Harmonization of summaries of product characteristics (SmPCs) of drugs with the same active ingredients: an evaluation of SmPCs of the most frequently prescribed active substances

Maximilian Gahr,Almuth Wolf,René Zeiss,Rainer Muche,Bernhard J Connemann

doi:10.1007/s00228-021-03209-7

Abstract

PurposeIn aut-idem or generic substitution, discrepancies between summaries of product characteristics (SmPCs) referring to the same active substance (AS) may cause difficulties regarding informed consent and medical liability. The qualitative and quantitative characteristics of such discrepancies are insufficiently studied, impeding harmonization of same-substance SmPCs and compromising safe drug treatment.MethodsSmPCs of the one hundred most frequently prescribed ASs in Germany were analyzed for discrepancies in the presentation of indications (Inds) and contraindications (CInds). Inclusion and exclusion criteria of drugs/SmPCs were chosen according to the standards of the aut-idem substitution in Germany.ResultsAccording to the study protocol, we identified 1486 drugs, of which 1426 SmPCs could be obtained. 41% respectively 65% of the ASs had same-substance SmPCs that differed from the respective reference SmPC in the number of listed Inds respectively CInds. The number of listed Inds/CInds varied considerably between same-substance SmPCs with maximum ranges in Inds of 7 in amoxicillin, and in CInds of 11 in lisinopril. Many ASs had large proportions (> 50%) of associated same-substance SmPCs that differed from the respective reference SmPC. A considerable proportion of ASs had same-substance SmPCs with formal and content-related differences other than the discrepancy in the number of Inds/CInds.ConclusionThis evaluation of same-substance SmPCs shows a clear lack of harmonization of same-substance SmPCs. Considering that generic substitution has become the rule and that physicians usually do not know which drug the patient receives in the pharmacy, these discrepancies raise several questions, that require a separate legal evaluation.

Highlights

For economic reasons, the supply with generic medication is politically preferred in most countries
Discrepancies between SmPCs of drugs with the same active ingredients were found in several studies [10,11,12,13], regulations of the European Medicines Agency (EMA) provide that the content of summaries of product characteristics (SmPCs, which are the European counterpart of the US prescribing information) of generic drugs "... should be in all relevant aspects consistent with that of the reference medicinal product except for indications or dosage form still covered by patent law..." [14] and the EMA and the Committee for Medicinal Products for Human Use (CHMP) are working with harmonization of SmPCs
It has to be considered that CInds that refer to pregnancy and lactation are usually listed in a separate standardized paragraph (4.6 Fertility, pregnancy and lactation); in some SmPcs, CInds referring to pregnancy and lactation are () listed under point 4.2 (CInds) and in other SmPCs referring to the same active substance these CInds are listed only under point 4.6; this was evaluated as a discrepancy in the number of contraindications in the present study

Summary

Introduction

The supply with generic medication is politically preferred in most countries. Should be in all relevant aspects consistent with that of the reference medicinal product except for indications or dosage form still covered by patent law..." [14] and the EMA and the Committee for Medicinal Products for Human Use (CHMP) are working with harmonization of SmPCs (by post-authorisation referral procedures [15] and guidelines [16]) These discrepancies between samesubstance SmPCs may refer to actual differences between the corresponding same-substance products (regarding regulatory aspects as approved indications, and pharmacologic aspect as excipients, additives, and carriers of the active substance, available strengths, dosage form, appearance and size of the drug, bioavailability, galenical properties, etc.) and/or may be self-referential in terms of discrepancies in form and content of SmPCs without clear reference to possible regulatory and/or pharmacologic/galenic differences between the corresponding same-substance products.

Ethical approval

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