Regulatory Information and Guidance for Drugs and Drug-Device Combinations

Medicinal products for delivery via respiratory tract (orally inhaled or intranasal drug products) typically combine the medicinal formulation (“drug”) and a delivery system (“device”).  Depending on their configuration and primary mode of action, they are regulated as drugs, or as devices, or as drug-device combination products.   

​

Regulatory agencies around the world have been actively supporting efforts to curb and combat the SARS-CoV-2 pandemic, and to adjust their other activities accordingly. 

​

United States - Guidance for Drugs and Drug-Device Combinations

• Recordings from the August 25, 2021 FDA workshop on chemistry, manufacturing and controls (CMC) inspections during the COVID-19 public health emergency.

• FDA Final Rule on “intended uses” clarifies definition of a product as a drug or a device – which, in turn, determines its regulatory pathway and requirements. The Rule is effective as of Sept. 1, 2021.

• FDA YouTube channel with educational resources for industry and consumers.  See, in particular, the Small Business and Industry Assistance (SBIA) playlist explaining fundamentals of Drug Master Files, Clean Rooms and other topics.  

• ​An explanation of which types of inhalers or components are regulated by which center at FDA – a “Jurisdictional Update” 

• A brief summary of the US regulatory requirements for inhalers and related products.  

• FDA guidances for drug-device combination products

• US FDA slides and recordings from the July-2020 webinar “Pharmaceutical Quality for Global Stakeholders”

  • These materials provide easy-to-understand advice and information related to US FDA quality requirements for pharmaceutical and biological (biotech) products.  Topics addressed include: drug shortages, manufacturing operations, data reliability, facilities inspections, quality surveillance and enforcement, FDA’s work outside the US, drug master files (DMFs), overview of existing and anticipated guidance documents, applicable international guidelines (such as from ICH), and other key areas.

• ​Up-to-date information on drug shortages and medical device shortages

• FDA guidance for inspections during the pandemic (August 2020)

• FDA guidance for development and licensure of vaccines to prevent COVID-19

• FDA commissioned independent report on PDUFA VI combination product review activities including pre-request for designations, request for designations, inter-center consult requests and application submissions (August 2020)

• FDA final guidance on control of nitrosamine impurities in human drugs (September 2020)

• “FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency” (March 2020, Updated: July 3, 2020)

• “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency” (Updated: May 2020)

• “Manufacturing, supply chain, and drug inspections | COVID-19” (April 9, 2020)

• “Coronavirus (COVID-19) Update: FDA Takes New Actions to Accelerate Development of Novel Prevention, Treatment Options for COVID-19” (May 11, 2020)

• “COVID-19: Developing Drugs and Biological Products for Treatment or Prevention – Guidance for Industry” (May 2020)

• “Bioequivalence Studies for Submission in ANDAs during the COVID-19 Pandemic” (April 28, 2020)

• “Effects of the COVID-19 Public Health Emergency on Formal Meetings and User Fee Applications — Questions and Answers” (May 2020)

• “Statistical Considerations for Clinical Trials During the COVID-19 Public Health Emergency Guidance for Industry” (June 2020)

• “Good Manufacturing Practice Considerations for Responding to COVID-19 Infection in Employees in Drug and Biological Products Manufacturing” (June 2020)

• “FDA OPQ Quality Report for Fiscal Year 2019” (February 2020)

• “Product-Specific Guidances for Generic Drug Development” (Date Unknown)

• The FDA created a special emergency program for potential COVID-19 therapies, the Coronavirus Treatment Acceleration Program (CTAP), to support clinical trials that are testing new treatments for COVID.

• For further guidance from the FDA, see its list of COVID-19 resources published in the Federal Register. 

• United States Pharmacopeia (USP)

• National Institute of Standards (NIST)

Europe - Guidance for Drugs and Drug-Device Combinations

​

• Drug Shortages

• EMA introduced new transparency measures due to COVID-19

• EMA issued updates to its guidance for virtual GCP inspections  

• “Points to consider on implications of Coronavirus disease 12 (COVID-19) on methodological aspects of ongoing clinical 13 trials” (March 2020, Updated: June 26, 2020)

• “Guidance on the Management of Clinical Trials During the COVID-19 (Coronavirus) Pandemic” (Updated: April 28, 2020)

• UK’s regulatory agency MHRA has issued a number of guidance documents for the post-transition period starting January 1, 2021.

• Updated Q&As, practical guidance, and templates for regulatory submissions provided by the Heads of Medicines Agencies

• British Pharmacopeia

• European Pharmacopeia

​

Brazil - Guidance for Drugs and Drug-Device Combinations

​

• Anvisa’s main page on COVID-19 provides links to pages containing legislations relevant to medicines and medical devices, approved clinical trials for treatments or preventative medicines, monitoring safety and quality of products being used to address COVID-19, and timelines of Anvisa actions.

• Notice on requirements for companies to report daily on manufacture, import and distribution of anesthetics, sedatives, neuromuscular blockers and adjuvant agents, and other drugs used to sustain COVID-19 patients.  

• Anvisa provides detailed information and resources on masks and standards for masks used in health care settings.    

• Anvisa has issued an updated guideline on conduct of clinical trials and bioequivalence studies during the COVID-19 health emergency. (June 15, 2020)

• Brazilian Pharmacopeia

​

China - Guidance for Drugs and Drug-Device Combinations

​

• “Chinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatment” (March 16, 2020)

• “Chinese Guideline(s) of Diagnosis and Treatment of COVID-19” (March 18, 2020)

• The Chinese State Administration for Market Regulation has finalized the “Administrative Measures for Drug Registration” and "Administrative Measures for Drug Production,” regulations that describe regulatory expectations and concepts for drug approval, registration and manufacture, respectively. 

• The NMPA’s main COVID-19 related site provides links to current news announcements, and NMPA actions related to COVID-19 medicines and medical devices.  It also contains a cases reported tracker.

• A general description of how the NMPA regulates SARS-CoV2 detection tests and protective equipment, including medical-grade masks.

• The CDE guideline on conductance of clinical trials during the COVID-19 is available.

• An overview of the standard system for pharmaceutical excipients and packaging materials in the fourth part of the 2020 edition of the Chinese Pharmacopoeia.