Preclinical good laboratory practice-compliant safety study to evaluate biodistribution and tumorigenicity of a cartilage advanced therapy medicinal product (ATMP).
J Transl Med
; 13: 160, 2015 May 20.
Article
en En
| MEDLINE
| ID: mdl-25990108
ABSTRACT
BACKGROUND:
The clinical development of advanced therapy medicinal products (ATMPs), a new class of drugs, requires initial safety studies that deviate from standard non-clinical safety protocols. The study provides a strategy to address the safety aspects of biodistribution and tumorigenicity of ATMPs under good laboratory practice (GLP) conditions avoiding cell product manipulation. Moreover, the strategy was applied on a human ATMP for cartilage repair.METHODS:
The testing strategy addresses biodistribution and tumorigenicity using a multi-step analysis without any cell manipulation to exclude changes of test item characteristics. As a safeguard measurement for meeting regulatory expectations, the project design and goals were discussed continuously with the regulatory authority using a staggered scientific advice concept. Subsequently, the strategy was applied to co.don chondrosphere® (huChon spheroid), a tissue-engineered matrix-free ATMP of human normal chondrocytes. In both the biodistribution and tumorigenicity studies, huChon spheroids were implanted subcutaneously into 40 immunodeficient mice. Biodistribution was studied 1 month after implantation. A skin disc containing the huChon spheroid, two surrounding skin rings and selected organs were analyzed by validated, gender-specific, highly-sensitive triplex qPCR and by immunohistochemistry (IHC).RESULTS:
No human DNA was detected in distant skin rings and analyzed organs. IHC revealed no direct or indirect indications of cell migration. Tumorigenicity was assessed 6 months after huChon spheroid implantation by palpation, macroscopic inspection, histology and IHC. No mice from the huChon spheroid group developed a tumor at the implantation site. In two mice, benign tumors were detected that were negative for HLA-ABC, suggesting that they were of spontaneous murine origin.CONCLUSIONS:
In summary, the presented strategy using a multi-step analysis was confirmed to be suitable for safety studies of ATMPs.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Cartílago
/
Ingeniería de Tejidos
/
Laboratorios
Tipo de estudio:
Guideline
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Observational_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Transl Med
Año:
2015
Tipo del documento:
Article
País de afiliación:
Alemania