Related Policy and Legislation

Overview Regarding Regulatory Requirements

Currently, clinical doses of PA-SSC are isolated by plating bone marrow (BM) mononuclear cells (MNC) on tissue culture plastics and sub-culturing over one or more passages. Due to the risk of microbial contamination, clinical PA-SSC preparation must be performed in a cleanroom using current Good Manufacturing Practices (cGMP) and is regulated as drug manufacturing under EU Regulations for Advanced Therapy Medicinal Products (ATMP). The EU current standards for defining a SSC-based ATMP are very basic and focus on SSC sterility and toxicology.

However, it is anticipated that cell therapy characterisation standards will become more stringent in the European Union (EU). In 2011, the EU Committee for Advanced Therapies (CAT) adopted a “Reflection paper on stem cell-based medicinal products” (CAT/571134). CAT/571134 is expected to form the basis of future EU ATMP legislation. Similarly, at the end of 2011, the British Standard Institute (BSI) released Publicly Available Specification-93 (PAS-93) regarding Characterization of cells and cell therapy products. Together with CAT/571134 from the EMA, PAS-93 is expected to formulate a British Standard for Cell Therapy in 2013. A number of key issues were identified by the EU and BSI which may be addressed in any future legislation/regulation in the area.

Key issues identified included the following:

  • Lack of Purity – Both EU and BSI documents highlight the BM-plating method of purifying PA-SSC as inadequate for defining or purifying SSC for clinical use. Both documents note a requirement for more markers to define and prospectively isolate cells for therapeutic use.
  • Bio-equivalence across species – Both documents highlight the need to show bioequivalence between human SSC and the murine/rodent SSC used in pre-clinical studies.
  • Mechanism of Action – Both documents suggest the need for evidence of biodistribution and mechanism of action (MoA) to be incorporated into future EU clinical SSC Investigation Medicinal Product Dossiers (IMPD) and Investigator Brochures (IB).

To comply with these future EU/UK regulations REDDSTAR partners (ORB) have identified a series of antibodies that prospectively purify equivalent SSC from human, rat, rabbit, equine and mouse BM.  In addition, the Nanosorter® used in the project will enable cGMP compliant production of cells with high levels of cell purity and sterility.  Data from REDDSTAR will address the requirements for evidence of biodistribution and mechanism of action (MoA) identified by the EU/BSI.

Links to relevant legislation

Participants in REDDSTAR will adhere to all relevant EU legislation and regulations in the area.

Legislation and guidelines relevant to the REDDSTAR Project include:-

  • British Standard Institute (BSI) Publicly Available Specification-93 (PAS-93) “Characterization of human cells for clinical applications”