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Release of Process Validation Batches

Hi,
As a CMO manufacturing products (eg VMS, OTC, Rx),our customers ask for us to perform process validation on specific products. However, sometimes the orders are weeks or months apart but they wish for us to release the product one by one so they can send it to market. Given that only one batch is completed and then released, how do people recommend tackling this issue from a valdiation perspective?
Should the batches be released provisionally based on all finished product, in-process testing being completed? Should an interim report be written based on data available?:slight_smile:

It depends on the intention and type of validation to be done, In case of prospective Validation, it is conducted prior to the distribution of either a new product or a product made under a modified production process where the modifications are significant and may affect the products and unless and untill three validation batches are run with all satisfactory results, product can not be distributed in the market. similarly in cae of concurrent valdation which is commenly used when when a already validated product is transfered to contract manufacturer to another manufacturing site or the product having diffrent strength. In both cases the final report must be reviewed and approved before the product is released for sale. Yes reterospective validation Product has no restriction for sale but its a fact that Reterospective validation is discouraged by many regulatory bodies.

It depends on the intention and type of validation to be done, In case of prospective Validation, it is conducted prior to the distribution of either a new product or a product made under a modified production process where the modifications are significant and may affect the products and unless and untill three validation batches are run with all satisfactory results, product can not be distributed in the market. similarly in cae of concurrent valdation which is commenly used when when a already validated product is transfered to contract manufacturer to another manufacturing site or the product having diffrent strength. In both cases the final report must be reviewed and approved before the product is released for sale. Yes reterospective validation Product has no restriction for sale but its a fact that Reterospective validation is discouraged by many regulatory bodies.

Plclarify the following example is covered under concurrent or prospective validation example X product of one batch completed and another Y product two batches were executed in the same equipments

Dear Ashok Reddy,

It will not come under both.
Because, prospective & concurrent process validation talks about the same product. It doesn’t apply for different products.

It comes under PQ of that particular equipment…if it is a new equipment.

With Best Regards,
Sudarshan Reddy
ys.sudarsan@gmail.com

[quote=Austin Stewart]Hi,
As a CMO manufacturing products (eg VMS, OTC, Rx),our customers ask for us to perform process validation on specific products. However, sometimes the orders are weeks or months apart but they wish for us to release the product one by one so they can send it to market. Given that only one batch is completed and then released, how do people recommend tackling this issue from a valdiation perspective?
Should the batches be released provisionally based on all finished product, in-process testing being completed? Should an interim report be written based on data available?:)[/quote]

Dear Austin,

In case of New Product Prospective validation, the release of Three consecutive batches into market, will be done only after the completion of finished product analysis and approval of PV Report.

If it is Prospective Validation (with Major Change), then the release of product can be done by considering ONE batch, instead of Three. But, it should be done after the finished product analysis and approval of INTERIM REPORT only. And Remarks shall specify that, since it is the requirement and based on ONE BATCH INTERIM REPORT approval. After completion of another consecutive two batches, a final summary report shall be made, reviewed & approved.

In case of Concurrent validation, any SINGLE batch can be released to market based on finished product analysis and Interim Report approval. Because, in general, concurrent validation will be performed only after completion of Prospective validation.

In case of Parenterals (Terminally sterilized products), the release of product into market, can be based on Finished Product Analysis & without considering STERILITY TEST i.e. Parametric Release.

I hope, it will help you out…if something is there, do let me know.

With Best Regards,
Sudarshan Reddy
ys.sudarsan@gmail.com

[quote=ys.sudarsan]Dear Austin,

In case of New Product Prospective validation, the release of Three consecutive batches into market, will be done only after the completion of finished product analysis and approval of PV Report.

If it is Prospective Validation (with Major Change), then the release of product can be done by considering ONE batch, instead of Three. But, it should be done after the finished product analysis and approval of INTERIM REPORT only. And Remarks shall specify that, since it is the requirement and based on ONE BATCH INTERIM REPORT approval. After completion of another consecutive two batches, a final summary report shall be made, reviewed & approved.

In case of Concurrent validation, any SINGLE batch can be released to market based on finished product analysis and Interim Report approval. Because, in general, concurrent validation will be performed only after completion of Prospective validation.

In case of Parenterals (Terminally sterilized products), the release of product into market, can be based on Finished Product Analysis & without considering STERILITY TEST i.e. Parametric Release.

I hope, it will help you out…if something is there, do let me know.

With Best Regards,
Sudarshan Reddy
ys.sudarsan@gmail.com[/quote]

Dear All,
I jusr want to add some points in above discussion.
To undertake that 3 consecutive full production batches are successfully validated before the product is marketed. For existing products already on the market for some time,retrospective validation may be performed. Retrospective validation involves the trend analysis (using control chart,
etc) of historical manufacturing and QC data of the product. Datafrom 10 -20 batches of the product produced using the same stable manufacturing process should be analysed, to demonstrate that the manufacturing process is under control. In the case of orphan drugs, when the number of production
batches per year is expected to be low, concurrent validation is acceptable.
[COLOR=“Navy”]Parametric Release
[/color]Elimination of the sterility test is only valid on the basis of successful demonstration that the sterility assurance system is fully robust and capable and processes and area should be qualify and validated. All sterile products must be manufactured using an adequate sterility assurance system, and in those cases where the system is fully capable and robust parametric release may be authorized. Means the area must be qualified, equipments (Autoclave, tunnels/ HAS, filling machines,e.tc), personnals, utilities are qualified.

Dear All
Read Guidance on Parametric Release - Pharmaceutical Inspection Co-Operation Scheme (PIC/S), I hope it would be very valueable.
This guidline clearly states that Only terminal sterilization processes that incorporate large safety margins will be considered for parametric release. If pharmacopeial reference cycles are not used for moist heat processes, each unit of product should receive a minimum Fo of 8 together with a SAL of 10-6 or better.
OVERALL CONSIDERATIONS
A clear description of the sterility assurance system should be documented and available for review. Ideally this document should refer to or incorporate a detailed breakdown of each element with a formal risk analysis including potential failure modes of equipment and procedures and the potential for human error. Having identified these risks the document should describe how features of design, procedures and training have reduced them to acceptable levels. In addition there should be assurance that all critical failure modes that do occur will be routinely detected.
The disciplines of Hazard Analysis and Critical Control Points (HACCP) Failure Mode Effects Analysis (FMEA) and the Reduction of Human Error can provide the formal basis for such analyses.

[quote=Shahid Ali]Dear All
Read Guidance on Parametric Release - Pharmaceutical Inspection Co-Operation Scheme (PIC/S), I hope it would be very valueable.
This guidline clearly states that Only terminal sterilization processes that incorporate large safety margins will be considered for parametric release. If pharmacopeial reference cycles are not used for moist heat processes, each unit of product should receive a minimum Fo of 8 together with a SAL of 10-6 or better.
OVERALL CONSIDERATIONS
A clear description of the sterility assurance system should be documented and available for review. Ideally this document should refer to or incorporate a detailed breakdown of each element with a formal risk analysis including potential failure modes of equipment and procedures and the potential for human error. Having identified these risks the document should describe how features of design, procedures and training have reduced them to acceptable levels. In addition there should be assurance that all critical failure modes that do occur will be routinely detected.
The disciplines of Hazard Analysis and Critical Control Points (HACCP) Failure Mode Effects Analysis (FMEA) and the Reduction of Human Error can provide the formal basis for such analyses.[/quote]

I agreed with Mr.Shahid comments