Pioglitazone

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 for Actos

EMA’s scientific discussion for Actos (pioglitazone), CHEPLAPHARM Arzneimittel GmbH, 2006‑04‑03.

"No environmental impact is anticipated from the clinical use of pioglitazone hydrochloride." No data have been presented in the assessment report.

Assessment report for Incresync

Assessment report for pioglitazone from Incresync (alogliptin, pioglitazone), Takeda Global Research and Development Centre, 25 July 2013, EMA/CHMP/208477/2013.

The CHMP concluded that pioglitazone does not pose an environmental risk and that no special precautions are needed. Pioglitazone has been authorised in the EU since 2000, and the 45 mg maximum daily dose was used in the PEC calculations. No increased environmental exposure is expected based on the use of Incresync.

No data have been presented in the assessment report.

Assessment reports for generics

There are assessment reports for Pioglitazone Actavis and Pioglitazone Accord containing similar information. Presented here is Pioglitazone Accord, 19 January 2012, EMA/CHMP/46573/2012.

"The introduction of Pioglitazone Accord in the market is considered unlikely to result in any significant increase in the combined sales volumes for all pioglitazone containing products and would thus not be expected to have an adverse effect upon the environment. With this regards and on the basis of CHMP Guideline on Environmental Risk Assessment of Medicinal Products for Human Use (CPMP/SWP/4447/00), a formal 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.