title: Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.
abstract: This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Division of Modified Release Products, Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Sanna
authors.initials: S
authors.lastname: Sander
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Duan
authors.affiliation: Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Rosencrance
authors.affiliation: Office of New Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Sarah Pope
authors.initials: SP
authors.lastname: Miksinski
authors.affiliation: Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yu
authors.affiliation: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Seo
authors.affiliation: Division of Modified Release Products, Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA. bhagwant.rege@fda.hhs.gov.
authors.forename: Bhagwant
authors.initials: B
authors.lastname: Rege
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001702:Biopharmaceutics / Q000331:legislation & jurisprudence / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000331:legislation & jurisprudence / Q000379:methods*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism; D055808:Drug Discovery / Q000331:legislation & jurisprudence / Q000379:methods*; D006801:Humans; D011786:Quality Control; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations
keywords: Biopharmaceutics; Clinically relevant specifications; Control strategy; Modified release; Product and process understanding