Dissolution Testing Development - Quality Control - and in vivo Relevance

Dissolution Testing Development - Quality Control - and in vivo Relevance

Copenhagen, Denmark

Course No 15916


Costs

This conference already took place.

If you have any questions, please contact us:
Tel.: +49 (0)6221 / 84 44 0 E-Mail: info@gmp-compliance.org

Speakers

Dr Thomas Fürst, Boehringer Ingelheim

Dr Kerstin Pauli, Bayer AG

Dr Alexander Pontius, Bayer AG

Dr Ferdinand Steierhoffer, Boehringer Ingelheim

Objectives

This GMP Education Course on Dissolution Testing aims at providing delegates with a sound understanding of the principles and best practices in dissolution testing. As dissolution testing has become increasingly important as a tool for predicting in vivo performance and for assessing drug product quality, this topic will be extensively discussed.

Background

The dissolution test is a key performance indicator for solid and semi-solid dosage forms in both drug development and quality control. In these fields it is used to assure batch-to-batch quality as well as providing process control information as part of the new approach to Process Validation.

Dissolution testing is usually connected to in vivo performance because the API must be
released from the formulation in the gastro-intestinal tract (GIT) before in vivo absorption can occur. Therefore dissolution testing is generally employed during drug product development and optimization. Where dissolution testing data can be shown to be correlated to in vivo performance, clinical trials may be avoided by in vitro dissolution studies under certain circumstances, thereby reducing development time and costs.

There are a many dissolution testing guidances and associated guidelines (e.g. FDA, EMA and the Pharmacopoeias) dealing with Scale-up and Post-Approval Changes, Bioequivalence studies, Waiver of in vivo Bioavailability and Bioequivalence Studies. Additionally, there are some country-specific dissolution requirements which are very challenging for global pharmaceutical companies.

This GMP Education Course will therefore cover the following topics:

  • physicochemical and biopharmaceutical foundations,
  • dissolution method development,
  • validation of the dissolution methodology,
  • approaches for setting specifications,
  • OOS and OOE Results in dissolution testing,
  • statistical methods for comparing dissolution profiles,
  • approaches for substitution of BE-studies (biowaiver) and,
  • approaches to establish in vitro in vivo correlations (IVIVC),
  • country-specific dissolution requirements and challenges.
In addition, the expectations of the European Medicines Agency (EMA) and of the pharmacopoeias (Ph.Eur. 2.9.3 and USP Chapters <711> and <1092>) including USP Reference Standard Tablets and Mechanical calibration for the dissolution apparatus qualification will be discussed.

The objective of this course is to cover all aspects of dissolution testing with a focus on practical examples. Workshops are also part of the course in order to encourage the
exchange of experience and to allow interactive and in depth discussions of the subject.

Target Group

Scientists and managers in the pharmaceutical industry working in:

  • Quality control
  • Quality assurance
  • Analytical development
  • Research and development
  • Regulatory affairs
This course is also intended for participants from contract laboratories, regulatory
authorities, and inspectorates.

Programme

Fundamentals of Dissolution Testing: From Physicochemistry to Bioavailability

  • Mechanism and theories of solid dissolution (e.g. diffusion layer model)
  • Intrinsic dissolution rate
  • Sink conditions
  • Kinetics of drug release
  • Relationship between dissolution and bioavailability
  • Quality control dissolution testing and in vivo predictive dissolution testing
  • Biopharmaceutics Classification System
  • Hurdles and limitations of dissolution testing
In vivo Relevance and Biowaivers
  • What is Biorelevance? Meaning and Misconceptions
  • How to establish a link between dissolution and bioavailability
  • The role of IVIVC
  • Setting biorelevant dissolution specifications
  • BCS based biowaivers
  • Waivers based on proportional similarity
  • Country specific regulatory differences
  • Case studies

Dissolution Testing – Regulatory Guidelines
  • Prerequisites of international and mostly harmonized pharmacopeia (USP, EP, Pharm Jap)
  • Miniaturization of dissolution tests
  • General guidelines for dissolution testing
  • Contents and differences in Chinese pharmacopeia
  • Validation of dissolution test methods
  • Bioequivalence considerations
  • Special in vitro bioequivalence applications in Japan
  • Waiving dissolution tests by disintegration tests
Mechanical Calibration & Performance Verification Test (PVT)
  • Regulatory basis
  • Fundamentals of instrument qualification
  • Qualification and calibration of dissolution apparatuses
  • Mechanical calibration
  • USP Performance Verification Test (PVT)
  • Deviations and OOC
Setting Specifications for Dissolution Methods
  • How to set adequate dissolution specifications for various types of formulations
  • Requirements of different Pharmacopoeias and Guidelines
  • Specifics and exceptions
OOS Results in Dissolution Testing
  • Regulatory aspects
  • Dissolution methods having appropriate discriminatory power
  • General OOS procedure for dissolution testing
  • Defining and handling of OOS results including CAPA
  • OOS evaluation for immediate release products, for capsules, for modified-release products
  • OOT/OOE results: Evaluating stability effects by applying dissolution testing
Development of Dissolution Methods with regard to Quality Control
  • Method development for Immediate Release, Extended Release and Delayed Release Formulations
  • Regulatory recommendations concerning method development
  • Dissolution apparatus and medium selection
  • Use of surfactants
  • Adequate discriminatory capability
  • Variability of dissolution results (stage/level testing)
  • Dissolution methods for developing an IVIVC
  • Case studies
Automation in Dissolution Testing
  • Why and when is automation valuable?
  • Various types of dissolution systems
  • New products on the market
Analytical Validation of Dissolution Testing Methods
  • Pharmacopoeial and Regulatory Recommendations (e.g., ICH Q2 (R1) and USP <1092>)
  • Validation characteristics: Specificity, Linearity, Precision, Accuracy and Robustness
  • Furthermore: filter-validation, selecting the right deaeration method, validation of automated methods
  • Some practical recommendations for performing the validation and recommended acceptance criteria
  • Dissolution method transfer
Dissolution Profile Comparison; Approaches and Issues
  • Statistics of the dissolution test
  • Dissolution processes and data variability
  • What are we trying to compare?
  • What do the agencies specify?
  • Model dependent and independent approaches
  • Examples
Application of Dissolution Testing in Industrial Drug Product Development
  • Discussion of various case studies occuring during product development
WORKSHOP I
How to Set Specifications: Sharing Information of the Learned Theories
Presentation of Case Studies and discussion of potential results
Q&A Session

WORKSHOP II
Analytical Validation of Dissolution Methods
Putting theory to work (case studies):
Develop validation protocol for validation of dissolution methods for different solid oral dosage forms
Pitfalls in performing the experiments

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