Homeopathic medicines marketed ope legis, for which the registration dossier was submitted to AIFA by 30 June 2017, can remain on the market until the evaluation by AIFA is completed.

Homeopathic medicines for which, on the other hand, a registration dossier has not been submitted to AIFA and which are present in the distribution channel as of 1 January 2020, are kept on the market until the expiry date of the medicine indicated on the label and, in any case, not beyond 1 January 2022.

Homeopathic medicines currently marketed in Italy have benefited from the transitional provisions defined by Art. 20 of Legislative Decree 219/2006 which allowed the products already on the market as of 6 June 1995 to remain on the market, by virtue of an ope legis provision. These transitional provisions ended on 31 December 2019.

Law 190/2014 provided that, in order to obtain a renewal of the marketing authorization, the holder had to submit the registration dossiers to AIFA by 30 June 2017. The Agency, in the event of a positive assessment of the dossier, grants a marketing authorization.

Law 160/2019 established the continuation of the marketing for the products involved in a MA application procedure filed with AIFA by 30 June 2017, while for the other products, for which the holder has not submitted the application for renewal, the disposal of stocks present in the distribution channel was granted as of 1 January 2020, until the expiry date indicated on the label and in any case no later than 1 January 2022.

Homeopathic medicines can access the following procedures to obtain a marketing authorization:

1. Simplified registration procedure

Access to this procedure is allowed only if the medicine meets the following requirements (Article 16) of Legislative Decree 219/2006:

a) it is intended to be administered orally or externally;

b) it does not bear specific therapeutic indications on the label or within information of any kind referring to the product;

c) it has a degree of dilution such as to guarantee safety; in any case the medicinal product cannot contain more than one part per ten thousand of mother tincture, nor more than 1/100 of the smallest dose possibly used in allopathy for active substances whose presence in an allopathic medicinal product entails the obligation of a medical prescription.

Law no. 190/2014 extended the possibility of accessing the simplified procedure also to medicines used for administration routes other than oral/external and in weight concentration (i.e. the substances used are analytically detectable).

2. Procedure for renewal of the ope legis authorization (Law no. 190/2014)

This procedure applies only to products already on the market under the transitional provisions, in the absence of therapeutic indications.

For these products the possibility was provided of:

• submitting the dossiers according to the requirements defined by AIFA (AIFA determination no. 365 of 31 March 2015);
• paying an ad hoc fee applicable only to these products and for the terms identified by the legislation;
• simplifying the documentation relating to Module 4 of the dossier (part of the registration dossier relating to the preclinical documentation, necessary to document the safety of the product), or the possibility of presenting, as an alternative to Module 4, a self-certified declaration signed by the legal representative of the owner company, bearing evidence of the safety of the product, having regard to its composition, pharmaceutical form and route of administration; consumer sales data for the last 5 years, and any Pharmacovigilance reports pursuant to the provisions of Title IX of Legislative Decree 219/2006.

The possibility was not granted of self-certifying the safety documentation for homeopathic medicines of biological origin, preparations for injectable use and preparations with weight concentrations of the homeopathic strain, in fact the obligation to submit Form 4 is confirmed.

In any case, the application of Pharmacovigilance is provided for homeopathic medicines which do not meet all the requirements of Art. 16, paragraph 1 of the Legislative Decree 219/2006.

AIFA has already issued numerous MAs for homeopathic medicines on the basis of this procedure. The authorized products are present in the Agency's Medicine Database.

For all dossiers under evaluation according to the procedures described above, AIFA establishes whether to issue specific warnings or restrictions on use for population groups.

In any case, since these are medicines with no therapeutic indications, it is recommended to consult your doctor or pharmacist before administration, when used in pregnancy and breastfeeding or in the paediatric age.

3. Ordinary authorization procedure (Art. 18, paragraph 1, first sentence, Legislative Decree 219/2006)

Homeopathic medicines which do not meet the requirements listed in Article 16 of Legislative Decree 219/2006, undergo a procedure similar to the one provided for allopathic medicines (Articles 8, 10, 11, 12, 13 and 14 of Legislative Decree no. 219/2006), which provides for the presentation of documentation relating to quality, safety and efficacy.

In this case, the authorization dossier must contain clinical studies supporting the therapeutic indications requested. Therefore, the homeopathic medicinal product authorized with this procedure will have therapeutic indications.

Currently, no medicine authorized by AIFA falls under this type of procedure.

4. Authorization procedure on the basis of homeopathic medicine practiced in Italy (Art. 18, paragraph 1, second sentence, Legislative Decree no. 219/2006)

Homeopathic medicines which do not meet the requirements listed in Article 16 of Legislative Decree 219/2006, may take advantage of an authorization procedure based on the homeopathic tradition recognized and practiced in Italy. In this case, specific rules for preclinical and clinical tests may be provided (by decree of the Ministry of Health after consulting AIFA), in line with the principles and characteristics of homeopathic medicine practiced in Italy.

At present this procedure has not been activated.

AIFA is currently evaluating the dossiers filed by 30 June 2017 and some of them received the MA. No specific therapeutic indication is envisaged for any product being evaluated; this means that no efficacy data obtained from clinical studies have been submitted to AIFA. Therefore, for these products, AIFA only evaluates the quality and safety of use, in accordance with international guidelines, but does not establish their therapeutic use. It is the doctor's responsibility, based on his/her experience, to define the methods of use.

Definitions:

• By weight concentration of substance, we mean a homeopathic preparation in which the substance is analytically detectable (it can be quantified according to the official analytical methods);
• By mother tinctures we mean liquid preparations obtained from the action of a suitable solvent, generally ethanol, on a raw material through an extraction process consisting of maceration, percolation or any other method possibly described in the individual monographs of the reference pharmacopoeias (Pharmacopoeia Europea- Mother tinctures for homoeopathic preparations 2029, general monograph).
• By glycerine macerate we mean the liquid preparation obtained from the action of glycerol (or ethanol or a sodium chloride solution of a suitable concentration) on a specific raw material (European Pharmacopoeia-Homoeopathic preparations 1038).