Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development

Min Li; Sanna Sander; John Duan; Susan Rosencrance; Sarah Pope Miksinski; Lawrence Yu; Paul Seo; Bhagwant Rege

doi:10.1208/s12248-016-9974-2

Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development

AAPS J. 2016 Nov;18(6):1406-1417. doi: 10.1208/s12248-016-9974-2. Epub 2016 Sep 20.

Authors

Min Li¹, Sanna Sander², John Duan¹, Susan Rosencrance³, Sarah Pope Miksinski⁴, Lawrence Yu⁵, Paul Seo¹, Bhagwant Rege⁶

Affiliations

¹ Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
² Division of Modified Release Products, Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
³ Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
⁴ Office of New Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
⁵ Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA.
⁶ 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.

PMID: 27650190
DOI: 10.1208/s12248-016-9974-2

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.

Keywords: Biopharmaceutics; Clinically relevant specifications; Control strategy; Modified release; Product and process understanding.

Publication types

Review

MeSH terms

Administration, Oral
Animals
Biopharmaceutics / legislation & jurisprudence
Biopharmaceutics / methods*
Chemistry, Pharmaceutical / legislation & jurisprudence
Chemistry, Pharmaceutical / methods*
Delayed-Action Preparations / administration & dosage
Delayed-Action Preparations / metabolism
Drug Discovery / legislation & jurisprudence
Drug Discovery / methods*
Humans
Quality Control*
Solubility

Substances

Delayed-Action Preparations