Xavier Luria: “Rolling Review and CMA (Conditional Marketing Authorisation) mechanisms have allowed to accelerate the approval of treatments against Covid-19”.

Xavier Luria studied medicine and later specialised in internal medicine and pharmaceutical medicine and biostatistics (UAB), he also did postgraduate studies in clinical pharmacology, drug development and regulation at Tufts University (Boston). He held leadership positions in the biopharmaceutical industry for more than eighteen years and was Head of Medicines Safety and Efficacy at the European Medicines Agency (EMA) during 2005-2012. He was founder and CEO of the consultancy DDR (Drug Development and Regulation) based in Barcelona, Amsterdam and London which was acquired by Veristat in 2021, becoming Vice president of that entity. He is also a member of the Board of Directors of the IFAPP-King’s College Postgraduate Course, a Senior Visiting Professor at King’s College London and a lecturer at several other academic institutions in Europe and the United States.

During the pandemic, the EMA used mechanisms to speed up the approval of medicines through fast-track procedures, are these mechanisms still in place today? 

The established mechanisms, basically the so-called Rolling Review and approval by Conditional Marketing Authorisation (CMA), are still in force until it is determined that the pandemic situation has disappeared.

The Rolling Review is a regulatory tool implemented by the EMA to accelerate the evaluation of data on a medicine or vaccine during a public health emergency. It is a mechanism agreed between the Agency and the manufacturer of the product for providing data from pre-clinical and clinical development of the product as they become available, and in this way the Agency evaluates them before they are all formally submitted in a marketing authorisation application.

On the other hand, the AMC is a procedure that has been in place for more than 15 years to facilitate access to innovative medicines for diseases for which no other treatment is available. It is also used in public health emergencies to facilitate earlier product authorisation once a positive benefit-risk balance is available, and the manufacturer continues to produce more clinical trials.

In addition to the above two regulatory procedures, the EMA has also put in place numerous internal organisational measures to facilitate consultations and interactions with different stakeholders, all of which are still in place today.

For an SME that has to authorise a new medicine, which is the more advantageous procedure, centralised or decentralised? Is it appropriate to delay the decision until the acquisition/licensing of a Big Pharma (usually at the end of Phase IIa)?

The first thing to consider is that designation as an SME is relatively straightforward and facilitates access through the centralised procedure. It is highly recommended that companies that qualify as SMEs obtain this designation from the EMA as early as possible before initiating contacts with the Agency.

The centralised procedure is mandatory for some types of products (e.g. orphan designation, biologics) and for some indications (e.g. oncology, neurodegenerative diseases and others). Therefore, when a product belongs to some of the types or indications that are mandatory, there is no choice and the procedure must be centralised. For details, see the description of the so-called “mandatory scope” on the EMA website.

For all other products, there is the option to either follow the centralised procedure or to follow some of the non-centralised procedures. The analysis of advantages and disadvantages requires an in-depth assessment of the product, the indication and the company’s licensing and/or marketing strategy.

Regarding the most appropriate time to make the decision on the most appropriate regulatory procedure, it should be noted that this is an option only for products that are not obliged to follow the centralised procedure (so-called mandatory scope).

In my personal opinion, I believe that it is better to make this decision relatively early during product development, not least because interactions with regulatory agencies will have to be made on the basis of the future regulatory path.

The PRIME option is intended for drugs and indications where there is an unmet need. When is the best time to apply for PRIME for an SME?

The right time to apply for a PRIME is identical for SME and non-SME and is when highly promising early clinical evidence is obtained. Delaying this application due to product acquisition or licensing processes may prejudice the acceptance of the application in the sense that, even if the preliminary clinical data are promising, if the company has started confirmatory clinical trials, the EMA may consider that there is no option to intervene in the development of the product.

What are the challenges in manufacturing ATMPs (Advanced Therapy Medicinal Product)?

The very nature of ATMPs, which are genetically, tissue or cellularly based, means that manufacturing requirements are usually very difficult. The most important thing, in my opinion, is to have professionals who are experts in the manufacture of products in each of these areas and who have had previous experience, and it must be said that in some cases this is a major challenge. In addition, manufacturing facilities have to be specific to these products and follow specific regulations.

Does the EMA accept or is it considering accepting predictive software to replace some of the pre-clinical animal testing or as a support tool in the authorisation control of a drug?

The EMA does not currently widely accept results generated by predictive software to avoid pre-clinical studies. However, like the FDA, it has shown interest in studying such approaches.