EDQM / Codema
consultation for commonly agreed hazard classifications of medicinal drugs
The CLP Regulation (Regulation EC No 1272/2008 on classification, labelling and packaging of substances and mixtures) requires the hazard re-classification of all chemical substances produced or imported into the EU, according to revised standards which are derived from the GHS (Globally Harmonised System). The CLP Regulation came into force on 20 January 2009 and is also applicable to active pharmaceutical ingredients, auxiliary ingredients (excipients) and their mixtures. Only medicinal products in their final form, intended for the final user (the patient), are exempt.
If you wish to place an active pharmaceutical ingredient (API) and/or an excipient alone or in a mixture on the market then it needs first to be classified, labelled and packaged in accordance with this regulation. The mere act of import into the EU is already considered as placing on the market, as is production for another pharmacy, even if you supply free of charge.
Requirement for notification and joint agreement on classification
One of the first duties put upon producers and importers of the active ingredients and excipients was a notification of the revised classifications to ECHA, the EU agency responsible for REACH and CLP, with as deadline 3 January 2011. In addition, according to article 41 of the CLP Regulation all stakeholders in a particular chemical substance need to discuss and decide on a commonly agreed classification.
EDQM (the European organisation responsible for the European Pharmacopoeia, part of the Council of Europe, and issuing all reference standards) has started these discussions by initiating a consultation based on proposed classifications for over 2000 different substances.
In collaboration with EDQM, Codema (www.codema-db.net), a database and communication platform for anyone concerned with API’s, facilitates these discussions by having made available the classifications as proposed by the EDQM in a more digestible way and by giving the opportunity for a discussion per individual substance in a separate and confidential SIEF-like environment. This initiative is intended to support, assist and widen the consultation as initiated by EDQM. The outcome of the discussions will be made available in the form of commonly agreed safety data sheets.
Although EDQM has put in every effort to make the proposed classifications as reliable as possible by searching for all publicly available data, they found this in a great many of cases insufficient. The information used by the EDQM for classification is incomplete, especially for synthesis by-products, degradation products and other impurities, as well as API’s for well-established use. The EDQM has no facilities to carry out any actual (eco) toxicological testing. It is hoped for that the consultation as carried out by EDQM and Codema will fill some of these data gaps, since many of these substances are no longer produced inside the EU while it is unclear whether the not publicly available information in (old) registration dossiers contains any of the needed information.
A correct classification is the corner stone of the safe use of any chemical, let alone medicinal drugs, and the continued existence of these data gaps is deemed unacceptable by the authorities.
In its Resolution of 19 January 2011 on the quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients, the Council of Europe calls for a safe, well documented and harmonised preparation of medicinal products in pharmacies which is currently lacking. Correct classifications are the basis for exposure estimations, risk assessments and the risk management measures and operational conditions to contain these risks.
While these may be well established inside the regular pharmaceutical industry, such is not necessarily the case in the production of generics, in (hospital) pharmacies and in health care establishments where workers and professionals are daily exposed when preparing and handling medicines. The REACH Regulation (Regulation EC No 1907/2006) would have covered this omission, were it not that medicinal drugs and their excipients are exempt from the relevant clauses. The CLP Regulation now effectively puts the responsibility for filling these safety gaps in the hands of importers of API’s.
The use of the Codema platform is free of charge for importers, distributors and producers. It is recommended by the Fecc and its national associations, since it gives you an excellent opportunity to meet the requirements of the CLP Regulation in a simple, efficient and inexpensive way.