Why do Manufacturing and Packaging Processes Have to be Validated?

Process validation

Process validation is time-consuming and has to be carried out on every single product before the marketing authorisation is granted. It must be carried out after the development of the manufacturing and packaging process has been completed and the process has been adapted to the manufacturing environment (optimised).

The planning and implementation of process validation can vary greatly depending on the company and products. For this reason, every pharmaceutical manufacturer must describe in a validation master plan (VMP) how validations are organised in practise, e.g. who belongs to the validation team, who creates, checks and approves the validation documents, and who is responsible for making what decisions.

A validation plan must be created for each individual product, describing the validation program for the respective product in detail. The effort required depends largely on the type of product.

• Is the manufacturing or packaging process straightforward or complex?
• Does it require special equipment and specially trained personnel?
• Is the product risk particularly high, e.g. because the product is very sensitive or because it must be sterile?
• How much experience does the company have with similar processes and products?
• Are reliable control mechanisms in place that detect quality issues before the product leaves the company?

The validation team evaluates these sorts of questions using quality risk analyses.

Depending on the results of the risk evaluation, the team decides on the extend of validation studies needed. For example:

• How many batches have to be produced as validation batches?
• What other tests have to be carried out?
• What results need to be achieved to ensure that the process is absolutely reliable (acceptance criteria)?

Everything must be described in detail in the validation plan and test plans and approved before manufacture of the validation batches begins.

The tests that are specified in the plans, and any observations or difficulties are documented in validation records during manufacture.

The validation report summarises the results for all validation batches and states if the manufacturing and packaging processes are reliable. The validation of the process is only complete when the validation report has been approved. The manufactured medicinal product may not be released for sale beforehand!

Validation shows that under routine conditions a process always results in high-quality products.

Process optimisation and process changes

A successful validation is only valid as long as the process and all of the conditions (e.g. facilities, specifications, starting materials, suppliers) remain within the specified ranges that were checked during validation. For this reason, manufacturing, packaging, cleaning and operating instructions must always be followed meticulously during routine production. If this is not possible in a particular case, the employees must record what was done instead in the batch record or deviation reports.

Changes to or improvements of validated processes, e.g. an increase in the process temperature or improvement of the formulation, must only be carried out after they have been examined thoroughly and approval is given (change control). Some changes, even require complete or partial repetition of the validation (revalidation). For certain changes a change request must be submitted to the authorisation authorities.