A.<Strong>Safety file</Strong>The dossier of safety tests shall include the following documents:
an index of all studies included in the dossier,a statement confirming that all data known to the applicant/requestor at the time of submission, whether favourable or unfavourable, are included,a justification for the omission of any type of study,an explanation for the inclusion of an alternative type of study,in cases where a study pre-dates Directive 2004/10/EC or Good Laboratory Practice status is unknown, a discussion of the contribution that any non-GLP study can make to the overall risk assessment.
Each study report shall include the following documents:
a copy of the study plan (protocol, including amendments and deviations),a signed statement of compliance with good laboratory practice, where applicable,a description of the methods, apparatus and materials used,a description and justification of the test system,a description of the results obtained, in sufficient detail to allow the results to be critically evaluated independently of their interpretation by the author,a statistical analysis of the results where appropriate,a discussion of the results, with comment on observed (adverse) effect levels and NO(A)ELs, and on any unusual findings,a detailed description and a thorough discussion of the results of the study.
A.0.Detailed and critical summaryThe detailed and critical summary shall be signed and dated. Information about the author's educational background, training and occupational experience shall be attached. The professional relationship of the author with the applicant/requestor shall be declared.
All the important data shall be summarised in an Annex, in tabular or graphic form whenever possible and the relevant bibliographic references shall also be included in the Annexes to the document. The relevance of the studies provided for the evaluation of potential risks presented by residues to humans shall be addressed. The detailed and critical summary and its Annexes shall contain precise cross-references to the information contained in the main documentation. This section shall not introduce new studies that are not included in the main documentation.
A.1.Precise identification of the substance concerned by the application/request:
INN,International Union of Pure and Applied Chemistry (IUPAC) name,Chemical Abstract Service (CAS) number,therapeutic, pharmacological and chemical classification,synonyms and abbreviations,structural formula,molecular formula,molecular weight,degree of impurity,qualitative and quantitative composition of impurities,.description of physical properties,melting point,boiling point,vapour pressure,solubility in water and organic solvents expressed in g/l, with indication of temperature,density,spectra of refraction, rotation, etc.,pKa,protein binding.
A.2.Pharmacology;
pharmacodynamics;pharmacokinetics in laboratory species (absorption, distribution, metabolism, excretion);
A.3.Toxicology (in laboratory species);
single-dose toxicity, where available;repeat-dose toxicity;repeat-dose (90-day) oral toxicity testing;repeat-dose (chronic) toxicity testing;tolerance in target species, where available;reproductive toxicity, including developmental toxicity;study of the effects on reproduction;study of developmental toxicity;genotoxicity;carcinogenicity;
A.4.Other requirements;
special studies (e.g. immunotoxicity, neurotoxicity);microbiological properties of residues (if relevant);potential effects on the human gut flora;potential effects on the microorganisms used for industrial food processing;observations in humans;
A.5.Determination of ADI or alternative limit.
B.<Strong>Residue File</Strong>The dossier of residue tests shall include the following documents:
an index of all studies included in the dossier;a statement confirming that all data known to the applicant/requestor at the time of submission, whether favourable or unfavourable, are included;a justification for the omission of any type of study;an explanation for the inclusion of an alternative type of study;in cases where a study pre-dates Directive 2004/10/EC or GLP status is unknown, a discussion of the contribution that any non-GLP study can make to the overall risk assessment.
Each study report shall include the following documents:
a copy of the study plan (protocol, including amendments and deviations);a signed statement of compliance with GLP, where applicable;a description of the methods, apparatus and materials used;a description and justification of the test system;a description of the results obtained, in sufficient detail to allow the results to be critically evaluated independently of their interpretation by the author;a statistical analysis of the results where appropriate;a discussion of the results;a detailed description and a thorough discussion of the results of the study.
B.0.Detailed and critical summary
The detailed and critical summary shall be signed and dated. Information about the author's educational background, training and occupational experience shall be attached. The professional relationship of the author with the applicant/requestor shall be declared.
All the important data shall be summarised in an Annex, in tabular or graphic form whenever possible and the relevant bibliographic references shall also be included in the Annexes to the document. The relevance for the studies provided for the establishment of maximum residue limits shall be discussed. The detailed and critical summary and the Annexes shall contain precise cross-references to the information contained in the main documentation. That section shall not introduce new studies that are not included in the main documentation.
B.1.Metabolism and residue kinetics:
pharmacokinetics in food producing species (absorption, distribution, metabolism, excretion);depletion of residues:identification of marker residue;ratio of marker to total residues;
B.2.monitoring and exposure data, if relevant;
B.3.residue analytical method;
description of the method, according to an internationally agreed format;validation of the method in accordance with relevant guidance published by the appropriate authority.