Institute for International Research

Course Description

This course details the technical, regulatory and quality practices necessary for setting specifications for a wide variety of biological and biotechnological products. The roles of specifications and control limits in a total quality system are emphasized. Justification for the selection and validation of stability-indicating analytical methods and the establishment of suitable shelf-life specifications is discussed. The scope and objectives of specifications used to release and monitor pre-clinical lots, clinical lots and commercial lots are compared. The types of stability and validation data that should be generated to support specifications are presented and you will learn the regulatory requirements for setting specifications, and the rationale behind them.

Who Should Attend?

This course is designed for scientific, regulatory, and quality personnel involved in setting and supporting specifications and control strategies for biotechnology-derived drug products, including managers, supervisors and staff members from R&D, Production, QC, Statistics, Quality Assurance and Regulatory Affairs groups.

Complete Course Agenda

Basic Principles of Stability and Specifications

• Potency and potency tests
• Current practices in regarding stability against specifications
• Principles of kinetics
• Statistical modeling of stability kinetics
• The effects of temperature: the Arrhenius equation
• Kinetics at high temperature: why are "realtime" studies needed?

Basic Statistical Principles

• The role of statistics in stability and specifications
• The association between variability and risk
• Interpreting statistical results
• Scale of analysis and other statistical "potholes"
• Using statistical design to improve information and reduce risk

Modeling Stability Data Using Regression Analysis

• Modeling linear kinetics using simple linear regression
• Uncertainty in the regression line and the slope
• Detecting nonlinear behavior and goodness-of-fit
• Theoretical and empirical stability models

Regulatory Overview

• Chemical guidances: ICH guidances on drug substance and drug product, photostability, bracketing and matrixing
• Biotechnology guidances: ICH guidance on Quality of Biotechnological Products
• Vaccine guidances: WHO Guideline on Stability Evaluation of Vaccines

Evaluation of Multiple Lots

• Shelf-life determination per ICH Q1E: Evaluation of Stability Data
• Testing poolability and determining shelf-life
• Release models using development stability data

Accelerated and Stressed Stability Studies

• Why conduct accelerated and stressed stability studies
• Kinetics at high and low temperatures
• Mechanisms of degradation of proteins and vaccines

Maintaining Specifications Post Licensure

• Ongoing stability studies: goals and issues
• Comparing stability after a process or facilities change
• Evaluating product quality after a temperature excursion

Course Instructors

William Egan, Ph.D., Vice President, PharmaNet Consulting, Inc.
William Egan has over 30 years of experience in the technical, quality and regulatory requirements of biopharmaceutical product development and commercialization. Bill spent 28 years in various capacities at the Center for Biologics Evaluation and Research (and its precursor organizations) and was the Acting Director for the Office of Vaccines at the time of his retirement in January 2005. Bill is an expert in biologics CMC issues, including biotechnology product characterization, release and stability testing, and product and process comparability studies.

Timothy Schofield, M.S., Senior Director, Merck Research Laboratories
Timothy Schofield is a Senior Director in the Nonclinical Statistics department of Merck Research Laboratories, West Point, PA. He received a Bachelor of Science degree in mathematics in 1973 from Lafayette College, Easton, PA, and a Master of Science degree in statistics in 1976 from the University of Pennsylvania in Philadelphia. Tim currently heads the Nonclinical Statistics unit, consisting of 18 full-time statisticians who support development of Merck drugs, vaccines, and biologics.