There has been a surge in the number of combination product (i.e. where a drug product is combined with a medical device) launches in recent years and this trend is set to continue as more companies seek to extend the life of existing branded medicines. According to analysts, the combination product market is currently worth 8 billion Euros and will grow by a staggering 40% during the next 3 years.

Combination of a drug with a medical device could allow medicines to be delivered locally and thus maximize therapeutic effect and minimize side effects. But many manufacturers — particularly in Europe — are not fully aware of the benefits that combination products offer.

After chairing a session at the recent Pharmapack meeting in Paris (France) about the regulatory framework and procedures for combination products in Europe, Yves Tillet, Director at White–Tillet Consultants & Experts, spoke exclusively to Pharmaceutical Technology Europe to provide further insight. According to him, many companies do not yet realize the opportunities presented by combination therapies.

“The firms have their projects — and in the largest companies these projects are still tuned towards the search for blockbusters. Companies are under the influence of a culture they cannot dismiss overnight; however, the landscape is changing little by little,” he said. “For the moment, there is little noise about combination products, but as soon as the firms see the dangers and opportunities, they will jump on them.”

This changing landscape is partly due to the arrival of generic products and new competitors with biologic products, cell therapy and gene therapy products, which may require the development of new medical devices. “Thanks to new medical devices, there will be a revolution; that of drugs placed in situ with much lower amounts, thus protecting targeted tissues, as well as the liver and the kidney,” said Tillet. “Pharmacology will be changed.”

Combination products clearly offer a lot of promise for the future, but many manufacturers in Europe still lack a thorough understanding of the European regulations that govern these products. Some companies may even have been manufacturing combination products, such as asthma inhalers, for a while without realising it. In Europe, a combination product can be either a drug or a medical device, but the rule is less clear for certain borderline products and different EU member states may have different positions. However, there are plans to form a European Commission committee that will comprise representatives from member states. This committee will, in the absence of a consensus, take a supranational decision.

“The regulation on combination products was born with the regulation on medical devices and, in particular, with the 93/42/CEE directive applied in 1998. Previously, drug delivery devices were very few and inadequately assessed (only according to pharmaceutical standards). The devices were an accessory to the drug — hardly better than an excipient,” Tillet explained.

However, medical devices have now been developed, the functions of which are assisted by drugs. In some instances, for drug eluting stents for example, the European Medicines Agency (EMA), has published guidelines to assess drugs that assist the stents in their functions, however Tillet also added: “But in another way, except for some isolated cases, little progress has been made in the field of drug delivery devices. We are at the beginning of innovative in situ drug delivery concepts using sophisticated medical devices. The regulatory framework and project assistance provided by registration agencies should favor the emergence of new combination products.”

So should we expect a massive overhaul of the European regulatory system? “The current regulation should not evolve so much in the future — at least in its current framework,” said Tillet. “Rather, I see the creation of many guidelines to frame and standardize the development of these new combination products, with major actions taken to provide information and training on their good use.”