Overcome Analytical Method Validation. Top Challenges!

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Overcome Analytical Method Validation Top Challenges! December 8, 2015 Lina Patel, Ph.D. Director, Quality Operations Laboratories lina.

1 Overcome Analytical Method Validation Top Challenges! December 8, 2015 Lina Patel, Ph.D. Director, Quality Operations Laboratories IVT s Lab Week Series Analytical Procedures and Methods Validation December 8-10, 2015 Philadelphia, PA 1

2 Overview Strategies for moving existing analytical test methods to newer technologies within site, site to site Challenges during technology transfer of validated test methods site to site How to avoid some common pitfalls? 2

3 Existing Test Methods to New Technologies For Biological assays Steps within the assay process not necessarily replacing the assay Manual operation to automation such as: plaque counting sample diluting pipetting labeling For Microbiology assays Sterility direct to rapid 3

4 Existing Test Methods to New Technologies New Challenges Developing technology support Equipment, Automation Building expertise and skill Finding unexpected problems Developing implementation strategy regulatory approvals and product release Meeting expectations! is release time faster? Risks and Impact to change in the current laboratory environment Resource constraints training & testing Potential delay in product release 4

5 Technology Transfer of Validated Methods Top challenges Method developed and validated on equipment model not current new model, different factory settings Method not optimized since first developed High variability Assay acceptance criteria based on limited data Standard Operating Procedures not clear Assay process not lean 5

6 How to avoid some common pitfalls? Good Scientific Practice Team Agreement who is the team? Review Method Validation Process Assay Development Analytical Procedures Pre-validation, Optimization, Qualification Determine sources of variability Understand method Parameters Characterization studies Good Documentation Practices 6

7 Good Scientific Practices Assay Development Scientifically sound and appropriate Repeatable Robust Good Documentation Practice Real time documentation Clear to follow methods Training Data Verified/Reviewed Calculations transparent Reproducible 7

8 Team all the right people? Groups Analytical Development Quality Laboratories Technical Experts Statisticians Marketing? Regulatory! Site to Site (Team agreement critical otherwise project can get derailed) 8

9 Team Agreement Quality Stakeholders Scientists AD /QC/SME/ Statisticians 9

10 Review of Method Validation Process Assay Development Analytical Procedure Prevalidation/ Optimization Qualification/ Method Validation Revalidation Check the necessary conditions for Methods, Material Standards, Controls, Reagents Equipment, Instrumentation 10

11 Assay Development Subject Matter Experts /Cross functional team Analytical Development QC Laboratory Technology Manufacturing Engineering Automation/IT QA Method & Materials Multivariate experiments Assay Development Standards, Controls & Reagents Equipment & Instrumentation Project Plan - monitor progress Organize documents 11

12 Analytical Procedure Stepwise instructions Clear process flow Equipment set up, operating parameters Reagents, Reference/Standard preparation, special handling, expiry date Sample preparation critical aspects? System Suitability criteria Assay acceptance criteria Calculations Data Reporting data forms, self directed, prompts 12

13 Pre-validation, Optimization, Qualification Equipment/ Instrument Laboratory environment (temp, humidity) Handling of Sample, Reference & Reagent Training Determine Sources of Method Variation Understand Method Parameters System suitability Assay acceptance Reference & reagent qualifications Assay critical parameters Automation Accelerated/Stability Studies Degradation studies Identity, Purity, etc. Characterization Studies & Analyses Good Documentation Practices Organization of raw data, notebooks, etc. Data verification Test method Roadmap Procedure visual guidance Data documentation sheets/forms 13

14 Determine Sources of Variation Sample Source of material Research material, clinical material, process validation, Handling conditions Storage, bench top handling, thawing process, equilibrating process Preparation Dilution automated pipetting? liquid handling system? Mixing 14

15 Determine Sources of Variation Standards, Controls, Reagents General handling Storage conditions, e.g. light sensitive? thawing process, equilibrating process, e.g. room temperature, water bath/incubator Vendor changes Grade changes Preparation Mixing Expiry date (freshly prepared?) 15

16 Determine Sources of Variation 16 Equipment, Instrumentation Qualified, calibrated Model changes/upgrades? Example: Automated pipetting, Moisture analysis Vendor changes Example: Chromatography columns, capillaries Technical differences? Example: Spectrophotometer dual beam, single beam, diode array Laboratory Environment Humidity control, Temperature control

17 Determine Sources of Variation Training Resources - Trainers Subject Matter Experts maybe located off-site Turnover laboratory personnel and contractors Challenges to sustain cohesive training plan after implementation 17

18 Understand Method Parameters System Suitability Criteria System Suitability Standard Define optimal settings e.g. Chromatography assays flow rate, column temperature, run time, detector settings Generally based on small data set Assay Acceptance Criteria Reference Standard/Material Qualification Periodic/real time control charts, monitor drift 18

19 Understand Method Parameters Automation check Parameters set upon qualification Monitor system breakdown Monitor system upgrades Raw Data Server LIMS LIMS Link 19

20 Good Documentation Practices Test method Provides roadmap Controls changes Provides visual guidance, where necessary Data documentation forms/sheets Clear, self directed Raw data and notebooks Data verification 20

21 in a nutshell Ensure Good Scientific Practices Team Agreement, engagement and support from project planning, knowledge transfer, troubleshooting to reagent supply, equipment operation/maintenance, automation Review Method Validation Process Assay Development new or process improvement Analytical Procedures key to consistent execution Pre-validation, Optimization, Qualification Determine sources of variability monitor, review Understand Method Parameters monitor, review Characterization studies help in troubleshooting Good Documentation Practices ALWAYS! 21

22 Regulatory Guidance Guidance for Industry: Analytical Procedures and Methods Validation for Drugs and Biologics (Feb 2014) Guidance for Industry: Analytical Procedures and Methods Validation (Aug 2000) Guidance for Industry: Submitting Samples and Analytical Data for Methods Validation (Feb 1997) Content and Format of Investigation New Drug Applications (INDs) for Phase I Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products. IND Meetings for Human Drugs and Biologics, Chemistry, Manufacturing, and Controls Information. Q2A: Text on Validation of Analytical Procedures (Mar 1995) Q2B: Validation of Analytical Procedures: Methodology (Nov 1996) Q6A, Q6B: Specifications (Dec 2000, Aug 1999) Q8 (R2): Pharmaceutical Development (Nov 2009) Q9: Quality Risk Management (Jun 2006) Q10: Pharmaceutical Quality System (Apr 2009) EMEA Guidance on Validation of Analytical Procedures: Text and Methodology 22

23 Expectation It is the responsibility of the applicant to choose the validation procedure and protocol most suitable of their product. The main objective of validation of an analytical procedure is to demonstrate that the procedure is suitable for its intended purpose. Well characterized reference materials, with documented purity should be used throughout the validation study. The degree of purity necessary depends on the intended use. All relevant data collected during validation and formulae used for calculating validation characteristics should be submitted and discussed as appropriate 23

24 Note New Analytical & Method Validation Guidance explicit on: Lines , If an analytical procedure can only meet the established system suitability requirements with repeated adjustments to the operating conditions stated in the analytical procedure, the analytical procedure should be reevaluated, revalidated, or amended, as appropriate. EMEA Guidance: Section 6.4: Quality Control personnel should have access to production areas for sampling and investigation as appropriate. 24

25 25 THANK YOU!

Analytical Method Transfer Program. Richard B. Nguyen. Associate Scientific Liaison, Chemical Medicines, USP

Analytical Method Transfer Program Richard B. Nguyen. Associate Scientific Liaison, Chemical Medicines, USP Outline Requirements for an AMT Program Develop Your AMT Program Qualify Your AMT Program On-going