Process validation
Definition
Process validation is the documented evidence that a process, conducted within established parameters, operates effectively and consistently, enabling the production of a medicinal product that meets the specified requirements and quality characteristics outlined in the Specification.
There are several types of process validation:
- Prospective validation (validation conducted before the initiation of routine production of
products intended for sale), - Concurrent validation (validation conducted in exceptional circumstances, justified by significant benefits for patients, where validation studies are conducted for batches intended for sale),
- Retrospective validation (this type of validation is no longer an acceptable approach for the manufacture of medicinal products. Retrospective validation can be conducted for the manufacture of active substances.)
Approaches to process validation:
Traditional Process Validation
Continuous Process Verification
Hybrid Approach
Periodic Verification of Ongoing Process During Lifecycle
Bracketing
The process validation strategy should be defined based on factors influencing the need for validation/revalidation, such as:
Product transfer
New product
New equipment/new line/new tools
Changes in raw materials/changes in material suppliers
Changes in process operational parameters
Scale-up
The purpose
The purpose of process validation is to determine whether all relevant quality attributes and process parameters, including:
Critical Quality Attributes
Critical Process Parameters
Critical Material Attributes
Critical Inter-Process Controls
The documentation of the assessment process for parameters, attributes, and their criticality should be clear and incorporate the results of risk analysis.
The validation process for new products should include all available doses for sale and all production sites where the product is manufactured for sale. This process should be carried out by personnel routinely involved in production.
Validation batches should be manufactured in quantities consistent with the registration dossier and using equipment intended for routine production batches.
Process validation should be based on statistical analysis of results (using process capability indices).
Before beginning the validation process, the following issues should be addressed:
Conducted (documented) personnel training
Validated analytical and microbiological methods
Raw materials and packaging should be supplied by qualified suppliers
Documentation must be approved before the start of the process
Facilities, equipment, utilities, and support systems must be qualified
Computerized systems must be validated
SAMPLE PROJECT:
Process Validation for Coated Tablet Manufacturing.
Scope
Validation of the tablet manufacturing process included:
Weighing of raw materials for given series
Tableting
Granule preparation and granulation
Coating
Outcome of Implementation
The validation process for the manufacture of coated tablets was carried out on a dedicated process line comprising the following equipment: weighing scales, tanks for preparing granulating fluid, a mixer-granulator, fluid bed dryer, granulation mill, rotary drum mixer, tablet press, mixer for preparing coating solution/film, and coating machine.
All of the above equipment had been previously qualified by our team (eCValidation).
During the process validation, critical process parameters were identified for:
- Wet granulation: mixing time, mixing speed, impeller speed, and granulation time (affecting homogeneity and granulation quality).
- Dry granulation: air and product temperature, drying time, mixing time and speed.
- Tablet compression: process speed, compression force.
Critical quality attributes for coated tablets were also identified, along with their testing frequency, including: mass loss after drying in the granulate, tablet mass, tablet hardness, tablet diameter, tablet thickness, disintegration time, tablet mass during and after the coating process.
Despite the short project timeline, significant workload, and complexity of the process, the validation was completed within the declared project timeframe (with a positive outcome).
A summary report was prepared after the validation process concluded.