September 18, 2013
Earlene Gibbons
Director, Operational Technology

• Green Field Construction
– Solid Dose Manufacturing
– 200,000 sq. ft. facility
– New Equipment
• Blank Slate
– No existing systems
– No in house experience
– No additional team members
• No formal budget allocated for GxP systems
– However…

• 100% Outsourced Manufacturing to Insourced
Manufacturing
• Systems to support the facility, manufacturing, and quality required identification, procurement, installation and qualification
• The schedule of system installations had to be prioritized and integrated into the construction schedule

• Building Management
• Calibration Management
• Maintenance Management
• Document Management
• ERP / Materials Management
• QMS
• LIMS / Chromatography Data

• One of the first systems required to be available for use was a calibration management system
– Manufacturers’ Bench Calibrations
– Installation Calibrations
– Validation Calibrations
• The calibration management system availability had to be closely coordinated with the BMS startup and commissioning

“Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product.
If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance.
Written records of those calibration checks and inspections shall be maintained .” CFR 211.68

System Requirements
Regulatory Compliant
Part 11 Compliant
Ease of Use
Paperless
Scalable
Vendor Selection Criteria
Project Management Services
Implementation Services
Training
Understanding of Best Practices
On –Going Support
Reporting (Standard & Ad Hoc) Reputation
Configurable Customer Service
Cal / PM Harmonization Life Sciences Industry
Experience
Audit Trail

• Start up is the series of events required to turn equipment or systems on for the first time
• Equipment Commissioning is the process of testing equipment to verify it functions according to the design specification
• Commissioning is performed under Good
Engineering Practice (GEP)

• Installation Qualification documents that the equipment was installed correctly:
– Design features
– Installation conditions
– Environmental conditions
– Calibration and PM schedules
– Safety features
– Software documentation
– Spare parts list
– Vendor documentation / Turn-over package
• Equipment Validation/ Qualification is documented evidence that provides a high degree of assurance that the equipment requirements and specifications are met and will fulfill its intended purpose

• Project Planning
• Data Migration
– External Calibration Manager to RAM
• Validation
• SOPs
• Training
• Go-Live

• Accurate
• Consistent
• Secure
• Scalable

Blue Mountain RAM is the system of record for our equipment / asset management
• Types
– Equipment
– System
– Location
– Personnel
– Loop
• Classification
– Critical / Direct
– Non Critical / Indirect

• A calibration management program ensures equipment and instruments are calibrated according to written instructions
• The calibration management program must document the calibration date, person performing the calibration and the date due of the next calibration
• Calibration Periods
– Manufacturers Recommended intervals
– Daily
– Monthly
– Quarterly
– Semi Annually
– Annually
– After an event

• Preventive maintenance should be performed at appropriate intervals to prevent equipment malfunctions that are preventable with regular monitoring
• PM activities include visual inspection of the equipment, following the manufacturer’s recommendations for routine maintenance and regular inspection / replacement of parts that routinely wear out or fail

• The equipment classifications identified and assigned for calibration management provide the foundation for the maintenance management program.
– Unique Equipment Numbers
– Preventive Maintenance Plans
– Work Instructions (R3)
– Historical Maintenance Records
– Scheduling
– Training
– Spare Parts
– Utilities

• Review and approve new and / or edited records for equipment, instruments and systems entered into RAM
• MDT
• Standards
• New Assets
• Calibrations
• PM
• Val (upgrade)
• SS (upgrade)
• WPT (upgrade)

• Calibration and Preventive Maintenance are required to maintain the equipment in good working order
• Quality review of both calibration and PM activities can be performed by exception – reviewing only the records that are out of tolerance
• Ease of reporting Calibration and
Maintenance activities provides regulatory authorities / auditors with the documentation of maintaining the equipment in compliance with cGMP

• Non-Compliant organizations risk
– Warning letters
– Delays in getting product to market
– Losing market share to competitors

• RTP upgrade to R3
• Silver Spring upgrade CalMan to R3
• Leveraged existing rules, workflows
• Workflow Improvements
• Integration with ERP and other corporate systems
• Multi-Site Harmonization

• Consistent Support Structure
• Consistent approach to compliance
• On-boarding New Facilities
• Global Harmonization

• Code of Federal Regulations, Title
21, Part 210
– Current Good Manufacturing Practice in
Manufacturing Processing, Packing, or
Holding of Drugs
• Code of Federal Regulations, Title
21, Part 211
– Current Good Manufacturing Practice for Finished Pharmaceuticals
• Blue Mountain RAM User Manual