The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a unique organisation consisting of representatives from the regulatory authorities in the European Union (EMA), Japan (MHLW) and the USA (FDA), and experts from the pharmaceutical industry in the three regions, in a single forum. ICH has concentrated on the preparation of the following quality related guidelines:

• ICH Q8 (R2) Pharmaceutical Development
• ICH Q9 Quality Risk Management
• ICH Q10 Pharmaceutical Quality System
• ICH Q11 Development and Manufacture of Drug Substances

• ICH Q12 Pharmaceutical Product Lifecycle Management
  

In the USA, the regulatory function is performed by the Food and Drug Administration (FDA) through two centers, the Center for Drug Evaluation and Research (CDER) in respect of medicines and the Center for Devices and Radiologic Health (CDRH) in respect of medical devices.

The FDA’s relevant current thinking for orally inhaled and nasal drug products is reflected in the following Regulatory Guidances for Industry:

(CDER 2018), Metered Dose Inhaler (MDI) & Dry Powder Inhaler (DPI) Products – Quality Considerations Guidance for Industry”, Pharmaceutical Quality/CMC Documentation – Draft

(CDER 2017), Bioequivalence Summary Table for Metered Dose Inhaler Products, Technical Specifications Documentation

(CDER 2003), Bioavailability and bioequivalence studies for nasal sprays for local action, Biopharmaceutics – Draft

(CDER 2003) Bioequivalence summary tables related to the in vitro tests recommended in “Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action

(CDER 2002), Nasal Spray and Inhalation Solution, Suspension and Spray Drug Products, Chemistry, Manufacturing and Controls

(CDER 2003), Integration of Dose-Counting Mechanisms into MDI Drug Products, Clinical Medical

(CDER 2001), Sterility Requirements for Aqueous-Based Drug Products for Oral Inhalation, Small Entity Compliance Guides

(CDER 2018), ANDA Submissions — Amendments to Abbreviated New Drug Applications Under, Generics

(CDER 2011), Process Validation: General Principles and Practices Guidance for Industry, Good Manufacturing Practices

(CDER 2004), Process Validation Requirements for Drug Products and Active Pharmaceutical Ingredients Subject to Pre-Market Approval

(CDER 1993) Reviewer Guidance for Nebulizers, Metered Dose Inhalers, Spacers and Actuators

(CDER 2017) Current Good Manufacturing Practice Requirements for Combination Products

(CDER 2017) Draft Guidance for Industry – Comparative Analyses and Related Comparative Use Human Factors Studies for A Drug-device Combination Product Submitted in an ANDA

(CDER 2016) Human Factors Studies and Related Clinical Study Considerations in Combination Product Design and Development: Draft Guidance for Industry and FDA Staff

(CDER 2016) List of Highest Priority Devices for Human Factors Review: Draft Guidance for Industry and Food and Drug Administration Staff

(CDER 2018) Allergic Rhinitis: Developing Drug Products for Treatment Guidance for Industry

(CDER 2018) Draft Guidance: Contents of a Complete Submission for Threshold Analyses and Human Factors Submissions to Drug and Biologic Applications  

(September 2018) Nonallergic Rhinitis: Developing Drug Products for Treatment

(CDER 2016) Applying Human Factors and Usability Engineering to Medical Devices – Guidance for Industry and Food and Drug Administration Staff

The FDA’s current thinking and expectations on how to develop generic drug products therapeutically equivalent to specific reference listed drugs is reflected in the following Product-Specific Guidances:

(CDER  2020) Draft Guidance for Sumatriptan, Nasal, Spray

(CDER 2019) Draft Guidance on Beclomethasone Dipropionate (Aerosol, Metered; Inhalation)

(CDER 2019) Draft Guidance on Budesonide (Spray, Metered; Nasal)

(CDER 2019) Draft Guidance on Fluticasone Furoate (Metered, Spray; Nasal)

(CDER 2019) Draft Guidance on Fluticasone Propionate (Powder; Inhalation)

(CDER 2019) Draft Guidance on Fluticasone Propionate; Salmeterol Xinafoate (Aerosol, Metered; Inhalation)

(CDER 2019) Draft Guidance on Azelastine Hydrochloride and Fluticasone Propionate (Spray, Metered; Nasal)

(CDER 2019) Draft Guidance on Fluticasone Propionate (Metered, Spray; Nasal)

(CDER 2019) Draft Guidance on Mometasone Furoate Monohydrate (Metered, Spray; Nasal)

(CDER 2019) Draft Guidance on Triamcinolone Acetonide (Metered, Spray; Nasal)  Recommended Oct 2016; Revised Feb 2019, Jun 2020

(CDER 2019) Draft Guidance on Fluticasone Propionate and Salmeterol Xinafoate (Powder; Inhalation)

(CDER 2019), Draft Guidance for Dihydroergotamine Mesylate, Nasal, Spray, Metered

(CDER 2018) Draft Guidance for Talc, Inhalation, Aerosol, Metered

CDER 2018), Draft Guidance for Zolmitriptan, Nasal, Spray

(CDER 2019) Draft Guidance on Beclomethasone Dipropionate (Aerosol, Metered; Nasal)

(CDER 2017) Draft Guidance on Azelastine Hydrochloride (Metered Spray; Nasal)

(CDER 2017) Draft Guidance on Fluticasone Propionate (Powder; Inhalation)

(CDER 2017) Draft Guidance on Mometasone Furoate (Powder; Inhalation)

(CDER 2017) Draft Guidance on Tiotropium Bromide (Powder; Inhalation)

(CDER 2017), Draft Guidance for Naloxone Hydrochloride, Nasal, Spray

(CDER 2016), Draft Guidance for Buprenorphine Hydrochloride; Naloxone Hydrochloride, Oral, Sublingual Tablet

(CDER 2016) Draft Guidance on Albuterol Sulfate (Aerosol, Metered; Inhalation)

(December 2016) Draft Guidance on Budesonide (Powder; Inhalation)

(CDER 2016) Draft Guidance on Olopatadine Hydrochloride (Metered Spray; Nasal)

(CDER 2016) Draft Guidance on Umeclidinium Bromide (Powder; Inhalation)

(CDER 2020) Draft Guidance on Umeclidinium Bromide and Vilanterol Trifenatate (Powder; Inhalation)

(CDER 2016) Draft Guidance on Fluticasone Furoate (Powder; Inhalation)

(CDER 2016) Draft Guidance on Fluticasone Furoate; Vilanterol Trifenatate (Powder; Inhalation)

(CDER 2016) Draft Guidance on Indacaterol Maleate (Powder; Inhalation)

(CDER 2016) Draft Guidance on Mometasone Furoate (Aerosol; Metered; Inhalation)

CDER 2015) Draft Guidance on Mometasone Furoate Monohydrate (Metered, Spray; Nasal) Recommended Sept 2015; Revised Feb 2019

(CDER 2016) Draft Guidance on Ciclesonide (Aerosol; Metered; Inhalation)

(CDER 2016) Draft Guidance on Formoterol Fumarate; Mometasone Furoate (Aerosol; Metered; Inhalation)

CDER 2017) Draft Guidance on Mometasone Furoate (Powder; inhalation)

(CDER 2015) Draft Guidance on Aclidinium Bromide (Powder, Metered; Inhalation)

(CDER 2022) Draft Guidance on Aclidinium Bromide; Formoterol Fumarate (Powder, Metered; Inhalation)

(CDER 2015) Draft Guidance on Fluticasone Propionate (OTC; Metered, Spray; Nasal)

(CDER 2015) Draft Guidance on Formoterol Fumarate (Powder; Inhalation)

(CDER 2015) Draft Guidance on Levalbuterol Tartrate (Aerosol, Metered; Inhalation)

(CDER 2015) Draft Guidance on Ipratropium Bromide (Aerosol, Metered; Inhalation)

(CDER 2015) Draft Guidance on Budesonide; Formoterol Fumarate Dihydrate (Aerosol; Metered; Inhalation)

(CDER 2013) Draft Guidance on Fluticasone Propionate; Salmeterol Xinafoate (Powder/inhalation)

(CDER 2012) Draft Guidance on Budesonide (Suspension / Inhalation)

(CDER 2012) Draft Guidance on Ciclesonide (Aerosol, Metered/nasal)

The European Medicines Agency (EMA) works with the European Directorate for the Quality of Medicines and HealthCare (EDQM), a directorate of the Council of Europe on matters aimed at ensuring the quality of medicines and protection of public health.

European Medicines Agency

Guidance applicable to Orally Inhaled and Nasal Drug Products:

(June 2006) Guideline on The Pharmaceutical Quality of Inhalation and Nasal Products

(January 2009) Guideline on The Requirements for Clinical Documentation for Orally Inhaled Products (OIP) Including the Requirements for Demonstration of Therapeutic Equivalence Between Two Inhaled Products for Use in The Treatment of Asthma and Chronic Obstructive Pulmonary Disease (COPD) In Adults and For Use in The Treatment of Asthma in Children and Adolescents

(June 2017) Concept Paper on Revision of the Guideline on the Requirements for Clinical Documentation for Orally Inhaled Products (OIP) Including the Requirements for Demonstration of Therapeutic Equivalence Between Two Inhaled Products for Use in the Treatment of Asthma and Chronic Obstructive Pulmonary Disease (COPD) in Adults and for the Treatment of Asthma in Children and Adolescents

European Directorate for the Quality of Medicines & HealthCare

Monographs applicable to Orally Inhaled and Nasal Drug Products from The European Pharmacopoeia* 2019,10^th Edition, published by EDQM:

Nasal Preparations, Dosage Forms 0676, European Pharmacopoeia: 2019 10^th Edition (10.3) 01/2021:0676, Pages 4823-4825 (for details, contact us)

*The European Pharmacopoeia, published by EDQM, provides a legal and scientific reference for the quality control of medicines. All producers of medicines and substances for pharmaceutical must follow these standards when applying to the EMA and include reference to the monographs in the quality part of their applications.

The Council of Europe has 38 member states and 30 observers of which 6 are European countries and 22 are non-European countries. The Taiwan Food and Drug Administration (TFDA) of the Ministry of Health and Welfare and the World Health Organization (WHO) are also observers.

In the UK, the Medicines and Healthcare products Regulatory Agency is an executive agency of the Department of Health and Social Care responsible for ensuring that medicines and medical devices work and are acceptably safe.

(June 2018) Guidance: Medical device stand-alone Software Including Apps (including IVDMDs)

(September 2017) Human Factors and Usability Engineering – Guidance for Medical Devices Including Drug-device Combination Products

MHRA website

In China, the National Medical Products Administration (NMPA) is the Chinese agency for regulating drugs and medical devices (formerly the China Food and Drug Administration or CFDA). Its responsibilities include drafting laws and regulations for drugs, medical devices, and cosmetics, as well as establishing medical device standards and classification systems.

NMPA Website

In Brazil, the Health Regulatory Agency, Anvisa, executes sanitary control of the production, marketing and use of products and services subject to health regulation, including related environments, processes, ingredients and technologies.

ANVISA Website

In Canada, Health Canada reviews drug products to assess their safety, efficacy and quality.

(October 2001) Guidance for Industry – Pharmaceutical Quality of Inhalation and Nasal Products

(April 1999) Guidance to Establish Equivalence or Relative Potency of Safety and Efficacy of a Second Entry Short-Acting Beta2-Agonist Metered Dose Inhaler (MDI)

(October 2018) Guidance Document: Data Requirements for Safety and Effectiveness of Subsequent Entry Inhaled Corticosteroid Products Used for the Treatment of Asthma – Summary

The Standards Council of Canada is the approval body for national standards.

(August 2011) CAN/CSA-Z264.1-02 (R2011) Spacers and Holding Chambers for Use with Metered-Dose Inhalers