Live Online Training: Stability by Design

Live Online Training: Stability by Design

Course No 19188

This course is part of the GMP Certification Programme "ECA Certified Quality Control Manager". Learn more.

All times mentioned are CEST.

Costs

ECA-Member*: EUR 1790,--
Non ECA Member*: EUR 1990,--
EU/GMP Inspectorates*: EUR 995,--
APIC Member Discount*: EUR 1890,--

(All prices excl. VAT)

* payable by credit card American Express Visa Mastercard

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, formerly with Teva, Israel
Dr Helmut Buschmann, AiCuris, Germany and RD&C, Vienna
Dr Norbert Handler, RD&C, Vienna

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
  • 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
  • Requirements, guidelines and risk assessment related to nitrosamine contamination

Target Group

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

Technical Requirements

For our Live Online Training Courses and Webinars, we use Cisco WebEx, one of the leading suppliers of online meetings. At http://www.webex.com/test-meeting.html you can check if your system meets the necessary requirements for the participation at a WebEx meeting and at the same time install the necessary plug-in. Please just enter your name and email address for the test. If the installation is not possible because of your rights for the computer system, please contact your IT department. WebEx is a standard nowadays and the necessary installation is fast and easy.

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
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 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)
Presentation and Workshop on Photostability of a Drug Product under Manufacturing Conditions
 
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 …)
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
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
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
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
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
Case Studies for Interaction and Incompatibilities
 
Mean Kinetic Temperature: Uses and Misuses
  • Mean Kinetic Temperature (MKT) and relative humidity
  • Interpretation of MKT
  • Temperature profile of a shipment of medicines
  • Global climatic zones by ICH and WHO
Nitrosamines
  • Latest requirements and guidelines from EDQM and EMA
  • Scientific and chemical Background
  • How to perform a successful and compliant Nitrosamine risk assessment (including API, excipients, drug product, packaging, transport, etc.)
  • Case Studies
Evaluation and Investigation of 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
Q&A sessions: Q&A sessions on both days ensure interaction and that your questions are answered.

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