Development and Validation of Matrix of Chemistry, Manufacturing, and Control (MoCMC) System for Intramammary Drug Products (IMM)

Nada A Helal; Marilyn N Martinez; David G Longstaff; Ziyaur Rahman; Mohammad T H Nutan; Mansoor A Khan

doi:10.1007/s11095-024-03689-z

Development and Validation of Matrix of Chemistry, Manufacturing, and Control (MoCMC) System for Intramammary Drug Products (IMM)

Pharm Res. 2024 Apr 1. doi: 10.1007/s11095-024-03689-z. Online ahead of print.

Authors

Nada A Helal¹, Marilyn N Martinez², David G Longstaff², Ziyaur Rahman¹, Mohammad T H Nutan¹, Mansoor A Khan³

Affiliations

¹ Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, TX, USA.
² US FDA Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Rockville, MD, USA.
³ Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, TX, USA. mkhan@tamu.edu.

PMID: 38561579
DOI: 10.1007/s11095-024-03689-z

Abstract

Purpose: Products formulated for intramammary (IMM) infusion are intended for the delivery of therapeutic moieties directly into the udder through the teat canal to maximize drug exposure at the targeted clinical site, the mammary gland, with little to no systemic drug exposure. Currently, to our knowledge, there has been no in-vitro matrix system available to differentiate between IMM formulations. Our goal is to develop A custom tailored in-vitro "Matrix of Chemistry, Manufacturing and Control" (MoCMC) System to be a promising future tool for identifying inequivalent IMM formulations. MoCMC can detect inter and intra batch variabilities, thereby identifying potential generics versus brand product similarities or differences with a single numeric value and a specific & distinctive fingerprint.

Methods: The FDA-approved IMM formulation, SPECTRAMAST^Ⓡ LC, was selected as the reference product for the MoCMC. Twelve in-house test formulations containing ceftiofur hydrochloride were formulated and characterized. The MoCMC was developed to include six input parameters and three output parameters. The MoCMC system was used to evaluate and compare SPECTRAMAST^Ⓡ LC with its in-house formulations.

Results: Based on the MoCMC generated parameters, the distinctive fingerprints of MoCMC for each IMM formulations, and the statistical analyses of MCI and PPI values, in-house formulations, F-01 and F-02 showed consistency while the rest of in-house formulations (F-03-F-12) were significantly different as compared to SPECTRAMAST^Ⓡ LC.

Conclusion: This research showed that the MoCMC approach can be used as a tool for intra batch variabilities, generics versus brand products comparisons, post-approval formulations changes, manufacturing changes, and formulation variabilities.

Keywords: in-vitro release; in-vivo; chemistry, manufacturing and control; generic product; intramammary; matrix; particle size analysis; physicochemical characterization.

Grants and funding

FDABAA-21-00123/Center for Veterinary Medicine