Background: nasal or oral sprays are often marketed as medical devices (MDs) in the European Union to prevent common cold (CC), with ColdZyme®/Viruprotect® (trypsin/glycerol) mouth spray claiming to prevent colds and the COVID-19 virus from infecting host cells and to shorten/reduce CC symptoms as an example. We analyzed the published (pre)-clinical evidence. Methods: preclinical: comparison of in vitro tests with validated host cell models to determine viral infectivity. Clinical: efficacy, proportion of users protected against virus (compared with non-users) and safety associated with trypsin/glycerol. Results: preclinical data showed that exogenous trypsin enhances SARSCoV2 infectivity and syncytia formation in host models, while culture passages in trypsin presence induce spike protein mutants. The manufacturer claims >98% SARSCoV2 deactivation, although clinically irrelevant as based on a tryptic viral digest, inserting trypsin inactivation before host cells exposure. Efficacy and safety were not adequately addressed in clinical studies or leaflets (no COVID-19 data). Protection was obtained among 9–39% of users, comparable to or lower than placebo-treated or non-users. Several potential safety risks (tissue digestion, bronchoconstriction) were identified. Conclusions: the current European MD regulations may result in insufficient exploration of (pre)clinical proof of action. Exogenous trypsin exposure even raises concerns (higher SARS-CoV-2 infectivity, mutations), whereas its clinical protective performance against respiratory viruses as published remains poor and substandard.

We have read the comment from Davison with great interest [...]

Introduction: Some medical devices (MDs) claim enteral barrier mechanisms as if it were medicinal drugs. MDs enter the EU market for direct dispensing as OTC products, through free movement of goods via CE-labelling, and bypass regulatory medicinal approval and control. Objectives and Methods: To analyse the regulatory quality of package inserts of 3 gastrointestinal products for paediatric use at time of entering EU. For diarrhea: Tasectan;/Gelenterum (gelatin tannate, GT) in EU and Tasectan/Gelenterum (GT+tyndalized heat-killed probiotics; GTTP) in IT+online. For GORD: Ziverel; Esoxx; (hyaluronic acid, chondroitinsulphate, poloxamer 407; HACDSPol) in IT,ES,FR, launch in AT,BE,LUX. Results: Product characteristics are inaccurately defined in the package insert: the tannate is not specified neither G bloom strength, ratio and free fraction of TA (added to 5 mL milk, 3 layers). GTTP powder contains heat-killed bacteria, but units are undisclosed)-. For HACDPol gel, doses of HA, CS and Pol 407, origin (rooster comb/bacterial) and polymerization grade of HA are missing. All leaflets allow unlimited use in children from birth onwards: GT and GTTP for effective relief of diarrhea., HACSPol GORD symptoms. Clinical documentation was poor, even lacking for children with GTTP and HACSPol. For GT, efficacy was claimed based on 'observations' in 2 'cohorts' (ORS+GT vs ORS) for 48hrs. The only placebo-controlled study in adults did not confirm the claim. For GTTP, studies in adults were even not retrieved; for HACSPol, gel or placebo was given add-on to standard-dose PPIs, even in PPI-naive adults: there are no data confirming efficacy as single product, neither in comparison to PPI. Safety: MD leaflets mention no known or no observed side effects. Yet, literature calls for attention (carcinogen, diarrhea, beyond amounts of approved food supplement, nephrotoxicity, drug-drug interactions, impaired wound healing, CYP450 and P-gp inhibition). Conclusion: EU regulation requires only national notification of MDs. This results in the marketing of poorly investigated and poorly labelled oral MDs claiming on barrier effects. They do not guarantee effective and safe 'medical' treatment of children.