Asthma

Chemical pollutants can change your skin bacteria and increase your eczema risk − new research explores how

Retrieved on: 
Tuesday, April 23, 2024
Research, Itch, Dicarboxylic acid, Temperature, Isocyanate, Polyurethane, Gene, Oil, Industrial Revolution, Growth, Atopic dermatitis, Paint, Environment, Risk, Genetics, Lipid, Inflammation, Revolution, Mouse, Child, Bacteria, Detergent, Life, Dermatitis, Staphylococcus aureus, Asthma, Staphylococcus epidermidis, Staphylococcus cohnii, Sensation, EPA, Skin, Plastic, Ceramide, Atmosphere, Lysine, Roseomonas, Staphylococcus, Pain, Air pollution, Wildfire, Vaccine

Also known as atopic dermatitis, this chronic skin disease affects about 1 in 5 children in the industrialized world.

Key Points: 
  • Also known as atopic dermatitis, this chronic skin disease affects about 1 in 5 children in the industrialized world.
  • Some studies have found rates of eczema in developing nations to be over thirtyfold lower compared with industrialized nations.
  • Scientists know that factors such as diets rich in processed foods as well as exposure to specific detergents and chemicals increase the risk of developing eczema.
  • Living near factories, major roadways or wildfires increase the risk of developing eczema.

There’s something in the air

  • Then we looked at databases from the U.S. Environmental Protection Agency to see which chemicals were most common in those areas.
  • Diisocyanates were first manufactured in the U.S. around 1970 for the production of spandex, nonlatex foam, paint and polyurethane.
  • The manufacture of xylene also increased around that time, alongside an increase in the production of polyester and other materials.
  • After 1975, when all new cars became outfitted with a new technology that converted exhaust gas to less toxic chemicals, isocyanate and xylene both became components of automobile exhaust.
  • How directly exposing mice to these toxins compares to the typical levels of exposure in people is still unclear.

Skin microbiome and pollution

  • Every person is coated with millions of microorganisms that live on the skin, collectively referred to as the skin microbiome.
  • You’ve probably seen moisturizers and other skin products containing ceramides, a group of lipids that play an important role in protecting the skin.
  • To see which toxins could prevent production of the beneficial lipids that prevent eczema, my team and I used skin bacteria as canaries in the coal mine.
  • Lysine helps protect the bacteria from the harms of the toxins but doesn’t provide the health benefits of ceramides.
  • Bacteria that help keep skin healthy could live on any fabric, but, just as with air pollution, the amount of beneficial lipids they made dropped to less than half the levels made when grown on fabrics like cotton.

Addressing pollution’s effects on skin

  • Detectors capable of sensing low levels of isocyanate or xylene could help track pollutants and predict eczema flare-ups across a community.
  • Better detectors can also help researchers identify air filtration systems that can scrub these chemicals from the environment.
  • In the meantime, improving your microbial balance may require avoiding products that limit the growth of healthy skin bacteria.
  • I believe that it may one day allow us to get back to a time when these diseases were uncommon.


Ian Myles receives funding from the Department of Intramural Research at the National Institute of Allergy and Infectious Diseases. He is the author of, and receives royalties for, the book GATTACA Has Fallen: How population genetics failed the populace. Although he is the co-discoverer of Roseomonas mucosa RSM2015 for eczema, he has donated the patent to the public and has no current conflict of interest for its sales.

Herbal medicinal product: Eucalypti aetheroleumArray,Array,Array, F: Assessment finalised

Retrieved on: 
Thursday, April 18, 2024
Eucalyptus oil, Bronchitis, Spasm, Seizure, System, Risk, Inflammation, Patient, Lung, Monograph, Committee, Inhalation, Steam, Herbal medicine, Date, Asthma, Heart failure, Plant, Mouth, Infection, Skin, Fever, Myalgia, Water, Larynx, Medicine, Dietary supplement

Herbal medicinal product: Eucalypti aetheroleumArray,Array,Array, F: Assessment finalised

Key Points: 


Herbal medicinal product: Eucalypti aetheroleumArray,Array,Array, F: Assessment finalised

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

Retrieved on: 
Thursday, April 18, 2024
Reproduction, Particle size, Q&A, Patient, Lung, Chronic obstructive pulmonary disease, DPI, Pharmacokinetics, Child, Isocyanate, International Council, Scope, Abbreviation, Asthma, OIP, European, COPD, APSD, Absorption, Rheumatology, Risk, Draft, EMA, Safety, TE, CHMP, MDI, Pharmacodynamics, IVIVC, Documentation, Taste, Comparison, Inhalation, Charcoal, Clinical Trials Directive, The central science, Drug development, Literature, ICH, Guideline, Gastrointestinal tract, GI, Marketing, Medication package insert, Excipient, Quality, QWP, Medical device

21

Key Points: 
    • 21

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

      22

      Table of contents

      23

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

      24

      1.

    • Primary PK parameters to be analysed and acceptance criteria .............................. 14

      43

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

      51

      6.4.

    • Definitions ........................................................................................... 18

      56

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

      57

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

      58

      Executive summary

      59

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

      60

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

      61

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

      62

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

      63

      asthma in children and adolescents?.

    • It addresses the requirements for demonstration of therapeutic

      64

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

    • It is generally not recommended to aim at demonstrating TE using pharmacodynamic

      70

      or clinical endpoints as these are deemed insensitive.

    • This

      83

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

      84

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

      85

      COPD.

    • 86

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

      87

      became guideline in 2009.

    • Since then, a number of Q&A documents have been published by Quality

      88

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

    • Scope

      93

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

      94

      both, single active substance products and combination products.

    • Also, in the case that there is a need

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

      98

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

      99

      applications), the same principles apply.

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

      132

      4.

    • Products for nebulisation

      177

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

      178

      performance of these is highly dependent on the nebuliser used.

    • In vitro criteria for demonstrating TE

      206

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

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

      211
      212

      2.

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

      353

      6.2.

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

      392

      6.3.

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

      432

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

      433

      vivo equivalence should be demonstrated with a bracketing approach.

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

      471

      6.4.

    • Griffin, 1964

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

      553

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

    • 568

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

      569

      10.

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

      Product strength

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

    • 570

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

      571

      List of Abbreviations
      APSD

      Aerodynamic Particle Size Distribution

      AUC

      Area Under the Curve

      CHMP

      Committee for Medicinal Products for Human
      Use

      CI

      Confidence Interval

      Cmax

      Peak concentration

      COPD

      Chronic Obstructive Pulmonary Disease

      DPI

      Dry Powder Inhaler

      FPD

      Fine Particle Dose

      GI

      Gastrointestinal

      ICH

      International Conference on Harmonisation

      IVIVC

      In vitro in vivo correlation

      MDI

      Metered Dose Inhaler

      OIP

      Orally Inhaled Product

      PD

      Pharmacodynamic

      PK

      Pharmacokinetic

      pMDI

      Pressurised Metered Dose Inhaler

      QWP

      Quality Working Party

      SmPC

      Summary of Product Characteristics

      TE

      Therapeutic equivalence

      tmax

      Time to peak concentration

      572

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

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

Retrieved on: 
Thursday, April 18, 2024
Reproduction, Midol, Medical device, Particle size, QRD, Patient, Chronic obstructive pulmonary disease, Food packaging, DPI, CTD, Isocyanate, European Pharmacopoeia, Roflumilast, GSD, Scope, Asthma, OIP, Clinical trial, European, COPD, APSD, Marketing, CQA, Nasal mucosa, Medical device regulation, Medication, Solvent, No-no, RH, Ageing, Draft, Gel, EMA, Freezing, Outline, Risk assessment, Uniformity, Chemistry, Pressurization, Micronization, Clutch (eggs), Blister, CHMP, Mass, MDI, Solubility, Documentation, Life cycle, Pharmacopoeia, Capsule, Bias, LDPE, Inhalation, Conformity, Publication, The central science, ICH, Orientation, NB, Lubricant, AIM, Excipient, Temperature, Monograph, Humidity, Cold, Light, Life, Medication package insert, Rugosity, Quality, Water, Yesa, Administration, Weight loss, Life insurance

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

Retrieved on: 
Thursday, April 18, 2024
Reproduction, Particle size, Q&A, Patient, Lung, Chronic obstructive pulmonary disease, DPI, Pharmacokinetics, Child, Isocyanate, International Council, Scope, Abbreviation, Asthma, OIP, European, COPD, APSD, Absorption, Rheumatology, Risk, Draft, EMA, Safety, TE, CHMP, MDI, Pharmacodynamics, IVIVC, Documentation, Taste, Comparison, Inhalation, Charcoal, Clinical Trials Directive, The central science, Drug development, Literature, ICH, Guideline, Gastrointestinal tract, GI, Marketing, Medication package insert, Excipient, Quality, QWP, Medical device

21

Key Points: 
    • 21

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

      22

      Table of contents

      23

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

      24

      1.

    • Primary PK parameters to be analysed and acceptance criteria .............................. 14

      43

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

      51

      6.4.

    • Definitions ........................................................................................... 18

      56

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

      57

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

      58

      Executive summary

      59

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

      60

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

      61

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

      62

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

      63

      asthma in children and adolescents?.

    • It addresses the requirements for demonstration of therapeutic

      64

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

    • It is generally not recommended to aim at demonstrating TE using pharmacodynamic

      70

      or clinical endpoints as these are deemed insensitive.

    • This

      83

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

      84

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

      85

      COPD.

    • 86

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

      87

      became guideline in 2009.

    • Since then, a number of Q&A documents have been published by Quality

      88

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

    • Scope

      93

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

      94

      both, single active substance products and combination products.

    • Also, in the case that there is a need

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

      98

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

      99

      applications), the same principles apply.

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

      132

      4.

    • Products for nebulisation

      177

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

      178

      performance of these is highly dependent on the nebuliser used.

    • In vitro criteria for demonstrating TE

      206

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

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

      211
      212

      2.

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

      353

      6.2.

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

      392

      6.3.

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

      432

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

      433

      vivo equivalence should be demonstrated with a bracketing approach.

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

      471

      6.4.

    • Griffin, 1964

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

      553

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

    • 568

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

      569

      10.

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

      Product strength

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

    • 570

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

      571

      List of Abbreviations
      APSD

      Aerodynamic Particle Size Distribution

      AUC

      Area Under the Curve

      CHMP

      Committee for Medicinal Products for Human
      Use

      CI

      Confidence Interval

      Cmax

      Peak concentration

      COPD

      Chronic Obstructive Pulmonary Disease

      DPI

      Dry Powder Inhaler

      FPD

      Fine Particle Dose

      GI

      Gastrointestinal

      ICH

      International Conference on Harmonisation

      IVIVC

      In vitro in vivo correlation

      MDI

      Metered Dose Inhaler

      OIP

      Orally Inhaled Product

      PD

      Pharmacodynamic

      PK

      Pharmacokinetic

      pMDI

      Pressurised Metered Dose Inhaler

      QWP

      Quality Working Party

      SmPC

      Summary of Product Characteristics

      TE

      Therapeutic equivalence

      tmax

      Time to peak concentration

      572

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

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

Retrieved on: 
Thursday, April 18, 2024
Reproduction, Midol, Medical device, Particle size, QRD, Patient, Chronic obstructive pulmonary disease, Food packaging, DPI, CTD, Isocyanate, European Pharmacopoeia, Roflumilast, GSD, Scope, Asthma, OIP, Clinical trial, European, COPD, APSD, Marketing, CQA, Nasal mucosa, Medical device regulation, Medication, Solvent, No-no, RH, Ageing, Draft, Gel, EMA, Freezing, Outline, Risk assessment, Uniformity, Chemistry, Pressurization, Micronization, Clutch (eggs), Blister, CHMP, Mass, MDI, Solubility, Documentation, Life cycle, Pharmacopoeia, Capsule, Bias, LDPE, Inhalation, Conformity, Publication, The central science, ICH, Orientation, NB, Lubricant, AIM, Excipient, Temperature, Monograph, Humidity, Cold, Light, Life, Medication package insert, Rugosity, Quality, Water, Yesa, Administration, Weight loss, Life insurance

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

EQS-News: APONTIS PHARMA enters five-year distribution and marketing agreement with Novartis for two asthma medications and raises forecast

Retrieved on: 
Wednesday, April 10, 2024
Asthma, Marketing, Ticker, Pharmaceutical industry

APONTIS PHARMA AG (Ticker APPH / ISIN DE000A3CMGM5 ) has entered into a five-year agreement with Novartis Pharma GmbH to take over the distribution and marketing of the patent-protected medications Enerzair® and Atectura® in the asthma indication for Germany.

Key Points: 
  • APONTIS PHARMA AG (Ticker APPH / ISIN DE000A3CMGM5 ) has entered into a five-year agreement with Novartis Pharma GmbH to take over the distribution and marketing of the patent-protected medications Enerzair® and Atectura® in the asthma indication for Germany.
  • Bruno Wohlschlegel, Chief Executive Officer of APONTIS PHARMA AG: “Taking over the distribution and marketing of the products Enerzair® and Atectura® from Novartis for a five-year period is an important contribution to the patient-oriented care of people with asthma in Germany.
  • Novartis and APONTIS PHARMA have a long-standing cooperation in the marketing of products, which will now be continued.
  • I am pleased that our new multi-channel-based go-to-market model in particular has convinced Novartis to transfer distribution and marketing to APONTIS PHARMA.”

AAFA's Advocacy for Health Equity Leads to White House Address on Asthma Inhaler Pricing

Retrieved on: 
Wednesday, April 3, 2024
AAFA, Conditional sentence, AstraZeneca, Health equity, Part, GSK, Boehringer Ingelheim, Patient, Asthma, Medicare (United States), Medicaid, Medicare, Inflation, Government

The White House invited AAFA President and CEO, Kenneth Mendez, and Jenna Riemenschneider, AAFA Senior Director of Policy and Advocacy, in recognition of the advocacy group’s work to advance health equity for people with asthma.

Key Points: 
  • The White House invited AAFA President and CEO, Kenneth Mendez, and Jenna Riemenschneider, AAFA Senior Director of Policy and Advocacy, in recognition of the advocacy group’s work to advance health equity for people with asthma.
  • “On behalf of the 27 million people in the United States with asthma, we appreciate the leadership of President Biden and Senator Sanders to bring down costs for asthma treatments.
  • Pricing announcements made in March by some manufacturers of inhalers will mean lower costs and improved access to asthma medicine for many people with asthma starting this June,” stated Mendez.
  • “Lower out-of-pocket costs have the potential to drastically improve asthma health outcomes.

CMS and Incyte Announce Collaboration and License Agreement for Povorcitinib in China and Southeast Asia

Retrieved on: 
Monday, April 1, 2024
Dermatology, Vitiligo, Prurigo nodularis, Patient, Collaboration, Research, Asthma, JAK1, HS, Hidradenitis suppurativa, PN, CMS, Autoimmunity, Pharmaceutical industry

Under the terms of the agreement, CMS will make an upfront payment to Incyte and Incyte is eligible to receive additional potential development and commercial milestones and royalties on net sales of the licensed product in CMS’ territory.

Key Points: 
  • Under the terms of the agreement, CMS will make an upfront payment to Incyte and Incyte is eligible to receive additional potential development and commercial milestones and royalties on net sales of the licensed product in CMS’ territory.
  • CMS will receive an exclusive license to develop and commercialize and a non-exclusive license to manufacture povorcitinib in autoimmune and inflammatory dermatologic diseases, including non-segmental vitiligo, hidradenitis suppurativa (HS), prurigo nodularis (PN), asthma and chronic spontaneous urticaria, for patients in mainland China, Hong Kong, Macau, Taiwan and certain countries in Southeast Asia.
  • “We are excited to announce the addition of this collaboration for povorcitinib, expanding our relationship with CMS in the Dermatology space beyond ruxolitinib cream, to include two products with the potential to help patients with limited treatment options,” said Herve Hoppenot, Chief Executive Officer, Incyte.
  • Upon approval, povorcitinib is poised to synergize with the innovative drugs in the commercialization stage of our pipeline ILUMETRI (tildrakizumab injection), original drugs including Hirudoid (mucopolysaccharide polysulfate cream) and Aethoxysklerol (polidocanol injection) in terms of our network and market resources, which will help the Product to realize its clinical and commercial value.”
    The transaction is effective immediately upon the execution of the Collaboration and License Agreement.

Pfizer Announces Positive Top-Line Results from Phase 3 Study of ABRYSVO® in Adults Aged 18 to 59 at Increased Risk for RSV Disease

Retrieved on: 
Tuesday, April 9, 2024
FDA, Health, Infectious Diseases, Clinical Trials, Pharmaceutical, Biotechnology, Development, Risk, Diabetes, Ageing, Chronic obstructive pulmonary disease, Head, RSV, Senior, Asthma, Safety, Vaccine, Person

Adults with certain underlying chronic conditions are at increased risk of developing, and being hospitalized for, RSV-associated LRTD1,2.

Key Points: 
  • Adults with certain underlying chronic conditions are at increased risk of developing, and being hospitalized for, RSV-associated LRTD1,2.
  • However, no RSV vaccines have been approved for use in adults 18 to 59 years of age.
  • The MONeT study was initiated to address this significant unmet need by investigating the immunogenicity and safety of ABRYSVO in adults aged 18 to 59 at increased risk for RSV disease, such as those with asthma, diabetes, and chronic obstructive pulmonary disease.
  • “These encouraging results provide evidence that ABRYSVO can help protect adults with increased risk against RSV-associated illness,” said Annaliesa Anderson, Ph.D., Senior Vice President and Head, Vaccine Research and Development, Pfizer.