title: How to achieve safe, high-quality clinical studies with non-Medicinal Investigational Products? A practical guideline by using intra-bronchial carbon nanoparticles as case study.
abstract: Clinical studies investigating medicinal products need to comply with laws concerning good clinical practice (GCP) and good manufacturing practice (GMP) to guarantee the quality and safety of the product, to protect the health of the participating individual and to assure proper performance of the study. However, there are no specific regulations or guidelines for non-Medicinal Investigational Products (non-MIPs) such as allergens, enriched food supplements, and air pollution components. As a consequence, investigators will avoid clinical research and prefer preclinical models or in vitro testing for e.g. toxicology studies.
  
  
  
  1) briefly review the current guidelines and regulations for Investigational Medicinal Products; 2) present a standardised approach to ensure the quality and safety of non-MIPs in human in vivo research; and 3) discuss some lessons we have learned.
  
  
  
  We propose a practical line of approach to compose a clarifying product dossier (PD), comprising the description of the production process, the analysis of the raw and final product, toxicological studies, and a thorough risk-benefit-analysis. This is illustrated by an example from a human in vivo research model to study exposure to air pollutants, by challenging volunteers with a suspension of carbon nanoparticles (the component of ink cartridges for laser printers).
  
  
  
  With this novel risk-based approach, the members of competent authorities are provided with standardised information on the quality of the product in relation to the safety of the participants, and the scientific goal of the study.
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Room F5-280, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. m.berger@amc.uva.nl.
authors.forename: M
authors.identifier: 0000-0001-7047-7320
authors.initials: M
authors.lastname: Berger
authors.affiliation: Section Catalysis Engineering, Department of Chemical Engineering, Faculty of Applied Sciences, Delft University of Technology, Julianalaan 136, NL 2628 BL, Delft, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Kooyman
authors.affiliation: Section Catalysis Engineering, Department of Chemical Engineering, Faculty of Applied Sciences, Delft University of Technology, Julianalaan 136, NL 2628 BL, Delft, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Makkee
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Room F5-280, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.|Department of Respiratory Diseases, Onze Lieve Vrouwe Hospital, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: van der Zee
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Room F5-280, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Yellow Research, Herengracht 495, 1017 BT, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Dijk
authors.affiliation: Department of Pharmacy, Academic Medical Centre Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Kemper
mesh_terms: D000280:Administration, Inhalation; D035843:Biomedical Research / Q000331:legislation & jurisprudence / Q000379:methods* / Q000592:standards; D002244:Carbon / Q000008:administration & dosage* / Q000009:adverse effects; D017408:Guidelines as Topic; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D036103:Nanotechnology / Q000331:legislation & jurisprudence / Q000379:methods* / Q000592:standards; D011050:Policy Making; D011634:Public Health / Q000331:legislation & jurisprudence / Q000592:standards; D018570:Risk Assessment; D014116:Toxicology / Q000331:legislation & jurisprudence / Q000379:methods* / Q000592:standards
chemical_list: D002244:Carbon
keywords: Good clinical practice; Good manufacturing practice; Guidelines; Intervention studies; Legislation; Non-medicinal products