Process Validation

[Julie_Sigotho]

Dear All
I just need an input here, we have a new product that’s being introduced to the facility. It has two different flavours, strawberry and orange. For process validation, do we have to validate both flavours or we can just do one flavour snce the manufacturing process is the same?

[sunilrbudhkar]

A Bracketing (or Matrixing) approach may be acceptable for different strengths, batch sizes and pack sizes. A validation scheme / protocol designed such that only batches on the extremes of certain
predetermined and justified design factors, e.g., strength, batch size, pack size are tested during
process validation. The design assumes that validation of any intermediate levels is represented by the
validation of the extremes. Where a range of strengths is to be validated, bracketing could be
applicable if the strengths are identical or very closely related in composition (e.g., for a tablet range
made with different compression weights of a similar basic granulation, or a capsule range made by filling different plug -fill weights of the same basic composition (capsule blend) into different size capsule shells.
Bracketing can be applied to different container sizes or different fills in the same container closure
system.
[Reference: EMA Guideline on process validation for finished products - information and data to be provided in regulatory submissions, November 2016]

A matrix approach is where multiple similar products, presentations or equipment are grouped together within one validation exercise to reduce the overall testing requirements. All parameters or variables must be assessed to identify the “worst case” or “extreme” conditions for a combination of parameters or variables. These conditions are used during validation of the process, rather than validating all possible combinations.
Because the combination contains overlap in the parameters or variables for each product/ presentation / equipment, the validation effort may be reduced. This approach assumes that there is minimal variation in the process from product type to product type.

The use of a bracketing or matrix approach for the process validation of a manufacturing process across different products should be approached with caution because of the risk of overlooking other possible sources of variation. This type of approach requires extensive process knowledge from the development stage in conjunction with an appropriate ongoing verification programme involved and the risks being assumed.
The use of a bracketing design or matrix approach would not be considered appropriate if it is not possible to demonstrate that the extremes are limited to the batches, products, strengths, container sizes or fills. For those excluded from the exercise there should be no risk to process capability.

To obtain the maximum benefit with minimum risk from bracketing and matrices, it is necessary to have a well-developed understanding of the impact of critical process parameters on critical quality attributes. There should be a documented and justified rationale that explains why one set of test conditions (e.g., manufacturing process, product presentation, etc.) is representative of one or more related test conditions.
Typically, the rationale is addressed by selecting parameters and/or products that represent the edges of a range or worst case of allowable conditions. The rationale and justification for the
Bracketing /matrixing strategy to be used in validating a process should be provided in the validation protocol, or in another document referenced in the protocol.

Based on the above aspects you may select any one product (with one type of flavour) and conduct process validation OR cosider a combination of 2 different flavours batches (For eg. 1 batch with strawberry flavour & 2 batches with orange flavour) with appropriate scientific justification of selection of the product & describe in the validation protocol.