Presentation is loading. Please wait.

Presentation is loading. Please wait.

Small-molecule Drug Development: Selecting And Working With Contract Manufacturing Organizations (CMOs). James M. Hamby, R.Ph., Ph.D. Director of Business.

Similar presentations

Presentation on theme: "Small-molecule Drug Development: Selecting And Working With Contract Manufacturing Organizations (CMOs). James M. Hamby, R.Ph., Ph.D. Director of Business."— Presentation transcript:

1 Small-molecule Drug Development: Selecting And Working With Contract Manufacturing Organizations (CMOs). James M. Hamby, R.Ph., Ph.D. Director of Business Development Ash Stevens, Inc. 18655 Krause Street Riverview, MI 48103 Tel: (734) 282-3370 ext. 1144 Email: Web:

2 Ash Stevens Inc.: an Established, Stable API Contractor  Early-Stage Development Through Commercial Manufacturing Of APIs  Eleven FDA Approved Commercial APIs: Velcade (5/03), Vidaza (5/04), and Clolar (12/04)  cGMP Compliant Operations  Provider Of Contract Research Services To The Federal Government (NIH &NCI)  Dun and Bradstreet Rating of “4A1”

3 Chemistry Milestones for an NDA NDA Filing Validatable Process One Batch Prior To Filing Development Report Impurities Identified 12 Months Stability – 3 Batches (API Shipping and Storage Only) FDA PAI One Validation Batch Complete Protocol for Two Additional Batches Approval to Market Phase II/III Parametric Studies Validated Analytical Methods; Starting Material, Intermediate, and Product Specifications; Packaging Phase I “Manageable” Process Process Hazard Review Cleaning Procedures Scientifically Sound Analytical Methods Development Candidate Stability Program Stability Studies Including Three Lots of API Mfg. Batch Definition Unit Operations Scale of Batch

4 cGMP Compliance  ICH Guidelines And US 21 CFR 210-211 Regulations Mandate That The Sponsor Company Is Responsible For Assuring Compliance With cGMP Regulations  Therefore, It Is Incumbent Upon The Sponsor To Ensure That Third Party Generated Data Is Of The Highest Quality And That The Sponsor Can Defend The Integrity Of The Data And The Process

5 Managing Drug Development  Ideal Situation Is to Have An In-House Drug Development Team Experienced At Working With CMOs  CMC Consultants And CRO’s  Experienced CMO (Turnkey)

6 Key Steps In Identifying A CMO  Due Diligence-Identifying Potential CMO Partners  Preparing the Technical Package (RFPs)  Evaluating the Proposal  Site Visit  Quality Systems Audit

7 Due Diligence-Identifying A CMO Partner

8  Provide Enough Time To Do Thorough Due Diligence  Avoid “I Need It Yesterday” And Unrealistic Expectations  Understand Your Project the Process, Timelines And Costs  Chemical Manufacturing Tradeshows (InformEx, ChemOutsourcing)  Rep Visits Due Diligence

9  Good Fit For Project Needs And Strategy  Capacities And Capabilities  Reputation For Quality And Delivering On Time and On Budget (# Of NCE API Approvals, References)  Regulatory Inspection History  Financial Stability  Location And Accessibility Due Diligence

10 The Request For Proposal (RFP) Technical Package

11 The Request For Proposal (RFP):  CDA In Place  Share All Pertinent Information (Better Quality Quote)  Provide Full Experimental Details And Yields  Clearly Communicate Required Deliverables, Quantities, And Timelines

12 The Request For Proposal (RFP):  Describe Intended Use Of Material (e.g. 500g For GLP Tox. And 3 Kg cGMP For Phase I Studies)  Define General Purity Specifications For Deliverables (e.g. >95% Pure For GLP Tox. Material)

13 Proposal/Quote Assessment

14  Comments And Strategy Section  All Costs and Work Clearly Defined  Risk-Based Proposals  Start Date  Intellectual Property

15 Early-Stage Project: Initial Tasks 1. Process Feasibility and Evaluation 2. Preliminary Process Development 3. Demonstration Batch (250-500g, non- GMP) 4. Initial Phase I GMP Batch (1-5 Kg) 5. Analytical Development

16 CMO: Site Visit

17  Meet “Key” People, Explain Expectations And Requirements, Timelines (A Team Vs. B Team)  Project Manager Key Person  Communication & Resolution Of Problems  EHS&S, Housekeeping & Cleanliness  Tech Transfer: Scale-up From Grams To Kilograms, non-GMP vs. GMP  Hours Of Operation And Vacation Schedules  Quality Systems (Audit?) CMO Site Visit

18  Modern Equipment And Facility, But Be Conscious Of The Wow Factor  Confidentiality: Chemical Structures Written on Hoods or Glassware, Client Names Or Client Compound Numbers Visible, Numbers Written On Hand or Scraps Of Paper,  How Busy Is The CMO, Are They Flexible  How Much Does the CMO Value Your Business (Win/Win) CMO Site Visit

19 Early-Stage Strategy: Proof Of Concept ASAP And Exit/Partner

20 Early-Stage Development Project  Developing An In-licensed Drug Or A Drug From In-house Discovery Effort  Discovery Route: Milligrams To A Few Grams  Strategy: Proof Of Concept; Find A Development Partner Or Sell Company  1-5 Kg GMP Required For Phase 1-2b (IND Path)  Partner: Approval ASAP And Commercialize (NDA Path)

21 Early-Stage Development Project  Sponsor Strategy: Hammer Out GMP API By The Discovery Route To Save Time And Money.  Often A Risky Strategy  Rarely Is The Discovery Route Amenable To GMP Scale-up  High Probability Of Encountering Chemistry Issues

22 Early-Stage Development Project  Partner May Need To Reinvent The Process For Plant Scale Production  The Lack Of A Robust GMP Process Can Effect The Value Of A Deal  An Experienced CMO Can Help The Sponsor Optimize The Their Strategy

23 The Challenge Time/ Reliability Quality Cost

24 Comprehensive Medicinal Chemistry Vol. II (Strategy And Drug Research) Vol. Editor Walter Moos, Publisher Elsevier, Chapter 2.05, Pages 159- 173 “The Role of the Chemical Development, Quality, and Regulatory Affairs Team in Turning a Potent Agent into a Registered Product” Stephen A. Munk, Ph.D. Ash Stevens Inc., Detroit, MI

Download ppt "Small-molecule Drug Development: Selecting And Working With Contract Manufacturing Organizations (CMOs). James M. Hamby, R.Ph., Ph.D. Director of Business."

Similar presentations

Ads by Google