FDA issues ICH Q12 guidance and others on clinical trials, safety testing and biowaivers
Regulatory News | 11 May 2021 |
The US Food and Drug Administration (FDA) on 11 May made available an International Council for Harmonisation’s (ICH) guideline on postapproval changes for drug products and issued four other final ICH documents and one draft guidance.
The ICH Q12 guideline aims to facilitate the management of postapproval chemistry, manufacturing and controls (CMC) changes for new and marketed pharmaceuticals and drug substances and is the same as the version endorsed by ICH as a step 4 document in November 2019.
“Effective implementation of this guidance will provide an opportunity for the FDA to focus attention and resources on higher risk postapproval changes, incentivizing manufactures with additional flexibilities to continually improve their manufacturing processes, which can reduce the likelihood of quality-related supply disruptions and related drug shortages,” Michael Kopcha, director of the Office of Pharmaceutical Quality said in a statement.
Changes from the draft remove the terms “implicit” and “explicit” as referred to as established conditions, removes the term “key process parameters,” and offers examples of the concept of critical process parameters. Other changes include a revision of the description for identifying established conditions for analytical methods, revisions to the product lifecycle management document and its location within the Common Technical Document, and editorial changes to improve clarity.
Most of the comments FDA received on the 2018 draft guideline expressed concerns that two of the central aspects of the guidelines, established conditions (ECs) and product lifecycle management (PCML) documents, are incompatible with the legal framework of certain ICH regions. (RELATED: Industry comments on ICH product lifecycle management guideline, Regulatory Focus, 21 January 2019).
FDA also published the Annex to ICH Q12 which contains illustrative examples describing how to use the principles in the guidance as a framework for managing postapproval changes.
Final M9
The final version of the ICH M9 guidance on biowaivers was among those issued by FDA. The guidance aims to reduce the need for human bioequivalence (BE) studies for certain products based on extensive in vitro characterization of the drug substance and the drug product. (RELATED: FDA consults on ICH biopharmaceutics classification system-based biowaivers guideline, Regulatory Focus 25 October 2018).
The guidance establishes a biopharmaceutical classification system (BCS) that categorizes drug substances into one of four BCS classes: Class I for high solubility, and high permeability, Class II for low solubility and high permeability and Class III for high solubility and low permeability and Class I for low solubility and low permeability. The BCS-biowaiver only applies to immediate release, solid oral dosage forms or suspensions designed to deliver a drug into systemic circulation. Fixed-dose combination products are eligible for the waiver if all included active drug substances meet the criteria, while products with a narrow therapeutic index are excluded.
Final E9(R1)
FDA also endorsed the final ICH E9(R1) guideline on statistical principles for clinical trials. The document describes a framework for planning, conducting and interpreting sensitivity analysis of clinical trial data. A final draft of the guideline was submitted to the ICH Assembly and endorsed by the regulators in November 2019. (RELATED: Industry seeks clarity on ICH guideline on estimands and sensitivity analysis in clinical trials, Regulatory Focus 1 May 2018).
Final S11
The final version of ICH’s guidance on nonclinical safety testing to support the development of pediatric pharmaceuticals received a nod from FDA as well. The guidance provides a “weight of evidence” approach to determine nonclinical toxicity studies. It was revised from the former version by refining the weight of evidence approach. (RELATED: ICH adopts S11 guideline on nonclinical safety testing for pediatric drugs, Regulatory Focus 14 April 2020).
Final S5(R3)
FDA also issued the final version of the ICH S5(R3) guideline which provides recommendations for developing a testing strategy to assess reproductive risk for pharmaceuticals.
Draft ICH Q3D(R2)
Lastly, FDA announced the availability of the draft ICH Q3D(R2) guideline on elemental impurities which provides permissible daily exposures (PDEs) for the cutaneous and transcutaneous routes of administration. In addition, the guideline amends a previous version by correcting previously identified PDEs for gold, silver and nickel.
FDA announcement of availability of ICH guidances
The ICH Q12 guideline aims to facilitate the management of postapproval chemistry, manufacturing and controls (CMC) changes for new and marketed pharmaceuticals and drug substances and is the same as the version endorsed by ICH as a step 4 document in November 2019.
“Effective implementation of this guidance will provide an opportunity for the FDA to focus attention and resources on higher risk postapproval changes, incentivizing manufactures with additional flexibilities to continually improve their manufacturing processes, which can reduce the likelihood of quality-related supply disruptions and related drug shortages,” Michael Kopcha, director of the Office of Pharmaceutical Quality said in a statement.
Changes from the draft remove the terms “implicit” and “explicit” as referred to as established conditions, removes the term “key process parameters,” and offers examples of the concept of critical process parameters. Other changes include a revision of the description for identifying established conditions for analytical methods, revisions to the product lifecycle management document and its location within the Common Technical Document, and editorial changes to improve clarity.
Most of the comments FDA received on the 2018 draft guideline expressed concerns that two of the central aspects of the guidelines, established conditions (ECs) and product lifecycle management (PCML) documents, are incompatible with the legal framework of certain ICH regions. (RELATED: Industry comments on ICH product lifecycle management guideline, Regulatory Focus, 21 January 2019).
FDA also published the Annex to ICH Q12 which contains illustrative examples describing how to use the principles in the guidance as a framework for managing postapproval changes.
Final M9
The final version of the ICH M9 guidance on biowaivers was among those issued by FDA. The guidance aims to reduce the need for human bioequivalence (BE) studies for certain products based on extensive in vitro characterization of the drug substance and the drug product. (RELATED: FDA consults on ICH biopharmaceutics classification system-based biowaivers guideline, Regulatory Focus 25 October 2018).
The guidance establishes a biopharmaceutical classification system (BCS) that categorizes drug substances into one of four BCS classes: Class I for high solubility, and high permeability, Class II for low solubility and high permeability and Class III for high solubility and low permeability and Class I for low solubility and low permeability. The BCS-biowaiver only applies to immediate release, solid oral dosage forms or suspensions designed to deliver a drug into systemic circulation. Fixed-dose combination products are eligible for the waiver if all included active drug substances meet the criteria, while products with a narrow therapeutic index are excluded.
Final E9(R1)
FDA also endorsed the final ICH E9(R1) guideline on statistical principles for clinical trials. The document describes a framework for planning, conducting and interpreting sensitivity analysis of clinical trial data. A final draft of the guideline was submitted to the ICH Assembly and endorsed by the regulators in November 2019. (RELATED: Industry seeks clarity on ICH guideline on estimands and sensitivity analysis in clinical trials, Regulatory Focus 1 May 2018).
Final S11
The final version of ICH’s guidance on nonclinical safety testing to support the development of pediatric pharmaceuticals received a nod from FDA as well. The guidance provides a “weight of evidence” approach to determine nonclinical toxicity studies. It was revised from the former version by refining the weight of evidence approach. (RELATED: ICH adopts S11 guideline on nonclinical safety testing for pediatric drugs, Regulatory Focus 14 April 2020).
Final S5(R3)
FDA also issued the final version of the ICH S5(R3) guideline which provides recommendations for developing a testing strategy to assess reproductive risk for pharmaceuticals.
Draft ICH Q3D(R2)
Lastly, FDA announced the availability of the draft ICH Q3D(R2) guideline on elemental impurities which provides permissible daily exposures (PDEs) for the cutaneous and transcutaneous routes of administration. In addition, the guideline amends a previous version by correcting previously identified PDEs for gold, silver and nickel.
FDA announcement of availability of ICH guidances
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