/Substances exempt from maximum residue limit evaluation

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Substances exempt from maximum residue limit evaluation

EMA

2026/04/08

Substances exempt from maximum residue limit evaluation

The substance types listed below may fall outside the scope of the Regulation (EC) No 470/2009, and thus be exempt from an MRL evaluation:

Active principles of biological origin used in immunological veterinary medicines
Biological substances other than active principles of biological origin used in immunological veterinary medicines
Non-active substances like excipients considered not to have any effect on the body (also referred to as pharmacological effects) - e.g. excipients, ingredients in a medicine that are not the active substance

For these substance types, applicants must notify EMA so that an assessment is conducted.

For more information, see:

Maximum residue limits (MRL)

Biological substances not requiring an MRL evaluation

Biological substances other than active principles of biological origin used in immunological veterinary medicines can be either 'chemical-like' or 'chemical-unlike'.

Chemical-like substances present similar concerns to chemical substances and are subject to a full MRL assessment.

Chemical-unlike substances are more complex and may contain multiple chemical types. Their residues can be cells, amino acids, lipids, carbohydrates, nucleic acids and their breakdown products. The CVMP decides on a case-by-case basis whether chemical-unlike substances require a full MRL assessment.

For full details, see Annex I.6 to Commission Regulation (EU) 2018/782.

Notifying chemical-unlike substances

Applicants who consider that a biological substance is chemical-unlike should notify EMA of their intention to submit an application at least two months in advance, via Service Now. They can do so by selecting Veterinary Regulatory > Pre-Submission-Vets > Intention to submit an MRL application > Biological substances not requiring an MRL evaluation.

The submission and the evaluation will follow the timetable for variations requiring assessment (standard timetable). Refer to the recommended submission dates available below.

The CVMP assesses whether a ‘No MRL required’ classification is appropriate without the need to conduct a full MRL evaluation.

To support this, the application should include a report and supporting information explaining the scientific basis for the request. It should address the points outlined in Annex I.7 to Commission Regulation (EU) 2018/782, as amended by Commission Regulation (EU) 2025/1101, which is available below.

Relevant information is also provided in the 'Guideline on determination of the need for an MRL evaluation for chemical-unlike biological substances'.

EMA charges a fee for evaluating the application. It invoices the fee to the applicant's address after it has validated the application.

Note: the former list of chemical-unlike substances considered as not requiring an MRL evaluation as per Regulation (EU) No. 2018/782, which was published by EMA, has been repealed. These substances are now included in Table 1 of the Annex to Commission Regulation (EU) No 37/2010 as per Commission Regulation (EU) 2025/1102.

Scientific advice on MRL classification of chemical-unlike biological substances considered as not requiring an MRL evaluation according to Regulation (EU) 2018/782

Adopted

Reference Number:

EMA/CVMP/375793/2024

English (EN) (233.63 KB - PDF)

First published:

06/10/2025

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Guideline on determination of the need for an MRL evaluation for chemical-unlike biological substances

Adopted

Reference Number:

EMA/CVMP/SWP/591282/2021

Legal effective date:

01/08/2024

English (EN) (340.42 KB - PDF)

First published:

26/01/2024

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For more information, see:

Substances considered not to exert pharmacological effects

Non-active ingredients considered not have any effect on the body, also described as not exerting pharmacological effects,fall outside the scope of the MRL Regulation. This includes many excipients, for example.

The CVMP determines on a case-by-case basis whether a non-active ingredient exhibits pharmacological effects and poses a risk to the consumer. If the CVMP concludes that no MRL evaluation is required, EMA includes the substance in the following list:

Substances considered as not falling within the scope of Regulation (EC) No. 470/2009, with regard to residues of veterinary medicinal products in foodstuffs of animal origin

Adopted

Reference Number:

EMA/CVMP/519714/2009 Rev. 62

English (EN) (215.08 KB - PDF)

First published:

23/09/2009

Last updated:

14/11/2025

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Notifying a non-active ingredient

Applicants who consider that a component of their product is not pharmacologically active should notify EMA via Service Now. They can do so by selecting Veterinary Regulatory > Pre-Submission-Vets to have the substance included in the above list.

Select the expandable panel below to find further guidance.

See guidance

Guideline on data to be provided in support of a request to include a substance in the list of substances considered as not falling within the scope of Regulation (EC) No 470/2009

Adopted

Reference Number:

EMA/CVMP/516817/2009

English (EN) (101.86 KB - PDF)

First published:

18/11/2010

Last updated:

18/11/2010

View

Questions and answers on standard animal weights for estimating worst-case consumer exposure scenarios

Reference Number:

EMA/250170/2024

English (EN) (156.07 KB - PDF)

First published:

26/07/2024

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Page update history

An update log is available to show the date and summary of changes to this webpage. It does not include updates to linked documents or minor edits like typos or broken link fixes.

The tracking of updates begins in April 2026.

See update history

8 April 2026

Page first published. Content transferred from the Maximum residue limits (MRL) page.

Summary

Certain biological substances and substances that do not have any effect on the body may fall outside the Maximum Residue Limit Regulation. Such substances do not require a full MRL evaluation.