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

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

A3: Method Transfer, partial and cross validation • 

Team members:

• 

Team lead

• 

Ray Briggs – EU

• 

Other members

•  •  •  •  •  •  •  •  •  •  • 

Richard Abbott-EU Margarete Brudny-Kloeppel -EU Patrick Duchene-EU Jan Busch-NA Bob Nicholson NA Naidong Weng-NA Faye Vazvaei-NA Mahesh Kumar-APAC Masanari Mabuchi-APAC Paulo Galvinas-LA Pei Hu (APAC)

Interdependencies  with  other  teams  –  if  any   –  –  –  –  – 

 

 

L1 Ligand Binding Run Acceptance S1 Small Molecule Run Acceptance A2 Tiered Approach for method validation A6 Stability A7 Repeat Analysis and ISR

In  scope  

Life cycle of a method after first full validation or relation with other validated methods. Partial validation Method transfer Cross validation Definitions of method transfer, partial and cross validations Recommendation on when to perform method transfer, partial and cross validations Specific requirements for the transfer, partial validation and cross validation of small and large molecules Recommendations of which experiments are desirable for each proposed steps after full validation Recommendations of acceptance criteria for cross validations and method transfers Use of quality control material and incurred samples for transfer, partial validation and cross validation Pre assessment activities in method transfer and their importance to successful transfer

  Out      of  scope  

Scope  will  be  limited  to  PK  analyses  only  at  this  5me  

 

    2  

Method Validation Life Cycle Development Method Feasibility Full Validation

Initial Method

New Species

Method Transfer

Internal/External

Partial Validation

Revised Method

Issue/Investigation

Cross Validation

Another Method/ Lab

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.