Guidelines for Investigational New Drugs (IND) Requirements Version 1.1 Guidelines for Investigational New Drugs (IND) Requirements Version 1.1 Drug Sector Saudi Food & Drug Authority Kingdom of Saudi Arabia Please visit SFDA’s website at http://www.sfda.gov.sa/En/Drug for the latest update 1 September 2010 Page 2 of 49 Document Control Version Date Author(s) Comments Product Evaluation and Standards Published for comments 1.0 01/08/2009 Setting Department Product Evaluation and Standards Final 1.1 01/09/2010 Setting Department 1 September 2010 Page 3 of 49 Contents Introduction .................................................................................................................................... 7 Definition ........................................................................................................................................ 8 Promotion and Commercial distribution of an IND ....................................................................... 8 Charging for and commercialization of investigational drugs: ..................................................... 9 Labeling of an IND ........................................................................................................................... 9 Pre‐IND Meetings ............................................................................................................................ 9 a) Purpose of the meeting ...................................................................................................... 10 b) Meeting Request ................................................................................................................ 10 c) Information Package .......................................................................................................... 10 Content & format of an IND application ...................................................................................... 11 1. Cover sheet ........................................................................................................................ 11 2. A table of contents ............................................................................................................. 12 3. Introductory statement and general investigational plan ................................................... 12 4. Investigator’s brochure ...................................................................................................... 13 5. Protocols ............................................................................................................................ 14 6. Chemistry, manufacturing, and control (CMC) information ............................................. 15 I. Drug Substance: ............................................................................................................ 16 II. Drug Product: ............................................................................................................... 18 7. Pharmacology and toxicology information ....................................................................... 19 I. Pharmacology and drug disposition: ............................................................................ 20 II. Toxicology ..................................................................................................................... 20 III. Compliance with the good laboratory practice regulations: .................................... 22 8. Previous human experience with the investigational drug ................................................ 22 Additional information .............................................................................................................. 23 Relevant information. ................................................................................................................ 24 Phases of an investigation ............................................................................................................ 25 • Phase 1 studies: ................................................................................................................. 25 • Phase 2 studies : ................................................................................................................ 25 • Phase 3 studies: ................................................................................................................. 26 Protocol amendments .................................................................................................................. 26 • New protocol: .................................................................................................................... 26 1 September 2010 Page 4 of 49 • Changes in a protocol ....................................................................................................... 26 IND safety reporting ..................................................................................................................... 27 • Review of safety information ............................................................................................. 27 • IND safety reports ............................................................................................................. 27 • Follow-up .......................................................................................................................... 28 IND annual report ......................................................................................................................... 29 IND Exemptions ............................................................................................................................ 30 Clinical holds and requests for modification ............................................................................... 31 • General .............................................................................................................................. 31 • Grounds for imposition of clinical hold ............................................................................ 31 • Discussion of deficiency .................................................................................................... 34 • Imposition of clinical hold ................................................................................................. 34 • Resumption of clinical investigations ................................................................................ 34 • Appeal ................................................................................................................................ 35 • Conversion of IND on clinical hold to inactive status ....................................................... 35 Inactive status ............................................................................................................................... 35 Withdrawal of an IND ................................................................................................................... 35 Termination of IND ....................................................................................................................... 36 • Reasons for termination .................................................................................................... 36 • Opportunity for sponsor response ..................................................................................... 37 • Immediate termination of IND ........................................................................................... 37 Responsibilities of Sponsors and Investigators ........................................................................... 38 I. Responsibilities of Sponsors: .......................................................................................... 38 • Selecting investigators and monitors ............................................................................. 38 • Informing investigators ................................................................................................. 41 • Record keeping and retention ........................................................................................ 42 • Inspection of sponsor's records and reports .................................................................. 43 • Disposition of unused supply of investigational drug ................................................... 43 • Transfer of obligations to a contract research organization (CRO) ............................. 44 II. Responsibilities of Investigators ................................................................................. 44 • Control of the investigational drug ............................................................................... 44 1 September 2010 Page 5 of 49 • Investigator record keeping and retention: ................................................................... 44 • Investigator reports ....................................................................................................... 45 • Assurance of IRB review ............................................................................................... 46 • Inspection of investigator's records and reports ........................................................... 46 • Handling of controlled substances ................................................................................ 46 • Disqualification of a clinical investigator ..................................................................... 47 Import and export requirements ................................................................................................. 47 • Imports ..............................................................................................................................