1

ANALYST TRAINING & REQUALIFICATION CONSIDERATIONS

Dr. Nishodh Saxena

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Topics of Discussion

Why it is required?

What is required?

Classification of Analyst training /

Qualification

Validation of Qualified Analyst

When Requalification is required?

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Why it is required?

cGMP regulations (CFR 21 parts 210 &

211) of US FDA recommends how to

investigate suspect or OOS test results,

including the responsibilities of laboratory

personnel ………..

To get consistent and accurate result.

To perform the allotted analysis effectively

and correctly.

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What it is required?

GMP regulations require an active

training program and documented

evaluation of the training of analysts.

Quality training program

Quality Analyst duties

Elements of Analyst Qualification

Responsibilities of the Analyst

Responsibilities of the supervisor

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Classification of Analyst Qualification

Analyst training and Qualification for new

recruitments in Quality control department.

Analyst training and Qualification at the

time of Qualification/validation of method.

Both category have,

Theoretical training

Practical training

On-going evaluation (need to retrain)

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Theoretical training

Preparation of training schedule.

Reading of the material provided by the trainer

with instructions and explanation by the trainee

(E.g. Principle, Validation status, sampling instructions,

specifications, critical analytical variables, Precautions,

documentation, flow of documents, reporting of the result, etc.)

Evaluation of the trainee based on his theoretical

understanding of the above.

Certification for “Hands on Work under supervision”.

Approval for Practical Training.

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Practical training.

1. Demonstration of the analytical method by the

trainer (Observe the trainer performing the

activity). The duration of this training will be

decided by the trainer.

2. Trainee analyses under supervision (Compare

results with that of the trainer)

3. Evaluation for the Job competency.

4. Certification of “Trained to perform Hands-On

Analysis Independently”

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Validation of Qualified Analyst.

Ongoing Qualification of Analyst .

Comprise of 4 levels of validation covering

following parameters.

Accuracy,

Precision and

Specificity.

Analyst error

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Continue…..

Level 1-Accuracy

On-job evaluation (an ongoing activity)

Accuracy of the Analyst can be

established during routine testing by:

Comparing the “Measured value”

with the “True Value” of a Ref. Std.

Inter-assay Slope, OD, Peak area

obtained with Ref. Std. (last 5

analysis)

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Continue…..

Example-Accuracy Accuracy in ELISA results.

Ref.

std.

value

True

conc.

(ng)

Meas

ured

conc.

Mean SD %CV

2 1.95 1.98 0.04 1.79

8 8.04 8.02 0.03 0.35

25 25.12 25.06 0.08 0.34

75 75.00 75.00 0.00 0.00

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Continue…..

Level 2 - Specificity

Periodic random blind test of

qualified analyst with already

reported OOS sample by other

Qualified / Validated Analyst.

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Continue…..

Example 1– Specificity Protein sample with high impurity

Lane No.: 1 2 3 4 5 6

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Continue…..

Example 2 – Specificity

OOS protein sample in SDS PAGE

Sample: OOS Normal OOS OOS Normal OOS

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Continue…..

Level 3 - Precision

By trending of different values (eg. OD,

slope, peak area etc. of Ref. Std.) over

5 last readings and comparing with

values obtained by other analyst. The

limits for inter-assay variance should be

determined from Method Validation.

Include this as part of system suitability.

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Continue…..

Example – Precision Trending of OD value of Ref. Std.-Inter assay

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Continue…..

Level 4 – Analyst Error

Number of test failures attributable to an

analyst error within 6 months or based

on last 10 analysis, whichever is earlier.

Investigate the cause of failure and

identify the most common cause. If it

has to do with analyst error, retraining

shall be recommended.

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Continue…..

Example – Analyst error A B C D

Sialic acid

standard

(mcg)

OD of

Analyst 1

OD of

Analyst

attributed

to error

%CV

2 0.031 0.008 83.40

4 0.059 0.029 48.21

6 0.09 0.075 12.86

8 0.115 0.125 5.89

10 0.147 0.152 2.36

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Continue…..

Example – Analyst error

Sequence of Investigation of above case study of test failure. Comparison of reference standard values with other

Qualified Analyst.

%CV is very high in lower concentrated standard and %CV is less when going towards the high concentrated standard.

There is an analyst error in making dilution.

MOA says make all different concentration of std from stock of 10 mcg and analyst has done the serial dilution.

Based on above results it is investigated that the analyst did not follow the method of Analysis for dilution of standard.

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CAPA

Root-cause analysis of the problem is required:

Frequent OOS attributed to Analyst error

SOP poorly written

Time-gap between analysis

Inadequate training / retraining need

If necessary, make changes in the Work

load, well-being, work environment

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When to retrain

OOS attributable to frequent Analyst error

(frequency pre-defined in Training SOP)

When new job responsibility assigned.

Change in the work system, procedure,

instrument, etc.

For LAL test the analyst must be requalify

yearly as per US FDA guideline.

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Requalification of LAL Analyst

Analyst have to done Lysate sensitivity test

for verification of

Analyst it self (Take Lysate of known

sensitivity)

Label claim sensitivity (For new Lysate).

Control curve is prepared by dilution the CSE

to bracket the label claim sensitivity (λ)

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Continue…..

Requalification of LAL Analyst Analyst is Qualified if results are as follows:

1 2 3

Dilution 0.125 0.25 0.06

Blank (LRW) -- -- -- -- -- --

2λ (0.25 EU/ml) ++ ++ ++

λ(0.125 EU/ml) ++ -- ++

λ/2 (0.06 EU/ml) -- -- ++

λ/4 (0.06 EU/ml) -- -- --

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Continue…..

Requalification of LAL Analyst Analyst is not Qualified if results are as follows:

Error Lysate/

Dilution

Dilution Accessor

ies/ LRW

Blank (LRW) -- -- -- -- ++

2λ (0.25 EU/ml) -- -- ++ ++

λ(0.125 EU/ml) -- -- ++ ++

λ/2 (0.06 EU/ml) -- -- ++ ++

λ/4 (0.06 EU/ml) -- -- ++ ++

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References

EU Guide to Good manufacturing

Practices (GMP) for Medical Products

(Chapter 2) 1998 Edition.

Therapeutic Good Administration

(TGA), Australian code of GMP for

Medical Products (Chapter 2).

PIC/S guide to GMP for Medical

Products (PH 1/97, Rev.2) (Chapter 4)

CFR 211.25 Personnel Qualification.

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Thanks QUALITY IS THE RESPONSIBILITY OF

EACH AND EVERY INDIVIDUAL

EMPLOYEE OF THE ORGANIZATION.

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