Method development customers

Ionomer resins are produced in multiple grades to meet market needs, and prospective customers are provided with information on key processing parameters such as melt-flow index. Nominal values for many other properties are Hsted in product brochures. The ASTM test methods developed for general-purpose thermoplastic resins are appHcable to ionomers. No special methods have been introduced specifically for the ionomers. 

Supplier partnerships or alliances have been used to control the cost of procurement. They are based on methods developed in Japan, initially in the automobile industry. These methods have been extended into the process industry and for the purchase of such items as compressor trains. Generally as originally conceived, they were intended mainly for commodity items. By using some innovative approaches, the concept of partnerships or alliances has been extended into the purchase of custom equipment. 

One of the primary requirements for methods is that it be practicable [Section 512(b)(1)(G)]. A method that cannot be used in Federal laboratories has no value in the protection of the food supply. Method developers should avoid the use of rare or custom-made equipment, prohibitively expensive equipment, untested technologies, or reagents that are not commercially available. For a determinative procedure, an analysis should not exceed two working days, and methods should have a minimum sample throughput of at least six samples per analyst-day. 

If no method exists for the analysis required, then either an existing method has to be adapted or a new method developed. The adapted or developed method will need to be optimized and the controls required identified, hence ensuring that the method can be used routinely in the laboratory. Evidence is then collected so as to demonstrate that the method is fit for purpose . The extent of validation, i.e. the amount of effort that needs to be applied, depends on the details of the problem and the information already available. Figure 4.3 indicates an approach that can be used to decide on the extent of validation required. The answer to DQ 4.2 has already mentioned that the customer may request a particular method. If... 

Finally, there are custom two-step quantitation methods such as chromatography or ELISA that require a capture step for isolating the protein and then a quantitation step based on a standard curve of the purified target protein. The preliminary capture step may also concentrate the protein for increased sensitivity. These techniques are typically not available in a commercial kit form and may require extensive method development. They are more labor intensive and complex than the colorimetric or absorbance-based assays. In addition, recovery of the protein from and reproducibility of the capture step complicate validation. Despite these disadvantages, the custom two-step quantitation methods are essential in situations requiring protein specificity. 

The actual Amb a 1 concentration of the extract can be quantitated using a reversed-phase HPLC method developed at Dynavax. This is a custom two-step method that employs chromatography to separate the Amb a 1 from the other extracted proteins. The Amb a 1 concentration is then determined from the resolved Amb a 1 peak area and a standard curve of purified Amb a 1. This is the only step at which the Amb a 1 concentration of the process material is measured by a two-step process. Following the extraction step, the Amb a 1 rapidly becomes enriched over two purification steps, and the Bradford assay adequately reflects Amb a 1 concentration through the remainder of the process. 

It is also useful to assure that internal (company specific) practices are adhered to in method development by making these considerations part of the MDRD. Based on the voice of the customer surveys, several technical and practical method attributes have been identified within our organization. 

While method transfer remains a formal process to demonstrate equal method performance between the development and the application laboratories, the continuous involvement of the customers during method development greatly facilitates the process. The final method is not new for the application laboratories at the time of transfer and the transfer process is not the primary challenge of the method. 

The following considerations, when applied during method development, are likely to produce more robust, reliable, and transferable methods (a) the concerns of the customer (user) are considered in advance, (b) key process input variables are identified, (c) criticaTto-quality factors are determined, (d) several method verification tests are installed, (e) proactive evaluation of method performance during development is performed, (f) continuous customer involvement and focus are institutionalized, and (g) method capability assessment (suitability to be applied for release testing against specification limits) is established. 

All requirements described in the MDR are considered during method development. Either an intuitive or an experimental design approach may be applied when optimizing methods, resulting in an optimal separation of the main compound and all relevant impurities in a reasonable analysis time using typical CE conditions. The development activities are mainly performed by the AD lab (Method Development Phase). Before submitting the method it should be evaluated for robustness and daily lab-to-lab application performance (Method Evaluation Phase). Is the method doable in all the application labs Is the method description acceptable Are all customer needs accounted for ... 

The method development and optimization phase is completed with test method description drafted according to the method development results. The following method evaluation tests will continue with direct involvement of the customer (receiving laboratory). The goal is to check whether the developed late phase method performs adequately in different labs. 

The effort required to get the necessary information can be minimized with careful planning. This is because a particular set of experiments often yields information on several parameters. Some of the parameters may have been determined during the method development stage. The laboratory makes the appropriate decision as to the degree of validation reqtrired taking into accormt the customer s requirements, existing experience in the use of the method and the need for compatibihty with other similar methods already in use within the laboratory or being used by other laboratories. 

Many researchers have put a considerable amount of effort into studies of the chiral recognition mechanisms (using, e.g., NMR and molecular modeling), but yet the choice of chiral selector or chiral phase for a new compound is often based on trial and error. Different strategies for chiral method development have been presented by many of the retailers of chiral columns as a service for the customers. In addition to the information supplied by these retailers, another source of knowledge is Chirbase, a database that contains more than 50,000 HPLC separations of more than 15,000 different chiral substances [61], which also can provide guidance to the analytical chemist. 

Extent of Validation Depends on Type of Method On the one hand, the extent of validation and the choice of performance parameters to be evaluated depend on the status and experience of the analytical method. On the other hand, the validation plan is determined by the analytical requirement(s) as defined on the basis of customer needs or as laid down in regulations. When the method has been fully validated according to an international protocol [63,68] before, the laboratory does not need to conduct extensive in-house validation studies. It must only verify that it can achieve the same performance characteristics as outlined in the collaborative study. As a minimum, precision, bias, linearity, and ruggedness studies should be undertaken. Similar limited vahdation is required in cases where it concerns a fully validated method which is apphed to a new matrix, a well-established but noncol-laboratively studied method, and a scientifically pubhshed method with characteristics given. More profound validation is needed for methods pubhshed as such in the literature, without any characteristic given, and for methods developed in-house [84]. 

The methods developed for the synthesis of ordered mesoporous carbons are simple and cost-efricient, and the pore size can be tailored. The synthesis process can be scaled up for production in bulk quantities. Recent works on the synthesis of mesoporous silicas brought about much improvement in the cost-efficient and custom-tailored synthesis of the templates [18]. The discovery of new mesoporous silicas is also expected to provide additional promising templates for the synthesis of new mesoporous carbons. The resulting high-surface-area materials with uniform pores promise to be suitable as... 

In Part 1 [1] we described a protocol for the evaluation of measurement uncertainty from validation studies such as precision, trueness and ruggedness testing. In this paper we illustrate the application of the protocol to a method developed for the determination of the dyes Cl solvent red 24 and Cl solvent yellow 124, and the chemical marker quinizarin (1,4-dihydroxyanthra-quinone) in road fuel. The analysis of road fuel samples suspected of containing rebated kerosene or rebated gas oil is required as the use of rebated fuels as road fuels or extenders to road fuels is illegal. To prevent illegal use of rebated fuels, HM Customs and Excise require them to be marked. This is achieved by adding solvent red 24, solvent yellow 124 and quinizarin to the fuel. A method for the quantitation of the markers was developed in this laboratory [2]. Over a period of time the method had been adapted to improve its performance and now required re-validation and an uncertainty estimate. This paper describes the experiments under-... 

Customer Evaluation Testing. Customer evaluation testing allows the testing and receiving laboratories (the expected customers) to check whether a method performs adequately for its intended purpose. This evaluation should consider the specific country s compliance requirements with respect to the analytical methods. The customer evaluation permits direct customer feedback to the development lab prior to validation studies. 

Fabrication methods develop working stresses in the equipment which may have to be relieved by heat ireating to impart maximum strength and prevent stress corrosion. A final hydraulic test at two to three times the rated operating pressure, as specified by code or local regulations, must be made before the vessel is delivered to the customer. 

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