Root cause analysis investigation of visible particulates in therapeutic protein drug products using morphologically directed Raman spectroscopy

DP:

Drug product

ES:

ETFE size

ETFE:

Ethylene tetrafluoroethylene

FTIR:

Fourier transform infrared spectroscopy

MDRS:

Morphologically directed Raman spectroscopy

mAb:

Monoclonal antibody

NIST:

National Institutes of Standards and Technology

PCA:

Principal component analysis

PC:

Principal component

PS:

Polystyrene

RCA:

Root cause analysis

USP:

United States Pharmacopeia

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Authors and Affiliations

1. Division of Pharmaceutical Quality Research VI, Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA

   Isabella F. de Luna, Thomas O’Connor, Scott Lute & Ashwinkumar Bhirde

2. Division of Product Quality Assessment II (DPQAII), Office of Product Quality Assessment (OPQA I), Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA

   Charudharshini Srinivasan

3. Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD, USA

   Srivalli N. Telikepalli, Michael Carrier & Dean Ripple

Contributions

I.D. designed and performed the experiments, analyzed the data, and wrote the paper, S.T. provided the NIST candidate reference materials, analyzed the data, and revised the paper, M.C. provided the NIST candidate reference materials and revised the paper, D.R. revised the paper, C.S. revised the paper, T.C. revised the paper, S.L. revised the paper, and A.B. designed the experiments, analyzed the data, and wrote the paper.

Corresponding author

Correspondence to Ashwinkumar Bhirde.

Competing interests

The authors declare no competing interests.

Disclaimer

This manuscript reflects the views of the author and should not be construed to represent FDA’s or NIST’s views or policies. Certain commercial equipment, instruments, or materials are identified in this manuscript to foster understanding. Such identification does not imply recommendation or endorsement by FDA or the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. This work was carried out in part in the NIST Center for Nanoscale Science and Technology NanoFab.

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