The Danish Medicines Agency suspends the Danish marketing authorisations of four generic medicines

Update 29 November 2023:

As of 29 November 2023, the Danish Medicines Agency has suspended the Danish marketing authorization for Alfacalcidol "Orifarm", soft capsules, 0.25 micrograms. Further postponement of the suspension is not possible.

Update 15 March 2023:

As of 5 January 2023, the Danish Medicines Agency has lifted the suspension of the Danish marketing authorisations for Atorvastatin "Mylan", filmcoated tablets, 10 mg, 20 mg, 40 mg and 80 mg based on the approval of a new bioequivalence study.

Update 26 December 2022:

As of 26 December 2022, the Danish Medicines Agency has suspended the Danish marketing authorization for Alfacalcidol "Orifarm", soft capsules, 0.5 micrograms and 1 microgram.

The suspension of Alfacalcidol "Orifarm", soft capsules, 0.25 micrograms has been postponed until further notice, as the medicine in the mentioned strength is still considered to be critical for the supply of the Danish market.

The European Commission has reached a decision in the case about the bioequivalence company Synchron Research, deciding that a number of generic medicines must be suspended in the EU counties where they are authorised. The Danish Medicines Agency therefore suspends the marketing authorisations of four medicines.

The case about Synchron Research, a company performing bioequivalence studies in which a generic medicine is compared to the original medicine, has been ongoing in Denmark and the EU since September 2021. The case originates from the U.S. Food and Drug Administration (FDA) who gave Synchron Research a serious warning and subsequently chose to change the therapeutic equivalence rating to “BX” for generic medicines on the US market whose bioequivalence studies had been performed by Synchron Research. In other words, the FDA discontinued the substitutability for these medicines, which meant that they could no longer be offered as an alternative to the original product.

This prompted the Danish Medicines Agency and other drug regulatory authorities in the EU to investigate if Europe was facing similar problems with the data supplied by Synchron Research as those the FDA had responded to in the USA. In January 2022, Denmark together with other EU countries decided to refer the case for further assessment by the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA). Since then, the CHMP has assessed data and obtained responses from Synchron Research, marketing authorisation holders and applicants for products whose authorisation is based on bioequivalence studies performed by Synchron Research.

From the very beginning of the case, the Danish Medicines Agency investigated if the Danish medicines affected by the case could pose a risk to patient safety. The Danish Medicines Agency assessed, in line with the overall assessment of the EMA, that there has been no safety risk or lack of effect with respect to any of the affected medicines. For this reason, there was no need to suspend the marketing authorisations of the medicines while the case was ongoing.

The CHMP’s review of the responses received caused the CHMP in September 2022 to submit a recommendation to the European Commission according to which the marketing authorisations of a number of medicines backed by bioequivalence studies provided by Synchron Research ought to be suspended. The CHMP recommended that following the decision of the Commission, the individual member states should assess whether the medicines affected by the case in their own countries are of critical importance in light of the available alternatives for patients.

The European Commission has followed the recommendation and decided on 28 November 2022 that 100 generic medicines at European level must be suspended for 30 days if they are not of critical importance. As a result thereof, the Danish Medicines Agency has suspended the marketing authorisations of four medicines. The medicines are recalled as of 12 December 2022.

The recall affects the following four generic products:

• Atorvastatin "Mylan", film-coated tablets, 10 mg, 20 mg, 40 mg and 80 mg
• Farmidur, prolonged-release tablets, 30 mg
• Carexarit, coated tablets, 25 microgram
• Ibuprofen "Bril", film-coated tablets, 200 mg, 400 mg and 600 mg

An additional fifth medicinal product has had its suspension postponed until further notice because the product is considered of critical importance for the supply to the Danish market:

• Alfacalcidol "Orifarm”, soft capsules, 0.25 microgram, 0.5 microgram and 1 microgram

Read more about the case here (text is in Danish):

EMA criticises data from the bioequivalence company Synchron Research in India (laegemiddelstyrelsen.dk) (Danish title: EMA kritiserer data fra bioækvivalensvirksomheden Synchron Research i Indien)

Synchron | European Medicines Agency (europa.eu)

Read more about generic medicines:

Generic medicines (generics) (laegemiddelstyrelsen.dk)

Generic substitution – questions and answers