Committee on Industry, Research and Energy
Chaired by Teodor-Cristian Borcan (RO)
Topic Pitch
Even though nanomedicine seems to be the next step in the advancement of medicine, being able to aid in the early-stage diagnosis, targeted treatment and even targeted release of medication, it is slowed down by a set of different challenges. Because of the field’s novelty, the data surrounding nanoparticles is still relatively scarce, preventing researchers from accurately predicting the properties of compounds under particular circumstances. Moreover, the legislation surrounding nanomedicine is still vague and somewhat lacking. This is because of nanoparticles’ complexity and the wide array of forms they can take. All in all, the great potential of nanomedicine seems to remain partly untapped because of over-cautious approaches and lacking data, despite efforts being made to alleviate this situation and further deepen research and our current understanding of the field.
Key learnings
- Progress in nanomedicine is slowed down by vague legislation.
- Market authorisations differ between Member States, creating discrepancies in the criteria and standards that need to be met.
- There is still not enough data for assumptions to be accurately made regarding the behaviour of some nanomedicines in vivo.
- Nanomedicine shows great promise in improving patient care standards, paving the way towards personalised medicine.
- Nanomedical approaches might provide cures or therapeutical alternatives for previously incurable diseases and syndromes.
The Present
Case Study
Sinerem, a contrast agent for magnetic resonance imaging (MRI), was declined a recommendation for marketing authorisation and was withdrawn from the market in 2008 by the European Medicines Agency (EMA) due to concerns raised in clinical trials. However, this over-cautious approach appears to be affecting the field, often the standards required for approval are still vague and resemble the regulation for small drug molecules which do not accurately reflect the nanomaterials’ potential and properties.
Abstract
This example shows how critical guidance is in the field of nanomedicine because its lack leaves manufacturers, the general public, and policymakers with little to no clarity and legal certainty. Despite showing great promise in terms of progress and improving standards for patient care and early-stage diagnosis, nanomedicine still seems to be hindered by vague and not-fit-for-purpose legislation. Furthermore, because it is such a novel field of study, the data regarding nanomaterials and nanomedicines is also scarce. This slows down the translation from labs and clinical trials to actual market commercialisation.
Stakeholders/Key Actors
European Commission
The EC is the executive branch of the EU. The Commission helps to shape the EU’s overall strategy, proposes new EU laws and policies, monitors their implementation and manages the EU budget. More precisely, the European Commission is responsible for the main pieces of legislation regarding research and some aspects of public health, areas which this topic falls under, while still maintaining a close collaboration with Member States, since the competences in these areas are shared.
Member States
As previously mentioned, research and some aspects of public health fall under the category of shared competences. This means that Member States also play a major role in legislation. Furthermore, because the approval of certain products can be given through a decentralised procedure, Member States are responsible for the assessment of the submitted applications. It is thus implied that the assessment of the product’s performance and all other parameters specified in the existing binding legislation must be done independently by Member States.
European Medicines Agency
EMA is an agency that evaluates and monitors medicines in the EU. It conducts research and uses the results to provide reliable information accessible to everyone. In the case of nanomedicine, EMA is responsible for the evaluation of marketing authorisation applications. The results of its experiments provide the base for the centralised authorisation of nanomedicine in the EU market. Moreover, EMA publishes scientific guidelines to help companies prepare their applications for the authorisation procedure.
Joint Research Centre
The JRC is the European Commission’s service for science. It works by employing experts to conduct research and experiments whose results are used to back EU policies. Its actions in public health that fit within the scope of this topic include human biomonitoring and research of health technologies. The JRC is one of the data hubs for nanomedicine as the results of its experiments can be used to alleviate the current lack of data.
Nanotechnology Industries Association
The NIA supports the development of the nanotechnology sector by uniting companies, as well as research centres, universities, and other support organisations. One of the ways it does this is through the creation of partnership opportunities between its members, allowing for shared progress and efficient collaboration. Furthermore, it provides industry insights to policymakers and regulators to help create a better, more reliable regulatory environment.
Legal Framework
Measures regarding all types of medication and medical products
These pieces of legislation fall behind in that they include nothing specific about nanomedicine. This is because, at the time of their publishing, this field had only begun to emerge. Despite not being precise in the case of nanopharmaceuticals, these measures play a role in their development, since their placement on the market is subject to these terms.
Directive 2001/83/EC establishes the standards a medicine must meet for market approval. Article 24 mentions the duration of authorisation, namely 5 years, with the possibility of renewing it for another 5 years. The conditions for which a product is refused authorisation are: if it is proven to be harmful under the recommended conditions, if its efficiency is insufficient or if its composition does not correspond with the declared one.
Regulation 2004/726/EC adds to the requirements mentioned in the Directive, including that the clinical trials carried out to obtain results for the application should be done respecting the standards of good clinical practice and that they meet ethical demands and that any changes in the manufacturing process and composition of the product have to be included into an application and be approved before they can be implemented. Furthermore, this regulation established the EMA and all of its attributions and committees, ensuring more efficient supervision and coordination of the EU medicine market.
Measures regarding nanomedicines
These measures are more specific to nanomedicines because they take into account the notable differences between them and all other types of medicines. These pieces of legislation regulate nanomedicines on risk/benefit-analysis principles.
The Commission’s recommendation on the definition of nanomaterial 2011 gave a definition for nanomaterials and aimed to help harmonise the legislation and progress that would follow. However, because of the rather vague and broad scope given by this definition, it has proved not to be as effective. Moreover, because it is a recommendation, it is not legally binding, rather coming as a suggestion and aid.
The Commission’s Regulation (EU) 2018/1881 came as an amendment to the already existing REACH regulation that concerned the registration, evaluation, authorisation and restriction of chemicals. This amendment includes so-called nanoforms of chemicals in its scope. In the context of this regulation, nanoforms can be thought of as just nanomaterials. Furthermore, it also details many of the needed parameters of the nanoforms, as well as the quality standards by which they must abide.
The Future
Key Challenges
Lack of a centralised approval procedure
Currently, there are two ways that can lead to the approval of a new nanomedical product: centralised and decentralised. In the centralised pathway, EMA conducts its own studies, after which the European Commission approves market authorisation. The de-centralised process, however, occurs individually in the Member States. This de-centralised approach leads to an inconsistent evaluation and authorisation of nanomedicines. Furthermore, because nanomedicines are borderline products, meaning they do not easily fit into regulatory pathways1, their classification can be interpreted differently by different Member States, thus increasing the discrepancies in evaluation and approval2.
Lack of a unified definition or classification of nanomedicines/ nanomaterials
The European Commission currently defines nanomaterials as materials that contain more than 50% particles with sizes ranging from 1 to 100 nm. This definition, however, is part of a recommendation and is thus not legally binding. The lack of a unified definition for nanomedicines/nanomaterials is also one of the factors that hinder their further development3 and proper implementation. Because of their versatile nature, definitions and guidance must be made for different classes of nanomedicines. A lack of consistency across states can hinder market approval and conditions that need to be met by the specific product. Therefore, the specific safety and efficacy standards it must pass to be on the market will differ and some countries will be able to use a nanomedicine that may not have passed regulatory standards in another country.
Lack of data
The lack of data regarding nanomaterials has been identified as a key issue in risk assessment by the Organisation for Economic Co-operation and Development (OECD). Due to their novelty4, the negative side effects of nanomedicines might not be fully understood. Nanoparticles can enter the human body and interact with it through an array of processes like inhalation, absorption and metabolisation. In time, they can accumulate and lead to negative side effects. This is a real issue because not much is known about how long nanoparticles stay in a specific location (cell, tissue or organ) before being excreted. Despite the increasing number of in vitro and in vivo experiments being carried out, the data is still lacking to fully assess the risk of using certain nanomedicines. Furthermore, the reliability of the experimental data heavily depends on the conditions under which the nanomedicine was tested. This can distort results in either favourable or unfavourable directions. However, despite this uncertainty and lack of knowledge, nanomedicine has shown great promise for revolutionising the way patient care and treatment are tackled. Nanomedicine approaches have helped researchers gain valuable insights5 into the mechanisms behind Alzheimer’s disease, various types of cancer or infectious diseases such as Ebola and malaria.
Measures Ahead
The European Commission has set up an initiative to review the EU pharmaceutical strategy, taking into account the lessons learnt from the recent Covid-19 pandemic. This revision aims to encourage and support further innovation in the field, and nanomedicine is one of the critical areas of interest, while also adapting to new developments in science. The public consultation period of this initiative ended in December 2021 and the Commission adoption is scheduled for the fourth quarter of 2022. This may be beneficial for the progress of nanomedicine, considering its major contribution to the development of Covid-19 vaccines as this can put it in the spotlight for global innovation and improvement. Another initiative meant to encourage and support research in the EU is Horizon 2020 which funded projects carrying out cutting-edge research, such as:
- The REFINE Nanomed project aims to create a consortium to help in the advancement of biomaterials and nanomedicines by gathering representatives from all stakeholder categories. Furthermore, one of its objectives is to improve the standardisation of regulations at a European level.
- The European Nanomedicine Characterization Laboratory (EU-NCL) is also a project whose aim is to carry out experiments to characterise nanoparticles for medical applications. This is meant to aid companies to improve their nanomedicine products before submitting their application for market authorisation.
Tech Corner
But what is nanomedicine and why do we care so much about it?
Nanomedicine is the medical application of nanotechnology. It paves the way towards personalised medicine, specific for each of us and may even reduce the frequency of certain medical procedures or traditional medication. The prefix nano- refers to a billionth of a meter or a millionth of a millimetre, therefore, nanoparticles have at least one dimension in the range of 1-100 nm. This size gives them unique properties and abilities to interact with our bodies in unprecedented ways. The following image shows a comparative scale of the nanoparticle size.
In vivo versus in vitro
Throughout this Topic Overview and during your own research regarding this topic, you might come across the terms in vitro and in vivo. But what do they mean and what do they tell us about the way the experiment was conducted? Firstly, both terms come from Latin and mean “in glass” and “in the living”, respectively. As the names suggest, in vivo experiments aim to replicate the real conditions that the nanomedicine would act in: either within a cell, a tissue, or an organ. However, before the nanomedicine can be tested in the complex environment that is a living organism, its properties and mechanism of action must be thoroughly studied. This is typically done through in vitro testing. In vitro experiments are carried out on isolated cells or tissues. These do not reflect the complexity of the real environment, but rather highlight one or more of its conditions.
Useful Links
Further Questions
- Is there anything similar to nanomedicines in the medicine market of the EU? If so, can its approval methodology be used as a model?
- How do you think Member States can collaborate to minimise the discrepancies in the approval procedures?
- Why do you think the legislation seems to be so much slower than the progress of research on nanomedicine?
- What else do you think contributes to the lack of data regarding nanomedicine? What about nanomedicines makes it so hard to study them and how can this be tackled in the future?
- Why is nanomedicine not as well known among the public? What action can be taken to raise more awareness about it?