1、PUBLISHED DOCUMENT PD CEN/TR 15356-1:2006 Validation and interpretation of analytical methods, migration testing and analytical data for materials and articles in contact with food Part 1: General considerations ICS 13.060.20; 23.060.50 PD CEN/TR 15356-1:2006 This Published Document was published un
2、der the authority of the Standards Policy and Strategy Committee on 31 May 2006 BSI 2006 ISBN 0 580 48304 5 National foreword This Published Document is the official English language version of CEN/TR 15356-1:2006. The UK participation in its preparation was entrusted to Technical Committee CW/47, M
3、aterials in contact with food, which has the responsibility to: A list of organizations represented on this committee can be obtained on request to its secretary. Cross-references The British Standards which implement international or European publications referred to in this document may be found i
4、n the BSI Catalogue under the section entitled “International Standards Correspondence Index”, or by using the “Search” facility of the BSI Electronic Catalogue or of British Standards Online. This publication does not purport to include all the necessary provisions of a contract. Users are responsi
5、ble for its correct application. Compliance with a Published Document does not of itself confer immunity from legal obligations. aid enquirers to understand the text; present to the responsible international/European committee any enquiries on the interpretation, or proposals for change, and keep UK
6、 interests informed; monitor related international and European developments and promulgate them in the UK. Summary of pages This document comprises a front cover, an inside front cover, the CEN/TR title page, pages 2 to 44, an inside back cover and a back cover. The BSI copyright notice displayed i
7、n this document indicates when the document was last issued. Amendments issued since publication Amd. No. Date CommentsTECHNICALREPORT RAPPORTTECHNIQUE TECHNISCHERBERICHT CEN/TR153561 March2006 ICS13.060.20;23.060.50 EnglishVersion Validationandinterpretationofanalyticalmethods,migration testinganda
8、nalyticaldataformaterialsandarticlesincontact withfoodPart1:Generalconsiderations Validationetinterprtationdesmthodesdanalyse,essais demigrationsetdonnesanalytiquesdesmatriauxet objetsencontactaveclesdenresalimentairesPartie1: Considrationsgnrales ValidierungundInterpretationanalytischerVerfahren, M
9、igrationsprfungundanalytischerDatenvonWerkstoffen undBedarfsgegenstndeninKontaktmitLebensmitteln Teil1:AllgemeineBetrachtungen ThisTechnicalReportwasapprovedbyCENon16January2006.IthasbeendrawnupbytheTechnicalCommitteeCEN/TC194. CENmembersarethenationalstandardsbodiesofAustria,Belgium,Cyprus,CzechRep
10、ublic,Denmark,Estonia,Finland,France, Germany,Greece,Hungary,Iceland,Ireland,Italy,Latvia,Lithuania,Luxembourg,Malta,Netherlands,Norway,Poland,Portugal, Romania, Slovakia,Slovenia,Spain,Sweden,SwitzerlandandUnitedKingdom. EUROPEANCOMMITTEEFORSTANDARDIZATION COMITEUROPENDENORMALISATION EUROPISCHESKOM
11、ITEEFRNORMUNG ManagementCentre:ruedeStassart,36B1050Brussels 2006CEN Allrightsofexploitationinanyformandbyanymeansreserved worldwideforCENnationalMembers. Ref.No.CEN/TR153561:2006:E2 Contents Page Foreword. 3 Introduction 4 1 Scope 6 2 Form of regulations 6 3 Terms and definitions. 7 4 Analytical to
12、lerances 10 5 Limits 12 6 Existing general legislation . 14 7 Difficulties with present situation regarding method validation 17 8 Analytical interpretation of results and limits 19 9 Single laboratory method validation - General protocol. 23 10 Single laboratory and second laboratory validation - F
13、or the food contact materials sector. 23 11 FDA requirements with respect to validation of analytical methods 25 12 Recovery 25 13 Reference materials 27 14 Costs 28 15 Sampling 29 16 Enforcement 30 17 Conclusions. 30 Annex A (informative) Food contact materials and articles: EU legislation. 31 Anne
14、x B (informative) List of methods currently available 37 Annex C (informative) Codex proposed draft guidelines on measurement uncertainty. 39 Annex D (informative) Characteristics of available certified reference materials 41 Bibliography . 42 CEN/TR 15356-1:20063 Foreword This document (CEN/TR 1535
15、6-1:2006) has been prepared by CEN /TC 194, “Utensils in contact with food“, the secretariat of which is held by BSI. CEN/TR 15356-1:20064 Introduction 0.1 Requirement for validation of analytical methods for enforcement of Directives Regulation (EC) No. 1935/2004 1has laid down the requirements tha
16、t may be included in specific Directives to protect human health. It allows for specific Directives to set overall migration limits and specific limits on the migration of certain constituents or groups of constituents into foodstuffs. Commission Directive 90/128/EEC 2and its subsequent amendments (
17、e.g. 3 )introduced specific migration limits for more than 300 substances. A consolidation of these directives has since been issued as Commission Directive 2002/72/EC 4 . In addition, some substances are subject to a maximum permitted quantity of the residual substance in the material or article. S
18、ome substances are subject to group limits. Continuously, additional substances are being evaluated and added to the Directive. New technical dossiers are being prepared for substances which could eventually be listed in future amendments to Directive 2002/72/EC. Methods of control will be required
19、for the majority of the abovementioned substances. The two Food Control Directives (European Council Directive 89/397/EEC 5and Council Directive 93/99/EEC 6 ) require that methods used for control purposes must be correctly and fully validated. So far only the methods developed by CEN as parts of EN
20、 13130 have been so validated. Methods developed in the project sponsored by DG Research (SM&T project, MAT1-CT92-0006, “Development of Methods of Analysis for Monomers“) have only been validated by two competent laboratories. Most methods from technical dossiers have only limited validation data at
21、 best. This Technical Report considers the background to whether or not acceptable validation of analytical methods could be achieved faster and at less cost. The Technical Report also considers the need for validation of the whole test procedure for enforcement purposes, for compliance purposes, an
22、d for the creation of data for risk assessment purposes. It should be noted that the considerations apply to both overall as well as specific migration. The list of current legislation currently adopted by the Commission is given in Annex A. The list of current methods adopted by CEN/TC 194/SC 1 is
23、given in Annex B. 0.2 Variability in the migration contact stage The determination of migration from plastics is quite unlike other measurement tasks in ensuring food safety and quality. Reliable measurements depend upon more than simply having validated analytical methods for measuring chemical con
24、centrations in foods. The Directives allows that, as an alternative to the analysis of foodstuff itself, migration testing can be carried out with food simulants applied under conditions which simulate actual use of the plastic material or article with food. This introduces many potential sources of
25、 variability in the final migration value. These are discussed in Clause 8. 0.3 Quality of data submitted for risk assessment purposes Migration data is usually an important part of the petition submitted for a risk assessment carried out by the Scientific Committee on Food (since 2003, by the Europ
26、ean Food Safety Authority, EFSA). For new substances it is unlikely that a fully validated method in food simulants will exist. A single laboratory (in-house) system of validation is required as part of the demonstration that the data submitted is of adequate quality. For example, validation of a me
27、thods intended use, the determination of accuracy and precision, usually involves replicate analyses of appropriate matrices CEN/TR 15356-1:20065 spiked with known amounts of the additive at concentrations similar to those encountered in the migration studies and determination of the percentage reco
28、very of the spiked additive. Where data are supplied to other authorities, e.g. the US-FDA, the data has to be applicable and acceptable to those authorities. Even when a validated method exists there is still the need for the laboratory carrying out the test to ensure the migration testing carried
29、out within the laboratory does not suffer from excessive error. The possibility of error may be reduced by taking part in proficiency testing schemes. Proficiency testing schemes aim to assess the competence of laboratories to carry out migration testing. At present there is at least one scheme whic
30、h is known to operate in this area. This is the Food Analysis Performance Assessment Scheme (FAPAS) operated by the FAPAS Secretariat, Central Science Laboratory, Sand Hutton, York (UK). Laboratories carrying out these methods will also be able to demonstrate their general competence by being accred
31、ited to EN ISO/IEC 17025:2005, which is administered by the appropriate Accreditation Agencies in the European Countries. For overall migration testing, samples of plastics with known overall migration values are available from the IRMM, Geel, Belgium. Spectra and a table of physical properties of t
32、he monomers and additives listed in Directives have been published to assist ensuring that substances used for calibration are of adequate and known purity 7, 8 . CEN/TR 15356-1:20066 1 Scope This Technical Report gives guidance in support of Directives adopted by the European Union in the Food Cont
33、act Materials Sector and is intended to aid Food Control Authorities and industry enforce and comply with those Directives. 2 Form of regulations 2.1 General The EU Directives on food contact plastics, provide for various types of quantitative restrictions i.e. specific migration limits (SML, expres
34、sed as mg (of substance) /kg of food), overall migration limit (OML, expressed as mg/kg of food or mg/dm 2of surface) and maximal quantity of the substance in the finished plastic article referred either to the quantity of article (QM, expressed as mg/kg of article) or to area of the surface in cont
35、act with the foodstuffs (QMA, expressed as mg/dm of surface). The determination of these quantities implies various procedural steps e.g. sampling, migration tests with different experimental conditions (OML, SML) or extraction (QM, QMA) as well the usual multi-step analytical determination. Each of
36、 these steps is subject to a certain variability and an overall variability will affect the value found by one laboratory (repeatability) or by more than one laboratories (reproducibility). In the past at the level of the Standing Committee for Foodstuffs a discussion took place on the method of ana
37、lysis for vinyl chloride. The Commission proposed then that the variability should be expressed as “Reproducibility“ but the majority of Member States were in favour of the “Repeatability“. Therefore the Commission services decided to avoid any further scientific discussion on this issue and decided
38、 to propose a new term, “Analytical Tolerance“ which shall comprise the variability due to all the above-mentioned procedural steps. Until now no Member States objected to this choice and no fundamental problems were raised from its application. Three options have been chosen by the Commission servi
39、ces as regards the various existing quantitative restrictions: a) restrictions affected by a specified analytical tolerance, b) restrictions affected by an unspecified analytical tolerance, and c) restrictions not affected by any analytical tolerance. The three options and their background are expla
40、ined in 2.2, 2.3 and 2.4. 2.2 Restriction and specified analytical tolerance This case applies to the overall migration limit, where the value of the OML in fatty simulants (60 mg/kg (ppm) or 10 mg/dm 2 ) is accompanied by an analytical tolerance of 20 mg/kg (ppm) (or 3 mg/dm 2 ). In this case the v
41、ariability should be added to the limit value and, only if the value found is greater than 80 mg/kg (ppm) (=60+20) or 13 mg/dm 2(=10+3), the article is considered not in compliance with the Directive. The choice to increase the OML by the value of the tolerance was due to the variability of the anal
42、ysis. NOTE This approach has the disadvantage that as the variability of sampling and analytical procedures becomes less, the overall limit becomes, effectively greater. However it is possible to change the value of the analytical tolerance by an amendment of the Plastics Directive. For example, as
43、practical experience was gained and as both standardised methods and certified reference materials became available it became clear that many laboratories struggled to meet the analytical tolerance value of 1 mg/dm 2set for tests using volatile simulants. Consequently, Commission Directive 2001/62/E
44、C was issued which, based on expert judgement rather than any statistical evaluation of the available results, raised this tolerance figure to 2 mg/dm 2 . The same problem would exist if an EN rather than a Directive establishes the value of the variability. If no value is specified, this issue is n
45、o longer harmonised and this should also be considered as disadvantage. The Member States and professional organisations requested, at unanimity, that an analytical tolerance should be fixed. CEN/TR 15356-1:20067 2.3 SML restriction which includes non specified analytical tolerance This case applies
46、 to the substances, which are classified by EFSA into EFSA list 4 (carcinogens or high toxic substances) and, therefore, in principle should not be detectable in foodstuffs. For these substances a detection limit value (= DL) is fixed. Because there is also a variability in determining the detection
47、 limit, an analytical tolerance was considered also in this case. Therefore the Directive includes a sentence “Not detectable (Detection Limit = 20 g/kg (ppb) analytical tolerance included). This choice, although not scientifically correct, was adopted pending the validation of the specific methods
48、of analysis for the substances. NOTE this approach suffers from the same disadvantage as above, except that the variabilities have not been quantified. However, it may also be argued that this is an advantage. For the analyst the lack of a specified variability could be a disadvantage and considered scientifically incorrect. But for a jury, a responsible of the production or enforcement laboratory is a great advantage, from the point of view of the juridical certainty, to know the limit which cannot be exceeded in any situation. It has also to be considered that the level chosen is
