21 / 11 / 10
Guideline on process validation for finished products - information and data to be provided in regulatory submissions
Definitions
At-line
Measurement where the sample is removed, isolated from, and analysed in close proximity to the process stream.
In-line
Measurement where the sample is analysed within the process stream and not removed from it.
On-line
Measurement where the sample is diverted from the manufacturing process, and may be returned to the process stream.
Bracketing approach
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 into different size capsule shells). Bracketing can be applied to different container sizes or different fills in the same container closure system.
Control strategy
A planned set of controls, derived from current product and process understanding that ensures process performance and product quality. The controls can include parameters and attributes related to active substance and finished product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control. (ICH Q10)
Continuous process verification
An alternative approach to process validation in which manufacturing process performance is continuously monitored and evaluated. (ICH Q8)
Critical process parameter (CPP)
A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality. (ICH Q8)
Critical quality attribute (CQA)
A physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. (ICH Q8)
Design space
The multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval. (ICH Q8)
Enhanced approach
A development approach where risk management and scientific knowledge is used to identify and understand the material attributes and process parameters which influence the critical quality attributes of a product.
In-line
Measurement where the sample is analysed within the process stream and not removed from it.
At-line
Measurement where the sample is removed, isolated from, and analysed in close proximity to the process stream.
On-line
Measurement where the sample is diverted from the manufacturing process, and may be returned to the process stream.
Lifecycle
All phases in the life of a product from the initial development through marketing until the product's discontinuation. (ICH Q8)
Ongoing process verification
Documented evidence that the process remains in a state of control during commercial manufacture.
On-line
Measurement where the sample is diverted from the manufacturing process, and may be returned to the process stream.
At-line
Measurement where the sample is removed, isolated from, and analysed in close proximity to the process stream.
In-line
Measurement where the sample is analysed within the process stream and not removed from it.
Pharmaceutical quality system (PQS)
Management system to direct and control a pharmaceutical company with regard to quality. (ICH Q10)
Process validation
The documented evidence that the process, operated within established parameters, can perform effectively and reproducibly to produce a medicinal product meeting its predetermined specifications and quality attributes.
Traditional approach
A product development approach where set points and operating ranges for process parameters are defined to ensure reproducibility.