Enforcement analytical methods

Table 4 Validation parameters and criteria appUed for the assessment of enforcement analytical methods...

The QPP has three laboratories the Environmental Chemistry Laboratory (ECL) in Bay St. Louis, MS, and the Analytical Chemistry Laboratory (ACL) and the Microbiology Laboratory at the Environmental Science Center, both at Fort Meade, MD. The ECL is heavily involved with method validation efforts. The ACL evaluates enforcement analytical methods for product chemistry to ensure that the ingredient statements on the label are accurate and evaluates residue analytical methods for... 

Regulation was developed in the 1950s and 1960s to include legal limits (tolerances) for residues on foods and in feeds and, with time, in water and air. Enforcing these regulations required analytical methods of ever-increasing sophistication and... 

Residue analytical methods are needed to enforce these legally based limits or guidance values and to perform monitoring projects. For existing a.i., validated analytical procedures for only a few selected compounds have been published in journals or... 

The purpose of this article is to clarify the assessment of residue analytical methods in the context of Directive 91/414/EEC. After discussing the legal and historical background, requirements for enforcement methods as well as data generation methods are reviewed. Finally, an outlook over further developments in the assessment and validation of analytical methods is provided. 

For certain naturally occurring nontoxic a.i., an enforcement is not sensible (e.g., lecithin, rape seed oil). Analytical methods for residues in soil are not necessary if the DTgo values of the a.i. and relevant metabolites are less than 3 days (e.g., fosetyl), because in general, the results from residue analyses are not meaningful if the a.i. is rapidly degraded. 

The majority of validation data required for analytical methods supporting authorization purposes are common to those described for enforcement methods (see Section 4). However, some of the requirements such as minimum cost and commonly available equipment do not apply to methods supporting pre-registration studies (e.g., the use of GC/MS/MS technology). 

The analytical methods for post-registration control and monitoring purposes submitted by industry to the authorization bodies help the enforcement laboratories. Data requirements from the authorization procedures are constantly compared with the needs of enforcement laboratories, in order to supply them with relevant data, and to avoid the generation of superfluous information. 

Until 1991, manufacturers seeking authorizations for pesticides had to fulfil country-specific requirements of validation of enforcement methods. The term enforcement method means analytical methods which are developed for post-registration control and monitoring purposes. The harmonization of these requirements was initiated with the European Economic Community (EEC) Council Directive 91/414/EEC and temporarily finalized with the Guidance Document on Residue Analytical Methods SANCO/825/00 rev. 6, dated 20 June 2000 [Santd et Protection des Consommateurs (SANCO)]. The evaluation of validation studies by the competent authority is conducted by comparison of these European Union (EU) requirements with the study results and most often without any practical experience of the method. Some details of this evaluation are discussed below. 

As discussed before, the efficiency of the extraction step is one of the fundamental performance characteristics of an analytical method. Unfortunately, the provisions regarding extraction efficiency in Council Directive 91/414/EEC (amended by Directive 96/68/EG) are listed in the metabolism section of the directive (Annex IIA 6.1 and 6.2). Nevertheless, results obtained in these studies are essential for the development of enforcement methods and must be reflected in this context. 

To understand how immunoassay-based analytical methods can be constructed to comply with tolerance enforcement requirements, a brief examination of those requirements is in order. This discussion is not intended to be comprehensive but to highlight aspects of special significance to immunoassay method development. The reader is urged to consult the literature " for further details. 

It is a regulatory requirement that analytical methods be developed to determine residues of concern in crops, feed, and food commodities as well as environmental samples (air, soil, and water). Methods for crops, feed, and food commodities are required for enforcement purposes but are also needed for a variety of other purposes, such as gathering monitoring data for risk assessment. For nearly any purpose, the methods must be robust, that is, when used by different analysts in several laboratories, they should provide reproducibly similar results. 

An analytical method must be properly validated if it is to be used at the national level for enforcement purposes. Validated methods stand on their own merits in contested legal actions in national courts. This situation has been recognized by all nations and international organizations. Initiatives to harmonize method validation criteria and approaches are currently being considered. 

If a pesticide is to be applied to livestock, or will result in residues in the feed of livestock, the possibility of residues in meat, milk, poultry, and eggs arises. Data on metabolism, analytical methods, and level of residue in animal food products are needed in those cases. The same considerations of identification of the terminal residue and developing analytical methods suitable for enforcement mentioned previously also apply to residues in animal products. The tolerances for animal products are based on the tolerances on the animal feed items, the significance of those feed items in the diet of livestock, and the potential... 

Having collected or received samples from each location, each laboratory prepared and analysed the samples in accordance with their own routine analytical methods using their own quality assured procedures i.e. no attempt was made to enforce the use of completely consistent methods or the use of single procedures by both laboratories. All of the samples were analysed by gamma spectrometry. In addition, samples collected at Heysham and Cardiff were analysed for Tc and Total H, respectively. Both laboratories use methods that are acceditated by the United Kingdom Accreditation Service (UKAS) to the 18017025 2005 standard. 

Guidelines on validation of analytical methods implemented. Guidelines on impurities in new drug substances implemented. Guidelines on clinical safety data management enforced. 

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