Dear All,
Is it necessary to perform the process validation on each batch size of same product. I am working with Biotechnology company, we have two different batch sizes of same product ( 100L and 400L fermentation batch sizes), our production heads are denying to perform process validation on each batch size, is there any guideline saying the bracketing of Batch sizes considering for process validation.
Please suggest.
Thanks in Advance…
[quote=rdasaratharamireddy]Dear All,
Is it necessary to perform the process validation on each batch size of same product.
is there any guideline saying the bracketing of Batch sizes considering for process validation.
)[/quote]
Yes it is necessary to perform the process validation on each batch size of same product. As different batch sizes may be done by different methods, may be by using different equipments, e.g. in our case we manufacture small batches by using Rapid Mixer Granulator and large batches by Mass mixer for mixing of the powders as the capacity of different equipment is different.
Moreover, if the same equipment is used, then the load (weight of the batch) itself plays a role. For example, equipments may mix properly, if the weight is very low for the mixer to mix or very high for the mixer to mix or for other parameters.
Yes, there are different guidelines available for bracketing of batch sizes considering for process validation.
You have to first know whether manufacturing process of both batch size are similar or not. In case of similar manufacturing process e.g. both the batch sizes are manufactured using same equipment and the equipment can perform the fermentation of both 100L and 400L, the organisms required for fermentation is directly dependent on the capacity of your batches etc. then you can validate one batch by taking not less than 3 consecutive batches for one batch size (say 400L) and then test one batch of another batch size (say 100L).
If the result are consistent, then you can have you process validation for both batch size. This is the concept of bracketing.
I donot know why your production head are not in favour of validating both batch size. Eventhough both the batch sizes have similar or same manufacturing processes, validation must be done considering at least 3 consecutive batches for one batch size and at least one batch of different batch size must be considered for validation.
With regards
Prawan Dahal
[quote=rdasaratharamireddy]Dear All,
Is it necessary to perform the process validation on each batch size of same product. I am working with Biotechnology company, we have two different batch sizes of same product ( 100L and 400L fermentation batch sizes), our production heads are denying to perform process validation on each batch size, is there any guideline saying the bracketing of Batch sizes considering for process validation.
Please suggest.
Thanks in Advance…:)[/quote]
There is no clear cut guideline for matrixing approach for this case. Logically it is necessary to perform Validation on each batch, as the batch sizes are different which may use different manufacturing equipment size.
Dear shahid and DRPRAWAN,
Thanks for valuavle suggestion, i will be thankfull if you suggest any guideline where this is captured in guidelines.
Hoping for positive response.
thnaks in advance…
Dasarath
Yep,
No shortcuts. Need to validate both batchsize. You need to do 3 batches for 400L and another 3 batches for 100L.
Tell u’r boss, you cannot register the product if PV was not submitted. But, you can still sell those batches if you want.
Sorry, I disagree with Mokhzanni Mustapa with the point You need to do 3 batches for 400L and another 3 batches for 100L.
Bracketing can be done for PV but the principle behind bracketing and the classification of individual products or procedures into one group must be justified before bracketing the same product with different batch size. For both batch size the worst case (e.g. the manufacturing procedure that is the most difficult to check) should be carefully determined and should be justified. Moreover, the variability of the process parameters should be carefully considered and the manufacturing process must be adequately optimized by suitable product design itself. By considering the risk factors for variability of the processes and considering the worst case you can have process validation without having 3 batches for both batch size.
Dear Mr. rdasaratharamireddy,
There are no clear cut guidance regarding the bracketing of products for process validation. What I think is that you should carefully considered all the aspects your manufacturing process, robustness of product design, justification for bracketing and other factors before deciding whether to validate both batch sizes with at least three batches or by doing bracketing concept.
Thanks Daprawan,
I’ve crossed check with FDA (Q&A session). they also mentioned that it is NOT necessery to perform PV for 3 batches.
FDA Quote:
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124782.htm
a)
No. Neither the CGMP regulations nor FDA policy specifies a minimum number of batches to validate a manufacturing process. The current industry guidance on APIs (see ICH Q7A for APIs) also does not specify a specific number of batches for process validation.
b)
However, a minimum number of conformance (a.k.a. validation) batches necessary to validate the manufacturing processes is not specified. The manufacturer is expected to have a sound rationale for its choices in this regard. The agency encourages the use of science based approaches to process validation.
From My POV,
The manufacturer should explain clearly the bracketing concepts and principles inside the protocol AND report. Your summary and conclusion must have scientific rationale which will justify all the equipment, variables, and parameters which have been validated. And again, you should prove you’ve had cover both ‘minimum and maximum’. (In your case is the variablity of the batch size). It is really important and it will help the auditor, regulator and yourself to understand the priciples.
Dear all.
I have a product to be validated.
Name/Strength : Liquid Inj 10mg/ml
Process Type : Mixing - Filtration - Autoclave (terminal sterilization)
Proposed batch size: 200L to 1000L (varied according to market)
Proposed Packing : Glass Ampoule 2ml, 5ml and 25ml
How should I do the PV to cover the varied batch size?
a)
i. 2ml: 3B x 200L
ii. 5ml: 3Bx 1000L
iii. 25ml: 3B x 200L.
OR
b)
i. 2ml: 3B x 200L & 3B x 1000L
ii. 5ml: 3B x 200L & 3B x 1000L
iii. 25ml: 3B x 200L & 3B x 1000L
[quote=Mokhzanni Mustapa]Dear all.
I have a product to be validated.
Name/Strength : Liquid Inj 10mg/ml
Process Type : Mixing - Filtration - Autoclave (terminal sterilization)
Proposed batch size: 200L to 1000L (varied according to market)
Proposed Packing : Glass Ampoule 2ml, 5ml and 25ml
How should I do the PV to cover the varied batch size?
[/quote]
I want to ask some question before that? Have you cover the impact of varied batch size on your equipment(mixer, filter and autoclave)? If you have not cover them, then first have that and if your equipment shows that there is no impact on the process by varying the batch size.
If you do this then you can take three consecutive batches of one batch size and 2 consecutive batches of another batch size (you can increase the number of batches).
But, if you do not have these then you should validate individually both batch size with considering at least three consecutive batches.
With regards,
I am looking for information, benchmarking, and best practices regarding Design Review Process.
Any ideas? comments.
Thanks in advance.
[quote=Mokhzanni Mustapa]Dear all.
I have a product to be validated.
Name/Strength : Liquid Inj 10mg/ml
Process Type : Mixing - Filtration - Autoclave (terminal sterilization)
Proposed batch size: 200L to 1000L (varied according to market)
Proposed Packing : Glass Ampoule 2ml, 5ml and 25ml
How should I do the PV to cover the varied batch size?
a)
i. 2ml: 3B x 200L
ii. 5ml: 3Bx 1000L
iii. 25ml: 3B x 200L.
OR
b)
i. 2ml: 3B x 200L & 3B x 1000L
ii. 5ml: 3B x 200L & 3B x 1000L
iii. 25ml: 3B x 200L & 3B x 1000L[/quote]
You should really separate your manufacturing and filling process.
For manufacturing, I would validate 3 batches in total, containing at least 1 batch of 200L and 1 batch 1000L (if the process parameter is the same). If they are different, you really should validate 3 batches of each.
For filling, I would think all parameters for each container size would be the same despite the bulk size, so you probably don’t need to do 3x for 200L and 3x for 1000L. Normally larger bulk size means longer fill time, which is worst case for validation, so I will just validate the longest fill time.
For the different container size, what do you think would be the worst case? Normally larger container is worst case for sterility, due to larger opening and longer fill time where product is exposed. But 2mL is worst case for particulate count if it’s faster. If you have the resources, you should validate 3x 2mL and 3x 25mL, at 1000L batch size each. Of course this also depends on what are the initial batch sizes and how often you are going to, e.g. fill 1000L batch in 2mL containers. As a minimum, you should do at least 1 batch of each worst case.
Dear All,
In process validation study is there any guidline for the challenges in Comperession machine speed or Hardness.
In other words, Is there any regulatory requirement to go for challenge study in process validation.
Thanks,
MUKESH VARDE
[quote=mukesh.dv]Dear All,
In process validation study is there any guidline for the challenges in Comperession machine speed or Hardness.
In other words, Is there any regulatory requirement to go for challenge study in process validation.
Thanks,
MUKESH VARDE[/quote]
Dear Mukesh,
There is no regulatory requirement for performing challenge study in process validation. The challenge study is to be done at scale-up or pre-validation stage. Compression speed can be challenged at different operational speeds of equipment and hardness challenge can be done at lower and higher specified range of hardness.