final report of a mission carried out in spain from 15 to

04/10/04 - 45413

EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL Directorate F - Food and Veterinary Office Director

DG(SANCO)/7264/2004 – MR Final

FINAL REPORT OF A MISSION

CARRIED OUT IN SPAIN

FROM 15 TO 23 JUNE 2004

CONCERNING THE EVALUATION OF THE CONTROL OF RESIDUES AND

CONTAMINANTS IN LIVE ANIMALS AND ANIMAL PRODUCTS, INCLUDING

CONTROLS ON VETERINARY MEDICINAL PRODUCTS

Certain comments received from the competent authorities in response to the draft report have been reflected in footnotes to the text

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EXECUTIVE SUMMARY

This report describes the outcome of a mission carried out by the Food and Veterinary Office (FVO) in Spain, from 15 to 23 June 2004.

The overall objective of the mission was to evaluate the control of residues and contaminants in live animals and animal products, including the controls on the distribution and use of veterinary medicinal products (VMPs) and feed additives, the use of which may give rise to residues in such products. The evaluation was based on the standards set out in Council Directive 96/23/EC, and other applicable EU legislation. The mission assessed the performance of the competent authorities and other officially authorised entities involved in residues and VMP controls and the legal and administrative measures put in place to give effect to the relevant EU requirements. The mission was part of a series of FVO missions on residue controls in all Member States.

A framework for residue controls, in line with EU requirements, is in place.

However, a number of shortcomings in relation to the range of substances included in the National Residue Control Plan (NRCP), methods of analysis, limits of detection, implementation of the plan and follow-up action taken in response to non-compliant results, adversely affect the effectiveness of the controls.

Problems in laboratories include lack of accreditation, method validation and quality controls. Three of the four National Reference Laboratories were not fulfilling their obligations under Community legislation. The reliability of the results obtained under the NRCP is undermined by these factors.

The inclusion in the vademecum of VMPs containing pharmacologically active substances not included in Annexes I, II or III of Regulation 2377/90, intended for use in food producing animals, could lead to inappropriate use of such products and may result in unacceptable residues being present in food. Furthermore, the controls on the manufacture of medicated feedingstuffs, are not in compliance with the relevant Community requirements and may result in unacceptable residues in animal products.

The report makes a number of recommendations to the Spanish competent authorities, aimed at addressing the shortcomings identified and further enhancing the implementing and control measures in place.

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TABLE OF CONTENTS

1. INTRODUCTION....................................................................................................... 1

2. OBJECTIVE OF THE MISSION ............................................................................... 1

3. LEGAL BASIS FOR THE MISSION......................................................................... 2

4. BACKGROUND......................................................................................................... 2

5. MAIN FINDINGS....................................................................................................... 2

5.1. Legislation ......................................................................................................... 2

5.2. The National Residue Control Plan................................................................... 2

5.3. Laboratories....................................................................................................... 7

5.4. Veterinary medicinal products and medicated feedingstuffs .......................... 10

6. CONCLUSIONS ....................................................................................................... 14

6.1. Legislation ....................................................................................................... 14

6.2. National Residue Control Plan ........................................................................ 14

6.3. Laboratories..................................................................................................... 14

6.4. Veterinary medicinal products and medicated feedingstuffs .......................... 14

6.5. Overall conclusion........................................................................................... 15

7. CLOSING MEETING............................................................................................... 15

8. RECOMMENDATIONS .......................................................................................... 16

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ABBREVIATIONS & SPECIAL TERMS USED IN THE REPORT

AC Autonomous Community (Comunidad Autónoma)

HPLC High Performance Liquid Chromatography

AESA Spanish Agency for Food Safety (Agencia Española de Seguridad Alimentaría),

HPLC-DAD High Performance Liquid Chromatography with Diode Array Detection

AGEMED Spanish Agency for Medicines and Health Products (Agencia Española de Medicamentos y Productos Sanitarios)

HPTLC High Performance Thin Layer Chromatography

CA

The competent authorities of the Autonomous Communities (Órganos Competentes de las Comunidades Autónomas)

ISO International Standardisation Organisation

CAP Chloramphenicol LC-MS-MS Liquid Chromatography-tandem Mass Spectrometry

CCA Central Competent Authority LOD Limit of detection

CCα Decision limit (definition given in Commission Decision 2002/657/EC)

MAPA Ministry of Agriculture, Fisheries and Food (Ministerio de Agricultura, Pesca y Alimentación)

CCβ Detection capability (definition given in Commission Decision 2002/657/EC)

MRL Maximum Residue Limit

CRL Community Reference Laboratory MRPL Minimum Residue Performance Level

ELISA Enzyme Linked Immuno Sorbent Assay MSC The Ministry of Health and Consumer

Affairs (Ministerio de Sanidad y Consumo)

FVO Food and Veterinary Office

NCC National Commission for Co-ordination of the Investigation and Control of Residues or Substances in Live Animals and their Products (Comisión Nacional de Coordinación de la Investigación, Control de Residuos o Sustancias en Animales Vivos y sus Productos)

GC-MS Gas chromatography with mass-spectrometric detection

NRCP National Residue Control Plan

Group A, B Categories of substances listed in Annex I to Council Directive 96/23/EC.

NRL National Reference Laboratory

A1 Stilbenes A2 Thyrostats A3 Steroids

PVP Private veterinary practitioner

A4 Resorcylic acid lactones (including zeranol)

A5 Beta-agonists A6 Substances listed in Annex IV to Council Regulation (EEC) No 2377/90.

QC Quality Control

RASFF Rapid Alert System for Food and Feed

RCL Routine control laboratory

RD Royal decree (Real Decreto)

SOP Standard Operating Procedure

B1 Inhibitors (antimicrobials) B2a Anthelmintics B2b Coccidiostats B2c Carbamates and pyrethroids B2d Sedatives B2e NSAIDs B2f Others (e.g. corticosteroids) B3a Organochlorines including PCBs B3b Organophosphorus compounds B3c Chemical elements B3d Mycotoxins B3e Dyes B3f Others

VMP Veterinary Medicinal Product

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1. INTRODUCTION

The mission took place in Spain from 15 to 23 June 2004. The mission team comprised 2 inspectors from the Food and Veterinary Office (FVO) and 1 national expert. The mission was undertaken as part of a series of missions to all Member States evaluating control systems and operational standards in this sector.

Representatives from the central competent authorities (CCA) accompanied the inspection team during the whole mission.

An opening meeting was held on 15 June with the CCA. At this meeting, the objectives of, and itinerary for, the mission were confirmed by the inspection team.

2. OBJECTIVE OF THE MISSION

The objective of the mission was to evaluate the control of residues and contaminants in live animals and animal products. The standards used were Council Directive 96/23/EC1 and other applicable Community legislation in this field, including legislation on the control and distribution of veterinary medicinal products (VMPs) and feed additives, the use of which may give rise to residues in animal products.

The mission focused on the role of the competent authorities, the legal and administrative measures in place to give effect to the relevant EU requirements, controls with regard to residues and VMPs and their operation, and the performance of residue laboratories.

In pursuit of this objective, the following sites were visited/meetings were held with:

COMPETENT AUTHORITY VISITS Comments Central 1 Opening and closing meetings Competent

authorities Regional 2 2 Autonomous Communities (Aragón and Murcia)

LABORATORY VISITS National Reference Laboratory 1 Centro Nacional de Alimentación del Ministerio

de Sanidad y Consumo Control Laboratories 3 LIVE ANIMAL CONTROL SITES Farms 5 2 pigs farms, 1 bovine farm, 1 fish farm and 1 bee

farm ESTABLISHMENTS Slaughterhouses 1 OTHERS Feed mills (producing medicated feedingstuffs)

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Direct acquisition outlet (retailer) of VMPs 3 Private veterinary practitioners 4 The veterinarians responsible for clinical care of

the holding were met during the course of each farm visit

1 EU legal acts quoted in this report refer, where applicable, to the last amended version.

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3. LEGAL BASIS FOR THE MISSION

The mission was carried out under the general provisions of Community legislation, in particular:

• Art 21 of Council Directive 96/23/EC;

• Commission Decision 98/139/EC of 4 February 1998, laying down certain detailed rules concerning on-the-spot checks carried out in the veterinary field by Commission experts in the Member States.

A full list of the legal instruments referred to in this report is provided at Annex I.

4. BACKGROUND

A previous residues mission to Spain was undertaken from 27 September to 1 October 1999, the report of which (XXIV/1142/1999), has been published on the DG SANCO website at:

http://europa.eu.int/comm/food/fs/inspections/vi/reports/spain/vi_rep_spai_1142-1999_en.pdf

5. MAIN FINDINGS

5.1. Legislation

A list of the Spanish national legal instruments transposing the Community legislation on residue controls is provided in Annex 2. The main relevant provisions of Community law are transposed.

Autonomous Communities (ACs) can adopt specific legal instruments for the implementation of national legislation in their territory.

The mission team noted that:

in one AC visited, the authorities were unable to authorise or carry out specific control visits to pharmacies and dispensaries (centros dispensadores) dealing with VMPs or feed mills producing medicated feedingstuffs, due to a lack of legislation designating the competent authority for these activities at the regional level.

5.2. The National Residue Control Plan

5.2.1. Planning

According to the Royal Decree (RD) 1749/1998, the competent authorities with regard to controls on residues in live animals and animal products are:

• The competent authorities of the Autonomous Communities (CA – Órganos Competentes de las Comunidades Autónomas), with regard to the internal market; and

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• The Ministry of Health and Consumer Affairs (MSC – Ministerio de Sanidad y Consumo) and Ministry of Agriculture, Fisheries and Food (MAPA - Ministerio de Agricultura, Pesca y Alimentación), for trade with third countries and for communication with the European Commission and other Member States.

RD 1749/1998 also established a co-ordination body, the National Commission for Co-ordination of the Investigation and Control of Residues or Substances in Live Animals and their Products (NCC - Comisión Nacional de Coordinación de la Investigación, Control de Residuos o Sustancias en animales vivos y sus productos).

The NCC is made up of representatives from the relevant competent authorities, the Spanish Agency for Food Safety (AESA – Agencia Española de Seguridad Alimentaría, an agency of MSC), MAPA and each AC. It is assisted in its work by the National Reference Laboratories (NRLs) and representatives from the Ministries of the Interior and Justice.

Each CA is responsible for drawing up residue control plans for their AC, following the suggestions of the NCC. Within each AC, the CA designates one co-ordinator to be responsible for the preparation of the residues monitoring plan. The NCC is responsible for preparing the National Residues Control Plan (NRCP), based on the information provided by each CA, and communicating this plan to the services of the European Commission. The NCC can also propose amendments to improve the effectiveness of the NRCP.

With regard to planning of the NRCP, the mission team noted the following points.

A procedure is in place for the elaboration of the NRCP, including participation of relevant departments within the CCA, the CA and the NRLs, through the NCC.

In general the number of samples foreseen in the NRCP is in excess of the minimum number of samples required by Directive 96/23/EC.

The information in the NRCP does not accurately reflect the plans being implemented at AC level2. In particular:

- limits of detection (LODs) used in the routine control laboratories (RCLs) are, in some cases, different to those quoted in the NRCP. For example in one AC visited, the LODs noted for group A2 (thyrostats) and A4 (resorcylic acid lactones) compounds were 200 and 4 µg/kg, while the LODs given in the NRCP were 100 and 2 µg/kg respectively;

- different ranges of substances are analysed. For example, the NRL was confirming a larger range of antibiotics than was indicated on the NRCP, and in one AC visited, one of the RCLs was able to detect and confirm a larger range of beta-agonists than was indicated in the plan, while another RCL was only able to detect and confirm a much narrower range.

2 In their response to the draft report, the CCA has commented on this point. The comments are appended

to this report.

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Data on veterinary medicinal product (VMP) usage in Spain is not available to the authorities and therefore can not be taken into account when deciding which substances to include in the NRCP. The CA stated that their professional knowledge of VMP usage was used in this context, however certain commonly used VMPs are not included in the plan, e.g. the only anthelmintics included are ivermectin and albendazol and detection and confirmation of antibiotics of the beta-lactam, aminoglycoside, cephalosporin and lincosamide groups are not included, detection of quinolones is limited to enrofloxacin and ciprofloxacin and detection of macrolides is limited to tylosin.

The only substances included in group B2b (coccidiostats) in the NRCP are sulfaquinoxaline and amprolium. Ionophore coccidiostats are not included, as the CCA does not consider that residues of these substances are covered by Directive 96/23/EC. Furthermore nicarbazin, which was the subject of a notification to the Rapid Alert System for Food and Feed (RASFF) for quail eggs from Spain in 2003, is not included in the NRCP3.

Most testing for nitrofurans is only carried out for the parent compounds. Nitrofurans are not included for honey, although nitrofuran residues in honey processed in Spain was the subject of a notification to the RASFF in January this year.

The NRCP includes inappropriate confirmatory methods and excessively high LODs (see section 5.3.1).

5.2.2. Implementation

Each CA is responsible for the implementation of the NRCP within its own AC.

Sampling of live animals is generally carried out by the services responsible for animal health, the Councils or Departments for Agriculture or Livestock Production (Consejerías o Departamentos de Agricultura/Ganadería). Sampling of animal products is carried out by the services responsible for food safety, the Councils or Departments for Health or Public Health (Consejerías o Departamentos de Sanidad/Salud Pública).


in the ACs visited, guidelines had been drawn up for officials collecting samples;

there were significant differences between the number of samples foreseen in the NRCP for 2003 and the results actually reported;

in the ACs visited, it was stated that the residue control programme can be altered during the year in response to changes in perceived risks. This can mean that analyses are stopped for one substance and resources are re-directed to another. Such changes are not always notified to the CCA or NCC.


to this report.

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5.2.3. Supervision of implementation

The NCC reviews the implementation of the previous year’s NRCP at one of its meetings. The mission team noted that:

while, following its annual review, the NCC may make observations and suggestions on how implementation may be improved, it does not have any power to require ACs to take action in response to its proposals4;

in each AC visited, the implementation of the NRCP was supervised by the central services of the AC, who received information from the samplers and the laboratories on samples collected and analysed within the region.

5.2.4. Follow-up of non-compliant results

5.2.4.1. Non-compliant results for authorised and unauthorised substances

In the case of suspicion of use of unauthorised substances or products, or when residues of authorised substances or products at a concentration exceeding the Maximum Residue Limit (MRL) are detected, the procedures for investigation and follow-up are laid down in Royal Decree 1749/1998. These procedures are in accordance with the requirements laid down in Council Directive 96/23/EC.

RD 1749/1998 foresees the possibility of imposing administrative sanctions (fines, movement restrictions, destruction of animals, etc.). Penal sanctions can also be imposed under the “Ley Orgánica 10/1995, del Código Penal” and RD 1945/1983.

During visits to the ACs, the mission team noted the following points.

A working group has drawn up draft guidelines at the request of the NCC in order to better harmonise the approach taken to follow up within the ACs.

In the results reported for 2003, in a case related to a group of animals sampled as suspects at an animal market, clenbuterol (5 animals), testosterone (1 animal) and 17β-oestradiol (1 animal) were found. In this case however no further follow-up was possible as the animals were reported to have disappeared and their origin could not be determined.

In one AC visited, in three cases related to the finding of non-compliant results examined by the mission team, a number of deficiencies in the procedures were noted:

– in one case related to the finding of natural hormones, the sex of the animals sampled was not recorded on the submission form accompanying the samples to the laboratory;

– undue delays occurred at every stage of the process, from sample collection to completion of the on-farm follow-up investigation; in one case the time taken from sampling to completion of the follow-up visit was in excess of 15 months;


to this report.

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– follow-up sampling was only carried out on feed and water, no sampling of live animals was carried out;

– in two cases, the final decision regarding the outcome of the investigation was that the results were due to physiological levels of the naturally occurring sex hormones. This decision was based on a document provided by the relevant NRL, giving guidance on naturally occurring levels of these hormones in pigs. However the laboratory results on which this decision was based were only qualitative and did not indicate the levels of hormones found.

In a case relating to a non-compliant result for dexamethasone in a bovine animal in another AC visited, the mission team noted that follow-up action was carried out in a timely manner. However, at the investigation visit to the farm, only feed was sampled and no further on-farm sampling of live animals was undertaken, even though illegal treatment had been established (no dexamethasone had been prescribed)5.

In cases where non-compliant results are found, sanctions are imposed. In 2002, 19 administrative and 10 penal sanctions were imposed. In addition, 18 holdings lost the right to receive European Community aid for 12 months. The final figures are not yet available for 2003 as a number of procedures are still on-going6.

5.2.4.2. Suspect samples

AESA receives notifications of non-compliant results from the relevant CA and disseminates this information to the rest of the CA. AESA also communicates the penalties imposed for each residue violation, to all CA, by the same route.


an effective system of exchange of information was in place which ensured that officials were informed of holdings where suspicion or proof of violations of residue requirements existed. This allowed effective targeting of animals from such holdings for intensified controls;

during 2003, in the breakdown of results of suspect sampling provided by the Spanish authorities, 2 of these samples gave non-compliant results for group A3 substances, 6 for A5, 2 for A6, 34 for B1, 1 for B2b (sulfaquinoxaline), 22 for B2f (corticosteroids), and 2 for B3a.

5.2.4.3. Contaminants

No specific measures are prescribed at national level for follow-up actions in relation to contaminants. Each CA decides on appropriate follow-up actions in its


to this report. Some additional information on a single case, which was not provided to the mission team during the course of the mission, is provided. However it should be noted that the Regional CA stated during the course of the mission that it was not their policy to sample live animals on farms following findings of illegal treatment with dexamethasone.

6 In their comments on the draft report the CCA stated that in 2003 50 administrative fines, totalling 88,275 Euro and one criminal sentence were imposed.

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own AC. The mission team did not see any examples of follow-up of non-compliant results for contaminants in the ACs visited.

The CCA provided information of specific contaminant surveillance introduced following a mining accident in 2002 (heavy metal surveillance) and marine oil spill in 2002 (polycyclic aromatic hydrocarbons surveillance).

5.3. Laboratories

5.3.1. General description

The designation of the NRLS is the responsibility of MAPA and AESA. The NRLs and their functions are laid down in RD 1749/1998.

There are 4 NRLs in Spain:

• Centro Nacional de Alimentación del Ministerio de Sanidad y Consumo, in Majadahonda, Madrid, which is responsible for groups A1, A3, A4, A5, B1, B2f (corticosteroids), B3c (only aquaculture), B3d and B3e.

• Laboratorio de Sanidad y Producción Animal, in Santa Fe (Granada), which is responsible for groups B2a, B2b, B2c, B2e and B2f (except corticosteroids).

• Laboratorio Central de Veterinaria, del Ministerio de Agricultura, Pesca y Alimentación ,in Algete, which is responsible for groups A2 and B2d.

• Laboratorio Arbitral Agroalimentario del Ministerio de Agricultura, Pesca y Alimentación, in Carretera de La Coruña, Madrid, which is responsible for groups B3a (including PCBs), B3b and B3c (except aquaculture).

• Responsibility for groups A6 and B3f are shared between the above laboratories, depending on the pharmacological action of the substance.

Each CA designates the RCLs responsible for the analyses carried out under the residues plan for its own AC. The RCL(s) in a given AC may be part of the services of the AC, part of the services of another AC, an NRL, a university laboratory or a private laboratory. In effect this means that in excess of 50 laboratories carry out RCL functions under the NRCP.

The mission team noted the following points.

Fewer than 30% of the RCLs mentioned in the NRCP are accredited, contrary to the requirements of Spanish and Community law (Point 1.2 of the Annex to Commission Decision 98/179/EC).

One of the NRLs, Laboratorio Central de Veterinaria, del Ministerio de Agricultura, Pesca y Alimentación,in Algete, is not accredited. Another NRL, the Laboratorio de Sanidad y Producción Animal, in Santa Fe (Granada) is in the process of accreditation.

One of the NRLs, the Centro Nacional de Alimentación del Ministerio de Sanidad y Consumo (CNA), was providing training, support and proficiency testing for RCLs. At the RCLs visited by the mission team, while frequent contacts with CNA were reported, no evidence could be found of contacts with the remaining NRLs. No communications were received from these NRLS, no

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training or support had been provided and no proficiency testing had been offered.

In many cases, RCLs are using unsuitable methods for confirmation of group A substances; HPLC/HPLC-DAD and HPTLC methods are used instead of mass spectrometric methods7.

In some RCLs, for certain analyses, the LOD does not meet the minimum required performance limit (MRPL), e.g. for chloramphenicol (CAP) a range of 0.3-10 ppb is given in the NRCP and for malachite green, 5-10 ppb. For others for which no MRPL exists, the LOD is inappropriately high, e.g. ivermectin in milk at 50ppb and dexamethasone in urine 10ppb.

5.3.2. National Reference Laboratory visited

The mission team visited the Centro Nacional de Alimentación del Ministerio de Sanidad y Consumo. CNA’s involvement in the NRCP is mainly limited to their role as NRL. It is not generally involved in routine analysis of samples, other than in cases where confirmation or arbitration is required. There are some exceptions, especially for those methods and analytes that cannot be performed by some RCLs e.g. nitrofuran metabolites and leucomalachite green.


CNA has been an ISO 17025 accredited laboratory since July 1999. The Spanish national accreditation body, ENAC (Entidad Nacional de Acreditación), performs annual inspections. The last inspection took place in October 2003, with a satisfactory outcome.

Relatively few analytical methods for residues fall under CNA’s scope of accreditation. There is, at present, no strategic plan to extend the scope of accreditation for residue control. It is obligatory in Spain to apply for accreditation for each analyte-matrix combination. CNA indicated that it is extremely burdensome to proceed in this way in order to obtain accreditation for all relevant methods. This view was also supported by the CCA. CNA is currently in discussion with ENAC to develop alternative approaches towards accreditation. A strategic plan to extend the scope of accreditation to include more residue methods is awaiting the outcome of these discussions.

CNA personnel participate in scientific meetings concerning residue control and Community Reference Laboratory (CRL) activities, including workshops and proficiency tests. Performance of CNA in recent proficiency tests is satisfactory.

The facilities and equipment at CNA are of a high standard; state-of-the-art analytical instruments are available.

The standard operation procedures (SOPs) inspected include instructions for quality control (QC) and criteria for interpreting and approving results.

7 In their comments on the draft report the NRL stated that, for substances in Group A, a Laboratory

Communication is being prepared for all of the laboratories in the Autonomous Communities and this will recommend that only testing methods that are sensitive and specific to the MRLs and MRPLs are used for residues of veterinary medicines. This Communication will include lists of the limits that have already been set and those that are under discussion

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From the SOPs checked by the mission team it was observed that Commission Decision 2002/657/EC was implemented for the analysis of nitrofuran metabolites, with regard to the determination of CCα and CCβ. However stability studies of the analyte and robustness testing, as required by this Decision, had not yet been performed8.

CNA has a well documented programme of NRL activities to support the RCLs. The programme includes technical training, workshops, annual meetings, supply of analytical support and provision of interlaboratory comparison studies for specific analytes. The latter are prioritised in consultation with the RCLs.

The NRL could not indicate whether or not all laboratories actively carrying out particular analyses had actually participated in the relevant interlaboratory tests. The NRL has no means to require follow up action from RCLs giving deviant results in interlaboratory trials9.

5.3.3. Control laboratory visited

Three RCLs, in two ACs, were visited during the course of the mission.


One of the RCLs visited is accredited and two are not10. One of the latter had applied for accreditation recently, however the analytic methods proposed for the initial scope of accreditation are not relevant for the NRCP.

In the accredited RCL only a limited number of the methods used for analyses under the NRCP are actually accredited. To date there is no strategic plan to increase the number of accredited methods.

Facilities and equipment differ between laboratories but in general are of a reasonable standard. Purchase of state-of-the-art instruments (LC-MS or LC-MS-MS) has been proposed by all laboratories. All control laboratories visited had GC-MS equipment.

The suitability of methods for control of the LODs stipulated in the NRCP is in some cases questionable. Moreover, for group A substances, some of the methods and techniques currently in use are insufficiently selective. There is no strategic plan to replace those methods and techniques with methods and techniques that could comply with the requirements of Commission Decision 2002/657/EC.

8 In their comments on the draft report, the NRL stated the following: “Regarding the inclusion of tests on

the stability of the residues in the Validation, we should like to refer back to the conclusions of the meeting on the interpretation of the implementation of Decision 2002/657/EC, which, on page 2, states that the stability of residues does not necessarily need to be studied by each laboratory, but can be obtained from the bibliography or from information received from the CRLs.” However, it should be noted that, during the course of the visit of the mission team to the laboratory, when laboratory staff were asked regarding evaluation of stability, no bibliography or information received from CRLs offered.

9 In their comments on the draft report the NRL stated that a suggestion has been made to bring the participating laboratories together to discuss the (anonymous) results.

10 The regional CA has commented on this point. These comments are appended to this report.

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Suitable equipment (GC-MS) is available in all the RCLs visited, which would allow the use of confirmatory analytical methods compliant with Commission Decision 2002/657/EC for certain analytes e.g. groups A1, A3 and A5. However, in some cases, such methods have not been developed or implemented.

Validation of analytical methods is very limited or nonexistent in the RCLs visited. In general, no initial validation study has been performed and method performance at best relies on QC procedures only. Those QC procedures however, are, in some cases, inadequate or nonexistent.

There is no validation plan to achieve validation of methods, to the standards laid down in Commission Decision 2002/657/EC, in particular for group A substances, by the deadline prescribed in that Decision.

While Commission Decision 2002/657/EC was available to the staff of the RCLs visited, knowledge and understanding of its requirements was limited. Only limited assistance (one lecture organised by CNA) had been made available to assist control laboratories in implementing this Decision.

SOPs are not always available for the methods in use and, in some cases, were observed to contain only a general or a partial description of the method.

Screening for B1 substances was examined by the mission team in one RCL visited and found to be incomplete. A 4-plate test method provided by the NRL has been modified into a 2-plate test, which was said to detect only tetracyclines, penicillins and sulfonamides. The test is not validated and hence it is not clear exactly which compounds can be detected at level of the MRL.

In the same laboratory, after microbiological screening, chemical methods for quantification and confirmation are only applied for sulfonamides and tetracyclines. Hence no other antibiotics are detected in the confirmation step. As a result, in 2003, from 57 samples screened positive on a plate sensitive to sulfonamides, 34 could not be confirmed and of the 43 samples screened positive on a plate sensitive to tetracyclines and penicillins, none could be confirmed.

In the RCLs visited, variable participation in relevant proficiency tests was noted. In two cases, regular participation, with generally satisfactory results, was demonstrated. However, in another RCL, there had been no participation in proficiency testing since the 1990s.

In two laboratories it was stated that no targets are defined for the turnaround time of sample analysis.

5.4. Veterinary medicinal products and medicated feedingstuffs

5.4.1. Authorisation of VMPs

At national level the Spanish Agency for Medicines and Health Products (AGEMED - Agencia Española de Medicamentos y Productos Sanitarios) is responsible for authorisation and control of the manufacture of veterinary medicinal products (VMPs). AGEMED is part of the MSC.

The distribution and use of VMPs is the responsibility of the ACs.

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A list of authorised VMPs is available on AGEMED’s web site. However, this list does not provide information on the active substances in the VMPs or the species indications. The mission team requested a copy of the AGEMED vademecum, listing authorised VMPs with their active substances and species indications, both prior to and during the course of the mission. The vademecum (on CD-ROM) was received only at the final meeting.


On studying the vademecum after the completion of the mission, a number of products were found which had been authorised for use in food producing animals but which contained pharmacologically active substances not included in Annexes I, II or III of Regulation 2377/90 for the species for which they had been authorised11. Examples include:

– a product containing nandrolone laurate, authorised for use in pigs and ruminants;

– products containing prednisolone, authorised for use in sheep, pigs and horses;

– a product containing methylprednisolone acetate and another containing gentamicin sulphate for use in horses, (with no limitation regarding subsequent use for human consumption of treated horses);

– a product containing permethrin for use in poultry and pigs (the provisional MRL expired 1.1.2003).

In addition, a number of products, containing pharmacologically active substances not included in Annexes I, II or III of Regulation 2377/90 are authorised for use in horses not intended for human consumption12. Examples include products containing phenylbutazone, suxibutazone, griseofulvin and nandrolone laurate. However, during on the spot visits, the representatives of the competent authorities stated that there is no system in place at present in Spain to ensure that horses treated with such products are not subsequently slaughtered for human consumption.

An effective procedure is in place for notifying recalls, alerts and changes in marketing authorisations. Evidence was seen at AC level of follow-up action by the CA following such notifications.

5.4.2. Distribution of VMPs

In Spain, sale of VMPs takes place either via pharmacies or authorised distributors (distribuidores) belonging to farmers associations (agrupaciones ganaderas). Veterinarians working in the private sector (private veterinary practitioners - PVPs) may carry sufficient VMPs for emergency use in their practices, but may not sell or

11 In their comments on the draft report the CCA stated that these products were included in the

vademecum due to a mistake which occurred during transfer of data from documents to the database and that the error has been rectified.

12 In their comments on the draft report the CCA stated that use of such products should always be linked to a declaration in accordance with Commission decisions 93/623/EEC and 2000/68/EC.

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dispense VMPs. They must write a prescription for any VMPs that they use from this supply.

RD 109/1995 requires that all VMPs for use in food-producing animals are prescription only medicines. PVPs can prescribe treatments other than VMPs authorised for a given indication in a given species, but only in accordance with the cascade system described in Article 10 of Council Directive 2001/82/EC, which is transposed into Spanish legislation by article 81 of RD 109/1995.

During the course of visits to a pharmacy and two authorised distributors operated by farmers’ co-operatives/associations, the mission team noted that:

in general, records kept of VMPs used or dispensed were correct.

5.4.3. Controls on VMPs

The CA of each AC is responsible for controls of all levels of manufacture, distribution and use of VMPs, including the manufacture of medicated feedingstuffs. In some ACs, guidelines and standard forms for controls have been drawn up.

5.4.3.1. Wholesale and retail level

Within the ACs, the Directorate General for Livestock Production (la Dirección General de Ganadería), or its equivalent, is usually responsible for authorisation of, and controls on, wholesalers and retailers of VMPs, as well as for controls on the storage and sale of VMPs by authorised distributors operated by farmers’ associations. According to Spanish legislation, such premises should be controlled at least once a year. Authorisation can be for a period of up to 5 years.

Retailers of VMPs are required to contract the services of an independent pharmacist who must carry out an inventory control and a check on the conditions of operation of the premises at monthly intervals. These checks are documented by means of monthly reports.

It was noted by the mission team that:

in one of the ACs visited, official controls were carried out at least as often as required by the legislation and were appropriately documented;

in the second AC visited, official services were not able to officially authorise such premises, or carry out control visits, since there was no regional legislation allocating competence for such matters.

5.4.3.2. Medicated pre-mixes and medicated feedingstuffs

Usually, within the ACs, the Directorate General for livestock production (la Dirección General de Ganadería), or its equivalent, is responsible for authorisation and registration of feed mills producing medicated feedingstuffs.

Some CA have established standard forms for use for inspections within their AC.


13

In one feed mill visited, the company’s auto-control programme included some checks on homogeneity and cross-contamination, but the CA representatives present during the visit stated that they did not supervise or check the implementation of the company’s auto-control programme13.

In a second feed mill visited, measures to prevent cross-contamination did not include one line dedicated to the manufacture of poultry and calf feed. Broiler feed, medicated with coccidiostats, could be produced immediately before laying hen feed and no measures were taken to prevent cross-contamination of the latter. No checks had been performed to investigate if such cross-contamination was occurring.

In the second AC visited, official services were not able to officially authorise feed mills manufacturing medicated feedingstuffs, or carry out control visits, since there was no regional legislation allocating competence for such matters. However some documentary control was achieved while carrying out general feedingstuffs controls and by controlling the documentation submitted with requests for authorisation.

The results of the NRCP for 2003 showed many findings of antibiotics in samples of non-medicated feedingstuffs collected on farms. Furthermore, there were indications, from the follow-up of a case of non-compliant results for antibiotics seen in one AC visited and from a RASFF notification, concerning, nicarbazin in quail eggs in 2003, that cross-contamination of feedingstuffs may be leading to residues in animal products.

No evidence was seen during the mission of the inappropriate use of pre-mixes by top-dressing, rather than by incorporation into a medicated feedingstuff.

5.4.3.3. Veterinary practices and farms

Usually, within the ACs, the Directorate General for livestock production, or its equivalent, is responsible for controls on prescription of VMPs and their use in farms. Some CA have developed standardised forms for use for these inspections within their own territories.


in each AC, the CA decides the frequency at which farms and veterinary practices are subject to control visits;

in the ACs visited, visits to farms, where a variety of different controls are carried out at the same time, are frequent. However, in one of the ACs visited, the controls on VMPs carried out during the visits were not always documented in cases where no deficiencies were found;

during farm visits medicines records, prescriptions and medicines in store were found to be kept as required.

13 The regional CA has commented on this point. These comments are appended to this report.

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6. CONCLUSIONS

6.1. Legislation

The main relevant provisions of Community law are transposed. A failure to introduce regional legislation allocating competence to an official service in relation to controls on Veterinary Medicinal Products (VMPs) was noted in one Autonomous Community visited.

6.2. National Residue Control Plan

The design of the National Residue Control Plan (NRCP) is in general in line with the EU requirements, as regards the coverage of commodities and mandatory substance groups. However the NRCP, as presented to the Commission Services, does not accurately reflect the actual testing carried out. Hence the central level in Spain, the National Co-ordination Committee (NCC), does not have a clear overview of the implementation of residues testing in Spain14. Furthermore, the range of substances analysed within each group, the methods of analysis and the limits of detection are not in all cases appropriate.

Examples of follow-up of non-compliant results examined by the team showed that follow-up actions were not always timely and did not always include sampling of live animals, which would be necessary to establish whether other animals in the holding had been subjected to illegal treatment.

These shortcomings reduce the possibility of detection of the misuse or illegal use of VMPs.

6.3. Laboratories

While National Reference Laboratories (NRLs) and routine control laboratories have been identified in the NRCP, serious problems with regard to lack of laboratory accreditation, lack of method validation, use of inappropriate analytical methods and failure of some NRLs to fulfil their functions, undermine the reliability of the results generated.

The finding that in the routine control laboratories visited, methods were not validated in line with the Commission Decision 2002/657/EC, together with the lack of any strategic planning for further validation, indicates that these laboratories are unlikely to meet the mandatory deadline for the validation of group A methods.

6.4. Veterinary medicinal products and medicated feedingstuffs

While a system of marketing authorisation for Veterinary Medicinal Products (VMPs) has been established in Spain, the inclusion in the AGEMED vademecum of VMPs containing pharmacologically active substances not included in Annexes I, II or III of Regulation 2377/90, intended for use in food producing animals, could

14 The CCA has commented on this point. These comments are appended to this report. The CCA

comment does not however appear to take account of the findings presented in the third arrowed paragraph of section 5.2.2.

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lead to inappropriate use of such products and may result in unacceptable residues being present in food.

The authorisation, for use in horses not intended for human consumption, of VMPs containing pharmacologically active substances not included in Annexes I, II or III of Regulation 2377/90, in the absence of any system to prevent the subsequent slaughter for human consumption of treated animals, could also result in unacceptable residues being present in food.

The system of controls on the distribution and use of VMPs is generally satisfactory, however controls seen on the manufacture of medicated feedingstuffs were weak and there was evidence of cross-contamination of non-medicated feedingstuffs by medicated feedingstuffs, leading to residues in animal products, although the range of substances included in the NRCP may not sufficient to detect this in all cases.

6.5. Overall conclusion

A framework for residue controls, in line with EU requirements, is in place.

However, a number of shortcomings in relation to the range of substances included in the NRCP, methods of analysis, limits of detection, implementation of the plan and follow-up action in response to non-compliant results, adversely affect the effectiveness of the controls.

Problems in laboratories include lack of accreditation, method validation and quality controls. Three of the four National Reference laboratories were not fulfilling their obligations under Community legislation. The reliability of the results obtained under the NRCP is undermined by these factors

The inclusion in the vademecum of VMPs containing pharmacologically active substances not included in Annexes I, II or III of Regulation 2377/90, intended for use in food producing animals, could lead to inappropriate use of such products and may result in unacceptable residues being present in food. Furthermore, the controls on the manufacture of medicated feedingstuffs, are not in compliance with the relevant Community requirements and may result in unacceptable residues in animal products.

7. CLOSING MEETING

A closing meeting was held on 23 June 2004 with the CCA, during which the inspection team presented the main findings and preliminary conclusions of the mission. The competent authorities indicated that they considered that the range of substances covered in the NRCP represented an appropriate prioritisation, in view of the resources available. Furthermore they emphasized the great efforts already made to improve both the NRCP and laboratory standards.

No representative from the Spanish Agency for Medicines and Health Products attended the final meeting.

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8. RECOMMENDATIONS

The competent authorities are invited to provide, within 25 working days of receipt of the report, an action plan containing details of the actions taken and planned, including deadlines for their completion, to address the following recommendations:

1. To consider, for future National Residue Control Plans, making greater use of information on veterinary medicinal product usage and from rapid alerts when choosing substances to be included in the plan.

2. To ensure that follow-up action in response to non-compliant results is timely and includes appropriate additional sampling of live animals, as specified in Articles 17 and 23(2) of Council Directive 96/23/EC, in cases where illegal treatment may be involved.

3. To ensure that samples collected in the context of the National Residue Control Plan are analysed in accredited laboratories using appropriate, validated methods.

4. To ensure that limits of detection, for methods of analysis used in the context of the National Residue Control Plan, are appropriate and comply with the Minimum Required Performance Limits, for substances for which such limits have been defined.

5. To ensure that methods of analysis for group A methods are validated to the standards laid down in Commission Decision 2002/657/EC, within the deadline specified in that Decision.

6. To ensure that all National Reference Laboratories fulfil the functions laid down in Article 14 of Council Directive 96/23/EC.

7. To ensure that all VMPs authorised for use in food producing animals or included in the AGEMED vademecum contain only pharmacologically active substances included in Annexes I, II or III of Regulation 2377/90.

8. To take action to ensure that horses treated with VMPs authorised only for use in animals not intended for human consumption are not subsequently slaughtered for human consumption.

9. To take action to ensure that in all Autonomous Communities, a suitable competent authority is designated and empowered to carry out authorisation of and controls on premises distributing and dispensing VMPs or manufacturing medicated feedingstuffs.

10. To take action to ensure that the competent official services effectively supervise the implementation of requirements of Article 4 of Council Directive 90/167/EEC, regarding the production of medicated feedingstuffs using pre-mixes, in feed mills.

9. ADDENDUM

The Spanish authorities (AESA, the National Reference laboratory and the competent authorities of the Autonomous Communities visited) responded to the draft report on 10 September, with additional comments, in a letter dated 3

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September, being sent from AGEMED to the FVO on 15 September. All of these comments are appended to the draft report.

Comments from the competent authorities have been taken into consideration when finalising the draft report.

On 20 July 2003, a meeting of the NCC was held in Madrid, during which the provisional conclusions reached by this mission were discussed, with particular emphasis on the laboratory issue.

Regarding recommendation 2, the CCA stated that:

“additional sampling of live animals will be carried out where this is required. Although the mission found that in some cases sampling of live animals was not included, this is not standard practice, since in other cases samples were indeed taken from live animals, in suspect cases from group B2f and from other groups of substances (we attach data for the year 2003, relating to Group B2f, stating that urine testing was performed on holdings, and providing other examples of other substances).”

The Department of Agriculture and Food of the Autonomous Community of Aragón and the Food Safety Service, Directorate-General for Public Health, Department of Health and Consumer Affairs of the, Government of Aragón provided detailed accounts of actions planned to address the recommendations of the report.

ANNEX I

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APPLICABLE COMMUNITY STANDARDS:

- Council Directive 96/23/EC of 29 April 1996 on measures to monitor certain substances and residues thereof in live animals and animal products, and repealing Directives 85/358/EEC and 86/469/EEC and Decisions 89/187/EEC and 91/664/EEC, and in particular Art. 21. Official Journal L 125, 23/05/1996 pp. 10 - 32.

- Council Directive 96/22/EC of 29 April 1996 concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists, and repealing Directives 81/602/EEC, 88/146/EEC and 88/299/EC. Official Journal L 125 , 23/05/1996 pp. 3 - 9

- Commission Decision 97/747/EC of 27 October 1997 fixing the levels and frequencies of sampling provided for by Council Directive 96/23/EC for the monitoring of certain substances and residues thereof in certain animal products. Official Journal L 303, 6.11.97, pp. 12 - 15

- Commission Decision 98/179/EC of 23 February 1998 laying down detailed rules on official sampling for the monitoring of certain substances and residues thereof in live animals and animal products. Official Journal L 65, 5.3.98, pp. 31 - 34

- Council Regulation (EEC) No 2377/90 of 26 June 1990 laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin. Official Journal L 224 , 18/08/1990 pp. 1-8 last amended by Commission Regulation (EC) No 2145/2003 of 8 December 2003. Official Journal L 322 , 09/12/2003 pp. 5 - 7

- Council Directive 90/167/EEC of 26 March 1990, laying down conditions governing the preparation, placing in the market and use of medicated feedingstuffs in the Community. Official Journal L 092 , 07/04/1990 pp.42 - 48

- Regulation (EC) No 1831/2003 of the European Parliament and of the Council of 22 September 2003 on additives for use in animal nutrition. Official Journal L 268 , 18/10/2003 pp. 29 - 43

- Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products. Official Journal L 311 , 28/11/2001 pp. 1 – 66

- Commission Decision 2002/657/EC of 12 August 2002 implementing Council Directive 96/23/EC concerning the performance of analytical methods and the interpretation of results. Official Journal L 221, 17.8.2002, pp. 8-36

- Council Directive 86/363/EEC of 24 July 1986 on the fixing of maximum levels for pesticide residues in and on foodstuffs of animal origin. Official Journal L 221 , 07/08/1986 pp. 43 - 47 last amended by Commission Directive 2002/42/EC of 17 May 2002, Official Journal L 134 , 22/05/2002 pp. 29 – 36.

- Commission Regulation (EC) No 466/2001 of 8 March 2001 setting maximum levels for certain contaminants in foodstuffs. Official Journal L 77, 16.3.2001, pp. 1-13

- Commission Directive 2001/22/EC of 8 March 2001 laying down the sampling methods and the methods of analysis for the official control of the levels of lead, cadmium, mercury and 3-MCPD in foodstuffs. Official Journal L 77, 16.3.2001, pp. 14-21

- Commission Directive 2002/63/EC of 11 July 2002 establishing Community methods of sampling for the official control of pesticide residues in and on products of plant and animal origin and repealing Directive 79/700/EEC. Official Journal L 187, 16.7.2002, pp. 30-43 last amended by Commission Directive 2004/2/EC of 9 January 2004, Official Journal L 014 , 21/01/2004 pp. 10 – 18.

ANNEX II

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TRANSPOSITION OF COMMUNITY LEGISLATION IN SPAIN: According to the information provided by the Spanish authorities: Council Directive 96/22/EC is transposed into Spanish national legislation by means of the following: Real Decreto 1373/1997, de 29 de agosto, por el que se prohíbe utilizar determinadas sustancias de efectos hormonales y tireostático y sustancias beta-agonistas en la cría de ganado (BOE núm. 208, 30.08.1997, pág.:26028 -26032) Council Directive 96/23/EC is transposed into Spanish national legislation by means of the following: Real Decreto 1749/1998, de 31 de julio, por el que se establecen las medidas de control aplicables a determinadas sustancias y sus residuos en los animales vivos y sus productos (BOE núm. 188, 07.08.1998, pág.: 26910 - 26927) Council Directive 90/167/EEC is transposed into Spanish national legislation by means of the following: Real Decreto 157/1995, de 3 de febrero, por el que se establecen las condiciones de preparación, de puesta en el mercado y de utilización de los piensos medicamentosos (BOE núm. 64, 16.03.95, pág.: 8392-8399) Although Regulation (EC) 1831/2003 is directly applicable and does not come into effect until October 2004, the following Spanish legislation is the transposition of Directive 70/524/EEC, as amended by Directive 96/51/EC: Real Decreto 2599/1998, de 4 de diciembre, sobre los aditivos en los alimentos de los animales y que constituye la incorporación de la Directiva 96/51/CE, de 23 de julio de 1996 por la que se modifica la Directiva 70/524/CEE sobre los aditivos en la alimentación animal Council Directive 2001/82/EC is transposed into Spanish national legislation by means of the following: Real Decreto 109/1995, de 27 de enero, sobre medicamentos veterinarios (BOE núm. 53, 03.03.1995, pág. 7353-7410) Council Directives 86/363/EEC and 200/42/EC are transposed into Spanish national legislation by means of the following: Real Decreto 569/1990, de 27 de abril, relativo a la fijación de contenidos máximos para los residuos de plaguicidas sobre y en los productos alimenticios de origen animal (BOE núm. 111, 09.05.1990, pág.:12398-12399) PRE/3107/2002, de 5 de diciembre, por la que se modifican los Anexos II de los reales decretos 280/1994, de 18 de febrero y 569/1990, de 27 de abril por la que se establecen los límites máximos de residuos de plaguicidas y su control en determinados productos de origen vegetal y animal. (BOE núm. 296, 11.12.2002, pág. 43005-43017) Commission Directive 2002/63/EC is transposed into Spanish national legislation by means of the following: Real Decreto 290/2003, de 7 de marzo, por el que se establecen los métodos de muestreo para le control de residuos de plaguicidas en los productos de origen vegetal y animal (BOE núm. 58, 08.03.2003, pág. 9299-9308) Regulation (EC) 726/2004 and Directive 2001/82/EC of the European Parliament and of the Council are transposed into Spanish national legislation by means of the following: Ley 25/1990, de 20 de diciembre, del Medicamento (BOE núm. 306, 22 .12.1990) Real Decreto 109/95, de 27 de enero, sobre medicamentos veterinario (BOE núm53, 03.03.1995, pág. 7353-7411) y modificado por el RD 1470/2001 (BOE número311, 18.12.2001, pág. 50004-5006) Commission Directive 2001/22/EC is transposed into Spanish national legislation by means of the following: Real Decreto 256/2003, 28 de febrero, por el que se fijan los métodos de toma de muestras y de análisis para le control oficial del contenido máximo de plomo, cadmio, mercurio y 3-MCPD en los productos alimenticios (BOE núm. 01.03.2003, pág. 8258-8261) Decisions 93/351/EEC and 90/515/EEC, and Council Directive 85/591/EEC, are transposed into Spanish national legislation by means of the following: ORDEN de 2 de agosto de 1991 por la que se aprueban las normas microbiológicas, los límites de contenido en metales pesados y los métodos analíticos para la determinación de metales pesados para los productos de la pesca y de la acuicultura (BOE núm. 195, 15.08.1991)

final report of a mission carried out in spain from 15 to

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