The ethics and regulation of cell and tissue therapies in the UK

MARK LOWDELL: Hello, I'm Mark Lowdell. I'm the Director of Cell Therapy here at the Royal Free Hospital & UCL Medical School. And today I'm going to talk to you about the field of cell and tissue therapies, how they're regulated, and the impact that regulation has on the ethics.

So I'm a Cell Therapist. I'm not a doctor here that treats cells. I'm a scientist that uses human cells and tissues to make medicines for tissue engineering, regenerative medicine, and treating cancer and immune deficiencies.

Now these types of medicines are called Advance Therapy Medicinal Products. It's a clumsy term, and it was defined really in the first directive of 2001, 83, the Medicines Directive. And they consist of gene therapies, somatic cell therapies, and tissue engineered products for the purposes of regenerative medicine. Here are some examples: In the lower screen there you can see a decellularized human trachea that we were using to rebuild a trachea in a child. On the right of that there is a bioengineered nose made out of a biocompatible material. On the right hand side, a photograph from a different group using a similar sort of bio materials to produce an ear structure.

So how are these things regulated? Well, as I said, in 2001 the European Medicines Directive came in and for the first time it included human blood and blood products as a medical substance, and there was an implicit application that somatic cells from humans could be regulated as medicines. And they talked about them being substantially modified, but no definition of what substantial meant. In 2004, when the clinical trials directives was enacted, the same term, 'substantially modified somatic cells' arose. And so these for the first time could be a trial medicine, an Investigational Medicinal Product, or IMP. And this required the manufacturer full pharmaceutical standards of good manufacturing practice, GMP, plus a manufacturing authorization held by the manufacturer. And in Europe, a qualified person, the person with a status to legally release these, was very challenging at the time because qualified persons were pharmacists, and they didn't come from a cell therapy background. In 2006, tissues and cells were regulated by the European Union under the Tissues and Cells Directives. And these were enacted into UK law, meaning that tissues and cells that are used for transplantation purposes are regulated. And indeed those that are used as starting materials to make ATMPs are also regulated. In 2007 those regulations were published and we had to start applying them. And procurement of the starting material in the UK is regulated by the Human Tissue Authority. And in each member state there is a different regulator, and that requires a license to procure. The problem of nonsubstantial manipulation was finally defined with some examples of what nonsubstantial manipulation was. But no definition of what substantial manipulation is. And this still comes down to a decision by each member state. Within the ATMP regulations there was this inclusion of a strange clause called the Hospital Exemption Clause. Which allowed these medicinal products to be made one-off in a non-routine basis, no definition of non-routine, and for non-clinical trials. So these work for patients in extreme need, who needed treatment with a therapy that was not yet licensed and was not in clinical trial. And all of these regulations were then combined together in a rewriting of the European Medicines Directive in 2009 to produce the new Medicines Directive which includes these advanced therapy medicinal products. So a quick race through the regulation, if anybody is interested obviously those references are there, and one can struggle through them.