Nasal spray – Drug or Medical Device?
Manufacturers of substance-based medical devices, including saline nasal sprays, cough syrups, and osmotic laxatives, are expected to face challenges under the MDR 2017/745. The classification of these products depends on whether their principal intended action is achieved through pharmacological, immunological, metabolic, or mechanical means.
The Definition of a Substance-Based Medical Device
Substance-based medical devices are medical devices that are composed of substances or combinations of substances. Although they are similar to medicinal products in their presentation and pharmaceutical form, they achieve their principal intended effect via a physicochemical and/or physical mechanism of action. Medicinal products, in contrast, have a pharmacological, immunological or metabolic mechanism of action (refer to MEDDEV 2.1/3 rev3, dated 18-May-2015).
Here are some examples of substance-based medical devices:
- Saline nasal drops or sprays
- Syrups, throat sprays or lozenges that moisten the mucous membranes
- Skin creams or ointments for moisturizing or sealing wounds
- Artificial tear fluids
- Oral agents to neutralize gastric acid
- Osmotic laxatives
- Products with defoaming effect for gas-related gastrointestinal conditions
- Vaginal creams or gels
Determining Nasal Spray Classification
According to Directive 2001/83/EC, if nasal spray achieves their intended action through pharmacological, immunological, or metabolic means, they are considered medicinal products and require marketing authorization. However, if the principal intended action is achieved through mechanical means, they are classified as medical devices under Article 2(1) of Regulation (EU) 2017/745.
To determine the risk class of nasal spray as medical devices, Annex VIII of the MDR 2017/745 provides guidelines:
- If the nasal sprays are composed of substances intended to be introduced into the human body and absorbed or locally dispersed, Rule 21 applies
- If the nasal sprays incorporate a substance that would be considered a medicinal product on its own, according to Directive 2001/83/EC, they should be classified according to Rule 14 of Annex VIII
This classification applies when the substance has an ancillary action to the principal physical or mechanical mode of action of the device.
Considering the classification of nasal sprays as class IIa medical devices at a minimum, based on Rule 21 of Annex VIII of the MDR, the conformity assessment process for these products requires the involvement of a notified body. For devices composed of substances that are absorbed by or locally dispersed in the human body, a specific procedure outlined in Annex IX, section 5.4 of Regulation (EU) 2017/745 must be followed.
These regulations ensure that the manufacturing and marketing of nasal sprays and similar substance-based medical devices adhere to the appropriate standards and safety requirements outlined by the MDR 2017/745.
Clinical Evidence for Nasal Spray Product
Clinical evidence plays a crucial role in demonstrating the safety and performance of substance-based medical devices, particularly those that come into direct contact with the human body. While pre-clinical and performance data can provide valuable insights, they often cannot fully establish the necessary evidence.
Clinical investigations are typically required to support the effectiveness of such devices. However, it should be noted that for low-risk devices that have been on the market for a significant period, specific clinical investigations may not be performed, as per Directive 93/42/EC (MDD).
Eclevar MEDTECH recognizes the importance of clinical evidence and aims to assist manufacturers in determining the appropriate level of clinical evaluation needed to comply with the general safety and performance requirements outlined in Regulation (EU) 2017/745. The extent and depth of the evaluation should be proportionate to the device’s intended purpose and associated risks, as well as the claims made by the manufacturer.
It is critical for manufacturers to design clinical investigations that are robust, unbiased, and incorporate adequate controls to ensure scientific validity. The clinical data should provide evidence of the claimed duration of action put forth by the manufacturer.
To comply with Regulation (EU) 2017/745, manufacturers are required to provide a detailed and quantitative description of the expected performance of the medical device. This information should be clearly stated on the device’s label, ensuring that users understand the intended purpose and the claims regarding the device’s proven benefits. Article 7 of the regulation specifically prohibits any misleading statements in the device’s labelling, instructions for use, and even on the manufacturer’s website.
Manufacturers are also obligated to communicate residual risks associated with the medical device. According to Annex I, Chapter III, point 23.1 g of Regulation (EU) 2017/745, manufacturers should inform users about limitations, contraindications, precautions, and warnings related to the device.
By effectively communicating residual risks, manufacturers can help users make informed decisions and take necessary precautions when utilizing the device, promoting safety and minimizing potential adverse effects.
After the preclinical phase and feasibility studies, the efficacy of a new medical device is assessed to determine its potential in delivering the desired results. Feasibility studies are conducted immediately following the preclinical phase, serving the purpose of refining the technique and identifying the appropriate efficacy endpoints.
To proceed with Post-Market Clinical Follow-up (PMCF) studies involving a larger patient population, the MEDTECH CRO must first ensure that their new medical device shows promising efficacy. This initial stage involves selecting an efficacy endpoint based on existing data in the literature or supported by expert opinion.
Methodological Specification for the Clinical Development of Nasal Spray as Medical Device
Saline nasal irrigation is a beneficial therapy for upper respiratory conditions, particularly chronic rhinosinusitis. It involves using spray or liquid saline to bathe the nasal cavity, providing relief for symptoms associated with this condition. While clinical evidence specifically addressing the use of saline nasal irrigation for mild to moderate allergic rhinitis and acute upper respiratory tract infections is limited, scientific guidelines recommend its use for other conditions such as rhinitis of pregnancy and acute rhinosinusitis.
It is generally considered a safe therapy, as no serious adverse events have been reported. Minor adverse effects can be avoided by modifying the technique and adjusting the salinity of the solution.
Chronic rhinosinusitis serves as an example of a condition where saline nasal irrigation is commonly employed, and a post-market clinical follow-up (PMCF) strategy can be utilized to collect clinical evidence. This condition involves inflammation of the nose and paranasal sinuses, characterized by persistent symptoms lasting for 12 weeks or longer. Symptoms include:
- Nasal blockage
- Nasal discharge
- Facial pain or pressure
- Diminished sense of smell
- Nasal polyps may or may not be present
By implementing a PMCF strategy, data can be gathered to assess the efficacy and safety of saline nasal irrigation in managing chronic rhinosinusitis, further supporting its use as a therapeutic option for this condition.
Patient Survey or Questionnaires
The incorporation of Patient-Reported Outcome Measures (PROMs) is gaining recognition for its importance in delivering high-quality care. Patient perspectives on the severity and impact of chronic rhinosinusitis symptoms can be assessed using tools such as the Visual Analog Scale (VAS), individual symptom severity rating, or validated symptom-based questionnaires.
PROMs are self-rated measures of health-related quality of life (HRQOL) directly reported by patients, offering insights into their perceived outcomes. Clinician-rated outcomes may not fully capture the efficacy of treatment from the patient’s perspective, making PROMs a valuable addition to evaluate treatment effectiveness.
PROMs can be generic or disease-specific:
- Generic PROMs enable comparisons between conditions or treatments, aiding in determining the impact of different diseases on patient groups and informing decision-making. However, they may lack sensitivity to detect small yet meaningful changes in disease-specific quality of life (QOL).
- Disease-specific PROMs focus on capturing specific symptoms and impacts related to a particular condition, providing more targeted insights.
Several rhinosinusitis-specific instruments exist, with varying aims, item numbers, settings, and ease of use. Notable examples include the SNOT-20 and SNOT-22, which have been extensively studied and demonstrate good psychometric quality. However, the SNOT-20 may lack content validity due to the absence of essential items related to nasal obstruction and reduced sense of smell, which are crucial for diagnosing chronic rhinosinusitis. Another widely used instrument, the CSS (Chronic rhinosinusitis Symptom Score), focuses solely on disease-specific items.
In terms of allergic rhinitis and chronic rhinosinusitis, there are fewer available tools, but the 22-item Sino nasal Outcome Test (SNOT-22) can be utilized as a common PROM for patients presenting with symptoms suggestive of either of these diseases. The SNOT-22 questionnaire covers classic nasal symptoms as well as extra nasal symptoms such as poor sleep, ear/facial discomfort, and mood disturbances.
While numerous generic HRQOL instruments exist, Short Form-36 is widely used and provides normative and comparative data across different chronic diseases, including rhinosinusitis. It measures eight domains of health and has been utilized to assess the impact of CRS on quality of life and treatment outcomes.
For further guidance on selecting the appropriate questionnaire or calculating sample sizes for patient populations, contacting the team at ECLEVAR can provide valuable assistance.
Interventional Non-Comparative Study-Saline Nasal Spray
Saline nasal spray have gained wide acceptance as a primary treatment option for individuals seeking relief from nasal congestion or dryness. Isotonic saline solutions are specifically formulated to cleanse and moisturize the nasal mucosa, making them suitable for addressing symptoms of a dry nose. On the other hand, hypertonic saline solutions are commonly utilized to decongest the nasal mucosa.
Given their distinct purposes, an interventional, non-comparative, single-center Post Marketing Clinical Follow-up (PMCF) study could be designed to assess the effectiveness and safety of nasal sprays in alleviating nasal congestion and dryness.
The proposed PMCF study aims to achieve several objectives:
- Validate the performance of nasal sprays in accordance with their designated use for relieving nasal congestion and dryness
- Gather additional safety data related to anticipated adverse events that may occur when using nasal spray as instructed
- Identify any unforeseen adverse events that could potentially arise from the use of nasal sprays
By pursuing these objectives, a comprehensive evaluation of the performance and safety of nasal sprays can be conducted, providing valuable insights into their effectiveness and potential risks. An interventional, non-comparative, single-center PMCF study represents a suitable approach to investigate the performance and safety of nasal spray in relieving nasal congestion and dryness.
Eclevar – A Competent CRO for Your Medical Device’s Market Entering
Eclevar MEDTECH can help the manufacturers ensure that their product is qualified and classified in line with the MDR, and in accordance with the intended purpose and the principal mode of action of the product. We are ready to comply with all regulatory demands needed for your medical device to reach the market.