Draft guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and chronic obstructive pulmonary disease (COPD)

Guideline on the requirements for demonstrating
therapeutic equivalence between orally inhaled products
(OIP) for asthma and chronic obstructive pulmonary
disease (COPD)

22

Table of contents

23

Executive summary ..................................................................................... 4

24

1.

43

Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
EMA/CHMP/101453/2024

51

6.4.

56

List of Abbreviations.................................................................................. 20

57

Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
EMA/CHMP/101453/2024

58

Executive summary

59

This guideline is the 2nd revision of the CHMP Guideline formerly called ?Guideline on the requirements

60

for clinical documentation for orally inhaled products (OIP) including the requirements for

61

demonstration of therapeutic equivalence between two inhaled products for use in the treatment of

62

asthma and chronic obstructive pulmonary disease (COPD) in adults and for use in the treatment of

63

asthma in children and adolescents?.

64

equivalence (TE) between orally inhaled products containing the same active moiety(ies).

70

or clinical endpoints as these are deemed insensitive.

83

guideline is directed particularly at the requirements for demonstrating TE between OIPs containing the

84

same active moiety(ies) and used in the management and treatment of patients with asthma and/or

85

COPD.

The guideline was first published as points to consider in 2004 and revised for the first time and

87

became guideline in 2009.

88

Working Party (QWP) and former Pharmacokinetic Working Party (PKWP).

93

This document provides guidance on the requirements for demonstrating TE between OIPs, including

94

both, single active substance products and combination products.

Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
EMA/CHMP/101453/2024

98

to confirm similarity to a product for which literature data is available (e.g., well-established use

99

applications), the same principles apply.

132

4.

177

This guideline applies also for products for nebulisation although it is acknowledged that the

178

performance of these is highly dependent on the nebuliser used.

206

The test and reference products should be compared in order to conclude on TE.

211
212

2.

353

6.2.

392

6.3.

432

different strengths of the test and the reference product are not shown to be proportional in vitro, in

433

vivo equivalence should be demonstrated with a bracketing approach.

471

6.4.

Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
EMA/CHMP/101453/2024

553

which both reference product-na?ve and experienced users should be included.

Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
EMA/CHMP/101453/2024

569

10.

Product strength

Product strength may be either the delivered
dose or the metered dose.

Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
EMA/CHMP/101453/2024

571

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

572

Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and
chronic obstructive pulmonary disease (COPD)
EMA/CHMP/101453/2024