Life insurance

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

Retrieved on:

Jeudi, avril 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 the pharmaceutical quality of inhalation and nasal medicinal products

Retrieved on:

Jeudi, avril 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

Form 8.3: GAMA Aviation Plc

Retrieved on:

Mercredi, avril 10, 2024

Disclosure, Aviation, Life insurance

(b) Owner or controller of interests and short positions disclosed, if different from 1(a):

Key Points:

(b) Owner or controller of interests and short positions disclosed, if different from 1(a):
The naming of nominee or vehicle companies is insufficient.
For a trust, the trustee(s), settlor and beneficiaries must be named.
If it is a cash offer or possible cash offer, state “N/A”
If there are positions or rights to subscribe to disclose in more than one class of relevant securities of the offeror or offeree named in 1(c), copy table 2(a) or (b) (as appropriate) for each additional class of relevant security.
GAMA Aviation Plc, ordinary shares of 1 pence, ISIN: GB00B3ZP1526

Travis Perkins: Directorate Change

Retrieved on:

Mercredi, avril 10, 2024

Remuneration, Account, MAR, RSP, Policy, Exercise, Life insurance

To note the following:

Key Points:

To note the following:
Nick Roberts’ remuneration will be treated in accordance with the Company’s approved Directors’ Remuneration Policy.
Nick will not receive any payments or compensation for loss of office.
The unvested award held under Deferred Share Bonus Plan will remain outstanding and capable of vesting on its normal vesting date.
Dissemination of a Regulatory Announcement that contains inside information in accordance with the Market Abuse Regulation (MAR), transmitted by EQS Group.

Fuller, Smith & Turner PLC: Director / PDMR Shareholding

Retrieved on:

Mercredi, avril 10, 2024

Trustee, Life insurance

The Company has been notified by Sir James Fuller, Non-Executive Director, of the following changes in his interests in the Company's share capital:

Key Points:

The Company has been notified by Sir James Fuller, Non-Executive Director, of the following changes in his interests in the Company's share capital:
the Trustees of a family trust of which the children of Sir James are beneficiaries as to one third, have agreed to sell 1,292,300 ‘B’ Ordinary Shares of 4p each and 37,066 ‘C’ Ordinary Shares of 40p each to a family member related to Sir James; and
Sir James has been gifted 14,500 ‘A’ Ordinary Shares of 40p each from a family trust in which he had no beneficial interest or acted as a trustee which has now been wound up.
Further information is detailed in the following PDMR dealing notifications.

AGL Investors: Investors with Significant Losses Should Contact Robbins LLP About the agilon health, inc. Class Action

Retrieved on:

Mardi, avril 9, 2024

AGL, Patient, SAN, Complaint, SPO, INC, LLP, Health, Person, Life insurance

For more information, submit a form , email attorney Aaron Dumas, Jr., or give us a call at (800) 350-6003.

Key Points:

For more information, submit a form , email attorney Aaron Dumas, Jr., or give us a call at (800) 350-6003.
The truth about the higher medical costs emerged as the Company reported lower-than-expected financial results and lower expectations for future revenue.
A lead plaintiff is a representative party who acts on behalf of other class members in directing the litigation.
If you choose to take no action, you can remain an absent class member.

TEN Ltd. Declares Dividend on its Series F Cumulative Redeemable Perpetual Preferred Shares

Retrieved on:

Lundi, avril 8, 2024

TNP, LNG, Life insurance

ATHENS, Greece, April 08, 2024 (GLOBE NEWSWIRE) -- TEN Ltd. (“TEN”) (NYSE: TNP) (the “Company”), a leading diversified crude, product and LNG tanker operator, today announced that its Board of Directors declared the regular quarterly cash dividend of approximately $0.59375 per share for its Series F Cumulative Redeemable Perpetual Preferred Shares (the “Series F Preferred Shares”; NYSE: TNPPRF).

Key Points:

ATHENS, Greece, April 08, 2024 (GLOBE NEWSWIRE) -- TEN Ltd. (“TEN”) (NYSE: TNP) (the “Company”), a leading diversified crude, product and LNG tanker operator, today announced that its Board of Directors declared the regular quarterly cash dividend of approximately $0.59375 per share for its Series F Cumulative Redeemable Perpetual Preferred Shares (the “Series F Preferred Shares”; NYSE: TNPPRF).
The dividend on the Series F Preferred Shares is for the period from the most recent dividend payment date on January 30, 2024 through April 29, 2024.
The dividend on the Series F Preferred Shares will be paid on April 30, 2024 to all holders of record of Series F Preferred Shares as of April 25, 2024.
TEN has 6,747,147 Series F Preferred Shares outstanding as of the date of this press release.

VIVOPOWER ANNOUNCES FURTHER STRATEGIC DIRECT INVESTMENT IN TEMBO FROM EMIRATI INVESTMENT OFFICE

Retrieved on:

Lundi, avril 8, 2024

Exercise, CCTS, Life insurance

LONDON, April 08, 2024 (GLOBE NEWSWIRE) -- VivoPower International PLC (Nasdaq: VVPR, “VivoPower” or the “Company”) is pleased to announce that its subsidiary Tembo e-LV B.V. (“Tembo”) has now met all the milestones to obtain the final follow-on strategic direct equity investment into Tembo, at a pre-money valuation of US$120 million.

Key Points:

Tembo has now met milestones to qualify for the final follow-on investment of US$2.5 million, for an aggregate total investment of US$10 million
LONDON, April 08, 2024 (GLOBE NEWSWIRE) -- VivoPower International PLC (Nasdaq: VVPR, “VivoPower” or the “Company”) is pleased to announce that its subsidiary Tembo e-LV B.V. (“Tembo”) has now met all the milestones to obtain the final follow-on strategic direct equity investment into Tembo, at a pre-money valuation of US$120 million.
This is pursuant to a commitment received in June 2023 from a UAE based private investment office backed by a member of the ruling Al Maktoum family of Dubai.
VivoPower will continue to retain its majority stake in Tembo.
Tembo recently announced a binding heads of agreement to execute a business combination agreement with CCTS, a NASDAQ listed SPAC at an indicative pre money equity valuation of US$838m.

INMD 8-DAY DEADLINE ALERT: Hagens Berman, National Trial Attorneys, Encourages InMode Ltd. (INMD) Investors with $100K+ Losses to Contact Firm’s Attorneys Before Apr. 15th Deadline in Securities Class Action

Retrieved on:

Dimanche, avril 7, 2024

Injury, SAN, Hagens Berman, FDA, Person, Life insurance

SAN FRANCISCO, April 07, 2024 (GLOBE NEWSWIRE) -- Hagens Berman urges InMode Ltd. (NASDAQ: INMD) investors who purchased during the class period and suffered at least $100,000 in losses to submit your losses now .

Key Points:

SAN FRANCISCO, April 07, 2024 (GLOBE NEWSWIRE) -- Hagens Berman urges InMode Ltd. (NASDAQ: INMD) investors who purchased during the class period and suffered at least $100,000 in losses to submit your losses now .
InMode Ltd. (NASDAQ: INMD) Securities Fraud Class Action:
The complaint alleges that InMode repeatedly touted the demand for its devices and told investors that the devices were never sold at a discount.
InMode also assured investors that it had FDA clearance for the current treatments for which it offered its products and that no third-party claims had been brought against it.
The truth began to emerge on Feb. 17, 2023, after an investigative publication revealed that InMode customers were threatened with legal action after filing complaints about InMode’s devices and sales tactics.

Grayscale® Digital Large Cap Fund, Grayscale® DeFi Fund, and Grayscale® Smart Contract Platform Ex-Ethereum Fund Announce Rebalancing of Funds for First Quarter 2024

Retrieved on:

Jeudi, avril 4, 2024

Sale, AUM, Index, Life insurance

Neither GDLC, nor DEFG, nor GSCPxE Fund generate any income, and all regularly distribute Fund Components to pay for ongoing expenses.

Key Points:

Neither GDLC, nor DEFG, nor GSCPxE Fund generate any income, and all regularly distribute Fund Components to pay for ongoing expenses.
Therefore, the amount of Fund Components represented by shares of each fund gradually decreases over time.
*Largest by AUM as of April 4, 2024
**The compositions of the GDLC, DEFG and GSCPxE Fund are evaluated on a quarterly basis to remove existing Fund Components or to include new Fund Components, in accordance with the index methodologies established by the Index Provider.
Holdings and weightings of each Fund are subject to change.