APQR and Retrospective Validation

GOOD DOCUMENTATION PRACTICE (GDocP)
1

Hi,

Can any one help me out to identify the difference between APQR (Annual Product Quality Review) and Retrospective validation.As per my knowledge both are having the same documentation procedure and one example for Retrospective validation bcoz i often c only Concurrent validation in pharma industry

Regards
Sowmya

2

Hi Sowmya,

The APQR is planned activity and the retrospctive validation is un planned. So to compile APQR you will have all the details but in retrospective validation you may not have all the information to prove the process is realiable and consistant.

Ofcourse the objective of APQR and retrospective validation is different.

Please let me know if you need further discussion on this

Vanmeeganathan B
+91 9704500710

3

Retrospective validation is process based and APQR is product based.

This is very clear from the definition of FDA guidance on Manufacturing, Processing or Holding API. It clearly defines the following conditions for retrospective validation.

    "[b][i] Retrospective validation could be conducted for a well-established process that has been used without significant changes that affect the critical quality attributes of the API."[/i][/b]
    "[b][i]All batches within the selected review period should have been manufactured by the same process and have the same documented history of controls and tests as current APIs."[/i][/b]

The scope for APQR is very much extended from Retrospective validation scope. APQR is the complete package of product related information review for quality improvement and cGMP / Regulatory compliance.

Hence now a days, APQR approach is well appreciated than retrospective validation approach for any product.

4

Hi nathan,
Just now i had a look at ur reply. I have a doubt, when u say retrospective validation may not have all the information to prove the process is reliable & consistent thn on what basis v can show them to regulatory audits?.
can u give me a example when & wher v can perform ths validation so that it can be still more clear to understand.

sowmya

[quote=nathanbv]Hi Sowmya,

The APQR is planned activity and the retrospctive validation is un planned. So to compile APQR you will have all the details but in retrospective validation you may not have all the information to prove the process is realiable and consistant.

Ofcourse the objective of APQR and retrospective validation is different.

Please let me know if you need further discussion on this

Vanmeeganathan B
+91 9704500710[/quote]

5

Thanks , i came to know the difference b/w retrospective validation & APQR
sowmya

[quote=ssnmd]Retrospective validation is process based and APQR is product based.

This is very clear from the definition of FDA guidance on Manufacturing, Processing or Holding API. It clearly defines the following conditions for retrospective validation.

    "[b][i] Retrospective validation could be conducted for a well-established process that has been used without significant changes that affect the critical quality attributes of the API."[/i][/b]
    "[b][i]All batches within the selected review period should have been manufactured by the same process and have the same documented history of controls and tests as current APIs."[/i][/b]

The scope for APQR is very much extended from Retrospective validation scope. APQR is the complete package of product related information review for quality improvement and cGMP / Regulatory compliance.

Hence now a days, APQR approach is well appreciated than retrospective validation approach for any product.[/quote]

6

Hi Sowmya,

The retrospective validation may be performed in the following instances,
(but there may be many other instances)

  • It was thought it did not require a validation
  • Regulations/ regulatory guidelines have changed
  • The initial validation was flawed
  • Re-assuring an out of use facility

The definition of retrspective validation goes like this…

Validation of a process for a product already in distribution based upon establishing documented evidence. The review and analysis of historical manufacturing and product testing data that verifies a specific process can be consistently produced meeting its predetermined specifications and quality attributes.

In all the above instances the process/ facility is already existing. The retrospective validation majorly involves review and and analysis of historical manufactuing and product testing data. Since the process is alredy in place you may not have all the data that are required to prove the consistancy and the reliability of the process. example, you may not have some in-process test for a commercial batch.

FDA stated that it encourages prospective validation.

7

In the recent FDA guidance for industry the Retrospective valtion was not mentioned and is no longer considered acceptable.

Vanmeeganathan B
+91 9704500710

8

Hi nathan,

Actually i got this doubt bcoz i hav seen no were validation protocol or report for ths validn instead they had this product quality review for products. so whether APQR can justify for retrospective validation, but now ny doubt is clarified .

Thanks a lot for the information given.

sowmya

9

I just checked the FDA website with new guidance:

Retrospective validation is mentioned in 12.4 (D). It is permitted only if the process is well-established processes, as such:

[i]"An exception can be made for retrospective validation of well-established processes that have been used without significant changes to API quality due to changes in raw materials, equipment, systems, facilities, or the production process. This validation approach may be used where:

  1. Critical quality attributes and critical process parameters have been identified

  2. Appropriate in-process acceptance criteria and controls have been established

  3. There have not been significant process/product failures attributable to causes other than operator error or equipment failures unrelated to equipment suitability

  4. Impurity profiles have been established for the existing API

Batches selected for retrospective validation should be representative of all batches produced during the review period, including any batches that failed to meet specifications, and should be sufficient in number to demonstrate process consistency. Retained samples can be tested to obtain data to retrospectively validate the process."[/i]