Post was updated 18 October, 2012 at 5:50 pm. EST
The recent troubles with US company Celltex, clash between Regenexx and FDA and some other cases demonstrate the uncertainty in regulation of autologous adult stem cells (AASC) for regenerative medicine. Developers, who are trying to bring AASC-based therapies to the bed side usually confused about regulatory path. Some of them assume (or pretend to know), that AASC is a practice of medicine/ tissue (graft) and, therefore, is not a subject of federal regulation as a drug or biologic. But those, who chose to contact regulators (be compliant) to clarify the path to the market, still confused about agency’s recommendations. The most frequent questions are:
- Should AASC product be regulated as a drug/ biologic or as a graft/ tissue? If yes, why?
- What regulatory agencies regulate the steps of AASC product development cycle (raw material procurement and testing, manufacturing, facility authorization, clinical trials, market approval…)? How do they interconnected and what documents at what period of time should we submit?
- Is GMP-grade manufacturing required?
- Should we conduct all phases of clinical trials?
From the other side, regulators may not be entirely sure about the right and appropriate path. This uncertainty usually associated with new kinds of therapies, which just left a lab bench and haven’t been implemented in patients. This is a typical case for AASC. Regulators have limited time to catch up with rapidly progressing field and, usually, lack of expertise. Therefore, the law and guidance development could lag behind of scientific and clinical progress. The group of authors, proposed to call this situation regulatory regress:
Regulatory regress reflects the potential for uncertainty in scientists’ attempts to achieve regulatory compliance, and regulators’ uncertainty in recognising when such compliance has been attained.
The authors analyzed regulatory regress for the case of GMP accreditation of clinical stem cells labs/ facilities in UK. One of their showcases included UK Stem Cell Bank. Clinical-grade stem cell lines manufacturing is regulated by few agencies. The authors called them “actors“. In UK, actors include:
(HFEA) Human Fertilisation & Embryology Authority (use of embryos and derivation of ESC), (HTA) Human Tissue Authority (storage of human tissue – raw material), (MHRA) Medicines & Healthcare products Regulatory Agency (clinical device) and (EMA) European Medicines Agency (medicinal product = drug for therapeutic use). In UK two different agencies grant clinical trial authorization and marketing authorization.
Some observations from their showcase analysis:
The analysis is led by the observation that both laboratories are investing considerable labour in (1) interpreting regulatory texts and (2) identifying which regulatory texts were the relevant ones for interpretation.
The main problem of regulatory regress:
Regulatory regress means that a regulatory actor does not know the correct interpretation of a regulation until the wider networks shaping its meaning are settled, yet these wider networks cannot be settled until a correct interpretation is agreed.
Ok, let’s get back to our case (AASC) and look at situation in US. I was trying to draw the scheme, which suppose to demonstrate the actors in potential regulatory regress for the case of AASC regulation in US:
FDA – Food and Drug Administration (manufacturing, clinical trials, market authorization, license)
FACT – Foundation for the Accreditation of Cellular Therapy (facility accreditation)
ICMS – International Cellular Medicine Society (facility accreditation)
AABB – American Association of Blood Banks (facility accreditation – jointly with ICMS)
IRB – Institutional Review Board (independent ethics committee, clinical trials with or without FDA)
This is hypothetical scheme. All of these actors are playing some role or/ and intend to play in AASC regulation in US. Right now, pretty much everything “covered” by FDA. So, developers, which chose to be compliant, communicate almost exclusively with FDA. You can add trials approval through IRB and facility accreditation through FACT.
I think, regulatory regress for use of AASC in regenerative medicine is open. Variety of actors will add more complexity and significantly wide open regulatory regress. One of the issues here is communication between actors. For example, ICMS is aimed to
“bypass” FDA* (*see comments) provide a framework for exclusive regulation of AASC for regenerative medicine. So, at the moment, developer may be confused about which way to go (ICMS or FDA). It may prolong the product development and may require consultants for interpritation of options and requirements.