General Aspects: Regulatory Requirements and FDA Inspections
- Regulatory Overview (US, Europe and the world)
- Regulatory requirements in the US (cGMP, CFR, Guidances for Industry, etc.)
- FDA Inspections
- Key issues during laboratory inspections
- 483s and Warning Letters
Sampling in Compliance with FDA Requirements
- Importance of the sampling procedure
- Regulatory requirements
- Sampling statistics / sampling plans
- Sampling procedures
- Sampling equipment and environment
- Training
- Retained samples
FDA Approaches to Laboratory Data Integrity
- FDA laboratory observations: falsification and fraud
- Compliance Program Guide 7346.832 on Pre-Approval Inspections: Objective 3 - Laboratory data integrity
- FDA inspector training: focus on the computer system not paper printouts
- What controls do you need to have in place to ensure data integrity?
Documentation for Quality Control Laboratories
- “Scientifically sound” GMP requirements of QC documents and approaches
- Types of QC laboratory documents:
- Test specifications and analytical procedures
- Standard Operating Procedures
- Instrument qualification protocols
- Complete data for analytical testing and Certificates of Analysis
- Compare and contrast FDA and EU documentation requirements
- Management of blank forms and data integrity issues
Qualification of Analytical Instruments in the QC
- Legal requirements (cGMP, CFR, etc.)
- USP General Chapter <1058> Analytical Instrument Qualification
- Qualification Phases (DQ/IQ/OQ/PQ)
- Qualification examples (problems and solutions)
- Analytical instrument life-cycle (Requalification, etc.)
Calibration for FDA Inspected Analytical Laboratories
- General approach to Calibration
- Instrument calibration in the USP
- Contrasting US and European approaches (important in the context of laboratories struggling to meet both requirements)
Transfer of Analytical Procedures
- USP General Chapter <1224>Transfer of Analytical Procedures (TAP)
- Key steps for a successful method transfers:
- Initiation phase (training method familiarization, etc.)
- Types of Transfer
- Analytical procedures
- Materials (samples and standards) and testing design
- Instruments
- Data assessment – Acceptance criteria
- Documentation (transfer protocol / report)
- Summary
Training Case Study
- Legal requirements
- Education / GMP-training / Training on the Job
- Training records
- Re-training frequency
Out of Specification Results
- Requirements of the FDA Guidance
- Efficient laboratory investigations
- Reanalysing, retesting, resampling
- Management of variability-caused OOS results
- Investigation of atypical results
- Proactive strategies to prevent OOS results
Validation of Analytical Procedures
- Regulatory requirements (ICH, FDA, compendia)
- Lifecycle approach (3-Stage-Model according to draft USP General Chapter <1220>))
- Verification of compendial procedures
- Rationale design of validation studies
- Identification of relevant performance Parameters
- Sensible use of statistics
- Suitable performance parameters for continuous monitoring
Practical Computer Validation in Analytical Laboratories
- Computerised system validation as a critical activity in the analytical laboratory
- 21 CFR Part 11 compliance
- FDA emphasis on data integrity for computerised Systems
- GAMP software categories and impact on validation Approach
- GAMP Good Practice Guide for Validation of Laboratory Systems second edition
- Case study examples: how to validate systems in a cost effective way and steps of what not to do!
Reference Standards and Reagents for FDA-Inspected Laboratories
- Regulatory requirements
- Types of reference standards: Official/primary/working standards/reference materials
- Traceability, characterisation, and retest date of Standards
- Risk-based approach for management, storage and shelf-life of laboratory reagents and solutions
- Stability investigation of solutions for quantitation
Recording from 04/05 October 2022
Duration of the recording: approx. 10 h.