Harmonization process

Any proposal for harmonization must be presented for public comment in each of the pharmacopeial journals, Phar-meuropa (EP), Japanese Pharmacopoeial Forum (JP), and Pharmacopeial Forum (USP). This was accomplished early in 2003 (21-23). Comments were collated and further PDG discussions conducted. Any agreement will be presented again, prior to implementation. The PDG harmonization process can be found as General Information Chapter < 1196 > in USP 27 (24). 

As a result of the pharmacopoeial harmonization process, general chapter 2.2.47. of the Ph.Eur. and general chapter 8 of the JP (Capillary Electrophoresis) and general chapter < 1047) of the USP (Biotechnology-Derived Articles — Tests, Capillary Electrophoresis ) have been harmonized to a major extent. At present some minor differences exist between the text and a few equations in the pharmacopoeia. In these chapters, the following definition of CE is given ... 

Implementation of the recommendations led to a change in configuration of the membership in the pharmacopeial harmonization process. Whereas the British Pharmacopoeia had been an independent member of the Quadripartite Group from its inception, implementation of harmonization of standards and tests for excipient was... 

In all, 61 excipient monographs and some general chapters (Table 2) are in various stages of the seven-stage harmonization process that are described below. 

The corresponding secretariats may have to add information essential to the understanding of the implementation of the texts (e.g., the description of an analytical procedure or of reagents that do not exist in the pharmacopeia) and a translation is added by the European and Japanese Pharmacopoeias. The style may be adapted to that of the pharmacopeia concerned or global style may be used. A pharmacopeia can add text, either to amplify some of the requirements with additional information or because national requirements and compendial policy dictate that the addition is necessary. However, there must be a clear indication that this additional information is not part of the harmonized document. This will avoid additional text being included after the harmonization process is completed, but will allow interested parties to review a complete text. The three pharmacopeias endeavor to publish the drafts simultaneously or as close together as possible. 

A ninth chapter, guest-authored by Carl A. Rockburne, a retired Canadian trade console and regulatory consultant, compares the FDA process with those in Canada, the European Union, Japan, and Australia, the four other major regulatory environments. Fie has included FDA documents describing the regulatory harmonization process in his chapter. 

Harmonization of regulatory requirements was pioneered by the European Community (now the European Union) in the 1980s, as it moved towards the development of a single market for pharmaceuticals. The success achieved in Europe demonstrated that harmonization was feasible. The harmonization process was then extended to include Japan and the United States. The ICH was formed from a government body and an industry association from each of these regions. These bodies and associations as listed by Molzon (2006) are ... 

As a consequence of EU Directive 78/142/EEC, which introduced a limitation of vinyl chloride monomer both as residual amount in final articles (QM lmg/kg) intended to come into contact with foodstuffs and in migration to food (SML not detectable LOD 0.01 mg/kg), the corresponding necessary analytical methods were developed between several European expert laboratories and laid down as agreed methods in EU Directives 80/766/EEC and 81/432/EEC, respectively. This piece of the EU harmonization process was too time- and work-consuming to continue in this way. The vinyl chloride Directives therefore remain a unique feature in EU food packaging legislation since this was found to be impractical for generalization. 

All the above-mentioned legal treatises apply to the European Economic Area (EEA this comprises the 27 EU member states plus Liechtenstein, Iceland, and Norway—Switzerland chose by referendum not to join the EEA, but has certain Swiss-EU bilateral agreements). Switzerland acts as the representative of the European Free Trade Association, which is an observer in the ICH (International Conference on Harmonization) process, accepts ICH guidelines, but is not part of the European Economic Area. There is a legal obligation for the Swiss competent authority, Swiss Agency for Therapeutic Products (Swissmedic), to take account of decisions/authorizations in other territories that have equivalent medicinal product control. 

This mandate was later analysed and refined in the harmonization process to identify the parameters of the GHS. As a result, the following clarification was adopted by the Interorganization Programme for the Sound Management of Chemicals (lOMC) Coordinating Group to ensure that participants were aware of the scope of the effort ... 

The ICH was very valuable in harmonizing terms and definitions as well as basic requirements for analytical validation. Of course, due to the nature of the harmonization process, there are some compromises and inconsistencies, but the importance of a proper validation is currently widely known and accepted. In Table 1, the required validation characteristics for the various types of analytical procedures are shown. In the following, the main ICH requirements for the validation characteristics are summarized. However, the ICH guidelines must not be regarded as a checklist. It is the responsibility of the applicant to choose the validation procedure and protocol most suitable for their product. ... 

The harmonization process is just beginning and is a major step in the right direction. 

The harmonization process affected all levels of drug handling, and thus has put strict requirements on the preparation and use of radioactive drugs in hospital facilities. The transition period may be characterized as a major communicative effort between European institutions in order to exchange scientific knowledge and gain practical experience for the implementation of GMP standards for the preparation of " Tc pharmaceuticals (Directive 91/356/EEC). 

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