The draft EU general pharmaceutical legislation (GPL) released in April 2023 shows promise for improving the ability to bring combination products to market in Europe, experts said at the 2024 Combinations Products in the EU Summit jointly held by DIA and the Regulatory Affairs Professionals Society (RAPS).
The draft legislation has six key political objectives, according to Lilia Luchianov, policy officer at the European Commission Directorate General for Health and Food Safety (DG-SANTE). It aims to eliminate single market access, ensure the availability and security of the supply chain, improve affordability, create a competitive regulatory framework, support environmental sustainability and combat antimicrobial resistance.
It also provides pre-authorization support for promising medicines to speed development and improve investment in the European medicinal products industry.
Notably, it clarifies the interplay between other EU legislative frameworks, including those for medical devices and substances of human origin, Luchianov said. “This is where we talk about combination products because that was one of the areas where we really had to look closer and to see what can be done to improve the situation.”
For combination products, existing pharmaceutical legislation “has not been fully able to accommodate emerging technologies and developments,” she added. In developing the draft legislation, they saw a need to improve clarity and coordination for all stakeholders further. They also sought to “future-proof” the draft legislation by providing leeway to address innovation and development as it happens.
Under the draft GPL, combination products fall into three categories. Category I includes the integral combination of a medicinal product with a medical device, which mirrors the current classification under the EU Medical Device Regulation (MDR). Marketing authorization applications (MAA) would be submitted to the competent authority to assess the safety, efficacy and benefit-risk balance of the integral combination, while a notified body would assess the device component’s compliance with MDR’s general safety and performance requirements.
“It’s important to note that the actor for these products is the marketing authorization holder of the medicinal product,” Luchianov said. “That person will then have to contact his or her counterpart from the medical device area and have the documentation at his or her disposal to submit to the authorities. We do not want multiple chains of information – we want this channel to be very precise and concise.”
Category II includes medicinal products exclusively used with a medical device; these combination products are generally referred to as a co-packaged product currently. For these products, manufacturers would need to provide data on the safe and effective use of the medicinal product with the medical device but may or may not need to provide additional benefit-risk information. A notified body would assess the device component.
Category III included medicinal products combined with a product other than a medical device (software and similar) and intended to be used in combination, according to the summary of product characteristics (SmPC). Similar to Category II, products in Category III may or may not need additional benefit-risk information, considering the use of the medicinal product with the other product.
“This is the futuristic category,” Luchianov said and could include software, artificial intelligence, food, clothing, or something not categorized as a medical device. “We didn’t want to restrict ourselves.”
Another provision included to support marketing authorization applicants changes how and where they can get scientific advice before submission. Under the GPL, EMA can consult experts with the Member States that have medical device expertise if needed, Luchianov said. Manufacturers can also request parallel scientific advice from EMA and expert panels referred to under MDR. For parallel advice, the draft legislation calls for information exchange between the respective authorities or bodies, synchronized timing, and attention to keeping separation between each respective remit.
“It’s really encouraging to see provisions within the proposed legislation that provide much more opportunity for the dialog, to provide the right expertise at the right time, certainly early enough to influence the development process,” according to panelist Tim Chesworth, senior director of devices and digital therapeutics regulatory affairs at AstraZeneca. “The ultimate goal is that European patients are able to experience the benefit of the transformative potential of modern medical technology and have prompt access to innovative medicines.”
He highlighted the potential for new or revised guidance to support the development of combination products in Europe, especially in light of the draft GPL.
“What we hope to see is the variations guideline aligned to the revisions of the GPL and also to incorporate the provisions of ICH Q12,” said Chesworth, who also serves as chair of the medical device regulatory group at EFPIA, the European pharmaceutical trade association. EFPIA identified combination products as a key area to address in the draft GPL. “It’s very important to us as an industry.”
He added, “it is important to point out that combination products are specifically called out in the provisions of Q12.” He added that the Q12 expert working group is developing training materials with specific examples on combination products.
“We hope that [work on the draft GPL] this year will provide the opportunity to bring about that actual, genuine convergence, that underpinning of the legal definition of combination products,” he said. “The reason we do what we do is to benefit patients – and patients don’t worry about any of this stuff. What matters is we are providing a regulatory framework that brings therapies to ultimately benefit European patients.”
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