Phase 1 Compliance


Published on

This Presentation was given at MichBio\'s Annual Expo. It discusses the guidance for Phase 1 compliance.

  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Phase 1 Compliance

  1. 1. Phase 1 - Compliance Presented By: John Wichelt ProPharma Group November 4, 2009 2009
  2. 2. Presentation Overview <ul><li>Introduction </li></ul><ul><li>Regulatory Requirements </li></ul><ul><li>Guidance Scope </li></ul><ul><li>General Guidance Requirements </li></ul><ul><li>Personnel and QC Functions </li></ul><ul><li>Facility and Equipment </li></ul><ul><li>Manufacturing and Records </li></ul><ul><li>Laboratory Controls </li></ul><ul><li>Packaging, Labeling and Distribution </li></ul><ul><li>Example Controls </li></ul>2009
  3. 3. Introduction <ul><li>Joint Guidance Document Created by CDER, CBER and ORA with FDA </li></ul><ul><li>Guidance for Industry CGMP for Phase 1 Investigational Drugs </li></ul><ul><li>Replaces 1991 Guidance </li></ul><ul><li>Preparation of Investigational New Drug Products (Human and Animal) </li></ul>2009
  4. 4. Guidance Objectives <ul><li>Phase 1 Guidance Objectives </li></ul><ul><ul><li>Ensure Patient Safety </li></ul></ul><ul><ul><li>CGMP Requirements </li></ul></ul><ul><ul><li>Quality Control </li></ul></ul><ul><ul><li>Manufacturing Requirements </li></ul></ul><ul><li>Approach recommended to comply with </li></ul><ul><li>501(a)(2)(B) of the FD&C Act </li></ul><ul><li>Phase 2 – Comply with 1991 Guideline and must comply with 21 CFR 210 and 211 </li></ul>2009
  5. 5. Regulatory Requirements <ul><li>Section 501(a)(2)(B) of FD&C Act requires: </li></ul><ul><li>“ A drug….shall be deemed adulterated….if…the methods used in, or the facilities or controls used for , its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with the current good manufacturing practice to assure that such drug meets the requirements of the Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.” </li></ul>2009
  6. 6. Guidance Scope <ul><li>Phase 1 Clinical Trials Stage </li></ul><ul><li>Small or Large Scale </li></ul><ul><li>GMP Controls increase through Phases </li></ul><ul><li>Does NOT apply to: </li></ul><ul><ul><li>Human Cell or Tissue Products </li></ul></ul><ul><ul><li>Trials for Device Approvals </li></ul></ul><ul><ul><li>Investigations for Phase 2 or Phase 3 </li></ul></ul><ul><ul><li>Approved Drugs being tested in Phase 1 for investigation </li></ul></ul><ul><ul><li>Positron Emission Topography (PET) Drugs </li></ul></ul>2009
  7. 7. General Requirements <ul><li>Adherence to Requirements Occurs Through: </li></ul><ul><ul><li>Well-defined, written procedures </li></ul></ul><ul><ul><li>Adequately Controlled Equipment </li></ul></ul><ul><ul><li>Adequately Controlled Manufacturing Environment </li></ul></ul><ul><ul><li>Accurate and Consistent Manufacturing Data </li></ul></ul><ul><li>ICH Q8,9,10 – Knowledge Management for Tech Transfer, training, procedures </li></ul><ul><li>Ensure controls meet standards of safety, identity, strength, quality and purity. </li></ul>2009
  8. 8. Personnel and QC <ul><li>Personnel </li></ul><ul><ul><li>Education, experience, training </li></ul></ul><ul><li>Quality Unit (QA/QC) Responsibilities </li></ul><ul><ul><li>Examining materials </li></ul></ul><ul><ul><li>Review/Approval </li></ul></ul><ul><ul><ul><li>Manufacturing Procedures </li></ul></ul></ul><ul><ul><ul><li>Testing Procedures </li></ul></ul></ul><ul><ul><ul><li>Acceptance Criteria </li></ul></ul></ul><ul><ul><li>Release and Rejection of Batches </li></ul></ul><ul><ul><li>Investigating Unexpected Results </li></ul></ul>2009
  9. 9. Facility and Equipment <ul><li>Sufficient Space and Clean Environment </li></ul><ul><li>Appropriate cooling, washing, sanitization </li></ul><ul><li>Appropriate air cleanliness </li></ul><ul><ul><li>HVAC and Laminar Flow Hoods </li></ul></ul><ul><li>Appropriate equipment </li></ul><ul><ul><li>Maintained, calibrated, cleaned </li></ul></ul><ul><li>Use Procedural Controls to promote orderly manufacturing and cross contamination </li></ul>2009
  10. 10. Manufacturing and Records <ul><li>Manufacturing Data ( Batch Record ) </li></ul><ul><ul><li>Materials </li></ul></ul><ul><ul><li>Equipment </li></ul></ul><ul><ul><li>Procedures </li></ul></ul><ul><ul><li>Deviations </li></ul></ul><ul><li>Record of Changes ( Change Control ) </li></ul><ul><li>Record of Microbiological Controls </li></ul><ul><ul><li>Aseptic Techniques </li></ul></ul><ul><ul><li>Micro Program – to prevent Microbial and Endotoxin Contamination </li></ul></ul>2009
  11. 11. Laboratory Controls <ul><li>Test under Controlled Conditions </li></ul><ul><ul><li>Approved Procedures </li></ul></ul><ul><ul><li>Change Control </li></ul></ul><ul><ul><li>Test Result Documentation </li></ul></ul><ul><ul><li>Calibrated Equipment </li></ul></ul><ul><ul><li>Equipment Maintenance </li></ul></ul><ul><ul><li>Analytical Methods should be verified for </li></ul></ul><ul><ul><ul><li>Accuracy </li></ul></ul></ul><ul><ul><ul><li>Suitability </li></ul></ul></ul><ul><ul><ul><li>Not Validated Yet </li></ul></ul></ul>2009
  12. 12. Packaging, Labeling and Distribution <ul><li>Achieve Effective Control Through </li></ul><ul><ul><li>Written procedures </li></ul></ul><ul><ul><li>Product segregation </li></ul></ul><ul><ul><li>QC Review </li></ul></ul><ul><ul><li>Distribution Record </li></ul></ul><ul><li>Handle Phase 1 drugs in accordance with label conditions </li></ul><ul><ul><li>eg. Temperature, humidity </li></ul></ul>2009
  13. 13. Example Utility Controls <ul><li>Commission and IOQ of product contact utilities </li></ul><ul><li>Use of Log Books </li></ul><ul><li>SOPs for product contact utilities </li></ul><ul><li>Change Control for critical utilities </li></ul><ul><li>IOQ for HVAC – air cleanliness </li></ul><ul><li>PQ for Water System (typically 30 days) </li></ul><ul><li>PQ for Pure Steam (~ 1 week) </li></ul><ul><li>PQs can be done concurrently </li></ul>2009
  14. 14. Example Equipment Controls <ul><li>Use of Log Books </li></ul><ul><li>Preventative Maintenance Program </li></ul><ul><li>Equipment SOPs </li></ul><ul><li>Change Control for product contact equipment </li></ul><ul><li>Calibration and Tagged as such </li></ul><ul><li>Validation of sterilization procedures </li></ul><ul><li>Equipment IOQs </li></ul><ul><li>PQs for product contact equipment </li></ul><ul><li>Cleaning Verification ( Not Validation ) - SOPs and Studies (Swab recoveries) </li></ul><ul><li>CIP cycle validation </li></ul><ul><li>Media Fill validation </li></ul>2009
  15. 15. Example Manufacturing Environment Controls <ul><li>Monitor Controlled Areas to meet class specification </li></ul><ul><li>Cleaning and Sanitization Controls </li></ul><ul><li>Environmental Monitoring Program </li></ul><ul><li>Filter Integrity Testing Qualification </li></ul><ul><li>Materials should be placed on stability for duration of clinical trials. </li></ul>2009
  16. 16. Thank You! John Wichelt Sr. Project Manager ProPharma Group 2009
  17. 17. References <ul><li>FDA Guidance for Industry “CGMP for Phase 1Investigational Drugs” (July 2008). </li></ul><ul><li>FDA guidance on the “Preparation of Investigational New Drug Products (Human and Animal)” 1991 (reprinted November 1992). </li></ul><ul><li>FDA “Guidance for Industry: Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients,” Section 19. </li></ul><ul><li>Anthony Luttrell, Raland Technologies (2009). </li></ul>2009