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Guideline on the requirements for demonstrating
therapeutic equivalence between orally inhaled products
(OIP) for asthma and chronic obstructive pulmonary
disease (COPD)
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Table of contents
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Executive summary ..................................................................................... 4
24
1.
- Primary PK parameters to be analysed and acceptance criteria .............................. 14
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Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
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6.4.
- Definitions ........................................................................................... 18
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List of Abbreviations.................................................................................. 20
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Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
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Executive summary
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This guideline is the 2nd revision of the CHMP Guideline formerly called ?Guideline on the requirements
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for clinical documentation for orally inhaled products (OIP) including the requirements for
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demonstration of therapeutic equivalence between two inhaled products for use in the treatment of
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asthma and chronic obstructive pulmonary disease (COPD) in adults and for use in the treatment of
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asthma in children and adolescents?.
- It addresses the requirements for demonstration of therapeutic
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equivalence (TE) between orally inhaled products containing the same active moiety(ies).
- It is generally not recommended to aim at demonstrating TE using pharmacodynamic
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or clinical endpoints as these are deemed insensitive.
- This
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guideline is directed particularly at the requirements for demonstrating TE between OIPs containing the
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same active moiety(ies) and used in the management and treatment of patients with asthma and/or
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COPD.
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The guideline was first published as points to consider in 2004 and revised for the first time and
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became guideline in 2009.
- Since then, a number of Q&A documents have been published by Quality
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Working Party (QWP) and former Pharmacokinetic Working Party (PKWP).
- Scope
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This document provides guidance on the requirements for demonstrating TE between OIPs, including
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both, single active substance products and combination products.
- Also, in the case that there is a need
Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
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to confirm similarity to a product for which literature data is available (e.g., well-established use
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applications), the same principles apply.
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4.
- Products for nebulisation
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This guideline applies also for products for nebulisation although it is acknowledged that the
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performance of these is highly dependent on the nebuliser used.
- In vitro criteria for demonstrating TE
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The test and reference products should be compared in order to conclude on TE.
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2.
- Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
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6.2.
- Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
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6.3.
- If the
Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
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different strengths of the test and the reference product are not shown to be proportional in vitro, in
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vivo equivalence should be demonstrated with a bracketing approach.
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6.4.
- Griffin, 1964
Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
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which both reference product-na?ve and experienced users should be included.
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10.
- Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
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Product strength
Product strength may be either the delivered
dose or the metered dose.
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List of Abbreviations
APSD
Aerodynamic Particle Size Distribution
AUC
Area Under the Curve
CHMP
Committee for Medicinal Products for Human
Use
CI
Confidence Interval
Cmax
Peak concentration
COPD
Chronic Obstructive Pulmonary Disease
DPI
Dry Powder Inhaler
FPD
Fine Particle Dose
GI
Gastrointestinal
ICH
International Conference on Harmonisation
IVIVC
In vitro in vivo correlation
MDI
Metered Dose Inhaler
OIP
Orally Inhaled Product
PD
Pharmacodynamic
PK
Pharmacokinetic
pMDI
Pressurised Metered Dose Inhaler
QWP
Quality Working Party
SmPC
Summary of Product Characteristics
TE
Therapeutic equivalence
tmax
Time to peak concentration
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Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
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