CMC Consulting Case Studies

• Managed API  Issues; Licensing Deal
• CMC Issue Resolution; Increase of Licensing Value
• Maximizing CMC Value
• CMC Due Diligence
• QA Audit & Commercial Strategy
• QA Audit Remediation & PAI Prep
• Maximizing Efficiency in CMC and Development Activities: CMC Approval
• Pre-IND & IND Preparation

Due to the confidential nature of the work Rondaxe does for our clients, we are unable to reveal specific informationabout projects or cases. The following case studies illustrate the type of work that Rondaxe performs and the results that we achieve.

API Issue Management; Licensing Deal

Situation:
Pre-IND candidate, API did not meet specifications

Rondaxe Team Actions:

• Identified and executed process improvements
• Reworked product
• New CRO is engaged and given technology transfer support

Results:
Increased yield 2X in the API process

• Lengthened client’s cash burn rate
• COG reduction thru increased yield
• Shortened time to achieve key milestones
• IND filed; Product licensed to Big Pharma for $215 million

CMC Issue Resolution; Licensing Value Increase

Situation:
Client had worldwide partnering discussions underway
Due diligence uncovers CMC issues threatening to devalue licensing event

Rondaxe Team Actions:

• Eliminated CoGS, Supply Chain and Regulatory issues
• Oversaw production through drug product
• Transferred process to two new vendors

Results:

• $10 Million licensee devaluation was overcome
• 6x productivity enhancement in the API process
• Licensee has successful End of Phase II meeting

Maximizing CMC Value

Situation:
Client needed to license out Phase II product to proceed to Phase III API & Drug Product had stability issues

Rondaxe Team Actions:

• Initiated development of comprehensive due diligence package
• Resolved API & Drug Product instability issues
• Designed & implemented improved supply chain / COG’s structure
• Solidified clients Intellectual Property position

Results:
Product Licensed to Big Pharma for $508 million

CMC Due Diligence

Situation:
Client required CMC due diligence on two clinical candidates with both IV and soft-gel formulations (4 products)
Client has resource constraints

Rondaxe Team Actions:

• Three content experts travel to Europe to execute due diligence and collect pertinent data
• Prepared complete due diligence report & strategic analysis for client

Results:

• Client receives comprehensive report including:
  • Detailed analysis of “show stoppers” & Gap analysis versus NDA timelines
  • Development and commercial COG’s forecast
  • 18 month projection of client development resource requirement
• Client narrowed negotiation to a single product
• Client amended staffing plans

QA Audit & Commercial Strategy

Situation:
US based emerging pharma company, licensed in Phase III product
Client desired strategic evaluation of supply chain

Rondaxe Team Actions:

• Rondaxe initiated a multi-phase program:
  • Performed QA audits of existing suppliers in India and Eastern Europe
  • Extracted critical COG’s data from suppliers
  • Assisted client with negotiation of supply contracts
  • Worked with client to establish commercial launch plan

Results:

• “At risk” suppliers eliminated from launch plan
• Robust, cost effective supply chain established

QA Audit Remediation & PAI Prep

Situation:
An API supplier in India failed a GMP inspection
Client desires a remediation program for the 38 audit observations

The Rondaxe Team:

• Rondaxe initiated a multi-phase program:
  • On-site meetings to develop and kick-off remediation action plan
  • Off-site monitoring and guidance of remediation team
  • Final on-site review and approval of remediation program
  • On-site Pre-Approval Inspection (PAI) training

Results:

• Successful remediation of all 38 observations
• Facility and staff positioned to pass a PAI from the FDA

CMC Issue Resolution &  Licensing Value Increase

Situation:
Client had worldwide partnering discussions underway
EMEA had questions requiring responses prior to initiation of Phase III studies
Supply Chain threatened by loss of Key Vendor

Rondaxe Team Actions:

• Provided response to EMEA within 14 days
• Established new supply chain plan within 21 days
• Transferred process to new vendors

Results:

• License negotiations continued to a successful close
• Phase III clinical plan stayed on track

Maximizing Efficiency in CMC and Development Activities: CMC Approval

Situation:
Rondaxe hired to manage Development and Regulatory activities
Client received unorganized historical information from Licensor
Client needed to develop a CMC Regulatory strategy and present to FDA at End of Phase II meeting

Rondaxe Team Actions:

• Organized historical information into logical development histories
• Prepared IND and IMPD updates
• Prepared CMC End of Phase II briefing package

Results:

• FDA agreed to all proposals at End of Phase II meeting
• CMC Data ready for go/no go to NDA

Pre-IND & IND Preparation

Situation:
Client preparing for Pre-IND meeting with FDA
API and DP Development work performed by Multiple CRO’s
Client lacked internal capabilities to address CMC issues or prepare Pre/IND documents

Rondaxe Team Actions:

• Organized all process information from CRO’s,
• Prepared Pre-IND briefing package and attended meeting with Client and FDA
• Prepared the CMC section of the IND

Results:

• FDA agreed to GMP starting materials as proposed
• No CMC related questions requiring a response to the FDA
• The IND was submitted and approved without any questions from FDA