Best Practices and Application of GMPs for Small Molecule Drugs in Early Development IQ Workshop, Feb 4-5, 2014, Wash

1. Best Practices and Application of GMPs for Small Molecule Drugs in Early DevelopmentIQ Workshop, Feb 4-5, 2014, Washington, D.C. Manufacturing Breakout Session 1

2. Survey Results: Drug Product Manufacturing in Early Development A total of 10 IQ member companies responded

3. Survey Results: Drug Product Manufacturing in Early Development A total of 10 IQ member companies responded

4. Topic 1: Batch Documentation IQ proposal to design batch records that accommodate manufacturing flexibility Raw materials or API do not necessarily need to be fully released at start of manufacture Room/line clearance does not necessarily need to be performed by Quality Process parameters do not need to be pre-determined in all cases Executed BR must serve as a record to allow replication of a process DISCUSSION What approaches have you successfully implemented What are typical lead-times before the start of a early development campaign? What is the role of Quality? Describe your early development manufacturing control strategy Defined process parameters versus in process control limits. Which process parameters should be pre-defined, which should be left undefined? What obstacles have you encountered 4

5. Topic 2: Change Control IQ proposal to design manufacturing practices that accommodate changes Process changes during manufacture should be documented as operations notes or modifications These would not require prior approval from Quality Changes should not trigger a formal CAPA unless the deviation is systemic and could apply across projects Product specific changes do not require CAPA Changes from Batch-to-Batch are expected and should be documented to capture development history DISCUSSION What change control approaches have you successfully implemented What is the role of Quality in approving planned and unplanned manufacturing deviations? How are manufacturing deviations handled in your quality management system? What are some examples of manufacturing changes that should require a CAPA? What obstacles have you encountered 5

6. Bonus Slides

7. GMPs in Early Development Part 3:Drug Product Manufacturing • Published in August 2012 issue of Pharmaceutical Technology • Volume 36, Issue 8, pp. 56-61

8. IQ DP Mfg Paper: Batch documentation Batch documentation preparation and execution Minimum requirements are given in available guidance. Must serve as a record to allow for replication of the process. are expected due to limited product and process knowledge Flexibility in specifying process parameters In the batch record; should record and document during batch execution, do not require prior approval by Quality in every case. Change control Changes from batch to batch are expected and should be documented to capture development history, and communicated to affected areas system should capture documented appropriately (Quality pre-approval not required before implementation but adequately justified, change control system is not required) Formal sampling plan not required when collecting data “for development purposes” 8

9. IQ DP Manufacturing Paper: Raw Materials Excipient specifications Should be based upon compendial specifications if available in at least one of the pharmacopeia (USP, EP, JP) Materials meeting specifications of at least one of the pharmacopeia are acceptable for use in early phase clinical studies in US, Europe and Japan If no compendial specifications are available, vendor specifications and/or alternative compendial specifications (e.g. USP Food Chemical Codex) should guide specification setting Approval for use Manufacturing can be initiated prior to final release of excipients & API Risk-based vendor qualification Vendors must be qualified, but extent of qualification can vary with phase of development and should include internal risk assessment Qualification can proceed in parallel to batch manufacture, but must be completed prior to final batch disposition. 9