For a good year now the 15^th supplementary guideline to the EC-GMP Guide (Annex 15) has been available in draft form (see GMP-News no. 54). The commentary on this draft was completed by spring of this year.

A very well-founded commentary of the PDA is explained below:

The main focus of the PDA is on the compatibility of Annex 15 with other bodies of regulations of the ICH regions (EU, USA, Japan) which also deal with the topic of validation.

The PDA also desires this compatibility for the document "Guidance on Process Validation" (CPMP/QWP/848/96/draft) issued by the CPMP (Committee for Proprietary Medicinal Products), the medicinal products specialty committee of the European regulatory authority EMEA (European Medicinal Evaluation Agency).

Furthermore, a stricter separation between validation aspects of pharmaceutical production and the manufacture of active pharmaceutical ingredients (ICH Q7a) is desired.

The desire for less regulation of details as regards process validation ("Process validation is a dynamic discipline requiring scientific judgement") is very well formulated.

It is also criticized that Annex 15 has a "tutorial tone". This is the result of the adoption of contents from the PIC/S document PR 1/99-1. This document primarily addresses inspectorates and not industry. For this reason it is desired that it be shortened in order to achieve comparability with the other supplementary guidelines.

Inconsistencies between individual terms within the document (text and definitions) are also criticized. The fact that performance qualification and process validation, which is not thoroughly accepted in industry, are treated as the same is given as an example of this.

ISPE (International Society of Pharmaceutical Engineers) has announced a new baseline on the topic of qualification entitled " Commissioning & Qualification Guide" for January 2001.

This document is to define key terms and enable a consistent and nevertheless flexible interpretation as regards a "designing, constructing, commissioning and qualifying of facilities, utilities and equipment".

This is therefore expressly a baseline which is neither a regulary nor seeks to replace any!

Nor is the topic of process validation dealt with within the baseline.

The document comprises 13 chapters

Source: ISPE Comissioning & Qualification Guide

Its philosophy is:

Placing premises and equipment into pharmaceutical use on the basis of Good Engineering Practice (GEP) supplemented by commissioning and, when needed, expanded by qualification. When needed means, it is only qualified if there is a direct influence on product quality (direct impact).

This "direct impact" should already been included in the calculations in order to be able to plan qualification work in good time.

The baseline understands GEP as applied engineering art according to the state of the art throughout the entire processing of the project in order to obtain an effective, cost-effective solution.

As a new term the baseline introduces "Enhanced Design Review". It is compared with Design Qualification as it is described in the draft of Annex 15. The term DQ was expressly avoided so as not to cause confusion with the design requirements of FDA as regards medical devices.

Under "commissioning" the baseline understands well-organized and documented engineering as regards "start-up" and "turnover" of premises, systems and equipment. Commissioning leads to a safe and function-oriented environment which meets the design specifications. Commissioning comprises the installation of equipment, adjustment work and test runs. It forms the basis for the installation and operational qualification and should also be laid down in a plan.

For the qualification work the baseline requires the active participation of quality assurance, a structured procedure supported by a corresponding (extensive) documentation and a change control system. The qualification is based on "Qualification Rationales".

The V-model already familiar from computer validation is now also used for "Direct Impact Systems", and therefore PQ is also integrated:

Source: ISPE Comissioning & Qualification Guide

Quality assurance is accorded a far greater role that has hitherto been the case. It is to be incorporated into new projects already at a very early stage in order to verify what qualification work is necessary and how this can be performed within commissioning. This saves double work and reduces the time input.

Within the framework of the further training series "Good Validation Practices" we will also inform you about current developments in the field of validation/qualification in the coming year, too.

Sources:
PDA Letter, April 2000
Pharmaceutical Engineering, May/June 2000
European Pharmaceutical Review, Vol 5 Issue 1, Spring 2000