Progress to Date in A3: Method Transfer, Partial Validation and - PowerPoint PPT Presentation

Progress to Date in A3: Method Transfer, Partial Validation and Cross validation

A3: Method Transfer, partial and cross validation • Team members: In ¡scope ¡ Life cycle of a method after first full validation or relation • Team lead with other validated methods. Partial validation • Ray Briggs – EU Method transfer • Other members Cross validation Definitions of method transfer, partial and cross validations • Richard Abbott-EU Recommendation on when to perform method transfer, • Margarete Brudny-Kloeppel -EU partial and cross validations Specific requirements for the transfer, partial validation and • Patrick Duchene-EU cross validation of small and large molecules • Jan Busch-NA Recommendations of which experiments are desirable for • Bob Nicholson NA each proposed steps after full validation Recommendations of acceptance criteria for cross • Naidong Weng-NA validations and method transfers • Faye Vazvaei-NA Use of quality control material and incurred samples for transfer, partial validation and cross validation • Mahesh Kumar-APAC Pre assessment activities in method transfer and their • Masanari Mabuchi-APAC importance to successful transfer • Paulo Galvinas-LA ¡ • Pei Hu (APAC) ¡ ¡ Interdependencies ¡with ¡other ¡teams ¡– ¡if ¡any ¡ Out ¡of ¡scope ¡ Scope ¡will ¡be ¡limited ¡to ¡PK ¡analyses ¡only ¡at ¡this ¡5me ¡ – L1 Ligand Binding Run Acceptance – S1 Small Molecule Run Acceptance – A2 Tiered Approach for method validation ¡ – A6 Stability – A7 Repeat Analysis and ISR ¡ ¡ ¡ ¡ 2 ¡ ¡ ¡

Method Validation Life Cycle Development Method Feasibility Partial Validation Full Validation Initial Method Revised Method New Species Issue/Investigation Another Method/ Lab Cross Method Transfer Validation Internal/External

Perspectives • There is considerable overlap in the terminology and definition of method, transfer, partial validation and cross validation • The life cycle of a bioanalytical method can be complex which adds to the confusion • Current Regulatory Guidance in these areas is minimal • The A3 team’s primary objective was to introduce clarity into the terminology and to reduce overlaps between the concepts as far as is possible, while avoiding being prescriptive.

Method Transfer • A specific activity which allows implementation of an existing analytical method in another laboratory. • Level of method validation dependant on whether the receiving laboratory can be considered internal (working with the same SOPs and facilities as the initiating laboratory) or as an external laboratory • May include use of spiked QCs to determine equivalence of methods

Method Transfer Requirements • Internal Transfers • 2 accuracy and precision batches (4 for ligand binding) • External Transfers (or where critical reagents are not shared ) • Full validation • Inter-laboratory Comparison The objective is to demonstrate that the transferred method performs as originally validated

Partial Validation • The demonstration of assay reliability following a minor modification of an existing bioanalytical method that has been fully validated previously. • The nature of the modification will determine the extent of validation required . • Level of validation will depend on the nature and extent of the method change (example will be provided including acceptance criteria)

Partial Validation Requirements • What should be included will vary according to the nature of the method change required • Experiments required will normally have acceptance criteria in line with full validation requirements • Matrix stability will not need to be repeated as part of partial validation • The team is preparing an example of the types of experiments that should be considered in each case but recognizes that it would be difficult to be prescriptive

Cross Validation • A comparison of data obtained from at least 2 different laboratories or within and across studies with at least 2 different validated analytical methods to determine whether the obtained data are reliable and comparable. • Cross validation consists of analysis of assessment samples, (spiked QCs and incurred samples) assayed using both validated methods, as appropriate.

Further Ongoing Discussions • To identify the general requirements for acceptance criteria to be employed in each case • To agree to the necessity and scope of employing incurred samples in these experiments • To determine the variance between current practise and current guidance • To discuss any regional variations in current practise.