- 17
Guideline on the pharmaceutical quality of inhalation and
nasal medicinal products
18
Table of contents
19
Executive summary ..................................................................................... 3
20
1.
- Lifecycle management ........................................................................................ 28
49
Definitions ................................................................................................. 29
16
50
51
Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 2/30
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).
- Quality aspects specific to inhalation and nasal medicinal products are discussed, the need for
66
safety testing (e.g., for excipients and leachables) is also considered.
- 69
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.
- Scope
74
The guideline addresses requirements "on the quality of inhalation and nasal medicinal products" in
75
new marketing authorisation applications, including abridged applications.
- Liquid inhalation anaesthetics and nasal ointments, creams and gels are
88
excluded, however the general principles described in this guideline should be considered.
- 118
Different polymorphic forms including any amorphous content could affect the quality or performance
119
of the finished medicinal product.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 4/30
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.
- Pharmaceutical
development study
(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
Page 5/30
Table 4.2.1.
- The last doses delivered by
Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 7/30
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.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 9/30
263
264
4.2.2.8.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 11/30
345
Instructions regarding cold temperature use should be provided in the product information.
- Finished medicinal
product
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
Page 15/30
Table 4.2.2.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 16/30
510
4.2.5.4.
- The proposed specification limits should take into account the shelf-life performance of the
Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 17/30
552
medicinal product.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 18/30
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.
- Stability (CTD 3.2.P.8)
598
All inhalation medicinal products should be tested on stability against the stability indicating tests
599
included in the finished medicinal product specification.
- Quality data requirements as
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.
- 621
For inhalation medicinal products comparative in vitro data between the abridged application medicinal
622
product and the reference medicinal product must be provided.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 20/30
670
Nature and contents of container: The type of the device and its components should be listed.
- Nasal medicinal products
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.
- One difference between inhalation and nasal medicinal products is the desired
698
particle/droplet size of the finished medicinal product.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 21/30
704
5.2.
- Nasal liquids
Pharmaceutical
development
study
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
Page 22/30
Table 5.2.1.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 23/30
728
5.2.2.2.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 24/30
769
5.2.5.
- Quality data requirements as described in
799
this guideline should be met, supplemented by appropriate comparative quality and clinical data with
800
respect to the chosen reference medicinal product.
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 27/30
849
5.5.
- 866
Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 28/30
867
Definitions
Activation:
The act of setting in motion the delivery device.
- 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).
- Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 29/30
Label claim:
The amount of active substance (usually on a per actuation basis) declared
on the label of the medicinal product.
- Nasal medicinal
A finished medicinal product (including the delivery device, where
product:
applicable) whose intended site of deposition is the nasal and/or pharyngeal
region.
- 868
Guideline on the pharmaceutical quality of inhalation and nasal medicinal products
EMA/CHMP/20607/2024
Page 30/30
