©2012, Genentech
Overcoming Tech Transfer Challenges and Optimizing CMO Management
6th Annual HPAPI Summit
June 21st ~22rd, 2017 Boston
Hairong (Angela) Zhou Sr. Sourcing Manager
SMPS, Genentech June 22nd, 2017
©2012, Genentech
Outline
• Assessing key factors involved for outsourcing in the highly potent space
• Managing CMO effectively and ensuring safety standards are maintained to the levels comparable to internal process
• Ensuring timeline and budget restrains are met by effectively working with CMOs throughout the process
2
©2012, Genentech
Key Factors for Outsourcing HP Materials
• Containment capabilities at CMOs • Proper equipment for each unit operation matching the material’s HHC • Trained and experienced staff • Proper SOPs for handling HP materials
• Timeline and cost • Longer and more expansive
• Technical capabilities
How will we start the process? Which CMO? What is the HHC for the to be outsourced material?
3
©2012, Genentech
Brief Introduction of Roche/Genentech • Genentech is a leading biotechnology company (founded in 1976)
• Discovers/develops medicines to treat patients with serious medical conditions • Biologics and small molecule divisions
• All small molecule drug candidates are development in SMPS department • Outsourced a significant amount of HPAPI production at CMOs • CMOs assumed all the responsibilities to ensure proper containment used
• Became a wholly owned member of the Roche Group in March 2009 • Roche would like to assume all the responsibilities
• Roche is a global pharmaceutical company (founded in 1896)
• About 80 years older than Genentech • Specializes in diagnostics, small molecule R&D, etc. • More systems in place • Gradually outsources more and more to third parties
4
©2012, Genentech
Roche Team’s Expectations
In general: • All workers must be safe when handling our product • Standards and working conditions at CMOs must be comparable to those we would require in-house
5
©2012, Genentech
Roche’s Group SHE 6
Roche’s mission of Safety, Security, Health and Environmental Protection
• It abstracts our everlasting efforts in SHE: • Build awareness • Motivate • Inform and educate • Audit • Report • Feedback for improvement to a higher level
©2012, Genentech
Expectations on Exposure Control
Engineering controls must be the primary means to control chemical exposure
• Control exposure: hardware • Elimination or substitution of the hazardous material or process step • Use of engineering controls (i.e. filter dryers, continuous liners, isolators for weighing
chemicals) as the primary protection • Use of personal protective equipment (PPE) as the secondary protection
• Required measures are: • Ensure all operators are trained on use and maintenance of equipment • Obtain air monitoring data • Must have an efficient cleaning method in place
7
©2012, Genentech
Expectations in General for CMOs
• Third parties are expected to meet internationally recognized standards of:
• Safety • Health and environmental performance • Ethical business practices and social responsibility
• Third parties are expected to operate in full compliance with all local applicable laws, rules and regulations.
• Third parties are expected to meet Roche’s SHE expectations • Group SHE will audit sites of suppliers that pose a high SHE risk • CMOs that manufacture API’s, intermediates, raw materials, which fall
into the occupational health categories 4, 3B, 3A and – at high quantities – even category 2
8
©2012, Genentech
Occupational Exposure Bands (OEL) 9
Category 1 Category 2 Category 3A Category 3B Category 4
100 µg/m3 10µg/m3 1µg/m3 50ng/m3
no/slight hazard moderate hazard high hazard high hazard very high hazard
• Occupational exposure levels defined as upper limit on the acceptable concentration of a chemical in air for a particular material or class of materials
• Apply not only to APIs but also to RSMs and any API intermediates
©2012, Genentech
Roche and Genentech: Building the Business Case 10
• Back in early 2010s: • Some CMOs did not have mature HPAPI evaluation process, nor proper
containment/cleaning at their facilities Could not continue our business as usual
• What would be a holistic approach?
• Work as one team to achieve the following goals at CMOs: • Deliver one and the same SHE message across the board • Help key partners to enhance their containment capabilities
Balance cost, quality, timeline, efficiency and SHE compliance for business continuity
©2012, Genentech
• It’s a multi-pronged approach • Exam our CMO portfolio and strategize who can do what and where
• Select key partners and provide help to close the SHE gaps ASAP
• Optimize CMO management with added-on SHE aspect
• Overcome new challenges in tech transfer related to material
handling
11 Working Together: Overall Strategies
©2012, Genentech
With selected key external collaborators
• Educate them with Roche’s SHE expectations
• Provide basic training, guidance and suggestions • Direct them to reputed SHE trainings, consulting firms and facility
designers • Conduct audit, provide feedback for improvement • Conduct follow up audit to bring them into compliance
12 Working Together
©2012, Genentech
Steps Taken to Bring CMOs Into Compliance
Educate CMOs through site visits and provide practical solutions • Visit plants and meet the EHS staff • Identify gaps in facilities, equipment and processes • Provide guidance and education • Help with SOP establishment and refinement • Consult on trainings and equipment purchase based on Roche standards • Follow up visit to close the gap • Follow up with audit to qualify the SHE operation
Potential exposure for HP chemical powder handling: key unit operations
• Solid sampling and dispensing • Solid charging • Material transferring • Drying and discharging of powder • Packaging
13
©2012, Genentech
Achieved So Far for Bringing CMOs to SHE Compliance
• Raised the awareness of Roche’s SHE expectations /requirements • Internally as well as at third parties
• Helped key partners to close the SHE gap • Kept high performers by providing trainings, consulting, etc. • Some partners already passed our audit • Key partners are totally aware of the containment concept, rational and
requirement
• Identified/built a network of capable CMOs who can safely
manufacture HPAPI and it’s intermediates • re-evaluated our original CMO network with additions and removals
14
©2012, Genentech
Key Factors for Outsourcing HP Materials
• Key factors:
• Potency assessment for each outsourced material • HHCs or ADEs, MSDS
• Make vs. buy • Type of chemistry, scale, capacity, timeline and cost
• CMO selection • Type of chemistry, scale, capacity, timeline and cost • Containment capability to handle the signed HHC category
Important aspect: plan ahead
15
©2012, Genentech
Optimizing CMO Management for HP Material Production
• Ensuring safety standards are maintained to the levels comparable to internal process
• Added HHC information to the RFP • Qualified CMOs and their equipment trains • Helped with setting up proper SOPs, procedures for handling Genentech
compound • Visited plants during the production
Key: know your partners and their plants/production trains
16
©2012, Genentech
Ensuring Timeline and Budget Restrains Are Met
• Communicate effectively • Plan ahead and get ready • Share project timeline and expectations • Bring awareness of how to handle potent materials
• Stay within the budget
• Plan ahead • HPAPI will cost more • Asian CMO’s price is still better than Western CMOs
17
©2012, Genentech
• Who are involved: (along with respective teams)
• Dr. Andreas Flueckiger • Chief Occupational Health Officer, Roche Group SHE, Roche Basel
• Dr. Michael Cerreta • EHS Administration, Genentech
• Dr. Shreen Babu
• SMPS sourcing team, Genentech
• Dr. Larry Fisher • PTDMX sourcing team, Roche Pharma Tech Dev
• CMO management team and EHS staff
18 Working Together
©2012, Genentech
Continuous Improvement Towards SHE Excellence
It is an ongoing effort… To balance the cost, quality, efficiency , timeline and safety in order to achieve robust HPAPI development and production
19
©2012, Genentech
CMOs’ Containment Level: The Landscape in 2017
A sourcing manager’s observation
• Western CMOs very much stayed the same
• Asian CMOs are catching up • key partners have improved significantly
• The gap is getting smaller
20
©2012, Genentech
Progress Made by Asian CMOs Since 2012
Hardware: • They built new facilities designed by world known designers
• e.g. Amec Foster Wheeler • They upgraded some existing plants • They learned to use the flexible containment technology
• e.g. the Doverpac
Software: • They hired experienced Western SHE personnel to head up the SHE team • They identified and participated SHE trainings available worldwide
• e.g. SafeBridge Boot Camp in Boston • They hired reputed SHE firm as their consultant
• e.g. Golder in Shanghai • They established regular trainings for their employees • Plus: more and more IH graduates went back to their home country
They are catching up quickly…
21
©2012, Genentech
22 Acknowledgements
• SMPS Leadership Team
• SMPS Sourcing Group
• EHS Team at Genentech
• Product Quality/Occupational Toxicology Team at Genentech
• PTDMX Team • Roche Group SHE • CMO Teams
Special thanks to: Dr. Andreas Flueckiger , Dr. Mike Cerreta, Dr. Shreen Babu, Mr. Herbert Yajima, Mr. Dave Stirling
Top Related