Safety and residues: pharmaceutical guidelines

EMA's scientific guidelines on the safety and residues of veterinary medicinal products help medicine developers prepare marketing authorisation applications.

For a complete list of scientific guidelines currently open for consultation, see:

• Public consultations

Toxicology

• Assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products
• Regulatory acceptance of 3R (replacement, reduction, refinement) testing approaches
• VICH GL22 Safety studies for veterinary drug residues in human food: reproduction studies
• VICH GL23 Studies to evaluate the safety of residues of veterinary drugs in human food: genotoxicity testing
• VICH GL28 Studies to evaluate the safety of veterinary drugs in human: carcinogenicity testing
• VICH GL31 Safety studies for veterinary drug residues in human food: repeat-dose (90) toxicity testing
• VICH GL32 Studies to evaluate the safety of residues of veterinary drugs in human food: developmental toxicity testing
• VICH GL33 Safety studies for veterinary drug residues in human food: general approach to testing
• VICH GL37 Safety of veterinary drugs in human food repeat-dose (chronic) toxicity testing
• VICH GL54 Studies to evaluate the safety of residues of veterinary drugs in human food: general approach to establish an acute reference dose (ARfD)
• Question and answer document on the Guideline on assessment and control of DNA reactive (mutagenic) impurities in veterinary medicinal products (EMA/CVMP/SWP/377245/2016)

User safety

• User safety for pharmaceutical veterinary medicinal products
• User safety of topically administered products

Environmental risk assessment

Guidelines

• Assessment of persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB) substances in veterinary medicinal products
• Assessing the toxicological risk to human health and groundwater communities from veterinary pharmaceuticals in groundwater
• Determining the fate of veterinary medicinal products in manure
• Environmental risk assessment for immunological veterinary medicinal products
• Environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL38
• Environmental risk assessment of ectoparasiticidal veterinary medicinal products used in cats and dogs
• Higher-tier testing of veterinary medicinal products to dung fauna
• Plant testing strategy in the risk assessment for veterinary medicinal products
• VICH GL6 Environmental impact assessment (EIAS) for veterinary medicinal products - Phase I
• VICH GL38 Environmental impact assessments for veterinary medicinal products - Phase II

Questions and answers

• Question and answer document in support of the guideline on the assessment of persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB) substances in veterinary medicinal products (EMA/CVMP/ERA/52740/2012)
• Questions and answers: implementation of CVMP guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 (Phase I) and GL38 (Phase II)

Reflection papers

• Criteria for determining that an active substance is essential when considered in the context of Article 37(2)(j) of Regulation 2019/6
• Environmental risk assessment of ectoparasiticidal veterinary medicinal products used in cats and dogs
• Interpretation of Article 72 of Regulation (EU) 2019/6 - Environmental safety documentation and environmental risk assessment of certain veterinary medicinal products
• Higher tier testing to investigate the effects of parasiticidal veterinary medicinal products on dung fauna
• Interpretation of Article 18(7) of 4 Regulation (EU) 2019/6
• Antimicrobial resistance in the environment: considerations for current and future risk assessment of veterinary medicinal products
• Authorisation of veterinary medicinal products containing (potential) persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB) substances
• Poorly extractable and/r non- radiolabelled substances
• Risk-mitigation measures related to the environmental risk assessment of veterinary medicinal products

Concept papers

• Assessment of public health risks related to antimicrobial resistance acquired via the environment, resulting from the use of a veterinary medicinal product
• Environmental risk assessment of veterinary medicinal products intended to be used in aquaculture
• Environmental risk assessment for parasiticide veterinary medicinal products used in companion animals
• Assessing the toxicological risk to humans and the environment of veterinary pharmaceuticals in groundwater
• Methodology of environmental risk assessment for ectoparasiticidal VMPs for cats and dogs

Residues and withdrawal periods

Guidelines

• Determination of withdrawal periods for edible tissue
• Determination of withdrawal periods for milk
• Injection-site residues
• Setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities
• VICH GL46 Studies to evaluate the metabolism and residue kinetics of veterinary drugs in food-producing animals: metabolism study to determine the quantity and identify the nature of residues
• VICH GL47 Studies to evaluate the metabolism and residue kinetics of veterinary drugs in food-producing animals: laboratory animal comparative metabolism studies
• VICH GL48 Studies to evaluate the metabolism and residue kinetics of veterinary drugs in food-producing animals: Marker-residue-depletion studies to establish product withdrawal periods
• VICH GL49 Studies to evaluate the metabolism and residue kinetics of veterinary drugs in food-producing animals: validation of analytical methods used in residue depletion studies
• VICH GL56 Studies to evaluate the metabolism and residue kinetics of veterinary drugs in food-producing species: study design recommendations for residue studies in honey for establishing MRLs and withdrawal periods
• VICH GL57 on studies to evaluate the metabolism and residue kinetics of veterinary drugs in food-producing species: marker residue depletion studies to establish product withdrawal periods in aquatic species

Reflection papers

• Injection-site residues: considerations for risk assessment and residue surveillance

Concept papers

• Concept paper for the revision of residues guidelines to align with the definitions for withdrawal periods provided in Regulation (EU) 2019/6
• Introducing a review and update of existing EU guidelines on residues studies to bring these into line with the VICH metabolism and residues guidelines GL46 to 49

Establishment of maximum residue limits

Guidelines

• Approach to establish a pharmacological acceptable daily intake (ADI)
• 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
• Risk-analysis approach for residues of VMPs in food of animal origin
• VICH GL36 Studies to evaluate the safety of residues of veterinary drugs in human food: General approach to establish a microbiological ADI
• Assessment of the effect of antimicrobial substances on dairy starter cultures

Reflection papers

• Assessment of bioavailability of bound residues in food commodities of animal origin in the context of Council Regulation (EEC) No 2377/90
• Consideration of adjuvants and preservatives under Council Regulation (EEC) No 2377/90 laying down a community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin
• New approach developed by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives for exposure and maximum residue limit assessment of residues of veterinary medicinal products

Concept papers

• Approaches on how to consider excipients in the context of Regulation 2377/90

Position papers

• Definition of substances capable of pharmacological action in the context of Council Directive 2001/82/EC as amended, with particular reference to excipients and manufacturing materials
• Establishment of maximum residue limits for milk considering the daily intake by children
• Antimicrobial resistance in the environment: considerations for current and future risk assessment of veterinary medicinal products

Note for guidance

• Establishment of maximum residue limits for Salmonidae and other fin fish