The 3rd Workshop on
Recent Issues in Regulated Bioanalysis
Wednesday, April 15th, 2009 - Level 1-2 Short Courses
"Issues in Regulated Bioanalysis:
Challenges, Solutions, and Applications in Bioanalytical Method Validation and Sample Analysis"
(Instructor: Dr. Fabio Garofolo - Scientific Affairs Director, CVG)
Level 1 (Morning) - "Fundamental of Bioanalysis: Bioanalytical Method Validation and Sample Analysis"
(Introductory Course)
08:00am-08:30am: Level 1 Course Registration - Breakfast
08:30am-09:00am: Introduction
09:00am-10:30am: Lesson 1 - Bioanalytical Method Validation: "History & Definitions"
- Definition of Bioanalytical Method Validation
- Regulatory Guidance on Bioanalytical Method Validation from Crystal City I to Crystal City III
- FDA Guidance for the Industry, Bioanalytical Method Validation (May 2001)
- FDA Good Laboratory Practice for Nonclinical Laboratory Studies: Title 21, Code of Federal Regulations, Part 58
- OECD Principles on Good Laboratory Practice (as revised in 1997)
- Drugs Directorate Guidelines, “Conduct and Analysis of Bioavailability and Bioequivalence Studies" Health Protection Branch, Health and Welfare Canada, 1992
- Statistics in Bioanalysis
- Statistical Mean
- Standard Deviation and Relative Standard Deviation
- Deviation from Theoretical and Percent Difference
- Correlation Coefficient
- Rejection of Outliers with T-test
- GLP Definitions
- Key Terms & Concepts in Bioanalysis
- GLP Documentation
- Analytical Method
- Data Review
10:30am-10:45am: Coffee Break
10:45am-11:45am: Lesson 2 - Bioanalytical Method Validation: "Criteria & Concepts"
- The Validation Process and the Validation Goals
- Uncertainty in Quantitative Analysis
- Validation Parameters and Method Validation
- Accuracy and Precision
- Analysis of Variance (ANOVA)
- Assessing Accuracy and Precision
- Stability Tests
- Recovery
- Approaches to Quantification
- Calibration Curve
- Limit of Quantification (LLOQ & ULOQ) and other Key Terms
- Quantitative Relationships in MS Instruments
- Nature of Regression Errors
- Standard Addition
- Defining Acceptance Criteria
- Essential Documentation
- System Suitability and its Importance
- The Steps in a Typical MS Quantitative Analysis
- Routine Sample Analysis
11:45am-12:30pm: Lesson 3 - LC-MS/MS & Bioanalysis
- Why LC-MS/MS?
- Advantages & Disadvantages of using LC-MS/MS in Bioanalysis
- Professor Fred McLafferty’s Four S’s of LC-MS Analysis
- Internal Standard
- Importance of Choosing the best Internal Standard
- Analogue vs. Stable Labeled Internal Standards
- Sample Preparation Pros and Con
- Protein Precipitation (PPT)
- Liquid-Liquid Extraction (LLE)
- Solid Phase Extraction (SPE)
- Matrix Effect and Ion Suppression/Enhancement Definitions
- Carryover Definition
12:30pm: Level 1 Course End and Level 1 CVG Course Certificate
12:30pm-01:30pm : Lunch ONLY for Level 1 & Level 2 Course attendees
Level 2 (Afternoon) - "Regulated Bioanalysis: Challenges Solutions and Applications"
(Advanced Course)
01:00pm-01:30pm: Level 2 Course Registration
01:30pm-03:00pm: Lesson 4 - Bioanalytical Method Validation and Sample Analysis: "Common Problems"
- Matrix Effect and Ion Suppression/Enhancement
- Matrix Effect in Electrospray (ESI) LC-MS/MS
- Remedy for Ionization Suppression in SPE-LC-ESI-MS/MS
- Matrix Induced Ionization Suppression in APCI
- Differential Suppression
- The 3 Different Scenarios of Matrix Effect
- Instrument Optimization to Reduce Matrix Effect
- Carry-Over Guidelines
- Impact of Carry-Over in Bioanalysis
- Fighting Carry-Over
- Drug Metabolism & Bioanalysis
- Metabolite Conversion During Sample Extraction
- Metabolite Conversion During Instrumental Analysis
- General Strategy for Method using UV or Fluorescence Detection
- General Strategy for Method using MS or MS/MS
- Study Cases
- Root Cause Analysis during Out of Specification investigation
- Importance of Trend Analysis in GLP Bioanalysis
03:00pm-03:15pm: Coffee Break
03:15pm-04:45pm: Lesson 5 - What's new in Bioanalysis?
- The Purpose of the 3rd AAPS/FDA Bioanalytical Workshop
- Crystal City III Conclusions
- Quality Controls: Conventional and New Approaches
- Evaluating Curve Models: Graphic & Mathematical Comparison
- Factors Contributing to Imprecision and/or Inaccuracy
- Carryover and Contamination Evaluation
- Evaluate Contamination in Validation
- Incurred Sample Re-Analysis (ISR)
- Reproducibility of QC vs. Incurred Samples
- Determination of Metabolites During Drug Development
- Documentation Issues
- Repeat Analyses
- Matrix Effects for MS-Based Assays
- Run Acceptance Criteria
- Stability Recommendations
- Autosampler Re-injection Reproducibility
- Blood Stability
- Method Evolution & Stability Measurements
- Internal Standard Stability
- Validation Topics with No Consensus:
- -70oC vs. – 20oC
- Reference Standard Expiration Date vs. Stock Stability
- Other Validation tests
- The 1st CVG Workshop on Recent Issues in Regulated Bioanalysis - 2007
- The 2nd CVG Workshop on Recent Issues in Regulated Bioanalysis -2008
- The 2008 AAPS Workshop (Feb) and the Industry consensus
04:45pm-05:15pm: Lesson 6 - Global Bioanalytical Outsourcing
- Current Life Science Industry Trends:
- Issues and Opportunities in the Pharmaceutical Industry
- Reducing Cost and Faster Time-to-Market
- Life Science Uncertainties:
- Regulatory uncertainties
- Scientific uncertainties
- IP
- Commercial and financial
- Challenges of Ageing Population:
- Large increase in disorders of old age
- Increasing unmet medical needs
- Old Big Pharma model (closed development: internal capabilities) vs. the new Biopharma model (open development: outsourcing/partnership)
- What is Driving Outsourcing for Pharmaceutical Companies?
- Advantages in outsourcing: Reducing the number of compounds that fail in early trials
- Regulatory best practices for first-time filers
- Collaborations and partnerships between Pharmas and CROs:
- Managing the relationship between the partners:
- Benefits of different processes
- Differences Needs, Cultures and operations
- Pharma Expectations
- Building and maintaining effective sponsor/CRO relationship:
- Vendor selection
- Contracting
- Criteria to Evaluating CRO
- Types of sponsor/CRO agreements
- The FDA Amendment Act (FDAAA - Sep. 2007):
- Current Prescription Drug User Fee Act (PDUFA IV)
- FDAAA new mandates and impact for pharmaceutical companies
- Title VIII Clinical trials database
- Title IX - Post-market Drug Safety
- Pharmaceutical Companies trend towards Global Outsourcing
- North America & Europe vs. India & China
- Why do Pharmaceutical companies turn to emerging markets?
- India and China as an opportunity for Pharma companies to accelerate clinical development programs
- R&D and Manufacturing costs abroad
- Shortcomings and potential pitfalls of outsourcing in Asia
- IP and legal protection
- Uncertainties around quality
- Different regulatory frameworks
- Language and cultural differences
05:15pm-05:30pm: Q&A and Level 2 CVG Course Certificate
