CRITICAL ASPECT ANALYTICAL TEST REVIEW · 2017. 12. 28. · Monitoring (EM), Microbial Limit Test...

CRITICAL ASPECT ANALYTICAL TEST REVIEW

Jakarta 14 December 2017

Speaker:

HERU PURNOMO, ST

ispe.orgConnecting Pharmaceutical Knowledge 2

Start

Review Lab Result

Submission

Lab Record to QA

Non Conformance or Out

of Specification

Investigation

Meet Specification

Stop

Sample Received

(In-Process & Finished

Good)

Testing

BATCH DISPOSITION

Yes

No

QC WORK FLOW


Analytical Test Result

Analytical Worksheet

Analytical Report

Certificate of Analysis

(CoA)

The analytical test report

is a compilation of the

results and states the

conclusions of the

examination of a sample

Internal document to be

used by the

analyst for recording

information about the

sample, the test

procedure,

calculations and the

results of testing. It is to

be complemented by

the raw data obtained in

the analysis

The list of test procedures

applied to a particular

sample with the results

obtained and the

acceptance criteria

applied. It indicates

whether or not the

sample complies with the

specification


Certificate of Analysis (CoA)

• A specification is defined as a list of tests, references to

analytical procedures, and appropriate acceptance criteria that

are numerical limits, ranges, or other criteria for the tests

described

• It establishes the set of criteria to which a drug substance or

drug product should conform to be considered acceptable for

its intended use. “Conformance to specifications” means that

the drug substance and/or drug product, when tested according

to the listed analytical procedures, will meet the listed

acceptance criteria


Review of Analytical Test Result

Written procedure should be in place when reviewing analytical result with

the following information:

• Provide general guideline for checking of analytical raw data, worksheet

and associated document in QC Lab

• Applies to GMP analytical raw data in physical – chemical, microbiology

and raw material

• Preparation steps, observation and calculation step should be

documented and show on the worksheet, these associated

documentations have to be reviewed for completeness and accuracy as

well

• The date of execution and analyst / chemist / microbiologist who perform

the testing is to be identified on worksheet

• All printout of raw data should be attached to the analytical worksheet.

Printout must signed or initialled across the edge of attachment


HPLC / GC Chromatographic Test

The following review for chromatographic data should be done for completeness

and accuracy:

1. Program setup:

Flow rate, detector wavelength, column temperature, mobile phase (e.g.

isocratic / gradient) & composition, need wash / seal wash setup

2. Sequence Setup

Injection Volume, Column ID, Sample Type, Sample Description, Sample

Weight, Reference accuracy weight

3. Integration Setup

SST Setup, Reference Standard Weight Entry, retention setup and

allowable window, proper integration peak

4. Chromatogram

Examine the blank chromatogram and note any extra peaks, particularly

those that co-eluate with any peak interest

5. Audit trail

Check data integrity of sequence by verifying the audit trail for any

unauthorized changes


HPLC / GC Chromatographic Test (cont)

6. Check the expiry of standard and test mix, use in the analysis, against the

relevant reference material certificate or preparation. Ensure they are within

the expiry date and preparation correct

7. Check that specified system suitability result are met against the relevant

testing method

8. Check the accuracy of all values that are manually calculated


Dissolution

Check should be carried out on both the dissolution procedure and method

analysis:

1. Dissolution medium used and the operating temperature

2. Type of Aparatus

3. Preparation standard and sample

4. Sampling procedure and technique (e.g. intervals, filtration, handling of

samples, dilution)

5. Calculations

6. The blank and standard solution spectra or chromatograms supporting the

dissolution test should either be available electronically or documented in lab

worksheet


Microbiological Testing for Water, Environment

Monitoring (EM), Microbial Limit Test (MLT)

1. Check that the analytical worksheet and SOP used were correct and the

sampling points were accurately recorded. Check the presence and

accuracy of the following minimum information:

• Date of sampling / performed date of testing

• Date of reading plate / result recording date

• Indicate the lot reference and expiry date of media used and verified that

the lot reference used is within expiry date at point of usage

• Date and temperature of incubation

• Equipment ID and ensure equipment are still within their qualification /

calibration status at point of usage

• Test result of negative or positive control which was carried out in

accordance to the test method

• Water sampling point (for microbiological testing for water) / legend (for

environment monitoring)

• Initial of analyst & reviewer and date

2. Check the result against the acceptance criteria in the relevant test

procedure


Other Tests

Hard copy, generated from test (for example: UV, infrared absorption)

should bear the following information:

Initial / name of analyst

• Sample Identity

• Instrument Number

• Spectrum (where applicable)

• Testing date

• Instrument Parameter (where applicable)

• Result / data obtained


Tolerance Limit & Specification Check

• If the test method requires tolerance limit check for the replicate

runs, check the replicate value against the pre-defined tolerance

limit in the test method

• Check the reported results against specification and trend limit (if

any)

• The review period of a GMP analytical result should be recorded in a

timely manner (e.g. 24 working hours from the test completion date)


Trend Rule Violation – Out of Trend

There are three (3) trend rule violations:

1. Result out of trend limits

2. Nine (9) or more consecutive data points shifted above or below the center line

3. Six (6) or more data points consecutively increasing or decreasing


OUT OF TREND (OOT) - NELSON TEST

Rule # 1

Any point outside

control limit

Rule # 2

9 consecutive point on

same side centreline

Rule # 3

6 consecutive point

decreasing or

increasing


What is an Audit Trail?

1. Systematic “story” of the data from creation, through interpretation

and final assessment and report

2. Each functional area that have GxP computer systems need to

perform audit trail

3. The information should be recorded in Audit Trail:

• Date and Time

• Name of person making change

• Original Change and value

• Reason of change made

• Invalid attempts to log on the system

If audit trail procedure is not available, the company has no

possibility to detect violations to data integrity executed by site

Operators due to errors / malfeasances, unintended or deliberate


Regulatory Guidance for Audit Trail Review


Audit Trail Review

• Evaluation of process risk associated to the system intended use

• An assessment must be performed for each system in order to

identify the most adequate method


Audit Trail Review

Risk class identification to define critical point:

• Frequency of audit trail

• Sampling Plan: The number of record to be reviewed


Audit Trail Review

Create form to define the

verification to be executed

and the relevant

acceptance criteria


Common Question During Inspection

• Is the audit trail activated? SOP?

• Record of review?

• How to prevent or detect any deletion of modification of audit trail

data? Training staff?

• Is predicate rule principle followed for changed?

Preserve of original data

Corrected data

Date of correction

Name of person who correction the data

Justification comment for correction

• What if there is no audit trail function?

• Can you prove data manipulation did not occur?


QA Responsibility

Do I need to review Analytical test result?

System & Facility

Culture

Confident

• Create robust procedure to review analytical test

result

• Qualified personnel

• Allocate budget to reduce potential data integrity

issue

• Develop management practises and supervision to

encourage reporting problem

• Identify root causes without finger pointing

Random check based on risk assessment

approach

ispe.orgConnecting Pharmaceutical Knowledge

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CRITICAL ASPECT ANALYTICAL TEST REVIEW · 2017. 12. 28. · Monitoring (EM), Microbial Limit Test...

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