South America's regulatory framework for the control of residues of veterinary drugs.

Adriana Fernández Suárez, Argentina

Foodstuffs obtained from animals treated with veterinary drugs must not contain residues which might constitute a health hazard to the consumer. Countries intending to export foods of animal origin must ensure that their products do not contain residues of banned drugs, or concentrations of legally applied drugs that exceed the MRLs set by the Codex Alimentarius Commission or those set by trading partners.

This paper provides an overview on South America's framework concerning the control of use of veterinary drugs and the monitoring of their residues.

The objectives to assure food safety were initially established in many South American Countries (SACs) upon request of importing countries. The situation varies considerably between the different countries of the region. This is linked mainly to the historical importance of animal food production and of the international trade with these products for their economies.

Three groups can be recognised according to their development in this subject:

1. Argentina and her associates in the MERCOSUR (Common Market of the South that also joins Brazil, Paraguay and Uruguay as members). These four countries are the traditional meat exporters of South America with a total bovine herd of more than 200 million heads. Argentina and Brazil are also the more important food producers of the region.
   
   
2. Chile as a very important commercial partner of MERCOSUR and probably future member. Chile is not a traditional meat exporting country but in the last twenty years has increased considerably the quality and quantity of its food production having now an important international trade of foods (fish, aquaculture, processed and fresh fruits, wines). Chile started recently also negotiations to provide bovine meat to the EU.
   
   
3. Bolivia, Peru, Ecuador, Venezuela, Colombia. These countries are not meat exporters but important exporters of fish and aquaculture products between another foods (coffee, fruits) with the exception of Bolivia that exports agricultural products to another SACs.

Concerning the control of use of veterinary drugs and the monitoring of their residues, the three groups mentioned present considerable differences that are reflected in legislation, priorities, plans and concrete actions to assure animal food safety. Even in the first group, Argentina has the broadest experience as the oldest and largest meat exporting country; Uruguay and Paraguay are also longstanding though smaller exporters whereas Brazil has become a large exporter in the last twenty years only.

Drugs used in food producing animals

Veterinary products use and registration for marketing - Corresponding legislation

Brazil and Argentina are important domestic manufacturers of veterinary drugs, Uruguay only in a small quantity. The rest of SACs import their veterinary products.

At present, all SACs have a national office for the registration of veterinary products. Argentine, Brazil, Uruguay and Chile have well developed registration systems, Bolivia and Colombia have made strong efforts to improve their systems and the other countries still need to improve them.

Historically, three steps may be outlined:

1. Individual actions of each country in order to have its own legislation

The early specific regulations for veterinary drugs were: Argentine: Law 19636 (1949), Uruguay: Law 13640 (1967), Brazil: Decision-Law 467 (1969), Chile: Decision 1391.

2. Common actions in the framework of MERCOSUR

a) Legal guidelines for veterinary products (Resolution 11/93)
b) Veterinary products registration application (Resolution 29/93)
c) Guidelines on legal framework for veterinary products (Resolution 39/96).

After these common actions, member countries adapted their own legislation to this new legal framework and there are ongoing activities in common.

3. Common actions in CAMEVET in the last years.

CAMEVET stands for the Committee of the Americas for Veterinary Medicines that function under the Program of OIE-Americas. It is formed by the representatives of national authorities responsible for veterinary drug registration in Central and South American countries with the full collaboration of FILASA (veterinary industry) and IFAH (veterinary medicine manufacturers). This Committee works since several years and serves as a regional entity that intend to harmonise and update the regulations and regulatory frameworks needed to determine the basic requisites for the registration and the control of veterinary drugs, as well as by the enterprises which produce and commercialise these products. MERCOSUR legal framework is taken into account. At present, CAMEVET achieved harmonisation of registrations of almost 80 veterinary products.

SACs are also represented at the VICH and implement the results of this harmonisation activities. (Harmonisation of technical requirements regarding marketing of veterinary products and development of harmonised guidelines).

Monitoring Veterinary Drugs Residues: Implementation of Residue Control Programs (RCPs) - Corresponding legislation

At present, all the meat exporting SACs to USA and EU must have RCPs.

The first actions in this field have been taken by Argentina that has an experience of more than 30 years of sampling in order to control residues of veterinary drugs and environmental. Part of these controls were not originally conceived as a general plan and the actions were taken when a public health risks were suspected, when claims were made or performed in great proportion by the exporter plants due to the requirements of the importing countries.

1. Since 1979 control programs on residues were put in place by Argentine national authorities and in 1989 were implemented as National Programs extended to plants dedicated to supply foods for local consumers and food importers.
   
   
2. Other MERCOSUR countries have implemented residue control actions too: Uruguay (1978), Brazil (1983) and Paraguay (1992).
   
   
3. Common actions in MERCOSUR to establish technical standards and legal instruments were the followings:

For the Res. No.53/94 the CES (Compound Evaluation System) of the USDA was taken into account: For the Res.No. 75/94, 57/94 and 46/98, the JECFA and Codex Regulations were taken into account. MERCOSUR also takes into account another references (USA and EU legislation)

4. Afterwards, MERCOSUR countries created or adapted their own RCPs based in this legal framework. These last legal instruments are: Argentine (Resolution 215/95), Brazil (Resolution 3/1999), Paraguay (Resolution 702/92), Uruguay (Decision-law 24/998), Chile (Resolution 23/96).
   
   
5. No actions on residue control harmonization have been done in CAMEVET until present.

The SACs that are fish or aquaculture exporters to USA and EU must have RCPs for this kind of foods (Chile, Brazil, Ecuador, and Colombia).

Responsible Authorities: Veterinary Drugs Registration (VDR) and Residue Control Programs (RCPs)

National Residue Control Programs (RCPs)

Notwithstanding the early actions to harmonize residue control between MERCOSUR countries, substantial differences are found at present between the RCPs of member countries partially due to their differences in animal food exportation volumes.

The RCPs contain information on the substances to be analysed, matrices, analytical methodologies, LODs, Action Levels (AL), species sampled, type of food, types of sampling and numbers of annual samples. The AL is the maximum allowed level for a residue compound. If this level is exceeded, corrective actions are taken.

Three types of sampling are applied:

Random Sampling (Monitoring): applied to obtain annual information about presence of residues in food or specific animal populations destined to food production. Based in annual statistics, the application of a surveillance plan is considered for the indicated substances.

Direct Sampling (Surveillance): applied to that substances that may be present at non desired levels in animals or derived food products.

Special Sampling: a country or an important market can request special conditions for the products imported (ex. no anabolics for EU, Plan NOANA in Argentine).

In 2003, the EU approved through the Decision 485/2003/CE the Plan CREHA-Argentine in food animal products exported to UE considering that it presented sufficient guarantees concerning all the foods and animal species indicated. This decision mentioned another countries with plans also approved: Chile, USA and Bulgaria. Recently, the Decision 432/2004/EC ratified the approval for Argentina.

Substances without ADI/MLR

Three groups may be outlined:

1. Veterinary products banned or not authorized for use in food producing animals (nitrofurans, chloramphenicol, Beta-agonists, Stilbenes).
   
   
2. Natural substances without numerical ADI/MRL for being products of metabolism in animal body (natural anabolics as estradiol, testosterone).
   
   
3. Synthetic substances with ADI/MRL that are banned for markets with prohibition of growth promoters (synthetic anabolics as zeranol, trembolone, nandrolone, boldenone and thyrostatics), but authorized for another markets, including internal market.

The requirement of the EU and other markets that animals must not be treated with growth promoters of any type led to the creation of a system where they are controlled as being substances without MRLs (not banned but used under restriction, groups 2 and 3). In Argentine this system has been named NO-ANA (no anabolics).

Anabolics are banned for use as growth promoters in Uruguay, Chile and Paraguay. Because of recent prohibition of anabolics in Argentine whole production (Resolution 447/2004), the system is still being rearranged.

The table presents the data and analytical methods used for residue monitoring of these substances in Argentine, and also the analytical methods, matrices and species sampled for Brazil, Uruguay and Chile (includes fish). Additional data about some non ADI/LMR substances that are controlled in some of the countries are at the bottom of the table (carbadox, malaquite green, gestagenic compounds).

The measures taken to control the use of the substances without ADI/MRL are described for the case of Argentina:

Control of the use of substances of groups 2 and 3 (growth promoters)

- The ALs established are equal to the LODs or to their natural biological levels for the natural anabolics.

- Inscription of farms in the system NOANA (last update Resolution 496/01 and 19/03)

- Monitoring residues in live animals and in animal feed in farms.

- Production systems are under traceability (bovine and poultry production for exportation)

- Classified prescriptions for growth promoters marketing.

In cases of non-compliance:

- Change in the RCP from monitoring sampling to surveillance sampling (see in table cases of estradiol, zeranol, and clenbuterol in bovines in Argentine). Food products are retained for exportation until laboratory results.

- Follow up to farm of origin and enforcement action, legal action prosecution

- Special sampling to the area or farms where the problem has been detected.

Control of the use of substances of groups 1(chloramphenicol, nitrofurans, stilbenes, B-agonists)

- These substances are not authorized for marketing in MERCOSUR countries nor in Chile and also in many SACs.

- The ALs established are equal to the LODs or the MRPLs.

- Monitoring residues in live animals and in animal feed or water for animals.

In cases of non compliance with the regulations, the same measures mentioned before are applied enforced by other complementary actions (improving traceability system, inspection of farms, auditory of banned or unauthorized products, analysis of veterinary drugs used to detect adulterated products, technical advice to producers, checking customs registrations of exportation and importation of drugs and purpose declared, etc).

Residue control of more problematic substances without ADI/MLR (e.g. chloramphenicol and nitrofurans) requires sophisticated analytical technology, in particular LC/MS/MS. Argentina is the only country that has LC/MS/MS equipments available to achieve the MRPLs established by the EU regulations (0.3 ppb) which are mandatory to the SACs exporting to UE. Brazil has less sensitive equipments and Chile and Uruguay have less performance methods.

General requirements of SACs for assuring residue control according to the present regulations are: investment on equipments, acquisition of theoretical knowledge and practical expertise, technical assistance for applying appropriate validation procedures.

Cases of residue detection of substances without ADI/MRL in SACs

April 2002- NFs in poultry and porcine meat from Brazil

April 2002- NFs and CL in prawns and shrimp from Equator

2003- Malaquite green in salmonids from Chile

August 2003- NFs and CLs in honey from Argentine.

An additional paper describes how the events in 2001/2002 affected the international trade of animal derived food from SACs and how the countries have responded to these challenges

Note: The RCPs of Argentine, Brazil, Uruguay and Chile will be available in electronic copies at the Workshop