Excipient

IFF to Showcase Science-backed Low Nitrite Excipients at Excipient World 2024

Retrieved on: 
måndag, april 29, 2024
Public affairs, Health, Nitrosamine, Excipient, Science, Nitrite, All rights reserved, Food, MCC, Creativity, Generic drug

NEW YORK, April 29, 2024 /PRNewswire/ -- IFF's Pharma Solutions division will highlight innovative solutions to help pharmaceutical manufacturers seeking science-backed excipients with effective strategies to support their nitrosamine risk mitigation plans at Excipient World 2024, May 13-15, Gaylord Palms Resort and Convention Center, Kissimmee, Florida at booth 214.

Key Points: 
  • "As the pharmaceutical landscape evolves, it is important to address and solve any challenges associated with nitrosamine risk," said Angela Strzelecki, president, Pharma Solutions, IFF.
  • "Collaborating with an excipient manufacturer with vital expertise, and robust formulation and analytical capabilities enables drug developers to confidently and efficiently incorporate low nitrite excipients into their formulations."
  • Register here to schedule a meeting at Excipient World 2024.
  • IFF, the IFF Logo, and all trademarks and service marks denoted with ™, SM or ® are owned by IFF or affiliates of IFF unless otherwise noted.

Global Corn Starch Market Analysis and Competitive Landscape Report 2024-2032 Featuring Cargill, Ingredion, ADM, Tate & Lyle, Associated British Foods, Tereos, Sudzucker, & Global Bio-Chem Technology - ResearchAndMarkets.com

Retrieved on: 
fredag, april 26, 2024
Agriculture, Natural Resources, Textile, Snack, Milk, GMO, Traction, Soy milk, Ingredion, Urbanization, Plant, Excipient, GFCO, Starch, Novozymes, Food, Fructose, Plastic, CO2, Growth, Plastics industry, Flour

The "Global Corn Starch Market Report by Type, Form, End-Use, Region and Company Analysis 2024-2032" report has been added to ResearchAndMarkets.com's offering.

Key Points: 
  • The "Global Corn Starch Market Report by Type, Form, End-Use, Region and Company Analysis 2024-2032" report has been added to ResearchAndMarkets.com's offering.
  • The growing demand for sweeteners derived from corn starch includes generating high fructose corn syrup, broadly used in liquids, baked goods, and confectionery.
  • Diversifying into new applications involves exploring alternative uses for corn starch, including producing biodegradable plastics as environmentally pleasant substitutes for traditional plastics.
  • These merchandises include Nutrofeli ST100, a native maize starch; Nutrofeli ST200, a partially pre-gelatinized maize starch; and Nutrofeli ST300, a fully gelatinized maize starch.

InnoGI Technologies and Simulations Plus Combine Forces to Offer Next-Level Modeling Solutions for the Prediction of Oral Drug Performance

Retrieved on: 
onsdag, april 17, 2024
Simulations Plus, Pharmacopoeia, USP, TIM, Solubility, Doctor of Philosophy, United States Pharmacopeia, PBPK, ADMET, MBA, Excipient, Medical device

DELFT, Netherlands, April 17, 2024 /PRNewswire/ -- InnoGI Technologies (formerly The TIM Company) is pleased to announce an exciting, market-driven collaboration with Simulations Plus to combine its TIM Technology, part of the InnoGI SurroGUT™ platform, with the GastroPlus® and ADMET Predictor® modelling software offered by Simulations Plus.

Key Points: 
  • DELFT, Netherlands, April 17, 2024 /PRNewswire/ -- InnoGI Technologies (formerly The TIM Company) is pleased to announce an exciting, market-driven collaboration with Simulations Plus to combine its TIM Technology, part of the InnoGI SurroGUT™ platform, with the GastroPlus® and ADMET Predictor® modelling software offered by Simulations Plus.
  • Understanding drug behavior following oral administration is important because solubility and absorption profiles affect dosing and efficacy.
  • However, dynamic interactions between sparingly-soluble active pharmaceutical ingredients, excipients and the gastrointestinal (GI) environment are oversimplified in all static in vitro dissolution models and are very difficult to model using purely computational (in silico) approaches.
  • This will improve the predictive accuracy of physiologically-based pharmacokinetic (PBPK) models, physiologically-based biopharmaceutics models (PBBMs), and facilitate the development of mechanistic IVIVCs."

AMGEN TO PRESENT TEZSPIRE® PHASE 2A COPD DATA AT ATS 2024

Retrieved on: 
tisdag, april 16, 2024
Fetus, AMGN, American Thoracic Society, Congress, Arthralgia, ATS, Chronic obstructive pulmonary disease, Emphysema, Pregnancy, Infection, Tezepelumab, PDT, Allergic conjunctivitis, Amgen, Research and development, Back pain, Conference, Placentalia, Vaccine, Miscarriage, Development, Ageing, Helminthiasis, Incidence, Patient, Anaphylaxis, Hypersensitivity, Rash, Pharyngitis, Birth, Asthma, Bronchitis, AstraZeneca, Excipient, Pharmaceutical industry

THOUSAND OAKS, Calif., April 16, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today provided an update regarding the results of the Phase 2a COURSE trial for TEZSPIRE® (tezepelumab-ekko) in chronic obstructive pulmonary disease (COPD), which were accepted for presentation in the Clinical Trials Symposium at The American Thoracic Society (ATS) 2024 International Conference on Monday, May 20, from 9:15-11:15 a.m. PDT. 

Key Points: 
  • Overall, tezepelumab numerically reduced the annualized rate of moderate or severe COPD exacerbations versus placebo by 17% (90% CI: −6, 36; p=0.1042).
  • Of note, more reductions were observed in a prespecified subgroup of patients with BEC ≥150 cells/μL (37% [95% CI: 7, 57]).
  • The trend in reduction was greater in a small number of subjects with BEC ≥300 cells/µL.
  • We look forward to presenting the full data set at the congress and based on these findings, we are actively planning for the Phase 3 development of tezepelumab in COPD.

EISAI TO PRESENT DATA ON ROBUST NEUROLOGY PORTFOLIO AT THE 76th AMERICAN ACADEMY OF NEUROLOGY® (AAN) ANNUAL MEETING

Retrieved on: 
fredag, april 12, 2024
Amyloid, Angioedema, Brain, Anticoagulant, Neuroimaging, Patient, Vascular malformation, Lecanemab, Siderosis, Dementia, Cell, Seizure, ARIA, Risk, Aspirin, Focal neurologic signs, Nausea, Cerebral edema, Dizziness, Paracetamol, Arthralgia, Cerebral amyloid angiopathy, Effectiveness, Genetic testing, Intraparenchymal hemorrhage, Observation, Confusion, Alzheimer's disease, Intracerebral hemorrhage, Status epilepticus, Vomiting, Incidence, Aneurysm, Anaphylaxis, Headache, Hypersensitivity, Hypertension, MRI, Magnetic resonance imaging, Chills, Neuron, Bronchospasm, Fatal, Hypotension, Tissue plasminogen activator, Edema, Fever, Excipient, Pharmaceutical industry

Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA.

Key Points: 
  • Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA.
  • Depending on ARIA severity, use clinical judgment in considering whether to continue dosing, temporarily discontinue treatment, or permanently discontinue LEQEMBI.
  • There is no experience in patients who continued dosing through symptomatic ARIA-E or through asymptomatic, but radiographically severe, ARIA-E.
  • There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E.

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

Retrieved on: 
torsdag, 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: 
torsdag, 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: 
torsdag, 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: 
torsdag, 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

Esperion Presents Important New Data from CLEAR Outcomes at ACC.24 Highlighting Value of NEXLETOL® (bempedoic acid) Tablets in Diverse Populations Including Women, Hispanics/Latinx and Patients with Obesity

Retrieved on: 
söndag, april 7, 2024
Uric acid, Urinary tract infection, Anaphylaxis, Myocardial infarction, Common, Bronchitis, Patient, Atherosclerosis, FAHA, Cleveland Clinic, Bempedoic acid, Ezetimibe, Therapy, Anemia, Pain, MACE, Sinusitis, ACC, FOMA, FNLA, FACC, Obesity, Cardiovascular disease, Esperion Therapeutics, Abdominal pain, Risk, Gout, Spasm, Woman, American College, Body mass index, ESPR, Back pain, Outcome, ATP, Safety, Fatigue, Arthralgia, ANN, Angioedema, Kidney, Journal, Constipation, University, Adverse event, Pregnancy, CLEAR, Rash, MPH, Rupture, FDA, Molina Healthcare, JACC, Hypersensitivity, Health, Circulatory system, Tablet, CVD, Incidence, Diarrhea, Fetus, Gallstone, Diet, Excipient, Upper respiratory tract infection, Dietary supplement

ANN ARBOR, Mich., April 07, 2024 (GLOBE NEWSWIRE) -- Esperion (Nasdaq: ESPR) today announced the presentation of results from three pre-specified subgroups from CLEAR Outcomes at the 2024 American College of Cardiology’s Annual Scientific Sessions (ACC.24): women, Hispanic/Latinx, and patients with obesity. These results align with the American College of Cardiology’s robust diversity, equity and inclusion programs to drive cultural change across the profession and ensure that the cardiovascular care team is as diverse as the patients they care for and that all patients are represented in cardiovascular research. The data also reinforce the mission of the ACC: transforming cardiovascular care for all.

Key Points: 
  • “Bempedoic acid is the only FDA approved non-statin LDL lowering therapy to demonstrate reductions in MACE in both primary prevention and secondary prevention patient populations.
  • The Hispanic population is the largest ethnic minority in the U.S., yet is a population historically underrepresented in clinical trials.
  • At Esperion, we discover, develop, and commercialize innovative medicines to help improve outcomes for patients with or at risk for cardiovascular and cardiometabolic diseases.
  • CLEAR Outcomes is part of the CLEAR clinical research program for NEXLETOL® (bempedoic acid) Tablet and NEXLIZET® (bempedoic acid and ezetimibe) Tablet.