title: Investigational New Drug applications: a 1-year pilot study on rates and reasons for clinical hold.
abstract: BACKGROUND
  The Food and Drug Administration (FDA)'s Center for Drug Evaluation and Research (CDER) receives about 1500 initial Investigational New Drug applications (INDs) per year. In the first 30 days after initial IND submission, FDA conducts a review to determine whether the proposed investigation is safe to proceed, and if not, the IND may be placed on clinical hold.
  
  
  METHODS
  A retrospective study of rates and reasons for clinical hold for all initial INDs submitted to CDER in fiscal year (FY) 2013 was performed. INDs were assessed for reasons that led to clinical hold, included chemistry, manufacturing and controls (CMC), animal toxicology or clinical issues. INDs were further categorized by commercial versus research sponsorship, and rare versus common disease indications. All INDs placed on hold were reassessed by whether they remained on hold within the first year following hold imposition.
  
  
  RESULTS
  CDER received 1410 initial INDs in FY 2013, of which 125 (8.9%) were placed on hold during the first 30 days after initial submission. Of the INDs placed on hold, more than half became active within the first year after first imposition of hold. CMC reasons were most commonly cited, followed by clinical, then toxicology reasons. There were no substantive differences in rates and reasons for hold between INDs for rare or common disease indications, or between commercial or research INDs.
  
  
  CONCLUSIONS
  The vast majority of initial INDs moved forward within 30 days after submission, and for those applications placed on hold, most became active within 1 year. The findings also suggest that many holds for new drug product programs can be avoided by following the available guidelines for investigational product development.
authors.affiliation: Division of Therapeutic Performance, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research (CDER), US Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Lapteva
authors.affiliation: Office of Translational Sciences, CDER, FDA, Silver Spring, Maryland, USA.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Pariser
mesh_terms: D006801:Humans; D017387:Investigational New Drug Application / Q000331:legislation & jurisprudence / Q000379:methods* / Q000706:statistics & numerical data*; D010865:Pilot Projects; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration
keywords: Clinical Research; Drugs, Investigational; Rare Diseases