When it comes to regulation of stem cells and its therapeutic use there is a wide interpretation what is legally possible and what is not allowed.
First viewpoint, is the ethical concern from where stem cells are harvested. The use of embryonic stem cells resulted in heavy debates about cloning humans, and potentially destroying emerging life for research purposes and had been banned consequently by many countries. The second viewpoint is the protection of consumers as there was an early movement that stem cells can heal everything without any proof. Prove in this context is the prove via clinical trial that the drug is safe and has a positive effect on a human being for a certain condition.
Regulators in many countries, therefore, declared all stem cells as drugs and imposed that treatment with stem cells has to be approved by regulators before given to patients. This concept is clearly valid for heavily manipulated products but when it comes to treatments with own stem cells,i.e. autologous stem cells regulators interpreted this in their own way in accordance with existing regulations.
Since the introduction of stem cells as drugs a decade ago basically only a handful of highly manipulated stem cell drugs had been approved by the FDA and EMA at prices reaching 1.2 Million Euros per treatment, resulting that most of them had been used only a few times for patients as the insurance companies reviewed each single case due to the very expensive cost associated with such a treatment.
As mentioned before there are two pathways to develop new medicinal products for patients, one is the clinical trial pathway for industrialized produced products intended to be sold at the mass-market to treat a specific symptom and the other pathway is the medical procedure pathway. The pathway used by the industry is, of course, more complex, takes much more time as it is using mainly allogeneic stem cells and often heavily manipulated gene technology or a combination with certain molecules which may trigger certain effects on the cellular structure of a body. It’s a complex procedure but has helped millions of patients especially in the 19 and 20th century to improve quality of life.
The medical procedure pathway is an established pathway to help patients with unmet medical needs too and is based on observation of individual patients and the trial to develop a therapy with latest scientific Know How to improve the condition of a singular patient. This approach is often used when mainstream medical procedure could not improve the conditions in such an individual case. This treatment is personalized and according to many countries can be implemented by a physician even as an unproven procedure in case the physician believes the procedure could help the patient in improving quality of life and reduce pain.
There is, however, a strong lobby against this “so-called unproven procedure” as this treatment besides being really personalized, is not following the expensive clinical trial path, to get an approval to be used as a new medicine for human beings.
The argument that autologous (OWN) stem cells are not a drug when used after concentration at the same person, as it is only improving and supporting the natural regeneration process, is not accepted by some regulators in this global medical scenario. Furthermore, regulators claim that those treatments are unproven for specific claims and therefore need to follow when used the clinical trial path.
It appears that this activity is more a political issue than an issue to help patients with early new technological know-how and methods and has divided regulators and medical advocates all over the world. Very often it is however forgotten that such early medical treatment is allowed by basically all countries even the US and EU although the regulations are not well known by the public and interpreted in a way stating that no stem cell treatment is authorized if not specifically approved by authorities! As a side effect of this understanding, there are only a few approved, new treatment methods available in Western regulated countries, while other countries have approved new science-driven technologies even though some of those technologies are still in their early exploration state.
In respect of regulation, we like to review the basis of stem cell treatment interpretation of the mostly discussed countries and try to clarify what is legally possible.
According to the FDA, all stem cells are drugs and any treatment has to be reviewed and approved before being used in humans. At the same time exist in the CFR 21 -1271 in the HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Regulation the paragraph 15b. stipulating besides others: “You are not required to comply with the requirements of this part if you are an establishment that removes HCT/P’s from an individual and implants such HCT/P’s into the same individual during the same surgical procedure”.
The FDA has issued non-binding guidelines in the last years to limit stem cell treatment as a medical procedure, but as long as 1271 15b, is unchanged stem cell treatment in the US is legally possible if no specific health claims are pursued.
The above overview is the latest (Nov. 2017) review of FDA understanding and interpreting of a medical procedure and fat stem cell. Again like all the other guidelines before, they are still unbinding guidelines at least for the next 3 years, but it shows strongly that the FDA is trying to regulate the nearly 500 stem cell clinics in the US. It is difficult to say what is the next move by the FDA, certain is only the FDA has started to find ways to regulate so-called unproven stem cell treatments provided via the 1271 15b paragraph allowing stem cell treatment without limitation when it comes to an ambulatory medical treatment with or without IRB approved protocol.
In the EU
According to EMA, all stem cells are considered as drugs and any treatment has to be reviewed and approved before being used in humans. At the same time exists in paragraph (8) of the statement in DIRECTIVE 2004/23/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells, that:(8) Tissues and cells used as an autologous graft (tissues removed and transplanted back to the same individual), within the same surgical procedure and without being subjected to any banking process, are also excluded from this Directive. The quality and safety considerations associated with this process are completely different.
From patients advocate point of view both FDA and EMA are exercising an interpretation which has resulted in a very high confusion in this new science-related medical treatment which causes uncertainty, although there are millions of patients already globally treated with own or expanded cord blood tissue-derived stem cells with quite good success and basically now advert events. FDA and EMA are arguing about a few cases which had been registered as adverse event for stem cell treatments not recognizing that according to their own statistics about 200 000 people die, in the USA alone, due to approved drug side effects.
Furthermore, in the EMA regulation it is clearly defined in Directive 2001/83/EC that:
“The scope of this Regulation should be to regulate advanced therapy medicinal products (ATMPs) which are intended to be placed on the market in the Member States and either prepared industrially or manufactured by a method involving an industrial process”. Those industrialized produced ATMPs have to follow the present drug regulation, i.e. it requires a pre-marketing approval.”
3. Medical Procedure
A medical procedure with or without the approval of an Ethical Committee in Europe or the Institutional Reviewing Board, in the US, has nothing to do with ” being prepared industrially or manufactured by a method involving an industrial process nor are intended to be placed on the market in the Member States” it is a personalized activity for a singular medical case.
The Declaration of Geneva of the World Medical Association (WMA), emphasizes and binds the physician with the words, “The health of my patient will be my first consideration,” and the International Code of Medical Ethics declares that “A physician shall act in the patient’s best interest when providing medical care.” Furthermore, the World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data. This declaration in its paragraph 37, stipulates:
Furthermore, the World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data. This declaration in its paragraph 37, stipulates:
Unproven Interventions in Clinical Practice
In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering. This intervention should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all cases, new information must be recorded and, where appropriate, made publicly available.
In the US there are about 750 clinics (2018) providing stem cell treatment in accordance with FDA regulation 1271 15b as a medical procedure while in Europe only a few have utilized the new treatment method, reflecting the treatment potential of stem cells in accordance with the Declaration of Helsinki.
Many countries outside the US and EU, having regulated adult stem cell treatments as a medical procedure, are supporting also those patients who cannot be treated easily in their own countries due to unfavorable regulatory interpretation. This situation has resulted in medical tourism to satisfy medical needs of patients, considered by FDA and EU regulated countries as an exploitation of the uneducated patients, where hope and profit come before scientific proof. This is certainly an unfair and a not justified statement as many clinics offering this treatment service have standards, not only matching but sometimes even out path established Western standards and treat certainly already very well educated and informed patients.
4. Japan Regulation
Japan has become the most favorable environment for regenerative medicine after changes to its national laws in November of 2013. The Japanese legal approval process for novel therapies was shortened to be world’s fastest, designed specifically for expedited treatment and trials of regenerative medical therapies.
Consequently, the Japanese market for regenerative treatment is now (2018) projected to experience rapid growth and to be worth US$12.7 Billion by 2030, capturing the major development and share in this field.