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:
• 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)

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

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Out ¡of ¡scope ¡

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

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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

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Method Validation Life Cycle

Initial Method Revised Method

Development Method Feasibility

Full Validation Partial Validation

New Species

Method Transfer Another Method/ Lab Cross Validation

Issue/Investigation Internal/External

• 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.

Perspectives

• 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

• 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

Method Transfer Requirements

• 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

• 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

Partial Validation Requirements

• 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.

Cross Validation

• 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.

Further Ongoing Discussions