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Contract Manufacturer's Journey To Higher Containment

Containment

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0% found this document useful (0 votes)
63 views24 pages

Contract Manufacturer's Journey To Higher Containment

Containment

Uploaded by

Bulent Inan
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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A CMO’s Journey to Higher

Containment
Gary M. Masse, Ph.D.
Cambridge Major Laboratories, Inc.
Outline of the Presentation

1. About Cambridge Major Laboratories, Inc.


2. Starting out on the Journey
3. Improved Engineering Controls for a current
commercial process
4. What’s next?

NOTE: The following is 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
Passion for Chemistry. Passion for Life™

Who We Are Why We Are Here What We Stand For

CML is a leading provider of We are proud to help At CML, we understand that


global, integrated drug thousands of people overcome market growth is a natural
development and some of life’s biggest outcome of listening to our
manufacturing services. Our challenges. Using our chemistry customers, adopting a
commitment to Quality, expertise we help our clients compliance focus, and making a
performance culture, and develop new, lifesaving commitment to invest in
project-focused organizational treatments for patients, so they technology and innovation.
alignment ensure a superior can sustain a high quality of life. These anchors focus our efforts
track record of exceeding client Our passion for chemistry is every day, and help reinforce a
expectations for outsourced what makes us so successful. culture of accountability and
Chemistry, Manufacturing, and Our passion for life is why CML mutual respect.
Controls (CMC) services. exists.

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

US Development Facility US Large-scale API Production Facility European Development Facility

 75,000 sq ft  200,000 sq ft  135,000 sq ft


Wide range of technologies  Acquired in 2007 (Chemshop)
  Footprint allows for significant
 Minimal investment required to
 4 separate analytical/QC labs additional capacity expand capacity
 6 R&D labs; 5 GMP kilo lab suites  Invested >$40MM  Solid state chemistry labs
 Pilot plant to 2000 L scale reactors  Reactors up to 8000 L scale  Efficient access to European
clients
Handling Higher Potency Compounds:

Starting out on the Journey


• Devise a Robust On-boarding Process for New Projects
– Determine what level of potent compounds can CML handle
– Develop Health Hazard Category (HHC) bands
– Adopt a Risk-based Exposure Assessment Process
– Use DEREK Nexus Software to obtain SAR data for new chemical entities
– Environmental and Occupational Toxicologist on retainer as needed
• Undertake a Multi-faceted System-wide Approach
– From raw material handling through API testing and shipment
– Address issues in R&D, Process Development, Manufacturing, Analytical
Sciences and Logistics
– Leverage Industry experts in containment strategies
• Provide adequate Worker Training Program to ensure Compliance
Health Hazard Category Banding Table

CML Health Hazard Category bands were generated:


CML Health Hazard Category (HHC) Table

Category SafeBridge OEL CML HHC OEL General Control

1 > 500 µg/m3 OEL > 100 µg/m3 Use good work practices and general ventilation

10 µg/m3 < OEL < 10 µg/m3 < OEL < 100


2 Use local exhaust ventilation and PPE
500 µg/m3 µg/m3

0.03 µg/m3 < OEL <


3 1 µg/m3 < OEL < 10 µg/m3 Enclose the process with containment
10 µg/m3

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

Installation of the EZI-


Dock system for
charging Raw
Materials and
Intermediates into
the reactor
Contained reactor
charging using
the ILC Dover
DoverPacSF &
FCG Valve.

NOTE: ILC Dover slide used with


Permission

www.ilcdover.com e: [email protected] p: 302-335-3911 x506 or 800-631-9567


Continuous Liner System

The continuous liner


system provides a
simple means to
protect both the
chemical and operator
from exposure
Agitated Filter Dryers with Containment
2 new Agitated Filter Dryers have been installed
• Steri Technologies 0.4 m2 Hastelloy C-22 unit at Grant Drive facility
• PSL 0.15 m2 Hastelloy C-22 unit at Washington Drive facility
• Both units have Gloveboxes for containment during discharge
Handling Higher Potency Compounds:
… and the Journey continues
• CML has been producing multi-tonne quantities of a
commercial API since 2009
• The current process has been changed and
improved.
• This is an example of CML commitment to
Sustainability.
The Current Process

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

Current Process New Process


People Issues
1. Hazardous Solvents Uses Chlorinated Solvents No Chlorinated Solvents
Uses Engineering Controls The process is contained.
2. Containment Strategy and PPE for the Containment Engineering Controls are
strategy improved; PPE is secondary

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?

• CML is engaged in a feasibility study to build


a High Containment API Manufacturing
Facility.

• More on this later…


Thank you!
Questions ?

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

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