceptable for incubators.

2.2C or 0.75%

2.2C or 2.0%

>0 to 1250C

-200 to 0C

K

OK for refrigerators, unacceptable for incubators and not rated for freezers.

2.2C or 0.75%>0 to 750CJ

ApplicationStandard Tolerance

Standard Range

TC

Note: A calibrated mapping system will have increased accuracy to that of standard.

Sensor Placement

Placement should follow risk based approach using design considerations and expected use.

Location considerations follow the same methodology regardless of chamber size.

Refrigerators, Freezers and Cold Rooms

• Use forced air flow through evaporator and ducting to remove heat.

• Proper air flow is essential to uniformity and temperature control.

Cold Wall Units

• Remove heat using evaporator coils encased in the chamber walls.

• Not subject to air flow issues.

• Uniformity determined by efficiency of refrigerant.

Incubators and Ovens

• Heating elements, and fans work together to

control temperature and achieve uniformity.

• Like refrigerators, proper air flow is essential.

Autoclaves

• Mapping should capture temperature and pressure.

• Software may assist in determining lethality.

Warehouses, Stability and Dry Storage Chambers

• Temperature and Humidity data should be captured.

• Proper air flow is essential.

Uniformity Testing

• Temperature mapping data helps determine areas in the chamber that may not meet specification.

Dynamic Testing

• Open Door testing gives chamber characteristics during normal use.

• Power Failure testing gives chamber characteristics during failure and recovery conditions.

Loaded versus Empty Chambers

• Empty chambers typically give “Worst Case”performance characteristics.

• Loaded chambers typically produce better data as the mass aids in buffering temperature fluctuations.