Dr Raphael Bar, Consultant, formerly with Teva, Israel
Dr Bernd Renger, Member of the Analytical QC Working Group of the ECA Foundation
Dr Ulrich Rose, EDQM, France
It is important to understand the structure and the procedures of the different Pharmacopoeias. Some general chapters and the monographs of some widely used excipients have already been harmonised between the most important Pharmacopoeias, USP, EP and JP in the context of the Pharmacopoeial Discussion Group (PDG). But for a large number of general methods differences still exist. Therefore some of the frequently asked questions are:
- How to use alternative procedures and interchangeable methods?
- What are the allowed exceptions to the obligation to perform all tests?
- How can multi-compendial testing strategies look like?
- How to prove equivalence?
In addition, PDG harmonisation does not include upcoming important pharmacopoeias like Indian and Chinese Pharmacopoeias.
This Education Course will discuss these issues and provides support in order to successfully deal with compendial methods and their differences.
Pharmaceutical companies have to follow Pharmacopoeia standards in order to meet regulatory requirements.
However, there is no single Pharmacopoeia which can be applied in all regions. The US FDA may enforce USP monographs which then become manadatory whereas compliance with EP is mandatory in 38 countries and the EU and is applied in over 100 countries worldwide. Moreover, also other Pharmacopoeias exist in the world like the Japanese (included in the PDG harmonisation process) , Chinese, Russian or Indian Pharmacopoeias.
But what are the differences and how to deal with quality standards and test methods if products are manufactured and released for different markets?
This Education Course addresses employees and managers from Quality Control Labs. It also addresses colleagues working in Quality Assurance and Regulatory Affairs department.
Session 1: Introduction to Pharmacopoeial Testing
Structure, General Methods and challenges of EP and USP and their enforcement
Additional Pharmacopoeias around the world – Japan, China, India, Int.Ph. (WHO)
- Structure of EP and USP
- Meeting Pharmacopoeial standards and
- Pharmacopoeial designation
- The USP approach: Single Testing
- Structure of USP monographs: modern monograph, flexible monograph
- Structure of European Pharmacopoeia
- Structure of EP monographs
- What the Pharmacopoeia does not say about a procedure
- Dietary Supplements, API and CEP of EP
Session 2: Important Monographs: Harmonisation, Differences, Solutions
Harmonisation of EP, USP, JP –General methods and excipients
- Historical developments
- The development of the International Pharmacopoeia
- JP, ChP, Russian Ph., and IP – similarities and differences
- Legal status and enforcement
- WHO Good pharmacopoeial Practices
EP, USP Testing for Organic Impurities
- Mechanisms of harmonisation between Pharmacopoeias
- History of PDG
- Examples for harmonised monographs and general chapters
- Typical obstacles and examples
- New PDG process
Implementation of ICH Q3D – Differences and similarities
- Types of impurities (EP 5.10 and USP <1086>)
- Impurity profile
- Impurities not referenced in EP
- Thresholds for reporting, identification and qualification (Phr. Eur. 2034)
- Quantification methods of impurities in a compendial monograph
Analytical Instrument Qualification according to EP and USP
- History of ICH Q3D
- Implementation strategy in EP
- General chapters/general monographs and strategy for specific monographs
- USP and JP strategies
- ICH Q3D in the harmonisation process
Session 3: Dealing with Testing Challenges
General Notices – Definitions and Requirements
- USP General Chapter <1058> Analytical Instrument Qualification and EP
- Type of instruments and risk assessment
- Qualification steps: DQ, IQ, OQ and PQ
- Roles and responsibilities
- Computerized data systems in laboratory
- Examples: Qualification of HPLC and analytical balances
Validation of Compendial Procedures
- Use of alternative procedures & interchangeable methods
- Waivers to the obligation to perform all tests
- Scope of general monographs
Reference Standards - similarities and differences
- ICH Q2(R1) “Validation of Analytical Procedures”
- Analytical Validation in Chemistry
- GUM – Guide to the Uncertainty of Measurement
- The USP approach: the more monographs - the better?
Verification of Compendial Procedures
- Definitions and guidelines
- Legal status of reference standards
- Types of standards
- Establishment and use/Testing and value assignment
- Similarities and differences between pharmacopoeias
Multicompendial Testing Strategies
- Difference between Verification and Transfer of an analytical procedure
- Chemical vs microbiological procedures
- Minimal performance characteristics to be verified
- What to verify in procedures for high-level (Assay by HPLC) and low-level analytes (Impurities by HPLC and TLC)
- When procedure verification is not required
- ISO 17025 requirements for method verification
- Documentation of procedure verification
Alternative methods to pharmacopoeial methods: Equivalence testing of two methods
- Divergent and conicting pharmacopoeial requirements
- CDER’s MAPP 5310.7 “Acceptability of Standards from Alternative Compendia”
- How to proceed in case of missing harmonization?
- Full Testing, Worst Case Testing, Alternative Testing
- How to proof equivalence?
- Is a compendial procedure equivalent to an in-house validated procedure?
- Critical performance characteristics to be compared
- Plotting the results of comparative testing
- Traditional way of comparison of two procedures
- Equivalence testing with two one-sided t-test (TOST)
- Case studies