The use of hand sanitisers and surface disinfection is one way to help combat the Covid-19 pandemic. The biocides sector is well placed to assist if appropriate products can find their way to users with sufficient speed. The commercial and regulatory challenges this task presents can be met. Companies and authorities just need to understand how. Steptoe & Johnson’s Darren Abrahams, Eléonore Mullier and Hannah Widemann (Europe) and Seth Goldberg, Deborah Attwood (US) examine the options.
Standard EU market access requirements
Hand and surface disinfectants are covered under product types (PTs) 1 and 2, respectively, under the EU biocidal products Regulation (BPR). The BPR’s standard pre-market authorisation procedures for formulations with approved active substances (ASs) apply timelines that are sufficiently swift to grant new market authorisations and make products available rapidly.
A biocidal product (whether its active substance is approved or not) may not be made available unless the AS/PT combination is from a supplier on the Echa-maintained Article 95 list (those suppliers accepted by Echa as having a complete AS/PT combination dossier). It is no surprise therefore that several member states are experiencing shortages of needed disinfectants meeting these requirements. Thankfully, the BPR provides a fast-track alternative to these standard requirements.
Derogations from pre-market authorisation
Article 55 of the BPR allows member states to put aside the standard BPR authorisation requirements in public health emergency situation. A national competent authority (CA) notifies the derogation they have applied in their territory to the European Commission and other CAs. National derogations cannot exceed 180 days but may be extended, on submission of a reasoned request, for a further 550 days by the Commission. For the Covid-19 derogations adopted in March, Commission decisions on extensions would need to be made in late summer. It is worth noting that some member states have adopted derogations for a period shorter than the maximum 180 days. Denmark’s derogation, for example, is valid until 30 June. The Commission’s decision to extend is adopted by way of an implementing Decision.
Member state derogations to date
At the time of writing (25 March) a number of member states, including Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Latvia, Lithuania, Poland, Spain and Sweden have made use of this mechanism to make more disinfectants available to fight Covid-19. Some derogations permit production and marketing of disinfectants following generic WHO formulations while others specifically identify certain products.
As public health measures have been progressively strengthened across Europe, the scope of derogations has widened. For example, Germany and France extended initial derogations granted to pharmacies, to manufacturers with experience producing certain PTs and legal entities under public law. Sweden extended the list of substances (initially propan-1-ol and propan-2-ol, extended to active chlorine) and uses (initially hand disinfectants, extended to hand and surface disinfectants).
There is no one-size-fits-all approach. For each territory, companies need to understand the scope of permitted products, the substances and uses covered, the entities that may make the products available, the periods of applicability of the derogations, and labelling requirements.
An additional layer of variation applies to products under national "transitional" regimes for products containing an AS such as ethanol, which is still being evaluated at the EU level. For such products, national rules may apply such as country-specific notification obligations.
Article 95 List derogation
While Article 55 expressly sets aside the BPR’s pre-market authorisation regime (set out in Articles 17 and 19) it makes no express reference to the Article 95 supplier list (noted above). Nonetheless, in our view a correct reading of the BPR derogation rules indicates that the Article 95(2) requirement is set aside in such cases, for several reasons.
First, Article 55 provides that a product benefitting from a derogation "does not have to fulfil the conditions for authorisation laid down in this Regulation" (emphasis added). This is not limited to the conditions in Articles 17 and 19, alone.
This reading is supported by Recital 48 of the BPR, which states: "In the event of an unforeseen danger threatening public health or the environment which cannot be contained by other means, it should be possible for Member States to permit, for a limited period of time, the making available on the market of biocidal products which do not comply with the requirements of this Regulation."
This is also reflected in the notified German derogations, for which the accompanying FAQs note that limitation of derogations to Article 95-listed companies would run counter to the purpose of the derogations procedure itself. Not all member states have been so emphatic.
Second, beyond the wording of the BPR, it is clear that the usefulness – the effet utile – of the entire BPR derogation system would be severely frustrated if the "peace time" Article 95 obligations remained applicable. Negotiation of data access rights for Article 95 listing is typically a lengthy process, entirely unconducive to making products available quickly for public health emergencies.
Third, even if derogations are generally interpreted narrowly, they may not be read so narrowly that the derogation itself ceases to be effective. As the Court of Justice has indicated, in the REACH context, "Such a literal interpretation is manifestly contrary to the objective (…) to protect health and the environment (…) incompatible with the general scheme of that regulation:". This seems no less true for the BPR.
Centralised action
On 20 March, Echa first announced its plans to work with member states and the Commission to support EU-wide action against Covid-19, addressing disinfectant shortages. These efforts include a dedicated Covid-19 webpage and a DG Sante paper advising member states on Possibilities for measures to increase availability of disinfectant products in member states. These measures could include member states permitting the placing on the market of products that do not satisfy the full requirements of technical equivalence set out in Article 19(1)(c) of the BPR. A fast-track technical equivalence procedure from Echa for new sources of ASs may also be introduced.
On 24 March, Echa further announced a ‘centralised submission’ procedure for applications by companies "that target several countries". Although the BPR gives no role to Echa in derogations, the idea that the agency should become a one-stop hub to address a Europe-wide issue is logical. Echa is also recommending compositional requirements for the use of propan-1-ol and propan-2-ol.
US market access requirements
Antimicrobials for use on surfaces are regulated by the US EPA as pesticides under the Federal Insecticide, Fungicide and Rodenticide Act (Fifra), while antimicrobials for use on humans or animals are regulated by the FDA as drugs under the Federal Food Drug and Cosmetics Act (FFDCA). Both agencies have taken important steps to ensure adequate supplies of antimicrobials to address the current pandemic.
EPA-regulated antimicrobials
Fifra requires product-specific approval by way of a ‘registration’ of antimicrobial products and sources of active ingredients. Efficacy against public health pests, such as the Covid-19 virus, must be demonstrated using specified EPA-approved studies. Well before the current outbreak, the EPA issued a policy permitting claims against emerging viral pathogens, provided a product meets certain efficacy tests. As of 29 January, product registrants could apply, providing supporting efficacy data to be listed under the policy. Products in the programme are considered by the EPA to be effective against Covid-19. The American Chemistry Council’s Center for Biocide Chemistries (CBC) published the first list of such products and the EPA has now issued an official list.
Registrants and sellers of products on the EPA’s list cannot expressly state on the label that the products are effective against Covid-19, but can state that they are on the EPA list. The EPA is now in the process of developing testing standards for companies to demonstrate effectiveness against Covid-19 and include such claims on their labels.
Many companies that market products not included on the EPA list are seeking inclusion on an expedited basis. The EPA is doing its best to be responsive and redirecting resources accordingly.
FDA-regulated antimicrobials
Antiseptic products, including hand sanitisers and hand wipes, are regulated by the FDA as over-the-counter (OTC) drugs. The FDA typically determines whether the active ingredients used in OTC drugs are generally recognised as safe and effective (Grase) through its monograph programme, although it is possible to submit a new drug application (NDA) for an OTC drug. In cases where the agency determines that an ingredient is not Grase, it requires submission of an NDA.
Currently, the FDA’s consumer antiseptic monographs allow the use of three active ingredients in consumer antiseptics:
- ethyl alcohol;
- isopropyl alcohol; and
- benzalkonium chloride.
Meanwhile the FDA’s healthcare antiseptic monographs allows use of six active ingredients in healthcare antiseptics:
- benzalkonium chloride;
- benzethonium chloride;
- chloroxylenol;
- ethyl alcohol;
- isopropyl alcohol; and
- povidone-iodine.
As OTC drugs, these products and their manufacturers ordinarily are subject to a slew of regulatory obligations. Domestic and foreign establishments that manufacture, repack or re-label drug products for sale in the US are required to register with the FDA and to list their products with the agency, and must comply with the FDA’s current good manufacturing practices (CGMP). OTC drugs are subject to a standardised labelling format, with certain label statements, such as the indications for use and warnings, specified by FDA.
As a result of the Covid-19 pandemic, the FDA has issued two guidance documents declaring that the agency will exercise enforcement discretion for manufacturers that produce alcohol-based consumer and healthcare hand sanitisers, and for manufacturers that produce ethyl alcohol for use as the active pharmaceutical ingredient (API), regardless of whether the manufacturer was already regulated by the FDA as a drug manufacturer.
The FDA’s hand sanitiser guidance, Temporary policy for preparation of certain alcohol-based hand sanitizer products during the public health emergency (Covid-19), permits production of one specific formulation of hand sanitiser, as identified in the guidance (using a WHO formula), with either ethyl alcohol (denatured) or isopropyl alcohol as the active ingredients.
The second FDA guidance, Temporary policy for manufacture of alcohol for incorporation into alcohol-based hand sanitizer products during the public health emergency (Covid-19) identifies the purity requirements applicable to the alcohol (United States Pharmacopoeia or Food Chemical Codex grade) and requires use of sterile water and specific denaturants. Although the strict record-keeping and CGMP requirements applicable to drugs are relaxed under these enforcement discretion policies, manufacturers must still document key steps and controls during manufacturing to confirm compliance with the guidance, including verification of the alcohol content, use "sanitary conditions" and equipment that is "well maintained and fit for the purpose", label the finished product only as indicated, and register facilities and list these products in the FDA Drug Registration and Listing System (DRLS).
Entities considering production of alcohol for use in hand sanitisers also need to consider the permitting requirements of the Alcohol and Tobacco Tax and Trade Bureau (TTB), as discussed in recent TTB guidance.
Notably, although the FDA and other federal agencies continue to recommend use of hand sanitisers when hand washing is not possible, manufacturers should not make claims in labelling or advertising that their products can treat or prevent specific diseases, including Covid-19.
On 19 March, the Cybersecurity and Infrastructure Agency (CISA), part of the Department of Homeland Security, issued a memorandum providing guidance to help state and local jurisdictions, as well as private industry, with the "identification of essential critical infrastructure workers during Covid-19 response". CISA's guidance includes manufacturers of antimicrobials designated as critical infrastructure workers. Employers must check with the state in which the workers are located to determine whether they are excluded and, if so, to identify state procedures for documenting the exemption.
Conclusion
The response to Covid-19 is a necessarily fast-moving field. An open dialogue and exchange of ideas between industry and public authorities will remain essential as the processes noted above, and others, emerge in the coming days and weeks. Stakeholders should make their constructive and solution-focused proposals to authorities, supported by the legal frameworks that already exist in the US and EU – and which, in our view, are capable of delivering the necessary results if used well.
The views in this article are the personal views of the authors and do not necessarily reflect those of Steptoe & Johnson or any of its clients and are not intended to constitute legal advice. Moreover, the views expressed in contributed articles are those of the expert authors and are not necessarily shared by Chemical Watch