The Biocidal Products Regulation N° 528/2012 in force in Europe since September 1st, 2013 will have an impact on the future of disinfectant products, on current practices as well on the methods of application used today. The objective of this article is to provide information about this regulation and its impact on use on pharmaceutical sites: which active substances are authorized, the timeline for filing MA applications, the responsibilities of disinfectant suppliers and user sites.

Reminder of regulations:
The Biocidal Products Regulation (BPR) concerns biocidal products and treated articles. It follows on from Biocidal Directive 98/8/CE of 16 February 1998 which for around 10 years, has put in place a process of identification then notification of active substances by manufacturers, and finally their assessment by the competent authorities of the European country concerned. A number of key steps followed and finally, from September 1st, 2013, the entry into force of the biocidal regulation on the marketing authorization and use of biocidal products to replace the directive.

The regulation was applicable immediately on this date in all Member States. It introduced new terminology, increased the overall requirement level for greater protection of human beings and the environment, covered treated articles as biocidal agents, introduced a data sharing system and the possibility of authorizing a product across all European Union countries.

The Biocidal Products Regulation restated the same objectives as the directive it replaced. It stemmed from a desire, at European level, to control the efficacy of biocidal products in keeping with the health of humans, animals and the environment. The two main principles that were introduced were the approval of active biocidal substances for some uses, called product type (PT), then the authorization of biocidal products for given applications.
This regulation follows on from several European texts, such as the REACH regulation, the CLP regulation, the medical devices directive, the cosmetics directive…so defining the regulatory status of many products on the market.

Définition :
The term biocide is applicable to all active substances, generated in situ or not, and to products which contain mixtures of active substances.
A biocidal product aims to destroy, repel or render innocuous harmful organisms, to prevent their action or to combat them in any other way, by a means other than a simple physical or mechanical action.

A treated article is defined in this way: any substance, any mixture or any article which has been treated with one or more biocidal products or in which one or more biocidal products have been deliberately incorporated.

The concept of a “product family” was also defined, grouping together biocidal products with: similar uses, the same biocidal active substances, a similar composition with specified variations and similar levels of risk and efficacy. Products which meet the definition of a biocide are classified in 4 groups within which 22 product types are defined.

The description of each product type appears in Annex V of Regulation N° 528/2012 (Figure 2).

• Group 1: Disinfectants
• Group 2: Preservatives (wood, leather, construction materials, cutting fluids, etc.)
• Group 3: Pest-control products
• Group 4: Other biocidal products

Five PT are defined within group 1 disinfectants
PT 1: Biocidal products used for human hygiene purposes
This does not apply to:
– antiseptic skin products that can be applied to skin that is lesioned or is liable to be lesioned (meeting the requirements of the directive on specialist pharmaceutical products)
– cosmetic products: bodily hygiene and skin care products (falling under the cosmetics regulation)

PT 2: Disinfectants and algicides not intended for direct application to humans or animals
This particularly involves :
– products used to disinfect surfaces, materials, equipment and furniture which are not
used for direct contact with food or animal feed,
– products used to disinfect the air, water not used for human or animal consumption, chemical toilets, waste water, hospital waste and floors.
This does not apply to:
products intended specifically for the disinfection of medical devices; these fall under the directive on medical devices.
PT3: Biocidal products used for veterinary hygiene purposes
PT4: Disinfectants for surfaces in contact with food and animal feed
PT5: Disinfectants for drinking water

So, in the pharmaceutical industry, biocidal products intended for the disinfection of environmental surfaces and the surfaces of equipment and production materials, are PT2 biocides in Group 1; PT1 biocidal hand disinfectants are also found on pharmaceutical sites, and in some sectors, PT4 products.

In some cases, certain products may have a dual status, such as a biocide and medical device and/or belong to two or three different PTs with different methods of use.

IMPLEMENTATION
This implementation of this regulation is centralized through ECHA, the European Chemicals Agency, located in Helsinki.

A specialized computer platform has been created (Biocidal Products Register: R4BP), to present applications and exchange data and information between the applicant, the ECHA, the competent authorities of the Member State and the European Commission.

All biocidal products intended to be marketed in Europe require an authorization by the Member State, that may be extended to other Member States by mutual recognition.

So, 4 types of authorization may be found:

The marketing of biocidal products in Europe will be subject to the procurement of a marketing authorization (Biocidal Product MA), once the review of the active substance(s) is completed.
Only biocidal products containing active substances that appear on the positive lists or are undergoing assessment can be the subject of a marketing authorization (MA) applicant.

The assessment is carried out in accordance with the benefit/risk ratio concept (appreciation of product performance taking account of the side effects in terms of danger to health and the environment).
Meanwhile, temporary general measures apply to products and the national provisions in place must be observed in the countries in which they are marketed.

The assessment of biocidal substances is currently ongoing at European level:
assessment by a competent authority of the Rapporteur Member State, in charge of the assessment; the results are sent to the ECHA Biocidal Products Committee which prepares an “opinion” that will serve as a basis for approval by the European Commission.
Approval is granted for a maximum of10 years and is renewable.

In principle, active substances that meet the exclusion criteria will not be approved. These include:
– carcinogenic, mutagenic and reprotoxic substances in category 1A or 1B in compliance with the CLP regulation,
– endocrine disruptors,
– persistent, bioaccumulative and toxic substances (PBT)
-very persistent and very bioaccumulative substances (vPvB).

Exemptions are provided for, particularly when the active substance is necessary for reasons of public health or public interest and there is no substitute; in this case, approval is granted for a maximum of five years.

Today, the assessment of biocidal substances is still ongoing and a substances review program which runs to 2024 has been put in place to complete the review of all biocidal substances.
This new deadline does not provide exemption from the obligations that are already applicable, particularly in terms of formulation (use of biocidal active ingredients currently undergoing review) and labelling.
As regards biocidal disinfectant substances, to date, the assessment of only a few substances has been completed

The approval of the active substance for use as a biocide in a given field of application is formalized by publication in the European Union Journal (Figure 5).

Examples of implementing regulations approving a AS/PT pair:
– Implementing regulation (EU) 2016/1083 of the Commission of 5 July 2016 approving “products of the reaction between chloroacetic acid and N-C10–16-alkyltrimethylenediamines” as an existing active substance intended to be used in biocidal products of product types 2, 3, and 4 (OJEU L180 of 6 July 2016).
– Implementing regulation (EU) 2016/1084 of the Commission of 5 July 2016 approving biphenyl-2-ol as an existing active substance intended to be used in biocidal products of product type 3 (OJEU L180 of 6 July 2016).

Currently, the review is continuing and approvals will be published progressively over the next five years. Marketing authorization applications for disinfectant products containing them must be filed in the 18 months to 2 years following the date of circulation of the opinion of the Biocidal Products Committee Group on the active substance (last date for approval in case of products containing several active substances).

Obligations also concern the suppliers of active substances:
Since 01/09/2015, a biocidal product can be made available on the European Union market only on condition that either the supplier of the substance, or the supplier of the product appear in the Article 95 list under the Biocidal Products Regulation for this type of product.

Only persons based in the EU can request inclusion on the active substances supplier list (Article 95 list).

What is the current situation in France? What are the consequences for users?
The transitional period defined by Article 89 of the Biocidal Products Regulation corresponds to the actual period during which the market availability and the use of biocidal products are governed by the national provisions in force in each Member State, pending Community-level approval of all active substances contained in these products.
Today in France, the competent authority is the ANSES (French Agency for Food, Environmental and Occupational Health & Safety).

The general transitional measures applicable in France are the following:
•the biocidal substances contained in a product must be in the European review program for the purpose of approval of use for the appropriate product type (only the use of biocidal disinfectant products and detergent disinfectant products formulated with active substances that are notified and undergoing assessment for their proper use is possible),
• proof of efficacy must be based on the normative systems available (EN 14885 conformity),
• the products must be declared on the Simmbad Site of the Ministry for the Environment identifying all biocidal products on the French market (http://simmbad.fr/servlet/accueilMinistere.html),
• the product composition must be declared to INRS for toxicovigilance purposes,
• the control of certain biocidal products by CERTIBIOCIDE (Order of 9 October 2013 on the conditions of practicing the activity of professional user and distributor of certain types of biocidal products).

In addition to the obligations applicable to the manufacturers of biocidal substances and to the formulators using these substances, the biocidal regulation includes obligations for the users of the said biocidal products.
After the end of the transitional period, the user will be obliged to use products with an MA (marketing authorization). It will be important to users to check that the indications for use (dilution, contact time, temperature) described in the hygiene protocols, match the MA conditions of the product. Any application of a biocidal product must be resumed under the strict conditions of the MA.

Because of the investment required, there will be a move in the future towards a situation where a reduced number of products are available with a specialization of the profession. This regulatory change at European level is admittedly restrictive, but nevertheless positive for the future of human beings and the environment, leading to products that are more respectful of humans beings and the environment; it provides a framework for better control of risks and side effects and a guarantee of increased performance.