Development and approval of novel injectables: enhancing therapeutic innovations

ABSTRACT

Introduction

Novel injectables possess applications in both local and systemic therapeutics delivery. The advancement in utilized materials for the construction of complex injectables has tremendously upgraded their safety and efficacy.

Areas covered

This review focuses on various strategies to produce novel injectables, including oily dispersions, in situ forming implants, injectable suspensions, microspheres, liposomes, and antibody-drug conjugates. We herein present a detailed description of complex injectable technologies and their related drug formulations permitted for clinical use by the United States Food and Drug Administration (USFDA). The excipients used, their purpose and the challenges faced during manufacturing such formulations have been critically discussed.

Expert opinion

Novel injectables can deliver therapeutic agents in a controlled way at the desired site. However, several challenges persist with respect to their genericization. Astronomical costs incurred by innovator companies during product development, complexity of the product itself, supply limitations with respect to raw materials, intricate manufacturing processes, patent evergreening, product life-cycle extensions, relatively few and protracted generic approvals contribute to the exorbitant prices and access crunch. Moreover, regulatory guidance are grossly underdeveloped and significant efforts have to be directed toward development of effective characterization techniques.

GRAPHICAL ABSTRACT

Various categories of novel injectables.

KEYWORDS:

• In-situ gels
• liposomes
• drug delivery
• antibody-drug conjugates
• polymeric microspheres
• crystalline suspensions

Article highlights

• Novel injectables offer variable therapeutic applications for both local and systemic delivery.

• Technological developments have enhanced the safety and efficacy of novel injectable products such as oily injectables, suspensions, liposomes and antibody drug conjugates.

• A detailed overview of injectable drug formulations and the technologies approved for clinical use by the United States Food and Drug Administration (USFDA) has been provided.

• Various excipients used, their composition, and the manufacturing challenges associated with them are discussed.

• This is a CSIR-CDRI communication 10789.

Abbreviations

ANDA Abbreviated new drug application; ADC Antibody Drug Conjugates; ADR Antibody-Drug ratio; API Active pharmaceutical ingredient; CMC critical micellar concentration; cGMP current good manufacturing practice; DBS Dibenzylidene sorbitol; FD&C Act Food, Drug, and Cosmetic Act; GMO glycerol monooleate; GDO glycerol dioleate; GnRH Gonadotropin-releasing hormone; T_g glass transition temperature; HEPES N-2-hydroxyethylpiperazine-N’-2-ethanesulfonic acid; HCl hydrochloride; HSA 12-hydroxystearic acid; IV intravenous; IM intramuscular; ISFI In situ forming implants; LAL Limulus Amebocyte Lysate; MAC mycobacterium avium complex; MVLs Multivesicular liposomes; MMAE monomethyl auristatin E; MCT medium-chain triglycerides; MMAF monomethyl auristatin F; NMP N-Methyl-2-pyrrolidone; NSAID Non-steroidal anti-inflammatory drug; OUD Opioid use disorder; PLA Polylactic acid; PCL Polycaprolactone; PGA polyglycolic acid; PLGA Poly (lactic-co-glycolic acid); PMMA Poly (methyl methacrylate); PABA para-aminobenzyl alcohol; PAT Process Analytical Technology; PEG Poly (ethylene glycol); SC subcutaneous; SMS Sorbitan monostearate; SPC soy phosphatidylcholine; SMCC succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate; USFDA United States Food and Drug Administration.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.