European Pharmacopoeia

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

Retrieved on:

torsdag, april 18, 2024

17

Key Points:

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
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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

Draft guideline on good agricultural and collection practice (GACP) for starting materials of herbal origin - Revision 1

Retrieved on:

torsdag, april 18, 2024

Reproduction, SCOPE, Eating, Pesticide, Convention, Change control, Confusion, Alkaloid, Climate, Fungus, Directive (European Union), Ethylene oxide, Wind, Wood, Glass, European Medicines Agency, HMPS, QDG, Hygiene, Water, Marketing, Fertilizer, Legislation, Manure, Distillation, Risk, Education, Committee, Compost, Draft, Policy, Person, EMA, Seed, Polycyclic aromatic hydrocarbon, Collection, Freezing, GMP, Risk assessment, GACP, Sunlight, Fermentation, Personal protective equipment, Animal, Herbal, Herbicide, Weather, INTRODUCTION, Documentation, Regeneration, Decontamination, EudraLex, Disease, International trade, European Pharmacopoeia, Part, Livestock, Public, Inhalation, Knowledge, Seedling, Factorization of polynomials, Record, Plant, Skin, API, Irrigation, Part Two, Soil, Directive, Pharmacopoeia, Codex, Guideline, Temperature, Attention, Hydrocarbon, Pyrrolizidine alkaloid, Polychlorinated biphenyl, Growth, Rotation, Incineration, Environment, Humidity, Smell, Ventilation, Light, Bird, Mineral, Fumigation, Pyrrolizidine, SOP, Housing, Smoking, Atmosphere, Postharvest, Rain, Liver, QWP, Medicinal plants

REFERENCES ....................................................................................................................................... 14

Key Points:

REFERENCES ....................................................................................................................................... 14
29

Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

Page 3/14

30

EXECUTIVE SUMMARY

31
32
33
34
35
36

This guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin

37

1.
Due to the inherent
complexity of medicinal plants and herbal substances the quality of these starting materials requires an
adequate quality assurance system for the collection and/or cultivation, harvest, and primary
processing.
(either outdoor, indoor or in greenhouses) should be carefully considered, since each of the mentioned
types could have several problems and advantages.
The used cultivation method may be dependent on
the final application of the herbal medicinal product.
primary processing of herbal substances that are used for the preparation of herbal medicinal products.
medicinal plants and herbal substances, ensuring that they are handled appropriately throughout all
stages of cultivation, collection, processing and storage.
their preparations are exposed to a large number of environmental contaminants of both biotic and
abiotic origin.
to existing wildlife habitats and must adhere to CITES (Convention on International Trade in
Endangered species of Wild Fauna and Flora).
https://health.ec.europa.eu/document/download/bd537ccf-9271-4230-bca1-2d...
4 https://health.ec.europa.eu/document/download/fd318dd6-2404-4e67-82b0232...
3
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

Page 5/14

104

4.
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005
Page 6/14

147
148
149

8.
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005
Page 7/14

185

7.
Where possible, stable varieties and cultivars naturally
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005
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227
228

resistant or tolerant to disease should preferably be used.
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005
Page 9/14

268
269
270
271
272
273

The application should be carried out only by qualified staff using approved equipment.
The following should be noted:
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

Page 10/14

309
310

?

311
312
313

?

314
315
316
317

?

318
319
320

?

321
322

?

323
324
325

?

326
327
328

?

Damaged plants or plant parts need to be excluded or limited in accordance with a specific
pharmacopoeia monograph, where relevant.
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005
Page 11/14

347
348

directly to the sun (except in cases where there is a specific need) and must be protected from
rainfall, insect infestation, etc.
The label must be clear, permanently fixed and made from
6

Reflection paper on the use of fumigants (EMEA/HMPC/125562/2006)

Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

Page 12/14

386
387

non-toxic material.
Certain exudates that have not been subjected to a specific treatment are
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

Page 13/14

425
426
427

also considered to be herbal substances.
European Pharmacopoeia General Monograph ?HERBAL DRUGS? 07/2017:1433
Are obtained by subjecting herbal substances to treatments such as
extraction, distillation, expression, fractionation, purification, concentration
or fermentation.

Draft revised Heads of Medicines Agency / European Medicines Agency guidance document on the identification of personal data and commercially confidential information within the structure of the marketing authorisation application dossier

Retrieved on:

torsdag, april 18, 2024

Steps, Union, Patient, CTD, Syndrome, CCI, Local, Disclosure, Toxicity, Process validation, MAH, Clinical trial, IP, RMP, Pharmacovigilance, Cell, Legislation, Annex, Trial of the century, Escherichia coli, Safety, Pediatrics, INTRODUCTION, Documentation, Prevalence, Vital signs, Tablet, Design, Transparency, Conclusion, Pip, Analysis, European Parliament, INN, Record, Quality, Generic, Biology, CMO, Genotoxicity, Composition, CTIS, Uncontrolled, Health care, European Medicines Agency, Prejudice, Committee, Policy, HCP, Animal, Characterization, Cell bank, Fertility, IRB, CMOS, Risk management, Private law, European Pharmacopoeia, Telephone, Research, Good, Data Protection Directive, Ampere-hour, IEC, QP, Human, Personal data, Labelling, Bibliography, Figure, MAA, R4, Institutional review board, Elucidation, Marketing, M4, ChromeOS, Contract research organization, Mental, Impairment, Toxicokinetics, NCA, Independent, Metabolite, Drug, Risk, Metabolism, GMO, Organ, EMA, Common Technical Document, General Data Protection Regulation, Confidentiality, PPD, PI, Language, DRUG, Privacy, Result, Claimed, Medication, Comparison, Ethics, Drive, PD, Narrative, EEA, Developmental toxicity, Saccharomyces cerevisiae, Pharmacopoeia, PIP, MCB, HMA, Physical chemistry, Midol, Particle size, Council, GCP, European Economic Area, Draft, Fermentation, Overview, Justification, Control, Dicarboxylic acid, Pharmacology, WCB, Expert, Immunogenicity, Data, Study, Publication, European, ICH, Element, Analytical procedures (finance auditing), Name, Common, Guideline, Exceptional circumstances, ID, Liver, Chin Na, Toxicology, Protein primary structure, Immunosuppressive drug, Vaccine

See websites for contact details

Key Points:

See websites for contact details
Heads of Medicines Agencies www.hma.eu
European Medicines Agency www.ema.europa.eu
11

Table of contents

12

Abbreviations .............................................................................................. 3

13

Definitions ................................................................................................... 4

14

1.
redaction, masking,
68

hiding) in such a manner that the recipient can no longer attribute the resulting information to a data

69

subject and make it identifiable.
81
Contract Manufacturing Organisation (CMO): shall mean an arrangement under which a

82

manufacturer provides upstream manufacturing services under contract on behalf of third-party

83

pharmaceutical companies.
94
Protected Personal Data (PPD): shall mean any personal data which should be protected from

95

disclosure.
?Finalised? shall mean that the marketing
102

authorisation (MA) has been granted or refused or that the MAA has been withdrawn.
The application of the general principles laid down in this guidance is without prejudice to
106

national rules on transparency.
The guidance should be read in conjunction with the relevant applicable
107

legislation and case law on transparency and data protection.
117
This guidance document is intended to apply to information/documents on medicinal products for

118

human use, for which the procedure has been finalised under the national, mutual recognition,

119

decentralised and centralised procedures.
Third
124

parties shall be informed or consulted as needed depending on respective national and European legal

125

frameworks.
140
In the following sections, the agreed principles on PD and CCI are presented, including guidance on

141

whether such information can be disclosed.
EMA/131365/2024
Page 5/50

142

Any information identified as PD or CCI must be subject to a preliminary review by the EMA/NCA prior

143

to the possible disclosure of the information/documents.
Principles on the protection of personal data (PD)
145

The protection of PD is enshrined in EU legislation; it is a fundamental right of EU citizens.
In
146

compliance with the applicable European/national legislation, PD should be anonymised in order to

147

avoid the disclosure of the document undermining the privacy and integrity of any individual.
EMA/NCA applies a risk-based approach to assess which PD elements are to be
152

removed from the information/documents in order to limit the risk of re-identification.
are included in the MAA dossier because they have a legally
164

defined role or responsibility and it is in the public interest to disclose this data.
168
Applicants are advised that non-essential information (e.g., personal address, personal phone number)

169

should not be included in the MAA dossier.
The
183

confidentiality of records that could identify subjects should be protected, respecting the privacy and

184

confidentiality rules in accordance with the applicable regulatory requirement(s).
185
The applicant remains responsible for compliance with the relevant legislation in cases where such data

186

is inadvertently included in the MAA dossier.
188
EMA/NCA applies a risk-based approach to assess which personal data elements need to be removed

189

from the information/documents in order to limit the risk of re-identification.
194
EMA/NCA applies a risk-based approach to assess which personal data elements need to be removed

195

from the information/documents in order to limit the risk of re-identification.
205
Any proposal to consider information as commercially confidential should be properly justified by the

206

owner of the information.
In this respect, any reference(s) to the risk of that interest being
209

undermined should be foreseeable and not purely hypothetical.
210
Information that is already in the public domain is not considered to be commercially confidential.
Information on the Quality and Manufacturing of medicines
226

A general principle regarding quality and manufacturing information is that detailed information could

227

be considered commercially confidential but general information should be disclosed.
234
In general, and if not in the public domain, the names of manufacturers or suppliers of the active

235

substance or the excipients are considered commercially confidential.
248
A general description of the type of test methods used and the appropriateness of the specification is

249

not commercially confidential.
General information on the fermentation and purification process
259

is not commercially confidential, although details including operating parameters and specific material

260

requirements are commercially confidential.
273
A general description of the type of test methods used and the appropriateness of the specification is

274

not commercially confidential.
In general, the data included in clinical trial study reports is considered to be data that can be
283

disclosed once PD has been anonymised.
338
In each module, a non-exhaustive list of information that may be considered protected personal data (PPD) or commercially confidential information

332
333

339

(CCI) is included.
?
Direct contact details such as telephone

Therefore, please refer to the appropriate sub-

number, fax number, email, postal address,

modules hereafter for guidance.
?
Information that may reveal strategic
(contractual) agreements

?

Any quality information on the clinical batches

principal investigator

that might be included here (such as e.g.
?
Information that may reveal strategic
(contractual) agreements

principal investigator

Study Reports
5.3.3.3

as the evaluation of new formulation, innovative

number, fax number, email, postal

Paediatric Development Plan (PIP), etc.
This may include taking into
More Than One Study
5.3.5.4

Other Clinical Study Reports

5.3.6

Reports of Post-Marketing
Experience

5.3.7

Direct identifiers such as name,
signature, contact details, etc.

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

Retrieved on:

torsdag, april 18, 2024

17

Key Points:

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

Draft guideline on good agricultural and collection practice (GACP) for starting materials of herbal origin - Revision 1

Retrieved on:

torsdag, april 18, 2024

REFERENCES ....................................................................................................................................... 14

Key Points:

REFERENCES ....................................................................................................................................... 14
29

Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

Page 3/14

30

EXECUTIVE SUMMARY

31
32
33
34
35
36

This guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin

37

1.
Due to the inherent
complexity of medicinal plants and herbal substances the quality of these starting materials requires an
adequate quality assurance system for the collection and/or cultivation, harvest, and primary
processing.
(either outdoor, indoor or in greenhouses) should be carefully considered, since each of the mentioned
types could have several problems and advantages.
The used cultivation method may be dependent on
the final application of the herbal medicinal product.
primary processing of herbal substances that are used for the preparation of herbal medicinal products.
medicinal plants and herbal substances, ensuring that they are handled appropriately throughout all
stages of cultivation, collection, processing and storage.
their preparations are exposed to a large number of environmental contaminants of both biotic and
abiotic origin.
to existing wildlife habitats and must adhere to CITES (Convention on International Trade in
Endangered species of Wild Fauna and Flora).
https://health.ec.europa.eu/document/download/bd537ccf-9271-4230-bca1-2d...
4 https://health.ec.europa.eu/document/download/fd318dd6-2404-4e67-82b0232...
3
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

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104

4.
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005
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147
148
149

8.
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005
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185

7.
Where possible, stable varieties and cultivars naturally
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
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227
228

resistant or tolerant to disease should preferably be used.
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EMA/HMPC/246816/2005
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268
269
270
271
272
273

The application should be carried out only by qualified staff using approved equipment.
The following should be noted:
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

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309
310

?

311
312
313

?

314
315
316
317

?

318
319
320

?

321
322

?

323
324
325

?

326
327
328

?

Damaged plants or plant parts need to be excluded or limited in accordance with a specific
pharmacopoeia monograph, where relevant.
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005
Page 11/14

347
348

directly to the sun (except in cases where there is a specific need) and must be protected from
rainfall, insect infestation, etc.
The label must be clear, permanently fixed and made from
6

Reflection paper on the use of fumigants (EMEA/HMPC/125562/2006)

Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

Page 12/14

386
387

non-toxic material.
Certain exudates that have not been subjected to a specific treatment are
Guideline on Good Agricultural and Collection Practice (GACP) for starting materials of herbal origin
EMA/HMPC/246816/2005

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425
426
427

also considered to be herbal substances.
European Pharmacopoeia General Monograph ?HERBAL DRUGS? 07/2017:1433
Are obtained by subjecting herbal substances to treatments such as
extraction, distillation, expression, fractionation, purification, concentration
or fermentation.

Draft template for assessment report for the development of European herbal monographs and European Union list entries - Revision 6

Retrieved on:

torsdag, april 18, 2024

The completed comments form should be sent to

Key Points:

The completed comments form should be sent to
[email protected]
10
11
Keywords
Committee on Herbal Medicinal Products; HMPC; European Union herbal
monographs; European Union list of herbal substances, preparations and
combinations thereof for use in traditional herbal medicinal products; herbal
medicinal products; traditional herbal medicinal products; traditional use;
well-established medicinal use; benefit-risk assessment; assessment report

12

1
2

Changes introduced in section 6 Overall conclusions.
Peer-reviewer

If not the same peer-reviewer
since last version, all peerreviewers should be listed, and
the version specified in
brackets.
22

23

on
.
It is a working
24

document, not yet edited, and shall be further developed after the release for consultation of the

25

.
The principle of the template is to make clear
distinctions between presentation of data (methodology and results)
and the assessment of the data (?assessor?s comment?).
likely from an article but it seems it is concluded by
the rapporteur; ?According to the author? to be added.
Chapters with
a heading including the word ?conclusion? should include a summary
of all critical assessment of the assessor for that particular
chapter.
If an assessor?s comment is not needed, the Rapporteur
should delete the box inserted in the template.
?
The report should be sufficiently detailed to allow for secondary
assessment of the available data by other HMPC experts.
Overview of available pharmacokinetic data regarding the herbal substance(s), herbal
preparation(s) and relevant constituents thereof ........................................................... 16
97
98

3.3.
Overall conclusions on clinical pharmacology and efficacy ........................................ 27
Assessment report on
EMA/HMPC/418902/2005

Page 4/41

119

5.
This sections is related to
available quality standards and there is no need to repeat information
on all preparations included in the monograph.
Search and assessment methodology
161

The Rapporteur shall undertake a comprehensive search of relevant
scientific literature and articles, Acts of law and regulations and
other relevant sources.
Cross-reference to the list of
references in Annex, which should list separately the references
supporting the assessment report.
143
144
145
150
151
152
153
154

162
163
164
165
166
167
168
169
170
171
172
173
174
175

Herbal substance(s)

Herbal preparation(s)

Relevant constituents for this assessment report

Examples of scientific databases to be searched are Medline, PubMed,
Cochrane Database of Systematic Reviews, EMBASE etc.
Assessment report on
EMA/HMPC/418902/2005
Page 6/41

176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192

Additional relevant references could also be retrieved from the checked
references.
Examples of books are Hagers Handbuch, The Complete German
Commission E Monographs, PDR for herbal medicines etc.
In addition, information from non-EU regulatory
authorities for examples Health Canada monographs or WHO monographs
could be searched, if relevant to herbal substances and preparations in
EU.
221
225
226
227

232

When the assessment report is revised, the rapporteur should briefly
summarise the main changes under this section.
Data are collected using the template entitled ?Document
for information exchange for the preparation of the assessment report
for the development of European Union monographs and for inclusion of
herbal substance(s), preparation(s) or combinations thereof in the
list? (EMEA/HMPC/137093/2006).
Assessment report on
EMA/HMPC/418902/2005
Page 8/41

Herbal substance/

Indication

Posology and
method of

preparation

administration

Posology, age
groups,
pharmaceutical
form, method of
administration,
duration of use
As reported in
the market
overview

As reported in
the market
overview

As reported in
the market
overview.
Assessment report on
EMA/HMPC/418902/2005
Page 10/41

Herbal substance/

Indication/Medicinal

Posology and

preparation

use

method of
administration

Posology, age
groups,
pharmaceutical
form, method of
administration,
duration of use

Regulatory Status

Type of
regulatory
status where
possible, date,
Country

287

This overview is not exhaustive.
Clinical Safety/Pharmacovigilance
836
837
838
839
840
841

See ?Assessment of clinical safety and efficacy in the preparation of
EU herbal monographs for well-established and traditional herbal
medicinal products?(EMA/HMPC/104613/2005) for further details.
Overall conclusions on clinical safety
1067

1068

In terms of structure, the conclusion should follow the presentation of
the results above.
Overall conclusions
1092

1093

1101

Describe key aspects only briefly, these will already have been
described in detail in the respective sections.
This section should
cover all recommended ?well-established use? and ?traditional use?
indications and conclusions shall be provided for each therapeutic
indication and each herbal preparation.
1102
Well established use monograph

1103
1104

The clinical studies supporting well-established use should be
specified for each therapeutic indication and each herbal preparation.
The choice for the wording of traditional use indications vis-?vis existing wordings in monographs in the same therapeutic area should
be briefly discussed/justified.
1153
List entry

1154

The conclusions should include a statement pointing to the
possibility/non-possibility to support a European Union list entry.

HYTN Provides Corporate Update, Outlines New Global Direction

Retrieved on:

onsdag, april 3, 2024

Certification, Good manufacturing practice, Therapeutic Goods Administration, The Company, DAB, European Pharmacopoeia, Quality management system, GMP, Cannabis, TGA, PIC/S, Drug

HYTN is announcing two strategic commercial initiatives underscoring the company’s commitment to leading the GMP-certified cannabis products industry.

Key Points:

HYTN is announcing two strategic commercial initiatives underscoring the company’s commitment to leading the GMP-certified cannabis products industry.
HYTN expects to commercialize both business to business and wholesale opportunities under this initiative.
Additionally, HYTN aims to unlock global markets for established cannabis brands by leveraging the company's regulatory compliance, supply chain capabilities and Quality Management System.
The authorization to process cannabis flower into pharmaceutical-grade products for export provides a significant advantage in a market actively seeking GMP-certified cannabis."

Draft guideline on allergen products development for immunotherapy and allergy diagnosis in moderate to low-sized study populations

Retrieved on:

tisdag, mars 12, 2024

Filtration, Vespula, Toxicity, Histamine, EAACI, Immunotherapy, Asthma, Report, Allergy, Skin, Pregnancy, PR, EEC, MITES, RNA, Criterion, History, CMR, Contraindication, HEP, Draft, Guideline, Patient, Ames test, Diagnosis, Dermatitis, Venom, Literature, Trial of the century, Reproduction, Silicon–germanium, SPT, Food allergy, Cosmetics, EECS, Absorption, Marketing, Safety, Data collection, Directive 2001/83/EC, GMP, ID50, Antibody, Documentation, European, Type IV hypersensitivity, Genotoxicity, Applicant (sketch), Aeroallergen, CHMP, PRIME, Immunoglobulin G, Type, Publication, Biology, Pollen, DNA, Environment, Immune system, Toolbox, NLN, AIT, Atopic dermatitis, Fatality, Chapter, Anaphylaxis, Process validation, ICH, Antigen, Rhinitis, Clinical trial, Erythema, Knowledge, Prescription, Human, Network, Medication, Scope, VIT, ICT, EMA, Collection, Macrophage, Outline, Metabolism, Registry, Inflammation, Immunoglobulin E, Nature, European Pharmacopoeia, Food, Risk, Prevalence, Mastocytosis, Observation, Cytokine, NPP, Patient safety, Disease, Finished, Medical device

16

Key Points:

16
Guideline on allergen products development for
immunotherapy and allergy diagnosis in moderate to lowsized study populations

17

Table of contents

18

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

19

1.
Specific effects ................................................................................................. 17
14
15

Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024

Page 2/18

53

12.
Management for allergies may involve avoidance of the allergen, medications to relieve
66

symptoms, or allergen immunotherapy (AIT) to desensitize the immune system to the allergen.
71
Recommendations are made on the clinical development, potential study designs and safety

72

considerations for allergen products within the scope of the guideline.
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024
Page 3/18

88

While allergen specific immunotherapy is the only known disease modifying therapy for type I allergies,

89

there is no such treatment available for type IV allergies.
93
Several guidelines applicable for allergen products are available (see section 3) and provide advice on

94

quality and clinical development according to the current knowledge.
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024
Page 4/18

127

However, this guideline does not cover the indication of atopic dermatitis or asthma as these

128

conditions will require separate clinical trials (see Section 6).
129
In addition, the guideline does not cover medicinal allergen products manufactured using recombinant

130

DNA technology, synthetic peptides, DNA or RNA constructs and/or cell preparations as they differ

131

substantially to the allergen products as discussed above.
1
156

?

Guideline on the clinical development of products for specific immunotherapy for the treatment

157
158

of allergic diseases - CHMP/EWP/18504/2006
?

159
160
161

Guideline on Allergen Products: Production and Quality Issues EMEA/CHMP/BWP/304831/2007

?

Guideline on process validation for finished products - information and data to be provided in
regulatory submissions - EMA/CHMP/CVMP/QWP/BWP/70278/2012-Rev1, Corr.1

Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024

Page 5/18

162

?

Recommendations on common regulatory approaches for allergen products - CMDh/399/2019

163

4.
In any
199

case, a reduced validation should include all relevant manufacturing process steps that are considered
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024

Page 6/18

200

product specific.
290
Diagnostic allergen products (Type I allergy)

291

A possible target indication is diagnosis of type I hypersensitivity (immediate-type allergy) by prick,

292

intracutaneous or provocation testing.
298
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024

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305
306

7.1.
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024
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377

8.
Clinical development of products for AIT: Study design,
efficacy and safety
378

In general, the clinical development should be performed according to current guidelines.
In such single trial, the suitability as a test allergen as well as the
376

Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024

Page 12/18

415

dose finding for the therapeutic allergen could be investigated.
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024
Page 13/18

454
455

8.2.1.
493
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024

Page 15/18

527

In general, sensitivity and specificity of the product should be determined.
540
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024

Page 16/18

561

10.2.
Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024
Page 17/18

595

4.
Allergol Immunopathol, 1989;
602

17(2):53-65

603

Guideline on allergen products development for immunotherapy and allergy diagnosis
in moderate to low-sized study populations
EMA/CHMP/72790/2024

Page 18/18

Questions and answers on the European Union framework for (traditional) herbal medicinal products, including those from a ‘non-European’ tradition

Retrieved on:

söndag, mars 10, 2024

Well, DER, Fungus, Capsule, TUR, Interest, Animal, Part, Exercise, Database, Viral, Hepatitis, Powder, Collection, Directive, Union, Nutrient, DSM-IV codes, Volume, CTD, Legislation, Literature, Fermentation, Diabetes, Pharmacopoeia, Inhalation, Committee, Monograph, NTA, WEU, DCP, AIDS, See, Mineral, Marketing, Safety, Plant, MRA, Autoimmunity, Directive 2001/83/EC, GMP, Documentation, Seed, Heart failure, Distillation, CHMP, MRP, European Medicines Agency, Guideline, Disorder, Mutual, Convention, State, Tablet, Community, Clinical trial, Rapporteur, European Commission, Woman, Medication package insert, Vitamin, Quality, Authority, GACP, SAWP, Pharmacovigilance, Civil service commission, HMPS, Science, Health, Bibliography, Section 4, Infection, Kampo, Commission, Abbreviation, Pathology, Prescription, Human, Medication, Reproduction, EMA, NCA, Chapter One, EDQM, TAM, European Pharmacopoeia, European Economic Area, Food, Regulation (European Union), COM, TCM, Administration, Mutual recognition, Procedure, Medicine, Herbal, Answer, Q&A, HIV, EudraLex, Cancer, Public, Medicinal plants

1

Key Points:

1
Committee on Herbal Medicinal Products (HMPC)
Questions & Answers on the European Union framework
for (traditional) herbal medicinal products, including those
from a ?non-European? tradition

Table of Content
1.
European Pharmacopoeia
SAWP

Scientific Advice Working Party

SmPC

Summary of Product Characteristics

THMP

Traditional Herbal Medicinal Product

TUR

Traditional Use Registration

WEU

Well-Established Use

Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Terminology of herbal medicinal products (Q&A 1-4)
Question 1
What are herbal substances, herbal preparations, and herbal medicinal products?
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Question 4
Are food supplements regulated under the European Union (EU) pharmaceutical legislation
for (traditional) herbal medicinal products ((T)HMPs)?
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Regulation of herbal medicinal products in the European Union (Q&A 511)
Question 5
Where to find the pharmaceutical legislation and dossier requirements for herbal medicinal
products (HMPs), including traditional herbal medicinal products (THMPs), in the European
Union (EU)?
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
These countries have,
through the EEA agreement, adopted the complete Union acquis on medicinal products and are
consequently parties to the Union procedures.
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Specific provisions for traditional herbal medicinal products (Q&A 1221)
Question 12
Which indications can be granted for traditional herbal medicinal products (THMPs)?
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Nov. 2023
Answer 17
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Question 29
Does the Committee on Herbal Medicinal Products (HMPC) hold a specific database on
(registered) authorised (traditional) herbal medicinal products ((T)HMPs)?
Discussion with Member States intended to be
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.
Questions & Answers on the European Union framework for (traditional) herbal
medicinal products, including those from a ?non-European? tradition
EMA/HMPC/402684/2013 Rev.

Loop Industries and Bormioli Pharma Unveil an Innovative Pharmaceutical Packaging Bottle Manufactured with 100% Recycled Virgin Quality Loop PET Resin at Pharmapack 2024

Retrieved on:

onsdag, januari 24, 2024

Polyethylene terephthalate, PET, USP, European Pharmacopoeia, Container, Recycling

Bormioli Pharma tested Loop(TM) PET resin in its packaging, commissioning to independent third parties' additional analysis to verify extractables levels with different solutions, also taking in consideration the worst-case scenario.

Key Points:

Bormioli Pharma tested Loop(TM) PET resin in its packaging, commissioning to independent third parties' additional analysis to verify extractables levels with different solutions, also taking in consideration the worst-case scenario.
"Through this collaboration with Loop we're strengthening our role as a solid, quality and reliable partner for the pharmaceutical industry" stated Andrea Lodetti, CEO of Bormioli Pharma.
Daniel Solomita, Founder and CEO of Loop Industries, commented "Through our collaboration with Bormioli Pharma, we have developed an innovative pharmaceutical packaging solution manufactured from 100% recycled virgin quality Loop(TM) PET resin.
1 Results from an extractables study conducted by an independent, external lab and performed on bottles manufactured with Loop(TM) PET resin using different simulating solutions.