Bernstein Training Courses

GMPs for Clinical Trial Materials and Investigational Medicinal Products:
Global Regulations, Guidances, Practical Approaches and Best Practices

Instructors:  Klaus Kehne, Ph. D. and David Bernstein, Ph. D.

This is an in-house customized course. Please contact David Bernstein for more details.

This educational and training program has been designed to define best practices for clinical supply activities and operations.  This unique program uses currently available regulations, guidance documents and good common sense to provide practical interpretations and examples of GMP for clinical supplies. It is well understood that the US cGMP 211 regulations represent minimum standards for the preparations of clinical trial materials (CTM). There are also several guidance documents issued by FDA, the EU (Annex 13), the Canadian HPFB and the Japanese MHLW that discuss alternative approaches to traditional compliance to GMP for clinical supply activities. This program will include interpretation of the new 2006 FDA Guidance "INDs - Approaches to Complying with cGMP During Phase 1 Clinical Trials

Is your organization using the applicable regulations and guidance documents to conduct clinical supply activities in compliance with quality principles and with maximal efficiency? This 2-day program provides a comprehensive evaluation of the alternative compliance strategies for CTM that represent acceptable approaches to cGMP, efficient operational practices, good compliance practices and best attainable practices.  Most importantly, this program provides the interpretation of  the applicable regulations and guidelines, the rationale for alternative approaches and explanations of what works and what has not.

Klaus Kehne

Klaus Kehne is currently a partner in PharmLink Consultants, who specializes in clinical supply chain activities. Previously he was Managing Director for Almedica GmbH where he was responsible for business development, planning, coordinating and monitoring activities associated with the preparation of clinical trial material and IMP.  His industrial training was two decades with Roche Diagnostics - Boehringer Mannheim where he was Director of Pharmaceutical Development, Clinical Supplies and Logistics. In this role he developed several computerized systems to support, control and document the entire clinical supply process and was responsible for development and application of new technologies to the clinical trial medication process. Dr. Kehne is a pharmacist and has a Ph. D. in Pharmaceutical Technology from the University of Heidelberg. He is an instructor in the DIA Investigational Supply Process course and is a well known chairman and speaker at international seminars, symposia and workshops.

David Bernstein

David Bernstein is the principal consultant at Bernstein CMC Regulatory Consulting. He has over 30 years of hands-on industrial and CMC regulatory consulting experience. Dr. Bernstein is a regulatory and technical consultant to several biotechnology and pharmaceutical companies and provides guidance in conceptual and implementation strategy and tactics for expediting the drug development process through integrating pre-clinical formulation efforts, preparation of investigational drug supplies and scale up to commercialization activities with the clinical development plan. He is the principal liaison between numerous virtual organizations and their CMC contractors.  He has authored over 160 CMC sections of IND, NDA, CTA and has represented numerous pharmaceutical and biotech firms at FDA. Dr. Bernstein conducts GLP/GMP audits and has prepared numerous firms for their first FDA PAI inspections, all of whom passed this milestone. He has published extensively on techniques to expedite drug development, GMPs in R&D, GMPs for Clinical Trial Materials. He holds a BS in Pharmacy from Columbia University and MS and PhD in Pharmaceutical Sciences from the University of Michigan.

Objective:

• explain the basic differences in investigational medicinal products and commercial products and why these differences require unique interpretations of GMP
• describe contemporary regulatory expectations for clinical supplies, including concepts drawn from the ICH E6 (Good Clinical Practice) Guideline, 2001/20/EC Directive, EU GMP 2003/94, EU Annex 13, 1991 FDA Guidance, new 2006 FDA GMP for Phase 1 clinical trial material guidance and new global guidance documents and regulations under consideration
• interpret global regulations and guidance for GMP in clinical phases 1, 2 and 3
• describe typical scientific and technical challenges in complying with traditional approaches to GMP
• propose best practice approaches for efficient CMC activities during clinical manufacturing, packaging, labeling, testing and distribution activities

Program content:

• The Drug Development Process
• The Clinical Supply Chain                          
• Uniqueness of Clinical Supply Activities; Why Alternative Approaches to GMP are necessary
• ICH E6 - Good Clinical Practice [Investigational Material Practices at the Interface of GCP and GMP]
• The 2001/20/EC Directive [its impact on CTM]
• Import and Export of Investigational Drugs between the US and the EU
• Global Regulations and Guidance Documents for GMP for Clinical Supply Activities and Operations
• FDA 1991 Guidance
• FDA Draft 2006 Guidance GMPs for Phase 1 Clinical Studies
• EU GMP 2003/94
• EU Annex 13
• Canadian Annex 2 to GMP: Manufacture of Drugs used in Clinical Trials
• Japanese MHLW guideline
• Best Practice Approaches to GMP for Clinical Supplies
• Workshops

This program answers these and many other difficult questions:

• What is the FDA expectation of the "graded nature and sliding scale" for GMP during development?
• What is the likely impact of the 2006 FDA Guidance "INDs - Approaches to Complying with cGMP During Phase 1" on big pharma? on CMC and CTM contractors? on analytical QC laboratories?  on your firm?  What relief does this guidance really allow?
• How can US companies adopt the concepts in the EU Annex 13 to their advantage?
• What areas of GMP are the same for phase 1, phase 3 and commercial products?
• What areas of GMP need to be different as development evolves and progresses? What are the differences and how they can be addressed?  How to comply when you can't comply.
• Where are the hidden exemptions to GMP and where is they documented?
• Do your current procedures represent an overkill scenario? Or a non-compliant situation?
• How to recognize a CTM time bomb GMP problem before the problem becomes real?
• We are only going to make this once; do we need a master production record?
• Do you need to place every clinical batch on stability? What are the criteria for not doing so?
• How do we predict expiration (use by, retest) dates early in development and how do we extend them?
• Exactly what must be kept as retain samples?  What level of accountability (per tablet, per vial, per bottle, per kilogram, per patient kit) is acceptable and prudent?
• What exactly must be on the immediate container label? What if the label is too small?  What must be on the secondary package (kit) label?
• When we re-package/re-process/manipulate an innovator's drug product to use as a comparator (positive control drug product) in our blinded clinical trial, what are our legal, regulatory and scientific requirements?

Comments from previous attendees:

"...most valuable part...was the interpretation and explanation of regulations and guidelines from instructors who clearly understand the intricacies and uniqueness of the clinical supply process"

"I appreciated the examples of alternative strategies for GMP compliance, especially the illustrations of the creative approaches."

"This program should be renamed 'Good Common Sense Practices'"