WorldWIDE
REGULATORY GUIDANCE
At present, there are no worldwide standards that are specifically applicable to Orally Inhaled and Nasal Drug Products (OINDPs). Below are regulatory agencies by region, a harmonizing organization, and selected recommended guidelines for safety, quality and efficacy.
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:
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 2003), Integration of Dose-Counting Mechanisms into MDI Drug Products, Clinical Medical
(CDER 2018), ANDA Submissions — Amendments to Abbreviated New Drug Applications Under, Generics
(CDER 1993) Reviewer Guidance for Nebulizers, Metered Dose Inhalers, Spacers and Actuators
(CDER 2017) Current Good Manufacturing Practice Requirements for Combination Products
(CDER 2018) Allergic Rhinitis: Developing Drug Products for Treatment Guidance for Industry
(September 2018) Nonallergic Rhinitis: Developing Drug Products for Treatment
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(CDER 2020) Draft Guidance for Sumatriptan, Nasal, Spray
(CDER 2019) Draft Guidance on Beclomethasone Dipropionate (Aerosol, Metered; Inhalation)
(CDER 2019) Draft Guidance on Budesonide (Spray, Metered; Nasal)
(CDER 2019) Draft Guidance on Fluticasone Furoate (Metered, Spray; Nasal)
(CDER 2019) Draft Guidance on Fluticasone Propionate (Powder; Inhalation)
(CDER 2019) Draft Guidance on Fluticasone Propionate (Metered, Spray; Nasal)
(CDER 2019) Draft Guidance on Mometasone Furoate Monohydrate (Metered, Spray; Nasal)
(CDER 2019) Draft Guidance on Triamcinolone Acetonide (Metered, Spray; Nasal) Recommended Oct 2016; Revised Feb 2019, Jun 2020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 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 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
European Directorate for the Quality of Medicines & HealthCare
Monographs applicable to Orally Inhaled and Nasal Drug Products from The European Pharmacopoeia* 2019,10th Edition, published by EDQM:
Nasal Preparations, Dosage Forms 0676, European Pharmacopoeia: 2019 10th Edition (10.3) 01/2021:0676, Pages 4823-4825 (for details, contact us)
Inhalation Preparations, Dosage Forms 0671 European Pharmacopoeia: 2019 10th Edition (10.5) 07/2021:0671, Pages 5706-5711 (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)
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.
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.
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
The Standards Council of Canada is the approval body for national standards.
Regulatory guidelines for in vitro testing of OINDPs include general descriptions for characterizing OINDP performance under fixed laboratory conditions to determine certain end-point oriented critical quality attributes (CQA) that drive product quality. Proveris instruments can perform these tests on a range of devices through the life of the device. Below are some of the commonly accepted tests:
- Single Actuation Container (SAC) Through Life
- Aerodynamic Particle Size Distribution (APSD) by Cascade Impaction (NGI, ACI)
- Spray Pattern
- Plume Geometry
- Priming/Re-priming
- Delivered Dose Uniformity
- Delivered Mass Uniformity
- Valve/Pump Delivery (Shot Weight)
- Drug Particle Size by Microscopy (Suspensions)
- Droplet Size Distribution (DSD) by Laser Diffraction
- Product Wasting for Through-Life Testing
- Inter-/Intra-container Through-Life Product Testing