Advanced Therapeutic Medicinal Products are innovative and complex biological therapies aiming to treat the root cause of diseases and disorders by altering the conditions in the body in a more permanent way. These therapies work through complex mechanisms, vastly different from conventional medicines therefore demanding a complex regulatory framework to determine a proper balance between the benefits versus the risk of a patient. As these therapies are right at the cutting edge of medical innovation, the regulatory considerations may be addressed for the very first time.  

The goal of gene and cell therapy is to develop a treatment that lasts the lifetime of the patient. Advanced therapies can be classified into three main types: 

Gene therapy is a technique that modifies a person’s genes to treat or cure disease and can work by different mechanisms: 

• Replacing a disease-causing gene with a healthy copy of the gene 
• Inactivating a disease-causing gene that is not functioning properly 
• Introducing a new or modified gene into the body to help treat a disease  

In practice, a gene can be corrected, silenced, reprogrammed, or eliminated. The transfer of gene material into the cells of a patient is done by a carrier, usually a virus or a plasmid*. Once inside the cells, the genetic material is handled by the cell’s normal machinery leading to the expression of the new protein and hopefully to restored function in the patient.  

Cell therapy aims to introduce new, healthy cells into a patient’s body, to replace or repair damaged cells or tissue. Many different types of cells can be used as part of a treatment for a variety of diseases and conditions.  Some of the cells that may be used include hematopoietic (blood-forming) stem cells, skeletal muscle stem cells and immune cells. The cells may originate from the patient (autologous cells) or a donor (allogeneic cells). The advantage of using stem cells is their ability to transform into the desired cell type and that they can self-renew and therefore last over a very long time.  

Tissue-engineered products contain cells or tissues that have been modified so they can be used to repair, regenerate, or replace human tissue. Artificial skin and cartilage are examples of engineered tissues. Key components of tissue engineering are: 

• a tissue, or cell sample, that constitutes the starting point of the process,  
• a scaffold that supports the sample and directs its growth into desired shape and location 
• a surrounding environment of signal substances and nutrition etc. that direct the growing cells towards the desired biological properties.  

Gene therapy is classified according to whether the therapy is administered to cells inside or outside the body. In vivo gene therapy means that therapy is administered directly into the patient to the targeted cells inside the body. With ex vivo gene/cell therapy the targeted cells are taken out of the patient and gene therapy is administered to the cells before they are returned into the patient’s body. 

Delivering the therapy to the right place is crucial; if it interferes with other than the intended process could have damaging effects.  When taking a conventional medicine, it is metabolised and in due course excreted from the body. This is not how advanced therapies work; they are cells and genes administered into a patient and may instead be integrated in the body or rejected. The administration may induce a strong immune response to the therapy, or the patient can develop resistance to the therapy which makes it ineffective. There could also be a risk for abnormal cell growth and tumour formation.  

Since advanced therapies are fundamentally different from conventional, chemical therapies, the manufacture cannot be controlled in the same precise way. Therefore, studies of the behaviour of advanced therapies need to be addressed in more detail to predict what will happen once the therapy enters the body.  As for many new medicines, especially the ones treating rare diseases, the testing can be challenging, especially when it comes to finding models that can give a reliable hint of the reaction when given to patients.  

In 2007 a regulation for advanced therapies was adopted in the EU with the intention to adapt to the technical specificities of the development of the products and to harmonise the regulation. The first step involves a classification procedure placing the product in the right category and enabling drug developers to adhere to the applicable regulation framework.  

Since advanced therapies are novel and highly innovative, some of the existing regulatory guidelines pose challenges and need to be flexible to enable proper development. The flexibility should not be mistaken for lowering of product quality standards, it rather demonstrates that there is wriggle room in the adoption of meaningful and appropriate methods and controls. The regulation sets specific rules on the authorisation and supervision of advanced therapies and on patient safety in relation to them. 

In many cases advanced therapies are a one-off, curative treatment replacing a lifetime of medical interventions. This places a high demand on the evidence provided to make a proper risk-assessment before authorisation and patient use. Despite the challenges to get from lab to patients, advanced therapies hold great promises for life-threatening diseases and patients with high unmet needs. 

For the past five years NDA has worked with more than 80 different advanced therapy products, connect with us, using the form below, to learn more.  

*A plasmid is a small circular DNA molecule that can be used as a tool to transfer new/altered genes into a cell.