ISPE GCLP COP PQRStabilityDocumentationPresentation

7/27/2019 ISPE GCLP COP PQRStabilityDocumentationPresentation

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DOCUMENTATION OF PRODUCT

QUALITY REVIEW AND STABILITYSTUDIES

Dr. A.V. Prabhu



6/21/2011 2

Quote

Quote attributed to Dr. Deming

(He expressed when asked to sum up his

quality Philosophy. He responded )

“ If I had to reduce my message for

management to just a few words, I’d say itall had to do with reducing variation.





ICH –Q-7A

2.5 Product Quality ReviewRegular quality reviews of API’s should be conducted with the objective

of the process. Such reviews should normally be conducted and

documented annually and should include at least

• A review of critical in process control and critical API test results

• A review of all batches that failed to meet the established specification

• A review of all critical deviations or non-conformities and related

investigations.

• A review of any changes carried out to the process and Analytical

methods

• A review of result of stability monitoring program.

• A review of all quality related Returns, Complaints and Recalls.

• A review of adequacy of corrective actions

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ICH Q-7A

2.51 The results of this review should be evaluated andan assessment made of whether corrective action or any

revalidation should be undertaken. Reasons for such

corrective action should be documented. Agreed

corrective actions should be completed in a timely and

effective manner.

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Content of APR

6/21/2011 6

Items Listed in 21

CFR 180 ( c)

Optional but

expected byFDA

Optional but

included bysome firms

Product Name /

Description

Time period of Batch

Finished Product Results

In-process Results

Process Deviation/

Investigation

Rework

Batch Rejection

Stability Data

Complaints



Content of APRItems Listed in 21

CFR 180 ( c)

Optional but

expected by FDA

Optional but

included bysome firms

Process Changes

Test Method Changes

Product Labeling

API Data

• OOS Results

• Yield Variances

• Regulatory

Correspondences

• Quality Unit

approvals

• Management

Review

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Test Data

• Meaningful data should be provided in Product Analysis

• Two forms of Data

Attribute

It is a limiting form of dataBasically responds to Yes or No answer

e.g. Sterility Testing, Identification testing

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Test Data

Variable Data

Qualifiable Results that are numerically expressed

Helps to trend or track a product or process, and allow

decisions to be based on a sound statistically based

analysis

Measure variability through variable data

e.g. First group of data to deal is batch release data

6/21/2011 9



Change Control

Critical information in Industry but overlooked in

preparation of APR

Process Change

Equipment Change

Facility Change

Analytical Method Change

Specification Changes Material Changes

6/21/2011 10



Benefits

• Satisfies Regulatory Needs

• Cost Control

• Prevention Failure

• Revalidation

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Re-validation

• When performed properly with the incorporation of the

required elements of a retrospective process validation,

and in the absence of a significant process changes an

APQR may negate or substitute the need for the periodic

prospective revalidation of the manufacturing process.

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Re-validation

• This is supported by the following statement in Sec 12.6of ICH Q7A

“ When no significant changes have been made to the

system or process, and a quality review conformsthat the system or process is consistently producing

material meeting its specifications, there is normally

no need for revalidation.”

A similar statement appears in item 44 of the EU GMP

Guide. Annex. 15

6/21/2011 13



References for APQR

ALL YOU WANTED TO KNOW ABOUT APQR BUT DID

NOT KNOW WHERE TO FIND

1.Conducting Effective Annual Product Review- Elder

Henson, Journal of GXP Compliance Vol. 6(2) 6-15,

January Issue

2.Evaluating Data for an Annual Product Review – Michal

Ferrante, Journal of GXP compliance Vol. 6(2) 16-20

(2002) January Issue

3.Product Annual Quality Review: US-EU Comparative

Analysis and Interpretations- John Y Lee Vol3 Issue 32,

March (2008)

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SIGNIFICANT CHANGES DURING

STABILITY

A 5 % change in Assay from its initial value

Any degradation product exceeding its acceptance

criteria

Failure to meet the acceptance criteria for Appearance,

Physical attributes and functionality test (e.g. Colour,

phase separation, hardness)

As appropriate for the dosage form

Dissolution specification for release of stability must be

same (may affect Bio Equivalence)

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CAUTION

The Assay value is still within limit but thechange during stability is more than 5.0 %

THIS IS A SIGNIFICANT CHANGE

Release Assay Limit 95.0 to 103 %Stability Assay Limit 92.5 to 103.0 %

Release Assay 101.0 %

24 month Assay 93.0 %

Loss in Potency 8.0 %

6/21/2011 16



WHAT IS THE ROLE OF QA IN

DEVELOPMENT

There is a need for an energized Quality Assurance

function that promotes changes and uses teams to

handle new regulatory challenges and exploit

technological opportunities. By turning Quality Assurance into a self challenging, manufacturing science

promoting organization, a true value will be added to its

traditional mission of guaranteeing that quality products

are put in market place and also realigning quality

objectives with customer expectations.

6/21/2011 17



6/21/2011 18

Documents

ISPE GCLP COP PQRStabilityDocumentationPresentation