Q3A – Impurities in New Drug Substances

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Q3A – Impurities in New Drug Substances

First recommended for adoption at Step 4 of the ICH Process on 30 March 1995, the Guideline was revised under Step 2 of the ICH Process on 7 October 1999 and finalised under Step 4 on 7 February 2002 (Q3A(R1)).

The Guideline addresses the chemistry and safety aspects of impurities, including the listing of impurities in specifications and defines the thresholds for reporting, identification and qualification. The revision of the Guideline has allowed clarifying some inconsistencies, to revise the decision tree, to harmonise with Q3B and to address some editorial issues.

The Attachment 2 of this Guideline has been revised under Step 4 without further public consultation on 25 October 2006 (Q3A(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

Q3A(R2) Guideline

Annexes

Guideline implementation

ANMAT, Argentina

Not yet implemented;

ANVISA, Brazil

Implemented; Date: 3 August 2020; Reference: RDC 359/2020 and RDC 753/2022

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 October 2006; Reference: CPMP/ICH/2737/99

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 June 2008; Reference: Published in the Federal Register

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: 5 June 2015; Reference: File #: 15-106606-354

JFDA, Jordan

Implemented; Date: 1 March 2008;

MFDS, Republic of Korea

Implemented; Date: 22 June 2018; Reference: Regulation on Pharmaceuticals Approval, Notification and Review [MFDS, Republic of Korea Notification]

MHLW/PMDA, Japan

Implemented; Date: 1 December 2006; Reference: PFSB/ELD Notification No. 1204001

MHRA, UK

Implemented; Date: 1 October 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: 25 October 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: Q3A(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)