title: In question: the scientific value of preclinical safety pharmacology and toxicology studies with cell-based therapies.
abstract: A new cell-based medicinal product containing human regulatory macrophages, known as Mreg_UKR, has been developed and conforms to expectations of a therapeutic drug. Here, Mreg_UKR was subjected to pharmacokinetic, safety pharmacology, and toxicological testing, which identified no adverse reactions. These results would normally be interpreted as evidence of the probable clinical safety of Mreg_UKR; however, we contend that, owing to their uncertain biological relevance, our data do not fully support this conclusion. This leads us to question whether there is adequate scientific justification for preclinical safety testing of similar novel cell-based medicinal products using animal models. In earlier work, two patients were treated with regulatory macrophages prior to kidney transplantation. In our opinion, the absence of acute or chronic adverse effects in these cases is the most convincing available evidence of the likely safety of Mreg_UKR in future recipients. On this basis, we consider that safety information from previous clinical investigations of related cell products should carry greater weight than preclinical data when evaluating the safety profile of novel cell-based medicinal products. By extension, we argue that omitting extensive preclinical safety studies before conducting small-scale exploratory clinical investigations of novel cell-based medicinal products data may be justifiable in some instances.
authors.affiliation: Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg , Regensburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Broichhausen
authors.affiliation: Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg , Regensburg, Germany.
authors.forename: Paloma
authors.initials: P
authors.lastname: Riquelme
authors.affiliation: Department of Transfusion Medicine, Institute for Clinical Chemistry, University Hospital Regensburg , Regensburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Ahrens
authors.affiliation: Department of Obstetrics and Gynaecology, University Hospital Regensburg , Regensburg, Germany.
authors.forename: Anja K
authors.initials: AK
authors.lastname: Wege
authors.affiliation: Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg , Regensburg, Germany.
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Koehl
authors.affiliation: Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg , Regensburg, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.affiliation: Nephrology Division, Department of Internal Medicine II, University Hospital Regensburg , Regensburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Banas
authors.affiliation: Institute for Applied Cell Therapy, University Hospital of Schleswig-Holstein , Campus Kiel, Kiel, Germany.
authors.forename: Fred
authors.initials: F
authors.lastname: Fändrich
authors.affiliation: Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg , Regensburg, Germany.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.affiliation: Division of Experimental Surgery, Department of Surgery, University Hospital Regensburg , Regensburg, Germany.
authors.forename: James A
authors.initials: JA
authors.lastname: Hutchinson