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Commission Regulation (EU) 2018/782 of 29 May 2018 establishing the methodological principles for the risk assessment and risk management recommendations referred to in Regulation (EC) No 470/2009 (Text with EEA relevance)

EU Regulation 2018/782 · Adopted 29 May 2018 · Extends to United Kingdom

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Commission Regulation (EU) 2018/782

of 29 May 2018

establishing the methodological principles for the risk assessment and risk management recommendations referred to in Regulation (EC) No 470/2009

(Text with EEA relevance)

THE EUROPEAN COMMISSION,

Having regard to the Treaty on the Functioning of the European Union,

Having regard to Regulation (EC) No 470/2009 of the European Parliament and of the Council of 6 May 2009 laying down Community procedures for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin, repealing Council Regulation (EEC) No 2377/90 and amending Directive 2001/82/EC of the European Parliament and of the Council and Regulation (EC) No 726/2004 of the European Parliament and of the Councilf1, and in particular Article 13(2)(a) thereof,

Whereas:

(1)

Regulation (EC) No 470/2009 provides that, except in cases where the Codex Alimentarius procedure applies, any pharmacologically active substance intended for use in the Union in veterinary medicinal products which are to be administered to food-producing animals shall be subject to an opinion of the European Medicines Agency (‘Agency’) on the maximum residue limits (‘MRLs’) of pharmacologically active substances used or intended to be used in veterinary medicinal products. The Agency's opinion should consist of a scientific risk assessment and risk management recommendations.

(2)

Regulation (EC) No 470/2009 empowers the Commission to adopt measures establishing the methodological principles for the risk assessment and risk management recommendations regarding the establishment of the MRLs of pharmacologically active substances.

(3)

In order to provide legal certainty, clarity and predictability with regard to the process of the establishment of MRLs, it is appropriate that the criteria against which the Agency appraise the applications are provided for in this Regulation.

(4)

The methodological principles for the risk assessment and risk management recommendations should aim to ensure a high level of human health protection, whilst also ensuring that human health, animal health and animal welfare are not negatively affected by the lack of availability of appropriate veterinary medicinal products.

(5)

Taking into account the requirements set out in Article 6 of Regulation (EC) No 470/2009, the detailed rules on the methodological principles for the scientific risk assessment part of the Agency's opinion should be laid down in this Regulation.

(6)

Taking into account the requirements set out in Article 7 of Regulation (EC) No 470/2009, the detailed rules on the methodological principles for the risk management recommendations part of Agency's opinion should be laid down in this Regulation. In the risk management recommendations, the Agency is also required to consider the availability of alternative substances and other legitimate factors, such as the technological aspects of food and feed production or the feasibility of controls. Therefore it is appropriate to lay down rules on that requirement.

(7)

The measures provided for in this Regulation are in accordance with the opinion of the Standing Committee on Veterinary Medicinal Products,

HAS ADOPTED THIS REGULATION:

Annotations to the whole text

Footnotes

f1

OJ L 152, 16.6.2009, p. 11.

Contents

  1. 1Subject matter
  2. 2Definitions
  3. 3Entry into force
  4. Signature
  5. Annex I: Methodological principles for the scientific risk assessment referred to in Article 6 of Regulation (EC) No 470/2009
  6. GENERAL PRINCIPLES
  7. I.1Division I.1
  8. I.2Division I.2
  9. I.3Division I.3
  10. I.4Division I.4
  11. I.5Division I.5
  12. I.6Division I.6
  13. I.7Division I.7
  14. I.8Division I.8
  15. I.9Division I.9
  16. SAFETY FILE
  17. II.1Division II.1
  18. II.2Division II.2
  19. II.3Division II.3
  20. Detailed and critical summary
  21. II.4.1Division II.4.1
  22. II.4.2Division II.4.2
  23. II.4.3Division II.4.3
  24. Precise identification of the substance concerned by the application
  25. II.5.1Division II.5.1
  26. II.5.2Division II.5.2
  27. II.5.3Division II.5.3
  28. Pharmacology
  29. Pharmacodynamics
  30. II.6.1.1Division II.6.1.1
  31. II.6.1.2Division II.6.1.2
  32. II.6.1.3Division II.6.1.3
  33. II.6.1.4Division II.6.1.4
  34. II.6.1.5Division II.6.1.5
  35. II.6.1.6Division II.6.1.6
  36. Pharmacokinetics
  37. II.6.2.1Division II.6.2.1
  38. II.6.2.2Division II.6.2.2
  39. II.6.2.3Division II.6.2.3
  40. II.6.2.4Division II.6.2.4
  41. II.6.2.5Division II.6.2.5
  42. Toxicology
  43. General principles
  44. II.6.3.1.1Division II.6.3.1.1
  45. II.6.3.1.2Division II.6.3.1.2
  46. II.6.3.1.3Division II.6.3.1.3
  47. II.6.3.1.4Division II.6.3.1.4
  48. Single-dose toxicity, if available
  49. II.6.3.2.1Division II.6.3.2.1
  50. II.6.3.2.2Division II.6.3.2.2
  51. Repeat dose toxicity
  52. Repeat dose (90 day) oral toxicity testing
  53. II.6.3.3.1.1Division II.6.3.3.1.1
  54. II.6.3.3.1.2Division II.6.3.3.1.2
  55. II.6.3.3.1.3Division II.6.3.3.1.3
  56. II.6.3.3.1.4Division II.6.3.3.1.4
  57. Repeat-dose (chronic) toxicity testing
  58. II.6.3.3.2.1Division II.6.3.3.2.1
  59. II.6.3.3.2.2Division II.6.3.3.2.2
  60. II.6.3.3.2.3Division II.6.3.3.2.3
  61. II.6.3.3.2.4Division II.6.3.3.2.4
  62. Tolerance in target species, if available
  63. II.6.3.4.1Division II.6.3.4.1
  64. II.6.3.4.2Division II.6.3.4.2
  65. Reproductive toxicity, including developmental toxicity
  66. Study of the effects on reproduction
  67. II.6.3.5.1.1Division II.6.3.5.1.1
  68. II.6.3.5.1.2Division II.6.3.5.1.2
  69. II.6.3.5.1.3Division II.6.3.5.1.3
  70. II.6.3.5.1.4Division II.6.3.5.1.4
  71. II.6.3.5.1.5Division II.6.3.5.1.5
  72. II.6.3.5.1.6Division II.6.3.5.1.6
  73. II.6.3.5.1.7Division II.6.3.5.1.7
  74. Study of developmental toxicity
  75. II.6.3.5.2.1Division II.6.3.5.2.1
  76. II.6.3.5.2.2Division II.6.3.5.2.2
  77. II.6.3.5.2.3Division II.6.3.5.2.3
  78. II.6.3.5.2.4Division II.6.3.5.2.4
  79. II.6.3.5.2.5Division II.6.3.5.2.5
  80. II.6.3.5.2.6Division II.6.3.5.2.6
  81. Genotoxicity
  82. II.6.3.6.1Division II.6.3.6.1
  83. II.6.3.6.2Division II.6.3.6.2
  84. II.6.3.6.3Division II.6.3.6.3
  85. II.6.3.6.4Division II.6.3.6.4
  86. II.6.3.6.5Division II.6.3.6.5
  87. II.6.3.6.6Division II.6.3.6.6
  88. II.6.3.6.7Division II.6.3.6.7
  89. II.6.3.6.8Division II.6.3.6.8
  90. II.6.3.6.9Division II.6.3.6.9
  91. II.6.3.6.10Division II.6.3.6.10
  92. II.6.3.6.11Division II.6.3.6.11
  93. II.6.3.6.12Division II.6.3.6.12
  94. II.6.3.6.13Division II.6.3.6.13
  95. II.6.3.6.14Division II.6.3.6.14
  96. II.6.3.6.15Division II.6.3.6.15
  97. II.6.3.6.16Division II.6.3.6.16
  98. II.6.3.6.17Division II.6.3.6.17
  99. II.6.3.6.18Division II.6.3.6.18
  100. Carcinogenicity
  101. Criteria for the selection of substances for carcinogenicity testing
  102. II.6.3.7.1.1Division II.6.3.7.1.1
  103. II.6.3.7.1.2Division II.6.3.7.1.2
  104. II.6.3.7.1.3Division II.6.3.7.1.3
  105. II.6.3.7.1.4Division II.6.3.7.1.4
  106. II.6.3.7.1.5Division II.6.3.7.1.5
  107. Other requirements
  108. General principles
  109. II.6.4.1.1Division II.6.4.1.1
  110. II.6.4.1.2Division II.6.4.1.2
  111. Special studies (e.g. immunotoxicity, neurotoxicity)
  112. Immunotoxicity
  113. II.6.4.2.1.1Division II.6.4.2.1.1
  114. II.6.4.2.1.2Division II.6.4.2.1.2
  115. II.6.4.2.1.3Division II.6.4.2.1.3
  116. II.6.4.2.1.4Division II.6.4.2.1.4
  117. Neurotoxicity, developmental neurotoxicity and delayed neurotoxicity
  118. II.6.4.2.2.1Division II.6.4.2.2.1
  119. II.6.4.2.2.2Division II.6.4.2.2.2
  120. II.6.4.2.2.3Division II.6.4.2.2.3
  121. II.6.4.2.2.4Division II.6.4.2.2.4
  122. II.6.4.2.2.5Division II.6.4.2.2.5
  123. II.6.4.2.2.6Division II.6.4.2.2.6
  124. II.6.4.2.2.7Division II.6.4.2.2.7
  125. Microbiological properties of residues
  126. Potential effects on the human gut flora
  127. II.6.4.3.1.1Division II.6.4.3.1.1
  128. II.6.4.3.1.2Division II.6.4.3.1.2
  129. II.6.4.3.1.3Division II.6.4.3.1.3
  130. II.6.4.3.1.4Division II.6.4.3.1.4
  131. II.6.4.3.1.5Division II.6.4.3.1.5
  132. II.6.4.3.1.6Division II.6.4.3.1.6
  133. Observations in humans
  134. II.6.4.4.1Division II.6.4.4.1
  135. II.6.4.4.2Division II.6.4.4.2
  136. Findings of other EU or international scientific bodies
  137. II.6.5.1Division II.6.5.1
  138. Determination of an ADI or alternative limit
  139. II.6.6.1Determination of an ADI
  140. Derivation of the toxicological ADI
  141. II.6.6.1.1.1Division II.6.6.1.1.1
  142. II.6.6.1.1.2Division II.6.6.1.1.2
  143. II.6.6.1.1.3Division II.6.6.1.1.3
  144. II.6.6.1.1.4Division II.6.6.1.1.4
  145. II.6.6.1.1.5Division II.6.6.1.1.5
  146. II.6.6.1.1.6Division II.6.6.1.1.6
  147. II.6.6.1.1.7Division II.6.6.1.1.7
  148. II.6.6.1.1.8Division II.6.6.1.1.8
  149. II.6.6.1.1.9Division II.6.6.1.1.9
  150. II.6.6.1.1.10Division II.6.6.1.1.10
  151. II.6.6.1.1.11Division II.6.6.1.1.11
  152. II.6.6.1.1.12Division II.6.6.1.1.12
  153. II.6.6.1.1.13Division II.6.6.1.1.13
  154. II.6.6.1.1.14Division II.6.6.1.1.14
  155. II.6.6.1.1.15Division II.6.6.1.1.15
  156. II.6.6.1.1.16Division II.6.6.1.1.16
  157. Derivation of the pharmacological ADI
  158. II.6.6.1.2.1Division II.6.6.1.2.1
  159. II.6.6.1.2.2Division II.6.6.1.2.2
  160. II.6.6.1.2.3Division II.6.6.1.2.3
  161. Derivation of a microbiological ADI
  162. II.6.6.1.3.1Division II.6.6.1.3.1
  163. II.6.6.1.4The overall ADI
  164. II.6.6.1.5Substances with non-threshold effects
  165. II.6.6.2Alternatives to the ADI
  166. Substances for which recommended dietary intake levels have been established
  167. II.6.6.2.1.1Division II.6.6.2.1.1
  168. II.6.6.2.1.2Division II.6.6.2.1.2
  169. II.6.6.2.1.3Division II.6.6.2.1.3
  170. Substances to which consumers are exposed via food or other sources and for which recommended intake levels have not been established
  171. II.6.6.2.2.1Division II.6.6.2.2.1
  172. II.6.6.2.2.2Division II.6.6.2.2.2
  173. II.6.6.2.2.3Division II.6.6.2.2.3
  174. Endogenous pharmacologically active substances
  175. II.6.6.2.3.1Division II.6.6.2.3.1
  176. II.6.6.2.3.2Division II.6.6.2.3.2
  177. II.6.6.2.3.3Division II.6.6.2.3.3
  178. II.6.6.2.3.4Division II.6.6.2.3.4
  179. Substances that lack bioavailability
  180. II.6.6.2.4.1Division II.6.6.2.4.1
  181. RESIDUE FILE
  182. III.1Division III.1
  183. Detailed and critical summary
  184. III.2.1Division III.2.1
  185. III.2.2Division III.2.2
  186. III.2.3Division III.2.3
  187. Metabolism and residue kinetics in the target species
  188. III.3.1Division III.3.1
  189. III.3.2Division III.3.2
  190. III.3.3Division III.3.3
  191. III.3.4Division III.3.4
  192. III.3.5Division III.3.5
  193. III.3.6Division III.3.6
  194. III.3.7Division III.3.7
  195. III.3.8Division III.3.8
  196. III.3.9Division III.3.9
  197. III.3.10Division III.3.10
  198. III.3.11Division III.3.11
  199. III.3.12Division III.3.12
  200. Monitoring and exposure data, if relevant
  201. III.4.1Division III.4.1
  202. Residue analytical method
  203. III.5.1Division III.5.1
  204. III.5.2Division III.5.2
  205. III.5.3Division III.5.3
  206. III.5.4Division III.5.4
  207. III.5.5Division III.5.5
  208. III.5.6Division III.5.6
  209. Potential effects on the microorganisms used for industrial food processing
  210. III.6.1Division III.6.1
  211. III.6.2Division III.6.2
  212. III.6.3Division III.6.3
  213. III.6.4Division III.6.4
  214. III.6.5Division III.6.5
  215. Findings of other EU or international scientific bodies
  216. III.7.1Division III.7.1
  217. Annex II: Methodological principles for the risk management recommendations referred to in Article 7 of Regulation (EC) No 470/2009
  218. ELABORATION OF MRLs
  219. Derivation of numerical MRLs
  220. I.1.1Division I.1.1
  221. I.1.2Division I.1.2
  222. I.1.3Division I.1.3
  223. I.1.4Division I.1.4
  224. I.1.5Division I.1.5
  225. The ‘No MRL required’ classification
  226. I.2.1Division I.2.1
  227. I.2.2Division I.2.2
  228. I.2.3Division I.2.3
  229. AVAILABILITY OF ALTERNATIVE MEDICINES AND OTHER LEGITIMATE FACTORS
  230. II.1Availability of alternative medicines
  231. Technological aspects of food and feed productions
  232. II.2.1Division II.2.1
  233. II.2.2Division II.2.2
  234. II.2.3Division II.2.3
  235. Feasibility of controls
  236. II.3.1Division II.3.1
  237. II.3.2Division II.3.2
  238. Conditions of use and application of the substances in veterinary medicinal products, good practice in the use of veterinary medicinal products and biocidal products, the likelihood of misuse or illegal use and other relevant factors
  239. II.4.1Division II.4.1
  240. II.4.2Division II.4.2
  241. II.4.3Division II.4.3
  242. II.4.4Division II.4.4
  243. Need for an unused portion of the ADI
  244. II.5.1Division II.5.1
  245. II.5.2Division II.5.2
  246. II.5.3Division II.5.3
  247. Exposure from other sources (combined exposure to dual-use substances)
  248. II.6.1Division II.6.1
  249. II.6.2Division II.6.2
  250. II.6.3Division II.6.3
  251. II.6.4Division II.6.4
  252. II.6.5Division II.6.5
  253. II.6.6Division II.6.6
  254. Injection site residues
  255. II.7.1Division II.7.1
  256. II.7.2Division II.7.2
  257. II.7.3Division II.7.3
  258. CONSIDERATIONS ON POSSIBLE EXTRAPOLATION OF MRLs
  259. III.1Division III.1
  260. III.2Division III.2