Process validation

Process validation is a 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.

Effective process validation contributes significantly to assuring drug quality. The basic principle of quality assurance is that a drug should be produced that is fit for its intended use. This principle incorporates the understanding that the following conditions exist:

• quality, safety, and efficacy are designed or built into the product
• quality cannot be adequately assured merely by in-process and finished-product inspection or testing
• each step of a manufacturing process is controlled to assure that the finished product meets all quality attributes including specifications

Process validation involves a series of activities taking place over the lifecycle of the product and process. This process validation can be described in three stages:

• Stage 1 – Process Design: The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities.
• Stage 2 – Process Qualification: During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.
• Stage 3 – Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.

A successful validation program depends upon information and knowledge from product and process development. This knowledge and understanding is the basis for establishing an approach to control of the manufacturing process that results in products with the desired quality attributes.

Manufacturers should:

• Understand the sources of variation
• Detect the presence and degree of variation
• Understand the impact of variation on the process and ultimately on product attributes
• Control the variation in a manner commensurate with the risk it represents to the process and product

Manufacturer should judge whether it has gained sufficient understanding to provide a high degree of assurance in its manufacturing process to justify commercial distribution of the product. Focusing exclusively on qualification efforts without also understanding the manufacturing process and associated variations may not lead to adequate assurance of quality.

The validation should be based on a risk analysis. Based on the risk analysis, a list and a scope of the tests are determined. The results of the risk analysis are reflected in the validation master plan.

We provide services for the:

• development of validation protocols
• supervise the validation
• preparation of the validation report

Our services based on bracketing approach. Bracketing approach is a risk-based validation approach such that only batches on the extremes of certain predetermined and justified design factors are tested during process validation.

We apply bracketing approach in case:

• strengths are identical or very closely related in composition:
  • for a tablet range made with different compression weights of a similar basic granulation
  • for a capsule range made by filling different plug fill weights of the same composition
• different container sizes
• different fills in the same container closure system

In case of changes (introduction of a new production recipe or a process), we will help to prepare the relevant documentation demonstrating their suitability for batch production. The prepared documentation will confirm that the established process with the use of appropriate materials and equipment allowing receive products of the appropriate quality on a constant basis.

We provide the following validation services:

• processes validation
  • production of finished medicinal products
  • auxiliary processes (including storage and transportation)
  • production API
• cleaning validation
• validation of computerized systems
• validation of aseptic processing (Media Fill Test – MFT)
• validation of ethylene oxide sterilization processes for medical devices
• validation of radiation sterilization process
• validation of packaging processes for medical devices subjected to final sterilization