Contract Manufacturer's Journey To Higher Containment
Contract Manufacturer's Journey To Higher Containment
Containment
Gary M. Masse, Ph.D.
Cambridge Major Laboratories, Inc.
Outline of the Presentation
In 2012, over one million patients were touched by Active Pharmaceutical Ingredients
developed and supplied by CML
Facilities Overview
Three production sites with over 400,000 square-feet, equipped with state-of-the-art
technology and infrastructure
– Nearly $70 million invested over the last four years, to build and improve CML’s state-
of-the-art facilities
– Strategically located in the U.S and Europe to serve the Company’s global customer
base
– US facility promotes "under one roof" capability
– Strong track record of environmental and regulatory compliance
1 > 500 µg/m3 OEL > 100 µg/m3 Use good work practices and general ventilation
4 OEL < 0.03 µg/m3 OEL < 1 µg/m3 Seek expert advice
Overall Implementation Strategy
• Upgraded Engineering controls for:
– R&D, Kilo Lab and QC personnel
– Reactor design, including solution transfer of
HPAPI during workups
– Weighing and dispensing of Raw Materials and
Intermediates during manufacture
– Discharging, weighing, analyzing and transporting
API’s after manufacture
• Worker training to understand HPAPI’s and current
EHS projects to improve containment
Engineering Controls for R&D
• Incorporation of Ductless Laminar flow technology from AirClean
Systems
• Meets ISO 5 and FS209E Class 100 clean bench standards
Engineering Controls for Quality Control
• Powdersafe B Enclosure from AirClean Systems
• Allows for effective weighing to 5 decimal places
• Continuous HEPA filter monitoring with HEPASafe™ filter change
technology
Dispensing Isolator from Powder
Systems Limited
Reactor Charging System
Reactor
Charging is
completed using
a De Dietrich
Powder Transfer
System
The Current Process
The product is
isolated by using
a Horizontal
peeler centrifuge
The Current Process
The product is
dried using a
Conical Dryer.
The New Process
• The process has been revisited, improved and is
currently going through revalidation.
• Reactor Charging will occur through Chargepoint
valves, using ILC Dover’s DoverPacs
The New Process
Solids isolation
and drying will
occur in 2
AFD’s with
Isolators for
improved
Engineering
controls
Comparison of the 2 Processes
Sustainable Development
Planet Issues
1. Waste Generated 200 L / kg API 110 L / kg API
2. Water Use 73 L / kg API 27 L / kg API
3. Catalyst recovery Too dilute for recovery Recovery Project being studied
4. Manufacturing Footprint 6 kg / unit vol 36 kg / unit vol
Prosperity Issues
1. Labor 3.6 h / kg API 1.5 h / kg API
2. Cycle Time 2.8 h / kg API 1.2 h / kg API
What’s Next on our Journey?
NOTE: This Presentation was based on a summary of quality control principles. It is not to be
interpreted as engineering, operational or legal advice. Circumstances vary, and any action based
on this presentation is taken at the reader's sole risk. Readers should consult with experts of their
own choosing before applying any aspect of this summary to their own situation