Stability by Design

Stability by Design

Berlin, Germany

Course No 15989


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 Raphael Bar, BR Consulting, Israel

Dr Helmut Buschmann, RD&C, Austria

Dr Norbert Handler, RD&C, Austria

Objectives

Forced degradations are the basis for development of analytical methods, for drug formulation development, for understanding the degradation mechanisms and for predicting the stability behavior of active ingredient and drug product. Stress testing is the basis for predicting the stability behavior during storage, shipping and distribution of active ingredient and marketed drug product. Both forced degradation and stress testing are regulatory requirements.

Background

After an overview of the basic chemistry of the common degradation reactions, this course will teach you how they are practiced in the pharmaceutical industry, and how you can carry them out on your own, while ensuring that all degradation products are chromatographically
detected and subjected to a mass balance.
Among the topics to be discussed will be:

  • An overview of the basic chemistry of the degradation reactions
  • Common practices of forced degradations in the pharmaceutical industry
  • Practical aspects in carrying out forced degradation studies
  • Photodegradation of active substance and drug product
  • How to ensure that all degradation products are detected
  • Peak purity by LC-UV
  • Set up a mass balance in degraded samples with guided exercises (A hand-held calculator is required!)
  • Comparing degradation rates to estimate impact of a process change on the drug quality
  • Performing stability studies to support shipping/distribution of medicines
  • Investigating an excursion from a label storage conditions

Target Group

Personnel from the following departments will highly benefit from this course:
Stability Personnel | Analytical R&D | Quality Control Formulation Development | Quality Assurance and RA | CROs offering analytical services | Qualified Persons (QP)

Workshops

Photostability of a drug product under manufacturing conditions
Workshop on Forced Degradations

Programme

What is Stress Testing and what are Forced Degradations – regulatory view

  • Regulations (ICH, EU and USFDA)
  • Chemical stress of drug substance and product
  • Physical stress of excipients and active pharmaceutical ingredient
  • Is a forced degradation study a GMP study?
  • Purposes of stress testing: a. development of stability-indicating methods, b. optimization of a formulation (API-Excipients compatibility study), c. Prediction of stability behavior (accelerated testing of pharmaceuticals), d. Evaluation of temperature excursions during shipment/distribution
Common degradation reactions of APIs and excipients
  • Reactivity of common chemical functional groups
  • Major mechanisms of chemical degradation
  • Hydrolysis (alkaline, acidic)
  • Oxidation (Autoxidation, peroxide and metal-mediated)
  • Photolysis
  • Case studies for APIs and excipients
Impurities and degradation products resulting from reactive APIs, excipients and their impurities
  • Reactivity of common chemical functional groups
  • Major mechanisms of chemical degradation
  • Hydrolysis (alkaline, acidic)
  • Oxidation (Autoxidation, peroxide and metal-mediated)
  • Photolysis
  • Case studies for excipients
Reactions and forced degradations in solid state – innovative approach
  • Differences liquid phase – solid state
  • Reactions and degradation in solid state
  • Kinetics
  • Alternative approach to mimic and predict solid state degradation
Forced degradation studies in the pharmaceutical industry
  • Common practices of forced degradations
  • Examples of forced degradations studies
  • Is there a general methodology for chemical stress?
How to perform your own forced degradation study with:
  • Heat (with and w/o humidity)
  • Acid and base
  • Oxidation
  • Mechanical stress factors (e.g. grinding, milling …)
Photodegradation
  • Essential terms of light irradiation
  • Light chambers: Options 1 and 2 according to ICH
  • Irradiation of drug substance and drug product samples
  • Sequential versus simultaneous irradiation of UV and visible light
Mass balance in degraded samples of pharmaceuticals
  • Definition and equations for mass balance
  • Determination from chromatographic analysis of degraded samples
  • Correction of mass balance for response factor
  • Correction of mass balance for molecular weights
  • Exercises of mass balance calculations
How to ensure chromatographic detection of all degradation products
  • Ensuring chromatographic elution of all degradation products (Gradient mode, varying mobile phase solvents; various modes of chromatography)
  • Detecting all degradation products (LC-PDA, LC-MS, universal detector)
  • Techniques to confirm undetected degradation products (Flow injection analysis, UV spectrophotometric analysis)
  • Determining peak purity by LC-PDA (spectral and matching homogeneity)
Comparative accelerated degradation rates
  • A quality control tool of pharmaceutical products - monitoring process changes
  • A development tool for optimizing drug formulations: Excipients, API compatibility studies
World Climatic zones for drug stability storage
  • Mean Kinetic Temperature (MKT) and relative humidity
  • Interpretation of MKT
  • Temperature profile of a shipment of medicines
  • Global climatic zones by ICH and WHO
Thermal Stress studies to support shipping/distribution
  • Studies at elevated extreme temperatures
  • Studies at low extreme conditions
  • When, how and what?
  • Cyclic studies to support shipping/distribution
Excursions from storage label conditions
  • Excursions and Time-out-of-Storage during shipping/distribution
  • Understanding the evaluation of the impact of
  • temperature excursion on shelf-life
  • What stability data are required to investigate
  • temperature excursions
  • Estimation of a maximal “Time-out-of-Storage” of a pharmaceutical

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