Validation (pharmaceutical technology)

The title of this article is ambiguous. Further meanings are listed under validation .

The validation provides documented evidence that a process or system fulfills the previously specified requirements (acceptance criteria) reproducibly in practical use. The US Food and Drug Safety Authority (FDA) defines validation as "the process by which, using specific laboratory test methods, it is demonstrated that the performance data of an analytical method are appropriate for its intended use" ((... ) the process of demonstrating, through the use of specific laboratory investigations, that the performance characteristics of an analytical method are suitable for its intented analytical use ).

The official GxP guidelines (Good x Practice, x = Laboratory, Clinical or Manufacturing, GLP , GCP , GMP ) require pharmaceutical companies to validate processes that have an impact on product quality, unless 100% control is implemented in the process.

Before starting the process validation , the following evidence must be available:

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

In the next step, the product requirements must be defined based on measurable acceptance criteria. This is usually done on the basis of the risk analysis and is described in a validation plan. Batches are then produced and checked against the acceptance criteria. The results are documented in a validation report, checked against the acceptance criteria, and if the process is fulfilled, the process can be described as valid.

Validation in pharmaceutical manufacturing

During validation in pharmaceutical production, tests are carried out on the end product to determine whether the process always achieves the intended result under the same conditions (e.g. temperature ). The validation must be carried out again for each new product (despite having the same or identical device). To be precise, it is at this step to process validation, as the validation as an umbrella term also includes the cleaning validation, method validation and qualification of technical systems.

For process validation, a process validation plan is created according to which the process validation is to be carried out. The plan must meet the regulatory requirements for the creation of validation plans (see EU GMP guidelines, FDA, PIC / S, etc.) and the methods proposed in it must conform to the relevant work instructions for validation. That this is the case is indicated by the manufacturer, e.g. B. Laboratory manager , head of quality control , head of production and quality assurance checked and approved by signature. For the (process) validation carried out according to this plan, a validation report is written after the implementation , which documents and evaluates the results and deviations (basically looks like the test report for the car inspection, only more extensive). Only validated methods and processes may be used to manufacture and test drugs that are intended for sale (placing on the market).

As part of the process validation, it must also be ensured that the devices used have been qualified and that reliable (reproducible) results can be guaranteed.

Validation of automated systems

The importance of computer-aided systems in pharmaceutical production is increasing. At the same time, the authorities and associations pay greater attention to the 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
• Production management level
  • Manufacturing Execution Systems (MES)
  • Laboratory information management systems (LIMS)
  • Production control systems
• Process control level
  • Process control systems
  • Analytical methods
  • Pharmacovigilance systems
• Calibration software
• Other applications in which relevant data is stored (e.g. also Excel spreadsheets, Access databases and other in-house developments)

Procedure for the validation of automated systems

The best-known model for the validation of computer-aided systems is the so-called V-model . The V-model of validation is described in the so-called GAMP guideline (Good Automated Manufacturing Practices). This GAMP guideline is not an official requirement from the authorities (as the name suggests), but a guideline developed by an interest group, which is often applied, but is only voluntary.

The Aide Mémoire 07121202 of the ZLG: "Monitoring computerized systems" describes how GMP inspectors can check the requirements of the GMP guidelines (EudraLex Vol. 4) - Annex 11 (en: Annex 11).

See also

• Food and Drug Administration
• GxP
• Qualification
• Procedural documentation

Web links

• Guideline on General Principles of Process Validation. FDA, May 1987, accessed June 13, 2009 . 
• http://www.ispe.org/gamp/ (ISPE): Good Automated Manufacturing Practices (GAMP) for the validation of computerized systems (no official document!)
• http://www.picscheme.org/ (PIC / S): Pharmaceutical Inspection Cooperation Scheme
• http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/homev4.htm (EU GMP guidelines, the most important work in Europe on the subject of GMP)
• https://www.gesetze-im-internet.de/amwhv/BJNR252310006.html : AMWHV §2 (Medicines and Active Substance Manufacturing Ordinance)

swell

1. ↑ Bioanalytical Method Validation (PDF; 65 kB) Food and Drug Administration . Retrieved March 30, 2010.
2. ↑ VOLUME 9A
3. ^ Aide Mémoire 07121202 of the ZLG: "Monitoring computerized systems". (PDF; 590 kB) (No longer available online.) Archived from the original on October 30, 2015 ; Retrieved August 6, 2013 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.