title: Completeness assessment of type II active pharmaceutical ingredient drug master files under generic drug user fee amendment: review metrics and common incomplete items.
abstract: Under the Generic Drug User Fee Amendments (GDUFA) of 2012, Type II active pharmaceutical ingredient (API) drug master files (DMFs) must pay a user fee and pass a Completeness Assessment (CA) before they can be referenced in an Abbreviated New Drug Application (ANDA), ANDA amendment, or ANDA prior approval supplement (PAS). During the first year of GDUFA implementation, from October 1, 2012 to September 30, 2013, approximately 1,500 Type II API DMFs received at least one cycle of CA review and more than 1,100 Type II DMFs were deemed complete and published on FDA's "Available for Reference List". The data from CA reviews were analyzed for factors that influenced the CA review process and metrics, as well as the areas of DMF submissions which most frequently led to an incomplete CA status. The metrics analysis revealed that electronic DMFs appear to improve the completeness of submission and shorten both the review and response times. Utilizing the CA checklist to compile and proactively update the DMFs improves the chance for the DMFs to pass the CA in the first cycle. However, given that the majority of DMFs require at least two cycles of CA before being deemed complete, it is recommended that DMF fees are paid 6 months in advance of the ANDA submissions in order to avoid negatively impacting the filling status of the ANDAs.
authors.affiliation: Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Huyi
authors.initials: H
authors.lastname: Zhang
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Diandian
authors.initials: D
authors.lastname: Shen
authors.forename: David
authors.initials: D
authors.lastname: Skanchy
authors.forename: Kun
authors.initials: K
authors.lastname: Shen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lionberger
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rosencrance
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
mesh_terms: D057189:Checklist; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D004345:Drug Industry / Q000331:legislation & jurisprudence* / Q000592:standards; D016568:Drugs, Generic / Q000592:standards / Q000627:therapeutic use*; D005249:Fees and Charges / Q000331:legislation & jurisprudence* / Q000592:standards; D019983:Guideline Adherence; D017408:Guidelines as Topic; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence* / Q000592:standards
chemical_list: D016568:Drugs, Generic