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Review on Implementation of Multivariate Approach for Forced Degradation Study and Impurity Profiling with Regulatory Considerations

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Abstract

Understanding of shelf-life, expiry periods, degradation kinetics, stability indications, and impurity profiling is of major concern. The present review focuses on the quality-by-design (QbD) approach for optimizing forced degradation conditions for impurity profiling. Analytical issues occurring at the last stage of long-term stability studies are related to unpredicted impurities, which can disturb monitoring of characterized impurities and raise many regulatory issues. The QbD multivariate approach was evaluated within the framework of the liquid chromatography (LC) method. The initial investigation is concerned with critical process parameters which can impact on critical quality attributes. Selection of primary and secondary parameters to define a design space with the help of a polynomial equation and Derringer’s desirability value is considered next. Sorting impurities using the multivariate design-of-experiments (DoE) approach can also be beneficial to reduce time and cost, whilst providing a robust process. Much emphasis is given to application of Q8 and Q9 International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines to improve quality, safety, and efficacy studies.

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Abbreviations

ANOVA:

Analysis of variance

ATPP:

Analytical target product profile

AQbD:

Analytical quality by design

C-CAD:

Corona charged aerosol detector

CPP:

Critical process parameter

CQA:

Critical quality attribute

DoE:

Design of experiments

DS:

Design space

DAHHB:

Diethylamino hydroxybenzoyl hexyl benzoate

FMEA:

Failure mode effect analysis

FMECA:

Failure mode, effects, and criticality analysis

ELSD:

Evaporative light scattering detector

FTA:

Fault tree analysis

GLC:

Gas–liquid chromatography

HACCP:

Hazard analysis and critical control points

ICH:

International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use

LOD:

Limit of detection

LOQ:

Limit of quantification

LC–MS/MS:

Liquid chromatography–tandem mass spectroscopy

MP:

Methyl paraben

MEKC:

Micellar electrokinetic chromatography

MFAT:

Multiple factors at a time

OCT:

Octinoxate

OFAT:

One factor at a time

PHA:

Primary hazard analysis

PP:

Propyl paraben

QTPP:

Quality target product profile

QbD:

Quality by design

QbT:

Quality by testing

TPP:

Target product profile

USFDA:

United States Food and Drug Administration

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  1. Department of Pharmaceutical Analysis, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Post: Chandlodia, Via, Gota, Ahmadabad, Gujarat, 382 481, India

    Mital N. Patel & Charmy S. Kothari

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Patel, M.N., Kothari, C.S. Review on Implementation of Multivariate Approach for Forced Degradation Study and Impurity Profiling with Regulatory Considerations. Chromatographia 81, 105–125 (2018). https://doi.org/10.1007/s10337-017-3393-0

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