Ibandronic acid

Detailed information

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.

EMA’s scientific discussion on Bondronat

EMA’s scientific discussion on Bondronat (ibandronic acid), 2005-10-21.

Environmental risk has been assessed. The predicted environmental concentration in water is over 100 times below the action limit, and even lower for soil. For the indication of tumour-induced hypercalcaemia, ibandronic acid poses no environmental concern. The expected risk to the aquatic environment is very low. No data are presented.

EMA’s scientific discussion on Bonviva 2006

EMA’s scientific discussion on Bonviva (ibandronic acid), dated 17 October 2006.

"The drug substance was tested for acute toxicity to aquatic organisms, inhibition of activated sludge and biodegradability according to OECD guidelines. It was concluded that exposure levels of concern to the environment are not to be expected." No data are presented.

EMA’s scientific discussion on Bonviva 2007

EMA’s scientific discussion on Bonviva, EMEA/104761/2007.

"A new ecotoxicity/environmental risk assessment was carried out according to OECD guidelines. It was concluded that no exposure levels of concern to the environment are to be expected." No data are presented.

Assessment reports for generics

Several assessment reports for generics such as Ibandronic Acid Accord, Ibandronic Acid Sandoz, and Ibandronic Acid Teva provide similar information. For example, in the case of the latter (EMA/598319/2010), it is stated that Ibandronic Acid Teva is a generic medicinal product expected to be used interchangeably with similar products already on the market. Its introduction is not anticipated to increase the overall sales of ibandronic acid-containing products, and therefore, no increased environmental exposure is expected. For this reason, an environmental risk assessment is not considered necessary.

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.