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Retrospective validation

Does anybody know about guidelines to retrospective method validation for a biological method that is used in routine drug analysis for over ten years?

In analytical method validation, there is no space of retrospective validation , because in AMV , we have to challenge the method at worst case scnerio.

I don’t think that the validation of the method is the place to challenge your method. The development phase is more suitable for this kind of experiments.
According to the ICHQ2R - robustness is a part of development work.

The validation purpose is to give evidence that the method is fit for it’s use.

Our method is running for ten years and there is a lot of data, that if summarized and analyzed, can give more accurate information about the method performance then any sort-term validation experiment design can give.

I found in the FDA website information regarding retrospective manufacturing process validation. In my eye manufacturing process validation should be equal (if not more strict) to analytical or biological method validation.

However retrospective validation has it’s downsize. Some method parameters could not be analyzed completely. For instance we will be able to calculate the method’s overall precision but we could not analyze intermediate precision between analysts. The method contains multiple steps and each step is usually performed by another analyst.

Is it enough for the authorities? I don’t know! That is why I posted the question!

Thanks guyalalouf

Very informative post

My dear friend,
Validation is a place to challenge the methodolgies at a worst case scnerio.
In developmemt phase,the method optimization studies should be conducted, once a method is optimized and established then validated, but both the studies can be conducted simultaneosly for time and money saving.
(your method is running for ten years and there is a lot of data, that if summarized and analyzed, can give more accurate information about the method performance then any sort-term validation experiment design can give.) How can you say that your results are accurate without spikking the known amount of analyte and with out recovery studies. u can do precission but not accuracy as well as the some other parametrs like solution stability, precision reproducibility e.t.c, thats y in AMV the retrospective validation is not recommended.
Thanks for your thoughts

I agree with Shahnawaz!!! `Coz if u see ICH Q2R1 u wont find even such terminology for the case of AMV, U can see USP or BP there is no description regarding reterospective AMV, even reterospective Validation for Manufacturing process is discouraged by many regulatory agencies.

Regards,
Shahid Ali
QA Manager
Addis Pharmaceutical Factory SC, Ethiopia

Can anyone suggest me about the Retropective validation for Multivitamins. As vitamins syrup/tablets, inculde the overages, whether we need to include the overages or not?

Thanking You

Kiran

Dear Kiran,
If the MVP (Multi vitamin product) are manufacturing since long time ago, then you may use retrorespective validation on recently 20 manufacture batches. In PV, overages should be consider and evaluate the impact on it.

Thanks

[quote=kvkiran]Can anyone suggest me about the Retropective validation for Multivitamins. As vitamins syrup/tablets, inculde the overages, whether we need to include the overages or not?

Thanking You

Kiran[/quote]
Dear Kiran
It seems that Formulation is not established for the multiviatmin products, as you mentioned and asked about the overages! Retrospective validation is only acceptable for well established formulation and process. Historical date may be utilized to Provide necessary documented evidence that the processes were stable and fomulation was optimized, The source of data should include BMRs, process control charts, maintenance log books, records of personnel changes, process capability studies, CoAs of FP, trend analysis and stability results. Reterospective validation still requires the preparation and execution of protocol, reporting results, data review leading to conclusion and recommendation, and if it is not complying then ultimatly you will have to go for Prospective validation. As far as overages are concerned it shoul be established earlier during product development based on stability studies, still you can decide if u have suffecient stability data.

Dear Shahnawaz
Can you indicate to me how to requalify the existing equipments especiaaly in the API when we do not have any data about the particulars of equipments?
Similarly how to carry out retrospective validation of the process which has been in operation for more than 5 years.
S.Vijay Kumar

[quote=S.Vijay Kumar]Dear Shahnawaz
Can you indicate to me how to requalify the existing equipments especiaaly in the API when we do not have any data about the particulars of equipments?
Similarly how to carry out retrospective validation of the process which has been in operation for more than 5 years.
S.Vijay Kumar[/quote]

Dear Vijay
If u dont have the particulars for equipment like operating and maintenance manual , then just note down all the observation on as is basis in IQ and OQ. It should match and satisfy the DQ. Cover the lackings in validation summery report. For PQ, verify production capability of Equipment, total change parameters of equipment during production, evaluate overall efficiency, evaluate rejection criteria.

Retrospective validation can be done with availabilty of suffecient data, but carefully you will have to analyze the data for all necessary documents like BRs, process control charts, maintenance log books, records of personnel changes, process capability studies, CoAs of Lots, trend analysis and stability results. You need to select consistent data for Lots manufactured for a defined period and u will have to establish the consistency in manufacturing process. Show List of LIR/OOS, corrective actions and changes to manufacturing process and documents. In case of some short comings u need to supplement the retrospective data with additional data generated with concurrent or prospective validation.

[quote=S.Vijay Kumar]Dear Shahnawaz
Can you indicate to me how to requalify the existing equipments especiaaly in the API when we do not have any data about the particulars of equipments?
Similarly how to carry out retrospective validation of the process which has been in operation for more than 5 years.
S.Vijay Kumar[/quote]

you must be qualify the equipment first by using dye placebo batch, once u qualify the equipment then take API studies or other new product.

Answer for secound question is that you can take large number of data and procedd retroresptic validation and determine the trend analysis and annual review of the product.

Dear Shahid Ali / Shahnawaz
Thanks for your clarification on the above topics.
S.Vijay Kumar