Challenges and opportunities in the development of complex generic long-acting injectable drug products

• Published in: Journal of controlled release Vol. 336; pp. 144 - 158
• Main Authors: O'Brien, Matthew N., Jiang, Wenlei, Wang, Yan, Loffredo, David M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 10.08.2021
• Subjects: Complex generic products; Controlled release; Depot; Drug delivery; Generics; Long-acting injectable; Q1; Mn; Q2; FDA; BE; IVR; PLA; QTPP; Drug delivery; Mw; NDA; RLD; DP; QA; SC; CDER; ORS; CQA; Tg; PDI; GDUFA; ISF; Controlled release; Generics; Cmax; LOE; IM; PSG; NME; Glu-PLGA; Long-acting injectable; PrEP; OGD; NMP; TE; PLGA; ANDA; HCP; HIV; MVLs; LAI; Complex generic products; LCM; Depot; API; PK
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.06.017

Long-acting injectable (LAI) drug products enable the controlled release of a drug over an extended duration of time to improve the therapeutic effect, safety profile, or administration of an injectable product. The development of generic [505(j)] and differentiated [505(b)(2)] LAI products helps to provide patients and healthcare providers with more treatment options and to reduce overall healthcare costs, including those associated with drug product administration and patient compliance. In this review, we analyze the landscape of LAI products and identify the most common technical challenges that potential generic product entrants face. We focus on five formulation technologies that account for ~90% of approved LAI products, including those eligible for generic product registration over the next five years, to illustrate technology-specific challenges. We then review efforts from the U.S. Food and Drug Administration (FDA) to promote more generic product competition and emphasize the importance of collaboration among government, industry, and academia to advance the knowledge and capabilities of the scientific community. Regulatory bodies, industry, and academia are encouraged to anticipate challenges with emerging innovative LAI technologies and to leverage the experiences built on established technologies to foster generic product development. [Display omitted] •The U.S. FDA has approved ~41 NDAs with long-acting injectable (LAI) formulations.•To date, only 7 LAIs have therapeutically equivalent generics available.•At least 9 high-value LAIs are eligible for generic registration within 5 years.•Technical challenges and investment requirements limit LAI generic competition.•Industry, academia, and FDA partnership de-risks development of generic LAIs.