Directive ICH Q3D aims to limit the presence of potentially toxicelemental impurities (also known as heavy metals) in pharmaceutical products intended for human use. This directive is linked to changes in the pharmacopoeias (Ph.Eur. & USP) with the introduction of new, safer, more selective and precise analytical methods with greater reproducibility and better recovery. Likewise the directive establishes the toxicity limits of potentially present elements. Directive ICH Q3D sets out a list of 24 elements divided into four categories (classes 1, 2A, 2B and 3), in relation to their toxicity and their probability of occurrence and the maximum permitted daily exposure (PDE: Permitted Daily Exposure) for each impurity according to the administration route (µg / day).

1. ICH Q3D
Risk evaluation for
elemental impurities
GUIDELINE FOR ELEMENTAL IMPURITIES

2. INTRODUCTION

3. • Substances non-intentional added with a therapeutical purpose.
• Impurities could be organic molecules, residual solvents or inorganic compounds.
• Impurities don’t have a therapeutical effect and they are potentially toxic
> Their presence must be limited.
> Their levels must be managed within aceptable limits for health.
• Inorganic elements.
• Elemental impurities are commonly called “heavy metals” and they are to be
considered for the risk evaluation.
Which elemental impurities do we have to take into account?
ELEMENTAL
IMPURITIES INTRODUCTION

4. 4
INTRODUCTION

5. 5
INTRODUCTION
‘Heavy metals’
Low detailed assessment
Old-fashioned methods
It doesn’t allow specialization
Lack of sensitivity
Low and variable recoveries for many
metals
Limits between 5 and 20 ppm
ICH Q3D :
‘Heavy Metals’ vs ICH Q3D
ICH Q3D
Totally detailed assessment
Updated methods
(ICP-MS, etc.)
Analysis of every element
Sensitivity and accuracy…
High and reliable recoveries for all metals
Differentiation between current elements
according its toxicological profile

6. IMPLEMENTATION

7. 7
IMPLEMENTATION
Guideline ICH Q3D
December: ICH
ICH Q3D, phase 4
2015
January: EMA
ICH Q3D (step 5)
December: USP
USP <232> and <233>
May: USP
Realease of USP <232> and <233> cancellation USP
<231>
2016
February: ICH
Release of training
June: EMA
ICH Q3D is applicable to New Marketing
Authorization.
2017
Enero: Ph. Eur. 9º edition.
Diciembre: EMA
ICH Q3D is applicable to all existing
products
2018
January: Ph. Eur and USP
2009 – 2013
2014
IMPLEMENTATION

8. ICH Q3D

9. 9
ICH Q3D is steered to limit the presence of
elemental impurities, potentially toxic, in
human use medicines
ICH Q3D

10. 10
ICH Q3D guideline contains:
Scope
A list with 24 elements classified in 4 categories, according to its toxicity and
probability to occur
PDE: Maximum admissible daily dose (PDE: Permitted daily exposure) for every
single impurity depending on route of administration (µg/day)
Análisis de riesgo: General principles to carry out a risk analysis to assess if
there is any risk of presence of one o more Elemental Impurities in a
significative quantity according to control treshold.
Control: A management strategy based on the outcome of the risk analysis
ICH Q3D

11. ICHQ3D
PDEPDEs for any elemental impurity

12. We design and develop tailored made action plans to implement this guideline
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Excipients
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