Validation (drug manufacture)

Validation of the documented evidence is provided that a process or system meets the previously specified requirements ( acceptance criteria) reproducible in practice. The U.S. Agency for Food and Drug Administration ( FDA) defines validation as " the process by means of which, is provided using specific laboratory test methods to prove that the performance of an analytical method are appropriate to their intended use " ( ( ... ) the process of demonstrating, through the use of specific laboratory investigations, did the performance characteristics of an analytical method are suitable for its intented analytical use).

In the regulatory GxP guidelines (Good x Practice, x = Laboratory, Clinical and Manufacturing, GLP, GCP, GMP ) requires that pharmaceutical companies validate processes with impact on product quality, if not 100% control is implemented in the process.

Before starting the process validation, the following must be present:

  • Qualification of systems and equipment
  • Method validation
  • Cleaning Validation
  • Computer software validation (CSV)
  • Risk analysis of the process

In the next step, the product requirements shall be determined on the basis of measurable acceptance criteria. This is usually done on the basis of risk analysis and is described in a validation plan. Then batches are produced and checked against the acceptance criteria. In a validation report documenting the results, check against the acceptance criteria carried out, and in the case of the fulfillment of the process can be described as valid.

Validation in pharmaceutical manufacturing

The validation in the pharmaceutical preparation is tested on the final product, if the process under the same conditions always achieved ( eg temperature) the intended result. The validation must be for each new product (despite baugleichem or the same device ) carried out again. To be exact, it is at this step to the process validation, because validation as an umbrella term also includes the cleaning validation, method validation and qualification of technical systems.

For process validation is a process validation plan is drawn up after the validation process is carried out. The plan must meet the regulatory requirements for the creation of validation plans meet (see the EU GMP Guide, FDA, PIC / S, etc. ) and its proposed methods must be in compliance with appropriate work instructions for validation. That this is the case, line quality control, production management and quality assurance by the manufacturer, such as laboratory director, reviewed and approved by signature. For the performed according to this plan (process) validation after performing a validation report is written, documenting the results and deviations and rated (looks in principle like the report at the car inspection, only extensive ). Only validated methods and processes may be used for the manufacture and testing of medicinal products which are intended for sale ( placing on the market ).

As part of the validation process is necessary to ensure that the equipment used have been qualified, and to guarantee safe ( reproducible ) results.

Validation of automated systems

The importance of computer systems in the pharmaceutical production is increasing more and more. At the same time authorities and associations take care with increased attention to relevant regulations and guidelines that cover the requirements for systems.

The following systems must be validated:

  • Corporate management level: ERP systems
  • Document Management Systems
  • Archiving systems
  • Manufacturing Execution Systems ( MES)
  • Laboratory Information Management Systems ( LIMS)
  • Production control systems
  • Process Control Systems
  • Analysis methods
  • Pharmacovigilance

Procedure for Validation of Automated Systems

The best-known model for the validation of computerized systems is the so-called V- model. The V-model validation is described among others in the so-called GAMP Directive ( Good Automated Manufacturing Practices). This GAMP Directive is not an official request by the authorities (as the name suggests ), but one of a interest group developed policy which, though frequently used, however, is only voluntary.

The Aide Mémoire 07121202 ZLG: "Monitoring of computer-based systems " describes how GMP inspectors with the GMP Guide ( EudraLex Vol 4 ) - Annex 11 ( en: Annex 11) can check.

Good Laboratory Practice Good Clinical Practice Good Manufacturing Practice
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