While supporting the development of stem cell banking companies, in the frame of certain consulting activities, we realized the difficulties of utilizing stem cell from this activities for treatment, not only in the US, but also in Europe. Most countries have established rules and regulations for the treatment of stem cells, although they may vary, even considerably, from country to country.

The main difficulty is, that in the present regulation by FDA and EMA, the usage of stem cells in medical treatments, is considered as an advanced medical product treatment / drug, which, for safety reasons, need to follow the established pathway of clinical trials before used in humans, if more than minimally manipulated.

We believe that this precautions are correct, especially when it comes to embryonic and allogeneic stem cell application, but recent technological advances as well as actual stem cell treatments have shown that the concerns in respect of safety and efficacy, especially with autologous stem cell treatment, can be well managed with next to no side effects.

The treatment possibility with autologous stem cells is considered by most stem cell treatment advocates and some progressive scientists even somewhat more favourable for patients with unmet medical need, than a continued treatment of symptoms with approved medical drugs. The side effects popping up while using regularly those human medication unfortunately is reflected in many adverse effects reported every year.

Various experimental treatments, clinical studies, even clinical trials have shown that especially autologous stem cell treatments are not only well tolerated by the treated person if performed in a qualified hospital / clinical environment and a well-trained physician, but also improved quality of life of the treated individual in most cases considerably without serious, respectively next to none side effects even if the targeted improvement was not achieved.

From our market investigation it can be concluded that three main models exist to advance with stem cell treatments, besides the clinical trial route favoured by the industry. Those experimental treatments in FDA and EMA regulated countries are considered by most regulators as unproven, though widely accepted / tolerated under certain criteria.

This models are considered to avoid potential conflicts with regulatory authorities, in the frame of existing Western regulations, but are able to help supporting the advancement of novel treatment methods, especially in cases standard treatment with prescription drugs have not been successful. The models are:

1. Potential Model
To perform stem cell treatment in the frame of “Practice of Medicine” of physicians
using autologous stem cells, minimal manipulated in a same day medical procedure. This method is basically provided globally, although US regulators are trying to restrict this further by implementing new guidelines, even those are not binding, at least at the moment.

Examples for this method, are various globally operating stem cell treatment groups like Cell Surgical Network (CSN) or stemMD or Regenestem. Various clinics / hospitals also in Europe have been recognized internationally for their stem cell treatment success, as well as various clinics in China, India, Panama and Mexico, to mention a few, although most of them abstain from doing much publicity, though it is common that treated patients are exposing themselves in testimonials.

It has been also noted, that in some countries outside the FDA and EMA influence, also processes with more than minimally manipulated cells (e.g. expansion) are used for stem cell treatments with quite some impressive success. Japan in view of this fast developing science and great potential for treating patients with unmet medical need, has changed end of 2014 already its regulatory pathway to support this new development in medicine, while FDA and EMA are discussing what, when and how they are going to accompany this developing field.

The rapidly evolving field of stem cell research continues to raise great hope among patients. Stem cells are undifferentiated cells capable of self-renewal that can differentiate into all the specialized cell types of the body when exposed to appropriate environmental cues. Adult stem cells are found in almost all tissues of the body, perhaps the best sources known being bone marrow, peripheral blood and adipose tissue, while embryonic stem cells are responsible for much of the ethical controversy that surrounds stem cells. The video below gives an overview of stem cells and the ideas of its application.


The current therapeutic applications of stem cells include bone marrow transplantation, but also treatments with stem cells from adipose tissues. In the future it is likely that stem cells will be used to treat diseases of the heart, central nervous system and endocrine system among others.

In FDA and EMA regulated countries, the expansion of stem cell is however outside the scope of minimal manipulation and therefore may be considered by regulatory authorities as a “new investigational medical product” which has to follow the established regulatory path of clinical trials. We are not discussing here whether this is right or wrong, but showing only the interpretation of existing regulations. Stem cell expansion and corresponding treatments outside the FDA and EMA regulated countries is often accepted in the frame of practice of medicine if performed in  qualified hospitals / clinic environment with much individual success.

2. Potential Model
To perform stem cell treatment in the frame of the “Hospital Exemption” in Europe.

Interpretation of hospital exemption vary in the European Union, as the member states have jurisdiction of the implementation and interpretation of Hospital Exemption. Best working example in respect of implementing Hospital Exemption is Germany. EU member states having not yet established any frame work can still develop their regulations or follow already existing regulations e.g. the German example (as e.g. a default procedure).

Hospitals, however, have to initiate and apply at their local health authorities a hospital exemption in order to perform certain stem cell treatments, especially once a stem cell treatment is a more than minimally manipulated activity.

Hospital exemption refers to the treatment with products not having yet a market authorization, but may be used in Hospitals under certain conditions if safety and efficacy can be assumed based on studies provided. Hospital exemption covers two main activities. First the treatment with stem cells more than minimally manipulated of a single individual and secondly the usage of an investigational personalized typed drug.

Related Link:
Northwest Biotherapeutics DCVax-L Germany Approval Under Hospital Exemption Early Access Program

3. Potential Model
To treat individuals with stem cell from cryopreserved stem cells harvested from umbilical cord or e.g. from adult adipose tissues. Here some specific conditions apply which are provided in countries like Panama, Mexico, India, to name a few.

Some companies are expanding the harvested stem cells before cryopreservation, others are expanding them after thawing. Regardless the method expansion of stem cell is outside the minimal manipulation regulation in FDA and EMA regulated countries and in such a case, the stem cell bank has to have an export licence in order to send the expanded cells to a qualified clinic outside the regulated country.

Examples are:     
Bioheart, US A with partners in Mexico, Costa Rica and India
Regenexx, USA with a partner in Cayman Islands                                        Cells4Health GmbH, Switzerland with Advancells, India
Other international  companies try to establish this partnership too

The corner stones of the legal framework for existing stem cell treatments can be summarized as follows:

  1. In FDA regulated territory
    Historically, the approach to regulating human cellular and tissue-based products in the US, now called Human Cells, Tissues, and Cellular and Tissue-based products (or HCT/Ps) was highly fragmented. In 1997, FDA proposed a new approach to the regulation of HCT/Ps and establish in chapter 21 of the Code of Federal Regulation (CFR) Part 1271, a comprehensive regulatory program for HCT/Ps. In accordance with a tiered, risk-based approach FDA decided that, some HCT/Ps would be regulated only under those new regulations and section 361 of the Public Health Service Act (PHS Act) (42 U.S.C. 264), while others would be regulated as drugs, devices, and/or biological products under section 351 of the PHS Act (42 U.S.C. 262) and/or the Federal Food, Drug, and Cosmetic Act (the act).  The FDA also changed the former definition of cells, (allogeneic transplants only) covering cells from allogeneic and autologous donors. With this, own stem cells (autologous) automatically became drugs and had to follow the clinical trial route before its application (351) if those cells where more than minimal manipulated. FDA regulations (21 Code of Federal Regulations Part 1271, define the concept of a minimally manipulated tissue graft (MMTG) as follows:

    • Criteria for an HCT/P to be regulated solely under section 361 of the Public Health Service Act. To qualify for 361 in the USA stem cell treatment has to follow the criteria of:

      ♦  Minimally manipulated
      ♦  Homologous use only
      ♦ The manufacture does not involve the combination of the.cells or tissues ….with another article
      ♦  Does not have a systemic effect
      ♦  Is for autologous use

    • Minimal manipulation / FDA Examples of minimally manipulated tissue grafts are:

      ♦  Traditionally or specially processed musculoskeletal allografts      ……(conceived to function similar to devices such as plates, screws)
      ♦  Demineralized bone matrix (DBM) with or without carriers Fresh ….cartilage allografts (whole or minced)
      ♦  Acellular soft-tissue allografts 

      ♦  Platelet-rich plasma concentrates

    • Intended for homologous use only, as reflected in the labelling, advertising, or other indications of the manufacturer’s objective intent

    • Not combined with a drug or device, except for water, crystalloids, or a sterilizing, preserving, or storage agent provided that the addition of the water, crystalloids, or sterilizing, preserving agent does not raise new clinical safety concerns with respect to the HCT/P

    • Not have a systemic effect and not depend on the metabolic activity of living cells for its primary function except if for autologous use, allogeneic use in a first-degree or second-degree blood relative, or reproductive use

    • “Minimal manipulation” for structural tissue is further defined as “processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement.”

    • Homologous use as defined in 21 CFR 1271.3.(C) as “replacement or supplementation of a recipient´s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the “donor” this statement refers to the function of the cells but does not have to go to the same site or homologous location from where the cells had been harvested.

Some BLOGs and Information from Scientists in the US are stating that applied stem cell treatment is not in the spirit of regulated stem cell drug treatment and the present knowledge of experimental science. Fact however is that the FDA and the relevant Medical boards are working in this frame provided by US regulators and show amazing success with this IRB approved treatment protocols and methods.

Beside this, countries like South Korea, China or Japan are already much more advanced in stem cell treatment and Know How while applying a legal framework more adequate to modern medical treatment methods.

2.  EMA regulated territory (Europe)

2.1 ATMPs
In December 2008 the Advanced Therapy Medicinal Products (ATMP) Regulation was implemented. Although a permanent growth in marketing authorization applications relating to the development of ATMPs was announced, together with measures from the Committee for Advanced Therapies (CAT) and close collaboration between the EMA and the stakeholders in the field, only very few products have made it to the market until now. On the basis of their therapeutic application, ATMPs are classified as:

a.  Gene therapy medicinal products,
b.  Somatic cell therapy medicinal products
c.  Tissue engineered products.

In the European Union (EU) a distinction can be made between EU Regulation and EU Directives. European Directives are considered to have direct effect, and they first require implementation by national legislation in the individual Member States. European Regulation are directly applicable, though, yet may still be in need of substantiation in a national context. Therefore, although European Law may proscribe the regulatory parameter, the interpretation and implementation of these stipulations in individual member states may differ.

2.2 EU regulation – minimal manipulation
Directive 2001/83/EC, Annex I, Part IV.2 (Directive 2009/120/EC) and Regulation (EC) No 1394/2007 Article 2(c) defines minimal manipulated as follows:

♦  Cutting
♦  Sterilization
♦  Grinding
♦  Filtering
♦  Freezing
♦  Cryopreservation
♦  Irradiation
Remarks: Lower ultraviolet,visible light (including laser light), infrared, microwaves, and radio waves are considered non-ionizing radiation.Ionizing radiation causes damage to living tissue, and can result in mutation, radiation sickness, cancer, and death.

♦  Centrifugation
♦  Soaking in antibiotic or antimicrobial solutions
♦  Shaping
♦  Vitrification
Twenty-First Century Medicine has vitrified a rabbit kidney to -135°C with their proprietary vitrification cocktail. Upon rewarming, the kidney was successfully transplanted into a rabbit, with complete functionality and viability, able to  sustain the rabbit indefinitely as the sole functioning kidney.

♦  Lyophilization
♦  Cell separation, concentration, or purification

2.3 Hospital Exemption
The hospital exemption in Europe is defined in Regulation 1394/2007, and was adopted in December 2008. Transposition into local legislation is ongoing.

A screening of the currently existing local guidelines and legislation on the provisions from article 28 indicates a wide interpretations among the different stakeholders and Member States.

♦  Germany  where  hospital  exemption is practised  since  long  and  has been defined in the German Legislation (15.AMG) Section 4b as stated beside and below in the frame of the EU regulation 1394/2007, is considered by various health professionals as a good example of the Hospital exemption clause

♦  Requested an authorization from federal authorities.

♦ Used in a specialized facility (interpreted as hospital / clinic environment) for health care under the professional responsibility of a doctor.

♦  Requested a regular report on the amount of the product released.

♦  Minimal manipulation (MM) of stem cells prepared on a non –routine basis according to specific quality standards (Hospital environment standards)

♦  Limited claims allowed in the frame of the EU regulation, details see at:

Hospital exemption may refer to the treatment with products not having yet a market authorization, but may be used in Hospitals under certain conditions if safety and efficacy can be assumed based on preliminary studies provided.

Hospital exemption may cover two main activities. First the treatment with stem cell of a single individual (Practice of Medicine) and secondly the usage of an investigational personalized typed drug.


March 10, 2014 /PRNewswire/ — Northwest Biotherapeutics (NASDAQ: NWBO) (NW Bio), a biotechnology company developing DCVax® personalized immune therapies for solid tumor cancers, announced today that it has received approval from the Paul Ehrlich Institute (“PEI”- the FDA of Germany) of a “Hospital Exemption” early access program under Section 4b of the German Drug Law.

Under this Hospital Exemption, NW Bio may provide DCVax-L to patients for the treatment of any glioma brain cancers (both Glioblastoma multiforme and lower grade gliomas), both newly diagnosed and recurrent, outside of the Company’s clinical trial and charge full price.  The patients may be from Germany or elsewhere.  This approval has a term of five years, and can be re-applied for and re-issued at the end of that period.

According to NW Bio, DCVax is activating the natural immune system in a human body against a patient’s cancer. This response can be effectively accomplished through the injection or Dendritic Cells that are “educated” to teach the immune system to recognize, and kill cancer cells.

NW Bio also announced today that the German reimbursement authority (Institut Fur Das Entgeltsystem Im Krankenhaus, or InEK) has determined that DCVax-L treatments for glioma brain cancers are eligible to obtain reimbursement from the Sickness Funds (health insurers) of the German healthcare system.  Applications for such reimbursement eligibility may only be submitted to InEK by German hospitals, not by a company.  Six major hospital centers across Germany applied for such reimbursement eligibility for DCVax-L for glioma brain cancers.

The amount and terms for such reimbursement will now be negotiated by NW Bio, the hospitals and the Sickness Funds over the coming months, and will be applied to patients case by case.  In the meantime, patients may self-pay for DCVax-L.

It is speculated that the price of DCVax-L will be in line with that of breakthrough cancer drugs i.e. roughly $50,000 to $100,000 per year!

2.4   Compassionate use in Europe was created by the European Legislature in 2004. Until then, France and Italy were the only two European countries with compassionate-use programmes incorporated into national law.

The term “compassionate use” is defined in Article 83 no. 2 of the Regulation (EC) no. 726/2004 of the European Parliament and of the Council as:

“… making a medicinal product belonging to the categories referred to in Article 3 (1) and (2) available for compassionate reasons to a group of patients with a chronically oror whose disease is considered to be life-threatening, and who cannot be treated satisfactorily by an authorized medicinal product. The medicinal product concerned must either be the subject of an application for a marketing authorization in accordance with Article 6 of this Regulation or must be undergoing clinical trials.”

Considering this legal framework, it can be concluded and had been observed that stem cell treatments are performed in many different countries in the frame of existing legislation.

In order that patients do benefit from this new, by mainstream medicine still considered as experimental treatment,  we are supporting those and their activities in the framework of legal possibilities.

In this connection we like to draw the attention to the “PRUDENT CELL PRACTICES” as follows:

♦  Do not advertise that cellular medicine cures or treats any specific  condition
♦  Use examples for educational purpose only
♦  Make certain that your fees are in line with similar procedures
♦ Make certain your consent promises no specific outcome and states clearly ….that this is experimental medicine
♦  Utilize fully characterized cell collection procedures
♦ Use IRB approved protocols, but make certain that patient outcome will be ….followed according to the IRB protocol.
♦  Stay in the legal frame of minimal manipulation and practice of medicine with ….autologous stem cell from adipose tissues or bone marrow and PRP

As mentioned before there are already many stem cell treatment offered in various countries but in order to be treated by a qualified clinic it is necessary to carefully evaluate the activity before being treated by an experimental stem cell treatment.

CellTheraPhy ARISTOLOFT in general, is SUPPORTING technology advances and its implementation to improve health naturally. 

♦ The development of treatment centers, offering health treatments that …..are focusing on maintaining vitality while aging.
♦ Those treatment centers may provide surgical and / or cosmetic …. procedures and are not involved in the use or manufacture of any …..investigational drugs, because we are not in the desease business.
the development of Energy Technology for health …..maintenance.
♦   Supporting Health and Wellness with natural means

If you are looking for a stem cell treatment please contact us we may be able to direct you to a qualified clinic.

in the frame of international regulations we like to draw your attention to the disclaimer of ARISTOLOFT, mentioning beside others that:

Articles on this Website / BLOG are not intended to provide any technical and / or medical advice, nor are intended to diagnose, treat, cure or prevent any diseases. Always consult your medical doctor regarding any health concern.

Products mentioned in this Website / BLOG, if not specifically marked as FDA registered, approved and evaluated, have not been evaluated by the FDA or any other medical related authorities.

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