Vildagliptin

Detailed information

Fass environmental information

Fass environmental information for Galvus (vildagliptin) from Novartis (retrieved on 2025-10-06).

Hazard

Persistence: Biotic degradation of vildagliptin shows it is not readily biodegradable, with 0% degradation after 28 days (OECD 301B). Simulation studies (OECD 308) indicate a degradation time (DT₅₀) of 386–488 days for the total system. Upon addition to the water layer, vildagliptin partitioned between water and sediment, with 55–65% degraded after 99 days. Mineralization to CO₂ was minimal (≤ 3%) and bound residues accounted for 7–10%. According to OECD 308 pass criteria, vildagliptin is classified as potentially persistent (DT₅₀) > 120 days).

Bioaccumulation: Log P = 0.056 (OECD107).

Toxicity: There are data for 3 trophic levels, most sensitive crustacean NOEC 5600 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2021.

PEC = 0.0015 microg/L.

PNEC = Lowest NOEC, 5600 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 560 microg/L.

PEC/PNEC = 0.000004 which gives the risk insignificant.

General information about assessment reports

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.

The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, as well as possibly other products from the same company, not all medicinal products containing the same active substance.

Scientific discussion

Scientific discussion on vildagliptin from Eucreas (metformin, vildagliptin), Novartis, 2007-03-12. Corresponding information is available for Galvus (vildagliptin), Novartis, 2007-04-04.

"The environmental risk assessment concluded that the concentrations expected to enter the environment are not expected to pose a risk." No data have been reported.

Assessment reports from Novartis

There are several assessment reports on vildagliptin from Novartis. The most recent one, concerning a Type II group of variations, is presented: Assessment report for Galvus, Xiliarx (vildagliptin), and Jalra (vildagliptin), Novartis, 20 May 2021, EMA/413658/2021.

"Regarding vildagliptin: The ERA remains to be updated by the data an OECD TG308 and OECD TG218 study was missing for vildagliptin. A commitment (with time schedule by June 2023) to submit an update has been made by the MAH. Depending on the outcome of the study a risk characterisation of the sediment is deemed necessary. If so, this will also involve recalculating the PEC_sediment for which adsorption data on soils and sludges would be needed. Data of adsorption/desorption studies is available for three types of sludges, but not for soils. The MAH intends to use a worst-case KOCsoil of 100 000." No such data have been found following a search on the EMA website (2025-10-06).

Assessment report Vildagliptin/Metformin hydrochloride Accord

Assessment report for vildagliptin from Vildagliptin/Metformin hydrochloride Accord, Accord Healthcare S.L.U., 27 January 2022, EMA/246681/2022.

"The Applicant´s justification for omission of a full Environmental Risk Assessment (ERA) based on generic nature of the product was not sufficient and consumption data were required in line with Questions and answers on 'Guideline on the environmental risk assessment of medicinal products for human use (EMA/CHMP/SWP/44609/2010 Rev. 1, 2006). Following the provided clarification on some aspects of submitted consumption data, it is concluded that market authorization of the generic product in question is not expected to pose additional risks to the environment." No data have been reported.

Comment on generics

After the implementation of the latest European Medicines Agency (EMA) ERA guideline (1 September 2024), a generic company has the following options for Article 10 procedures under Directive 2001/83/EC:

i) to argue that a full ERA is not required because the pharmaceutical substance belongs to certain substance groups (e.g., so-called natural substances);

ii) to identify an official ERA from a previously accepted product and use it; or

iii) to develop its own ERA according to the latest EMA ERA guideline.

Arguments for not submitting an Environmental Risk Assessment (ERA) based on the claim that total environmental exposure has not increased (via total sales volumes) belong to the previous ERA guideline system (2006–2024) and are no longer applicable. Regarding option ii), it should be noted that if a reference ERA exists, the generic company must demonstrate that its conclusions remain technically relevant (since the latest ERA guideline introduced several new technical requirements absent in the previous ERA guideline) and in terms of exposure (showing that the estimated exposure used in the reference ERA remains reasonable). Regulatory authorities (national and EMA) recommend that generic companies attempt to obtain reference ERA documentation from other companies via a so-called Letter of Access (LoA). However, if this is not possible, it remains feasible to argue that the conclusions of an existing reference ERA are still relevant based on information gathered from public assessment reports (summarized descriptions of environmental risk assessments) and product information (to confirm that dosages, indications, etc., have not changed). It should be noted that in some cases, reference ERAs approved between 2006 and 2024 may need to be modified (e.g., with additional experimental studies). If no previous reference ERA can be identified or used, the generic company must commit to developing its own ERA.