Q3B – Impurities in New Drug Products

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Q3B – Impurities in New Drug Products

This Guideline has been first revised and finalised under Step 4 in February 2003. It complements the Guideline on impurities in new drug substances and provides advice in regard to impurities in products containing new, chemically synthesized drug substances. The Guideline specifically deals with those impurities which might arise as degradation products of the drug substance, or arising from interactions between drug substance and excipients or components of primary packaging materials. The Guideline sets out a rationale for the reporting, identification and qualification of such impurities based on a scientific appraisal of likely and actual impurities observed, and of the safety implications, following the principles elaborated in the parent Guideline. Threshold values for reporting and control of impurities are proposed, based on the maximum daily dose of the drug substance administered in the product.

The Attachment 2 of this Guideline has been revised under Step 4 without further public consultation on 2 June 2006 (Q3B(R2)).

The ICH Harmonised Guideline was finalised under Step 4 in July 1997. This document covers the preclinical safety testing requirements for biotechnological products. It addresses the use of animal models of disease, determination of when genotoxicity assays and carcinogenicity studies should be performed, and the impact of antibody formation on duration of toxicology studies.

An addendum was proposed to provide clarification on S6 and an update of the following topics discussed in the original ICH S6 Guideline: species selection, study design, immunogenicity, reproductive and developmental toxicity and assessment of carcinogenic potential. The Harmonised addendum provides further complementary guidance to the S6 Guideline and helps to define the current recommendations and reduce the likelihood that substantial differences will exist among regions.

The addendum reached Step 4 of the harmonisation process in June 2011 and was integrated as part II in the core Guideline that was then renamed S6(R1).

Guideline

Q3B(R2) Guideline

Annexes

Guideline implementation

ANMAT, Argentina

Not yet implemented;

ANVISA, Brazil

In the process of implementation; Date: 24 February 2025; Reference: RDC 964/2025

COFEPRIS, Mexico

In the process of implementation; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0.

EC, Europe

Implemented; Date: 1 June 2006; Reference: CPMP/ICH/2738/99

EDA, Egypt

Implemented; Date: 31 December 2015; Reference: (Egyptian Guidelines on CTD Quality Module for Human Pharmaceuticals) and (Guidelines for File Assessment for Pharmaceutical Products for Human Use)

FDA, United States

Implemented; Date: 1 November 2003; Reference: Vol, 68, No. 220, p. 64628-9

HSA, Singapore

Implemented; Date: 1 January 2008; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance.

Health Canada, Canada

Implemented; Date: 15 June 2015; Reference: File #: 15-106634-508

JFDA, Jordan

Implemented; Date: 1 March 2008;

MFDS, Republic of Korea

Implemented; Date: 30 July 2018; Reference: Impurities in New Drug Products[Guideline-0877-01]

MHLW/PMDA, Japan

Implemented; Date: 1 July 2006; Reference: PFSB/ELD Notification No. 0703004

MHRA, UK

Implemented; Date: 1 June 2006;

NAFDAC, Nigeria

Not yet implemented;

NMPA, China

Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 7 (2020)

SAHPRA, South Africa

Implemented; Date: 1 May 2003; Reference: SAHPGL-PEM-02

SFDA, Saudi Arabia

Implemented; Date: 22 September 2011;

Swissmedic, Switzerland

Implemented; Date: 2 June 2006; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504

TFDA, Chinese Taipei

Implemented; Date: 26 October 2021; Reference: Guidance for Impurities in New Drug Substances and New Drug Products

TITCK, Türkiye

Implemented; Date: 11 December 2021; Reference: Q3B(R2) is referred to in Guideline on Requirements for Quality of Biological İnvestigational Medicinal Products in Clinical Trials; and Guideline on Common Technical Document (CTD)