Application for OTC legal status and change of OTC legal status

​​​​Introduction

These guidelines are for use by marketing authorisation holders (MAH) who consider applying for OTC status for a medicinal product, through either an application for a new marketing authorisation or a variation application for reclassification of a medicinal product. These guidelines also cover changes of the terms approved for an OTC product (e.g., new OTC indication or increased package size).

These guidelines provide general advice about the procedure to facilitate an effective and transparent process and define responsibilities and obligations. The guidelines also contribute to the submission of applications with high quality.

The legal classification of a medicinal product can be changed from C to CF or F through a reclassification procedure, if extensive use in Norway and/or Europe has proven that the product is safe. The medicinal product and the indication must also meet the criteria for OTC status in accordance with the European guideline for reclassification:

• A guideline on changing the classification for the supply of a medical product for human use.

In some cases, additional risk minimization measures for dispensing of the medicinal products in pharmacies may be necessary to ensure safe use after the active substance/medicinal product is reclassified from C to CF or F. Such measures may for example be:

• dispensing under the supervision of a pharmacist and/or other qualified healthcare professional in the pharmacy
• structured guidance or information in addition to the information available on the outer package and in the package leaflet.

Such additional risk minimization measures must be reviewed by the MAH after a certain time period and applied for to be removed if it is found that these are no longer necessary.

Other risk minimization measures are limitations for OTC compared to Rx:

• indications
• patient/age groups
• strength
• posology
• pharmaceutical form
• package size

Risk minimization measures that are adopted for a medicinal product will be specified in the letter of marketing authorisation. 

Backgro​und

For medicinal products approved through the Decentralised Procedure (DCP), the Mutual Recognition Procedure (MRP) and the National Procedure (NAP), the legal status is a national concern. The Norwegian Medical Products Agency (NoMA) determines the legal classification in accordance with the Norwegian Regulation on Medicinal products (Forskrift om legemidler), ref. Directive 2001/83/EC.

For medicinal products approved through the Centralised Procedure (CP) the legal status is a European concern and is determined jointly by all member states within the EU/EEA.

In Norway, OTC products can be classified as F (non-prescription medicines) or CF (prescription medicines, where certain packages, strengths, pharmaceutical forms etc. are exempt from prescription).

The term OTC (Over The Counter) is usually used for all medicines available without prescription.

Overview of the procedures

When applying for OTC status for a medicinal product through an application for a new marketing authorisation the MAH is requested to check if there is an OTC Substance Report published for the active substance(s) concerned in the application.
The NoMA will assess suitability of the medicinal product in prescription group CF or F in the following cases:

• Where there is no active substance report
• Where there is a lack of accordance with an existing active substance report (including new package sizes)
• It is a fixed combination application where there is an active substance report for the individual active substances, but not for the combination

Common assessment time of OTC status when applying for a new marketing authorisation has initially a total timeframe of 90 days for DCP procedure and 50 days for MRP procedure. In cases where there are questions raised to the MAH, a clock-stop period of up to 30 days can be implemented.
In order to handle OTC variation applications effectively, the NoMA asks the MAH to classify such variations as type II C.I.z, the procedure will follow a 90 day time table.

Changes of risk minimization measures can be classified as C.I.4 or C.I.11 according to CMDh's classification table. New indications (in both the SmPC and OTC PIL), must be applied as change(s) to therapeutic indication(s) type II C.I.6.avariation. Please clearly state that the application concerns a reclassification, change in OTC legal status and/or change of risk minimization measures and/or change of indications in the application form and cover letter.
MAHs may also apply for a change in the conditions approved for an OTC product, e.g., extension of an indication or a new package size for the OTC products that already have a marketing authorisation.

Regulatory and scientific guidance (pre-submission)

We recommend our regulatory and scientific guidance if the active substance is the first in its therapeutic class to be available without prescription, especially if additional risk minimization measures are proposed.

In such guidance meetings, it is possible to discuss the suitability of the medicinal product as an OTC product (CF or F) in Norway, suitable indication(s), posology, target groups and risk minimization measures, such as educational material to pharmacists/patients or checklists to be used at dispensing of the medicinal product(s) (if necessary).

The MAHs must familiarize themselves in advance with safety challenges associated with OTC use of their product and available professional guidelines such as:

• current (national) treatment guidelines
• treatment recommendations, guidelines from professional organizations and resource centres within health eg. Legevakthåndboken (reference book on emergency primary health care), RELIS (national network of four regional medicines information and pharmacovigilance centres in Norway), Norsk legemiddelhåndbok (Norwegian reference book on medicines as treatment options), Den norske legeforening (The Norwegian Medical Association), Norsk barnelegeforening (Norwegian pediatricians association) etc.
• recommendations published by patient organisations

In addition, the MAH must seek advice from the Norwegian pharmacy Association if proposed additional risk minimization measures require the pharmacies to perform an additional service upon dispensing the medicinal product. The MAH must ensure that their application contains relevant documentation and that the proposed risk management plan is adapted to the needs.

Further information can be found at: Scientific and regulatory advice

Application

The application must be written in accordance with relevant legislation and shall contain the following parts:

A clinical overview

The clinical overview must include a critical analysis of the suitability, the potential for misuse/abuse and the safety in self-medication for the proposed OTC indication of the medicinal product, package size, strength and pharmaceutical form. The overview must be written in accordance with the European guideline “A guideline on changing the classification for the supply of a medical product for human use”. The target patient population must be specified for the OTC indication and the written indication must be self-explanatory for all potential users.

For applications changing conditions of an OTC status (e.g. extention of the OTC indication), it is sufficient that the significance of the change is discussed.

An OTC substance report

For medicinal products in national procedures (NAP, MRP/DCP) the application process may be simplified if there is an OTC substance report published at our web site:

• OTC substance reports

If the indication, posology, package size, pharmaceutical form and strength are in accordance with the specifications outlined in the OTC substance report, a clinical overview is not necessary. More information about the OTC substance reports can also be found at our web site:

• Information OTC substance reports

If the MAH plans to extend the indication, posology, increase the package size, increase the strength or other pharmaceutical form than described in an OTC substance report, the sections that are intended to be extended must be discussed in the clinical overview. The MAH must argue in the justification why the extended indication/posology/package size or changed pharmaceutical form/strength has positive benefit-risk balance for the patient.

Risk management plan (RMP)

For medicinal products in the NAP, reclassification requires submission of a RMP (if the product has no RMP) or variation of the RMP (if the product already has a RMP).

For medicinal products in the MRP/DCP, a reclassification post marketing must be applied as a national variation. Additional risk minimization measures must be described in the application, and will be assessed and approved nationally.

After the national approval of the additional risk minimization measure(s), the MAH must submit a type IA notification to update the EU-RMP with a standard sentence that briefly mentions that additional risk minimization measures are available in some member states within the EU/EEA.

For new marketing authoris​ation applications in the MRP/DCP, this information must already be proposed during the procedure to be included into the EU-RMP. The details of the measures are to be described, assessed and approved nationally.

Examples of risk minimization measures linked to dispensing may be:

• Checklist for use during guidance of a patient in a pharmacy
• Question list for use during dispensing in a pharmacy
• Qualification requirement for health care personal dispensing the medicinal product
• Check of previous prescriptions

Guidelines and standardized templates for such measures will be published continuously as an attachment to this guideline.

Product information

Norwegian SmPC, PIL and mock-ups must be attached to the application. The applicant must take into account the OTC substance report for same or similar active substance when the product information is prepared. Medicinal products in prescription group CF must have an OTC PIL and OTC mock-ups for packages without prescription in addition to the Rx-PIL and the Rx mock-ups for prescription-only packages (if these are marketed). In the OTC PIL, only OTC indications and the corresponding posology must be described.

Readability test

Readability test is mandatory when changing the OTC legal status for a medicinal product. The applicant must submit a full readability test, or a “bridging report” which is based on a previously performed readability test. A justification is needed for bridging reports.

• Guideline on the readability of the labelling and package leaflet of medicinal products for human use.
• Consultation with target patient groups – meeting the requirements of article 59(3) without the need for a full user test – recommendations for bridging.

Assessment at the NoMA

When applying for an OTC status (with or without special risk minimisation measures that are linked to the dispensing of the medicinal product), the NoMA will assess suitability of the medicinal product in prescription group CF or F and if proposed additional risk minimisation measures are necessary and/or sufficient. The NoMA will consult relevant stakeholders and/or arrange a (public) consultation to clarify professional and practical consequences of the change in question, if necessary. A consultation shall never delay the procedure.

If additional risk minimisation measures linked to dispensing of a medicinal product in pharmacies are necessary, the following supplementary points must be considered and clarified:

• Qualification requirement for dispensing of the medical products in pharmacies?
• Need for education of pharmacy staff?
• Is a letter of attorney acceptable?
• Will online pharmacies be able to perform the proposed risk minimization measures?
• Is a previous prescription required?
• Is there a need for a checklist?​

Decision

In the NoMA database «Legemiddelsøk» (www.legemiddelsok.no) and in the Norwegian Pharmaceutical Product Compendium (Felleskatalogen) information on the legal status is found for all products approved and marketed.

Information about approved OTC indications, posology, package sizes, strengths and any risk minimisation measures linked to the dispensing of the medicinal products, will be defined in the letter of marketing authorisation at medicinal product level and published in the OTC substance reports at active substance level. For all active substances that may be dispensed without prescription, the NoMA will prepare and publish OTC substance reports. Both the OTC-substance report and the letter of marketing authorisation, will contain information on all the requirements linked to the additional risk minimization measure:

• Qualification requirements of the pharmacy staff dispensing and performing the additional risk minimisation measures
• Through which channels is the pharmacy staff planned to be trained
• If power of attorney is acceptable
• If an online pharmacy may dispense the medicinal product and if so, under what conditions
• Is a previous prescription required and if so, where this information should be obtained from
• Checklist, if this is adopted

Through a footnote linked to the product number in the common article number register (Vareregisteret) in FarmaPro, the pharmacy staff will be informed if additional risk minimization are linked to the dispensing of an OTC drug. Depending on the scope of an approved risk minimization measure, this footnote will contain all necessary information, or a link to supplementary information such as educational material and checklists.

Obligations after approval

Medicinal products with an OTC status and special risk minimisation measures linked to the dispensing cannot be sold outside the pharmacies (LUA, legemidler utenom apotek) or as ordinary medicinal products with an OTC status. The MAH is obliged to distribute approved educational material and checklists in accordance with the approval.

During the approval process, the NoMA will ensure that educational material and checklists are generic and identical decisions will be made for medicinal products with the same active substance.

The pharmacies/national pharmacy association has the responsibility to ensure training of the pharmacy staff who are supposed to perform the additional risk minimisation measures. Preferably, the training should be adapted established training structures to ensure a unified and generic training regardless of manufacturer, pharmacy chain and/or region.

The NoMA will also be able to impose the individual MAH to prepare educational material (e.g. e-learning) based on the approval. As for other educational materials, this has to be approved by the NoMA and then distributed to pharmacies.