[co-author: Vicky Vlontzou]
On 10 April 2020, the European Commission, the EMA and the European medicines regulatory network published a notice providing guidance to stakeholders regarding regulatory expectations for medicinal products for human use during the COVID-19 pandemic. The guidance provided covers marketing authorizations, manufacturing and importation of active pharmaceutical ingredients (APIs) and finished products, quality variations, and labeling and packaging requirements.
The guidance is published in the form of a question-and-answer document. It is intended to introduce flexibility to facilitate the movement of medicinal products within the EU during the period of the COVID-19 crisis. The document also provides an overview of existing flexibility measures that may be employed.
Issues related to marketing authorizations and marketing authorization procedure
Marketing medicinal products intended for use in COVID-19 patients in the absence of a marketing authorization
The guidance recommends that, where no centralized or relevant national marketing authorization exists, EU Member States make use of the possibilities provided in Directive 83/2001/EC on medicinal products for human use regarding compassionate use, and permitted distribution of an unauthorized medicinal product provided in Article 5 (2) of the Directive.
For the prompt assessment of related requests applicants are requested to contact the relevant national competent authority with the message “CONCERNS COVID-19”.
The guidance provides that EU Member States may, on the basis of Article 126(a) of Directive 83/2001/EC, authorize a medicinal product that has already been authorized in another EU Member State.
Postponement of the renewal application
According to the guidance, marketing authorization holders facing difficulties in meeting deadlines for submitting an application for renewal of marketing authorization due to exceptional circumstances related to COVID-19 are advised to contact the EMA for centrally authorized products or the reference Member State in relation to products authorized in accordance with the mutual recognition procedure (MRP) and the decentralized procedure (DCP). This contact must take place before the deadline for submission of the renewal application has expired and must be accompanied with a justified request to postpone the submission. Applicants for renewal of conditional marketing authorizations are also permitted to rely on this procedure.
Application of the “sunset clause” during the pandemic
In principle, authorized medicinal products that have not been placed on the EU market within three years of grant of a related marketing authorization result in the authorization being declared invalid. This invalidation also applies to medicinal products that have previously been placed on the market in the EU but that have ceased to be placed on the market for a period of three consecutive years. This is known as the "sunset" clause.
The guidance provides that marketing authorization holders may request an exemption from the “sunset clause" in view of exceptional circumstances and on public health grounds. For centrally authorized medicinal products, a request must be submitted to the European Commission on the basis of Article 14 (6) of Regulation 726/2004. Mention of the pandemic as a reason for the exemption is sufficient without the need for any further justification. For nationally authorized products the request must be submitted to the national competent authorities of the individual EU Member States. Related decisions will be taken on the basis of the applicable national laws.
Manufacturing and importation of finished products and active pharmaceutical ingredients
To reduce risks of shortages or disruptions in the manufacturing and supply chain for medicinal products used for the treatment of COVID-19 patients, the guidance introduces an exceptional chain management process (ECMP).
Under the ECMP, marketing authorization holders will be able to obtain starting materials, reagents, intermediates or active substances from suppliers not specifically mentioned in the related marketing authorization of the medicinal product. Where this is necessary to prevent shortages of supplies within the EU, the marketing authorization holders will also be able to use manufacturing sites and sites responsible for quality control that are not mentioned in the marketing authorization.
To rely on the ECMP marketing authorization holders must notify either the relevant national competent authority or, for centrally authorized products, the EMA.
In the notification, the marketing authorization holder should:
- Specify their intention to use the ECMP;
- Commit to ensuring that the quality of the finished medicinal product will not be compromised;
- Commit to notifying any changes to the EMA or the relevant competent authorities within 48 hours after the change is implemented by the marketing authorization holder;
- Commit to submitting the corresponding variation application to the competent authorities no later than 6 months following the implementation of the change.
Quality Variations
Marketing authorization holders facing difficulties in the performance of the quality controls foreseen in their marketing authorization due to circumstances related to the COVID-19 pandemic are invited to contact the competent authorities and to present an adapted control scheme. This adapted control scheme must be risk-based. The request must be submitted as a variation in accordance with the Commission Regulation (EC) No 1234/2008.
Applicants are requested to identify any such communication with the subject line “CONCERNS COVID-19” next to the procedure number in the email heading.
Product Information and labeling
The guidance provides that EU Member States may, in their territory, accept medicinal products in relation to which the SMPC and patient information leaflet have not yet been translated into the official national language. The competent national authorities may also accept packaging and labeling that does not include country- specific information or presentations that differ from the presentations authorized in the EU Member State in which the product is marketed. This flexibility is available in relation to are medicinal products that are crucial for COVID-19 patients. Marketing authorization holders are, however, required to notify the competent national authorities in advance and to provide a link to a website at which the product information in the official national language of the territory may be obtained.
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