Draft guideline on the pharmaceutical quality of inhalation and nasal medicinal products

Guideline on the pharmaceutical quality of inhalation and
nasal medicinal products

18

Table of contents

19

Executive summary ..................................................................................... 3

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1.

49

Definitions ................................................................................................. 29

16

50
51

Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024

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52

Executive summary

53

This guideline is the first revision of the guideline on pharmaceutical quality of inhalation and nasal

54

products (EMEA/CHMP/QWP/49313/2005 Corr).

66

safety testing (e.g., for excipients and leachables) is also considered.

Detailed guidance on pharmaceutical development study designs (e.g., priming studies) and the

70

analytical procedures primarily used for inhalation and nasal medicinal products (e.g., cascade

71

impactor analysis) is not included in this guideline.

74

The guideline addresses requirements "on the quality of inhalation and nasal medicinal products" in

75

new marketing authorisation applications, including abridged applications.

88

excluded, however the general principles described in this guideline should be considered.

Different polymorphic forms including any amorphous content could affect the quality or performance

119

of the finished medicinal product.

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132

The primary packaging, type of inhaler and, if necessary, the secondary packaging or other

133

components required for reasons of stability should be described.

(a) Physical
characterisation
(b) Minimum fill
justification
(c) Extractable
volume

Pressurised

Dry powder

Preparations for

Non-

metered-

inhalers (DPI)

nebulisation

pressurised

dose

metered-

Device-

Pre-

Single-

Multi-

(pMDI)

metered

metered

dose

dose

inhalers

Yesa

Yes

Yes

Yesa

Yesa

Yesa

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No

Yes

No

No

inhalers

Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024

dose

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Table 4.2.1.

Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024

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179

the inhaler as defined by the label claim, should meet the finished medicinal product specification limits

180

for delivered dose and fine particle dose.

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263
264

4.2.2.8.

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345

Instructions regarding cold temperature use should be provided in the product information.

Pressurised

Dry powder inhalers

Preparations for

metered-

(DPI)

nebulisation

dose

Nonpressurised
metered-dose

Device-

Pre-

Single-

Multi-

(pMDI)

metered

metered

dose

dose

inhalers

(a) Description

Yes

Yes

Yes

Yes

Yes

Yes

(b) Assay

Yes

Yes

Yes

Yes

Yes

Yes

(c) Moisture content

Yes

Yes

Yes

No

No

No

Yes

Yes

Yes

No

No

Yes

Yes

Yes

Yes

No

No

Yes

specification test

(d) Mean delivered
dose
(e) Uniformity of
delivered dose

inhalers

Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024

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Table 4.2.2.

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510

4.2.5.4.

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552

medicinal product.

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586

All medical devices, including inhalers and nasal devices, have to fulfil the general requirements as

587

outlined in the Medical Device Regulation (EU) 2017/745.

598

All inhalation medicinal products should be tested on stability against the stability indicating tests

599

included in the finished medicinal product specification.

619

described in this guideline should be met, supplemented by appropriate comparative quality and

620

clinical data with respect to the chosen reference medicinal product.

For inhalation medicinal products comparative in vitro data between the abridged application medicinal

622

product and the reference medicinal product must be provided.

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670

Nature and contents of container: The type of the device and its components should be listed.

695

Inhalation and nasal medicinal products have many similarities and therefore, most of the

696

requirements specified for inhalation medicinal products in section 4 also apply for nasal medicinal

697

products.

698

particle/droplet size of the finished medicinal product.

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704

5.2.

Pressurised

Nasal

metered-

powders,

dose nasal

device-

spray

metered

NonSingledose
drops

Multidose
drops

Single-

pressurised

dose

multidose

spray

metereddose spray

(a) Physical
characterisation
(b) Minimum fill
justification
(d) Extractables /
leachables

Yesa

Yes

Yesa

Yesa

Yesa

Yesa

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

Yes

Yes

Yes

Yes

Yes

Yes

No

No

Yes

Yes

Yes

Yes

No

No

No

Yes

Yes

Yes

No

No

Yes

Yes

(f) Particle /
droplet size
distribution
(g) Uniformity of
delivered dose
through container
life
(j) Actuator /
mouthpiece
deposition

Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024

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Table 5.2.1.

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728

5.2.2.2.

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769

5.2.5.

799

this guideline should be met, supplemented by appropriate comparative quality and clinical data with

800

respect to the chosen reference medicinal product.

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849

5.5.

Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024

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867

Definitions
Activation:

The act of setting in motion the delivery device.

The sum of component(s) of the container closure system responsible for
delivering the active substance to the respiratory tract (inhalation medicinal
product) or the nasal and/or pharyngeal region (nasal medicinal product).

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Label claim:

The amount of active substance (usually on a per actuation basis) declared
on the label of the medicinal product.

A finished medicinal product (including the delivery device, where

product:

applicable) whose intended site of deposition is the nasal and/or pharyngeal
region.

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