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Quality-by-Design Concepts to Improve Nanotechnology-Based Drug Development

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Abstract

The purpose of this review is to discuss the challenges associated with the development of nanoparticle-based quality drug products in adhering to the principles of quality by design (QbD) and defining appropriate quality parameters towards successful product development. With the advent of nanotechnology into the pharmaceutical field, the novel field of nanomedicine was born. Due to their unique properties in terms of size, conformation and targeted delivery, nanomedicines are able to overcome many drawbacks of conventional medicine. As nano-sized formulations have made their way into more and more therapies, it has became clear that these very unique properties create hurdles for nanomedicines in successfully traversing the regulatory pathways and there is a need to develop nanomedicines in a more controlled and consistent fashion. The elements of a QbD methodology explained in this review enable the development of nano-based formulations in a way that maximizes the possibility of success. The identification of critical quality attributes (CQA) of the drug product and its intermediates are discussed in detail with a focus on nanomaterial-based formulations. In conclusion, QbD and the identification and specification of CQAs at its core are critical to the design, development and growth of nanomaterials in pharmaceuticals.

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Abbreviations

ADME:

Absorption, Distribution, Metabolism and Excretion

ANDA:

Abbreviated new drug application

API:

Active pharmaceutical ingredients

CE:

Coating efficiency

CMC:

Chemistry, Manufacturing and Controls

CPP:

Critical process parameter

CQA:

Critical quality attribute

DLS:

Dynamic light scattering

DS:

Design space

EDAX:

Energy dispersive analysis of X-ray

EE:

Encapsulation efficiency

ELISA:

Enzyme-Linked immunosorbent assay

EU-NCL:

European nanomedicine characterization lab

FDA:

Food and drug administration (United States)

FMEA:

Failure mode and effects analysis

GRAS:

Generally regarded as safe

ICH:

International conference on harmonisation

IND:

Investigational new drug

IVIVC:

In Vitro In Vivo correlation

MPS:

Mononuclear phagocyte system

NCI:

National cancer institute

NCL:

National characterization lab

NIR:

Near Infra-Red

NNI:

National nanotechnology initiative

NTA:

Nanoparticle tracking analysis

PALS:

Phase analysis light scattering

PAT:

Process analytical technology

PCR:

Polymerase chain reaction

PDI:

Polydispersity index

PEG:

Polyethylene glycol

PK/PD:

Pharmacokinetics/Pharmacodynamics

QbD:

Quality by design

QbT:

Quality by testing

QTPP:

Quality target product profile

PKM:

Process knowledge map

PLA:

Polylactic acid

PLGA:

Poly(Lactic-co-Glycolic Acid)

PSMA:

Prostate specific membrane antigen

SANS:

Small Angle neutron scattering

SAXS:

Small angle X-ray scattering

SEC:

Size exclusion chromatography

TOF-SIMS:

Time-of-flight secondary ion mass spectrometry

TRPS:

Tunable resistive pulse sensing

XPS:

X-ray photoelectron spectroscopy

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Authors and Affiliations

  1. AllExcel Inc., 1 Controls Drive, Shelton, Connecticut, 06484, USA

    Meghana Rawal

  2. PureTech Health, 6 Tide Street, Boston, Massachusetts, 02110, USA

    Amit Singh

  3. Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts, 02115, USA

    Mansoor M. Amiji

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  1. Meghana Rawal
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Correspondence to Meghana Rawal.

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Rawal, M., Singh, A. & Amiji, M.M. Quality-by-Design Concepts to Improve Nanotechnology-Based Drug Development. Pharm Res 36, 153 (2019). https://doi.org/10.1007/s11095-019-2692-6

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