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The pharmacopoeia The handbook of medicinal product quality

The task of Swissmedic is to ensure that only high-quality, safe and effective therapeutic products are placed on the market. The pharmacopoeia, which contains binding quality regulations, plays a major role in this undertaking. In Switzerland, the pharmacopoeia comprises both a European and a Swiss volume. As head of the Pharmacopoeia Department, Tobias Gosdschan is responsible for this area. From June 2016 to June 2019 he had the great honour of chairing the European Pharmacopoeia Commission.

Pharmacopoea Helvetica and Pharmacopoea Europaea — Photos and films recorded at the University of Basel’s pharmacy museum.

A joint undertaking

The pharmacopoeia is a compendium of regulations relating to the quality of medicinal products. Its provisions are of a binding nature and have legal force. They apply to all medicinal products placed on the market in Switzerland. The objective is to create uniform framework conditions in terms of quality, and to thereby provide all patients with medicinal products of the same high quality. In this country the pharmacopoeia consists of the Swiss volume (Pharmacopoea Helvetica, Ph. Helv.) and the European volume (Pharmacopoeia Europaea, Ph. Eur.). The latter contains more than 2000 regulatory texts known as “monographs”. These describe the requirements that have to be met by active substances, pharmaceutical excipients, dosage forms, medicinal plants, vaccines, blood products and homeopathic preparations. The national pharmacopoeia, the Ph. Helv., contains roughly 110 monographs and supplements the Ph. Eur. with regulatory texts in areas not covered by the Ph. Eur. This is of particular significance for medicinal products that are only distributed on the national market. “Or for medicinal products that do not require authorisation and are produced by pharmacies for their own customers. These are known as extemporaneous preparations,” Gosdschan explains. The electronic version of the Ph. Helv. introduced in 2012 has been available online free of charge since 1 July 2019 ((link to e-version)) – the print version is now available only as an additional service.

“The outcome can be fatal if the product doesn’t actually contain what’s on the label.”

The European Pharmacopoeia enters into force simultaneously in 39 Member States and in the EU as an organisation. It is produced under the direction of the Council of Europe. A number of non-European countries and national authorities and international governmental organisations such as the World Health Organisation (WHO) are also interested in collaborating on this publication and have acquired observer status. There is also a move to standardise the pharmacopoeial requirements worldwide. Alongside the European volume, the American and Japanese pharmacopoeias are also important compilations. “It’s no easy task to harmonise these. Primarily because of the different authorisation situations, which are the result of historical developments. Nonetheless, strenuous efforts are being made to bring them closer together – although it will probably be quite a while before a pharmacopoeia applicable to the whole world is published,” explains Tobias Gosdschan, head of the Pharmacopoeia Department at Swissmedic.

The mission

The pharmacopoeia ensures the quality of medicinal products. These and pharmaceutical excipients are analysed using the three test elements identification, purity and assay. “The identification test examines whether the product actually contains what the label says. This is essential for infusion solutions, for example, in which concentrated solutions of medicinal products are often added to a carrier solution. If the composition of one of these solutions is not correct, this can have a fatal outcome,” Gosdschan explains. The purity test is performed to evaluate the purity profile of the product and to exclude the possibility that products might contain a high level of impurities. Some impurities can be harmful even in trace quantities. The test methods and analytical techniques need to be very precise in order to identify the tiniest quantities. “For example, when analysing nitrosamines the aim is to identify 30 parts per billion, which is 30 millilitres in 1 million litres or 1 millilitre in a road tanker containing 33,000 litres – an incredibly small amount,” Tobias Gosdschan says. And finally, the assay establishes whether the declared amount of active substance is present. This is important so that a medicinal product can be dosed correctly. “If the content is too low, the dose needed to produce the desired effect may not be reached.” In the case of anti-infective medications, antibiotics for example, this leads to a risk of the pathogens that need to be eliminated becoming increasingly resistant,” Gosdschan says. A content that is too high is also dangerous because this may lead to adverse effects or, in a worst case scenario, poisoning. These three test elements together demonstrate the quality of the product and are the patients’ guarantee that the medicinal products used are safe and effective.

The Chair of the European Pharmacopoeia

The European Pharmacopoeia was established in 1964 with Switzerland as one of eight founding countries. The European Directorate for the Quality of Medicines (EDQM) is responsible for drawing it up and keeping it updated. This body acts as the secretariat of the European Pharmacopoeia Commission with its 60 groups of experts and working parties. Tobias Gosdschan is head of the Swiss delegation, which was nominated by the Federal Council at the suggestion of Swissmedic. The delegation comprises three main members and up to three alternates. The Commission elects a new Presidium every three years. Tobias Gosdschan was initially appointed Vice-Chair from 2013 to 2016, and subsequently became the first Swiss Chair from 2016 to 2019 – a tremendous honour. “I was naturally very proud after the election. In addition to the personal recognition, it was also the result of decades of outstanding Swiss contributions to the European Pharmacopoeia,” he adds. “I really enjoyed the three years in this role, even if it was pretty demanding at times,” is how he summarises his time as Chair of the Commission. The Commission takes decisions by consensus; otherwise they are not valid. “It was a real challenge to get all the members on board in some cases. The debates produced some strongly contrasting opinions. But my Swiss mentality – one that always seeks to find a compromise – enabled me to keep the opposing factions talking and thus to find solutions,” summarises Tobias Gosdschan with satisfaction.

“If the content is too low, the dose needed to produce the desired effect may not be reached.”

Committee work in times of covid-19

Tobias Gosdschan and his eight-strong team look after a network of around 130 experts. Since the coronavirus pandemic broke out, the expert committees have been meeting in video conferences. “It’s basically working pretty well. What’s missing, of course, is the informal part. In many cases it’s very important to be able to talk to people directly if you’re trying to find a solution, and we can’t do that now,” Gosdschan says. The EDQM organises informal conference calls with the national pharmacopoeia authorities, for example, in an effort to compensate for this. These were initially held on a weekly basis and now take place once a month. But Gosdschan and his team hope they can go back to meeting in person in the foreseeable future and talk to people directly again. However they meet, though, the daily effort that goes into ensuring the quality of medicinal products continues unabated.