GMP Compliance Adviser Update No. 8/2019

With this GMP Compliance Adviser UPDATE you have direct access to all prime regulatory changes and to our GMP expert interpretations. Here are the new features at a glance:


GMP in Practice

Chapter 5
Pharmaceutical Water

5.A Water qualities
5.B Pharmaceutical Water Generation

GMP Regulations

Chapter C
EU Directives and Guidelines

C.10.1 Regulation (EU) 2017/745 of the European Parliament and of the Council (EU MDR)

Chapter H
WHO Guidelines

H.19.2 WHO: Guidelines on heating, vantilation and air-conditioning systems for non-sterile pharmaceutical products (Technical Report Series, No. 1019, 2019, Annex 2)

GMP in Practice

Chapter 5.A Water Qualities

The European Pharmacopoeia (Ph. Eur.) and the American Pharmacopoeia (USP) describe requirements for Purified Water (PW) and Water for Injection (WFI). In addition, both pharmacopoeias describe further water qualities for special purposes.

Since the European Pharmacopoeia now also permits the use of membrane systems for the production of WFI, the water quality Highly Purified Water (HPW) was eliminated in supplement 9.7. Due to the fact that HPW can still be found in various approval documents for drugs, this water quality is likely to be used in practice for even longer. In addition, there is still a need for discussion in industry as to how WFI can be produced exactly using cold processes. The regulatory situation is not clear.

The quality of each type of water must be proven by a number of tests described in the monographs. Physical-chemical tests include the determination of conductivity, tests for certain ions and the determination of TOC. Microbiological monitoring is required for all water qualities.

There is no monograph for pharmaceutical steam in the European Pharmacopoeia. In contrast, the USP contains a monograph on Pure Steam. (Herbert Bendlin, PhD, Fritz Röder)

Chapter 5.B Pharmaceutical Water Generation

When generating pharmaceutical water, drinking water is pre-treated to remove substances that are not desired during further processing. The pre-treatment processes include filtration, chemical stabilisation, UV irradiation and softening of the water using ion exchange. The processes that are used depend on the initial quality of the feed -water. This is determined by water analysis.

To produce Purified Water, different processes are combined in so-called treatment plants. Reverse osmosis is widely used to produce Purified Water and is often combined with electro-deionisation.

Purified Water is the starting product for generating Water for Injections (WFI). For WFI, distillation was for a long time the sole method of production. Since April 2017, the new EP monograph has applied to WFI, which also permits the production using membrane technology. As a result of this change, the monograph for Highly Purified Water (HPW) was removed from the European Pharmacopoeia in April 2019. The advantages and possible risks of cold WFI production using membrane technology are discussed in detail.

The functionality and potential application of different technologies such as ion exchange, reverse osmosis, electro-deionisation, ultrafiltration and the various technologies used during distillation are described in detail and evaluated based on their advantages and disadvantages. (Herbert Bendlin, PhD, Fritz Röder)

GMP Regulations

Chapter C: EU Directives and Guidelines

C.10.1 Regulation (EU) 2017/745 of the European Parliament and of the Council (EU MDR)
(including Corrigendum 15409/1/18 REV 1 and Corrigendum 13081/19 of the Council of the EU)

On 25 November 2019, the European Commission published the second corrigendum 13081/19 to the EU Medical Devices Regulation (MDR). The corrections mainly concern Class I medical devices. The timetable for these products will be extended to 26 May 2024. This provides additional four years for manufacturers of Class I devices to meet MDR requirements.

Changes and additions were also made to the following sections:

  • Article 78(8), Article 84, Article 88(1), Article 120(8), Article 122
  • Annex I and Annex III.

Chapter H: WHO Guidelines

H.19.2 WHO: Guidelines on heating, ventilation and air-conditioning systems for non-sterile pharmaceutical products

This document represents Part 2 of the guidelines for HVAC systems. It contains non-binding examples, drawings, technical representations and interpretation in support of Part 1 of the HVAC systems guidelines (chapter H.19.1). It is intended to be a basic and explanatory guide for use by pharmaceutical manufacturers and GMP inspectors. It is not intended to be prescriptive in specifying requirements and design parameters. It rather aims to facilitate a harmonized understanding of expectations for HVAC systems of non-sterile products.

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