New USP & FDA Approaches for HPLC Ensuring HPLC Data Integrity

15-17 May 2018, Prague, Czech Republic

Course No. 16639



Dr Markus Dathe, F. Hoffmann-La Roche AG, Switzerland

Dr Joachim Ermer, Sanofi, Germany

Dr Manfred Fischer, SkyePharma (member of Vectura Group), Switzerland

Dr Bob McDowall, R D McDowall Ltd., UK

Dr Christine Mladek, Boehringer Ingelheim, Germany


The purpose of this course is to provide attendees with practical information to perform and manage HPLC analyses within GMP-/FDA-regulated environments as well as ensure the integrity of the data generated. The course content includes the latest information on USP with proposed approaches on HPLC method development, validation and continued verification and new version of USP <1058> on Analytical Instrument Qualification (AIQ). This is reinforced by outlining the requirements for ensuring data integrity.

Quality by Design throughout the life of an analytical procedure is the new approach to method development and validation. The USP will be writing <1220> to complement <1224>, <1225> and <1226>. ICH Q2(R1) is also due to be updated as a consequence. The FDA method validation guidance issued in 2015 includes a section on lifecycle management, as well as the amendment of USP <1225>.

Data falsification and fraud as a result of poor data management practices and manipulation of chromatography data system (CDS) files continues to be a major regulatory topic. It is not confined to India and China but a global issue. Data management includes generating “complete data” to comply with 21 CFR 211 but also good chromatographic integration practices – when can manual integration be performed and when can’t it? What measures should GMP regulated analytical laboratories have in place to ensure the integrity of their chromatographic data? What should a second person reviewer do to ensure that procedures are complied with, data meet the ALCOA+ requirements and that audit trails are reviewed. The course will include the latest FDA, WHO, MHRA, PIC/S and GAMP guidance on the subject and other guidance documents due to be published or updated.


High performance liquid chromatography is a key analytical technique used in nearly all analytical laboratories in the pharmaceutical industry. As such it is regulated with sections in all of the major pharmacopoeias (Ph.Eur., USP, etc.) as well as the subject of an FDA reviewer guidance document. However, HPLC and the associated CDS applications are also the source of some major non-compliances involving falsification and fraud. Therefore, attendees will be given practical advice on ways to ensure chromatographic data integrity and carry out effective second person reviews.

This HPLC course will deal with helping attendees understand the latest USP and FDA requirements for the successful application of HPLC in a regulated GMP laboratory. The emphasis will be on the following issues:

  • QbD method development and validation including understanding and trouble-shooting problems
  • Analytical Target Profile (ATP) as focal point of the lifecycle approach
  • Sampling practices and pitfalls
  • Sample preparation for HPLC
  • Documentation and Review
  • Latest enforcement issues and lessons for CDS
  • Understanding the new USP <1058>
  • Transitioning from HPLC to UPLC
  • USP and EP system suitability tests
  • Monitoring and trending of HPLC performance parameters
  • Chromatographic integration in an GMP context
  • Better working to avoid OOS investigations
  • Fast and efficient validation of a CDS
  • Defining and protecting CDS electronic records
  • Understanding the requirements for complete data, raw data and primary analytical record
It is the aim of this course to provide guidance on ways of attaining best regulatory practice (GMP, FDA, pharmacopoeias, etc.) and to address tools to increase analytical HPLC labs’ efficiency and effectiveness.
e analytical HPLC labs’ efficiency and effectiveness.

Target Group

This course is intended for experienced chromatographers, HPLC Laboratory supervisors, QC Laboratory Managers and employees in Quality Assurance.


Introduction: Overview of HPLC in a GMP Laboratory

  • Overview of the conference
  • Role of HPLC in a regulated laboratory
  • FDA Quality Metrics – impact on the laboratory?
  • FDA issues with HPLC data integrity
  • Quality by Design for HPLC analytical procedures -
  • the proposed USP updates
  • Overview of the proposed changes for USP <1058> on Analytical Instrument Qualification
Sampling and Sample Preparation Practices and Pitfalls for HPLC Analysis
  • Sampling and sampling equipment
  • Sampling plans and rationals
  • Possible pitfalls during sample preparation incl. some examples for automation
  • Consequences for the analysis
  • Data Integrity for samples and sample preparation
Supporting Documentation for HPLC
  • Minimizing documentation - maintaining clarity - keep it simple
  • Use of electronic recording systems
  • Standardizing processes and procedures
  • Operator responsibilities and training
  • Servicing – internal and external provider responsibilities
Quality by Design and Lifecycle Approach to Pharmaceutical Analysis
  • Alignment with process terminology: QbD in analytics
  • Defining the measurement requirements: Analytical Target Profile (ATP)
  • 3-Stage concept of the analytical lifecycle: Method Design and Understanding, Method Performance Qualification, Continued Method Performance Verification
Method Design and Understanding
  • ATP as the starting point for QbD-method development
  • Identification of critical method parameters to establish the Method Robustness Range
  • Understanding the components that make a robust assay
Translating from Traditional Chromatography to Fast Chromatography
  • Minimizing the changes
  • Maximising the advantages
  • Improving efficiency and productivity
Efficient and FDA-conform Investigation of Out of Specification HPLC Results
  • Requirements of the FDA Guidance
  • Efficient laboratory investigations
  • Reanalysing, retesting, resampling
  • Proactive strategies to prevent OOS results
  • Controls of equipment and method, data trending
Risk-based HPLC Instrument Qualification: Good Science and Compliance
  • Changes to USP <1058> for AIQ in 2017
  • Difference between the new and old versions of USP <1058>
  • ‘Fitness for purpose’ and traceability
  • Qualification and validation challenge – an integrated approach
Validation and Verification of HPLC Procedures
  • Validation according to ICH and FDA Guidelines
  • Identification of relevant performance parameters
  • Evaluation of validation results
  • Sensible use of statistics and validation software
  • Verification of compendial procedures, USP Chapter <1226>
System Suitability Requirements for HPLC according to Ph.Eur. and USP
  • Ph.Eur and USP monographs for chromatographic techniques
  • Chromatographic parameters
  • System suitability requirements
  • Adjustments of chromatographic conditions
  • Continued method performance verification –
  • Monitoring of SST data
Practical Interpretation of HPLC Chromatograms: Ensuring Data Integrity and Quality of Results
  • Basics of integration
  • How do you judge if the chromatogram is OK?
  • Setting the integration parameters
  • System suitability for integration?
Ensuring HPLC and CDS Data Integrity
  • Hear and understand the ten compliance requirements for chromatography data systems and the benefits they will bring to your laboratory
  • Learn from the mistakes of others: Able Laboratories, Ohm Laboratories, Ranbaxy, Wockhardt and many other worthy organisations
Reference Standards for HPLC
  • Different types of reference standards
  • Requirements and how to quality a reference standard
Practical Interpretation of Electronic Records for a CDS
  • Defining the main electronic records for a CDS to comply with 21 CFR 11 and EU GMP Chapter 4
  • Additional e-records that can be created depending on your ways of working
  • Further e-records created depending on your HPLC equipment
  • Effective protection of the electronic records to meet regulatory expectations
  • Paper or electronic records are our raw data?
Effective Analytical Method Technology Transfer
  • Determining requirements
  • Assigning responsibilities
  • Secrets of successful method transfer
  • Standardising and harmonising the process
  • Regulatory issues
Second Person Review of HPLC Analysis Records including Audit Trails
  • The HPLC report and an approach to review
  • CTQ - which parameter are important to check
  • Audit trails - best case and worst case scenario
Risk Based Validation of a CDS including Implementing Electronic Signatures for Productivity
  • Understanding your working practices
  • Eliminating Excel from the process
  • Plan for electronic working including electronic signatures
  • Understanding the regulatory requirements for electronic signatures
  • Validation of the CDS: expected documentation
  • Case study examples of productivity gains
From Analytical Target Profile (ATP) to HPLC Assay Performance Criteria

  • Measurement requirements for the Quality Attribute Assay
  • Precision and Accuracy of the reportable result
  • Method selection to meet the ATP
  • “Translation” into HPLC Assay performance criteria
Risk Assessment for Analytical Instruments and Computerised Systems

  • Topics to be covered in the workshop are:
  • Understanding the risk assessment methodology
  • Facilitated discussion for a simple instrument
  • Workshop and discussion for more complex systems
Common Method Validation Problems and How to Troubleshoot Them

  • Examples from published papers
  • Discussion in groups:
  • What are the mistakes?
  • What are possible improvements?
HPLC System Suitability Tests

Identifying the Common Pitfalls in the Validation of a Chromatography Data System


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

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