Method development report

The following information should generally be included in the dissolution method development report for solid oral dosage forms ... 

If USP and/or FDA methods are not available, the dissolution method development report described above should be submitted. 

At this stage in the development of a V-TR AP method, the method is expected to meet the requirements of the proposed testing laboratory. The method should be efficient and practical reagents, standards, and necessary equipment should be readily available to the testing laboratory. In addition, the validation documentation should be completed and approved along with a background method development report. 

Method development report. The report should review the method development and provide some justification for the choice of key operational parameters and choice of related compounds for purity methods. 

The value of a method development report (in addition to the validation report) cannot be stressed enough. Such a report can allow future users of the method to efficiently review the work that was done and serve as a starting point for future development (for example, life-cycle development) or redevelopment. In addition, if a related compound comes into development, the method development report can provide useful information that may assist in method development for the new project. 

The validation documentation typically consists of a protocol, analytical data, and a final report. One approach to simplifying validation documentation is to focus on a thorough protocol with preapproved acceptance criteria, which are necessary to determine whether the validation results demonstrate that the method is fit for purpose. In early development, this protocol may be captured in a lab notebook which could be in either a paper or an electronic environment. There is an ever increasing trend in the use of electronic laboratory notebooks which makes it simple to execute previously developed protocols. Later in development, the protocol should be a unique document, which may have data tables to enter the test results, requiring only a short executive summary to summarize the results and a reference or attachment of raw data. A development lab will often use these well-developed and optimized master method validation protocols" " as templates for subsequent validations. A copy of the method procedure and, where available, a method development report may be appended to the validation protocol. In general, the validation protocol should contain the following ... 

Includes review of procedures, validation reports, method development reports, and specrfications. 

Developing a meaningful method for reporting an experiment s result requires the ability to predict the true central value and true spread of the population under investigation from a limited sampling of that population. In this section we will take a quantitative look at how individual measurements and results are distributed around a central value. 

Method Transfer. Method transfer involves the implementation of a method developed at another laboratory. Typically the method is prepared in an analytical R D department and then transferred to quahty control at the plant. Method transfer demonstrates that the test method, as mn at the plant, provides results equivalent to that reported in R D. A vaUdated method containing documentation eases the transfer process by providing the recipient lab with detailed method instmctions, accuracy and precision, limits of detection, quantitation, and linearity. 

Nakajima reported the use of a chiral bipyridine N,N -dioxide 18 in the desym-metrization of acyclic meso epoxides (Figure 7.3). Although the enantioselectivity was not as high as in the method developed by Fu for meso-stilbene oxide (90% ee vs. 94% ee), it was higher for the same aliphatic epoxide (74% ee vs. 50% ee) [57]. Nakajima showed that mono-N-oxide derivatives 19 and 20 were much less effective than 18 in tenns of both yield and enantioselectivity, and accordingly proposed a unique mechanism for 18 involving a hexacoordinate silicon intermediate coordinated to both N-oxides of the catalyst. 

A method has been reported for the quantification of five fungicides (shown in Figure 5.39) used to control post-harvest decay in citrus fruits to ensure that unacceptable levels of these are not present in fruit entering the food chain [26]. A survey of the literature showed that previously [27] APCl and electrospray ionization (ESI) had been compared for the analysis of ten pesticides, including two of the five of interest, i.e. carbendazim and thiabendazole, and since it was found that APCl was more sensitive for some of these and had direct flow rate compatibility with the HPLC system being used, APCl was chosen as the basis for method development. 

Research reports—Research reports such as stability reports, method validation and transfer reports, and pharmaceutical development reports are key documents used for NDA/MAA filings. These documents are strictly version controlled. 

Much of the early work with certified reference materials was linked to the derivation of reference methods and there was a period in which primary or definitive (i.e. very accurate but usually very complex) and secondary (or usable) methods were reported e.g. steroid hormones (Siekmann 1979), creatinine (Siekmann 1985), urea (Welch et al. 1984) and nickel (Brown et al. 1981). Although there are some application areas, such as checking the concentrations of preparations listed in a pharmacopoeia, where a prescribed, defined method has to be used, in practice such work is limited. However, this approach to chemical analysis is no longer widely used and will not be further discussed. The emphasis now is placed on using RMs to demonstrate that a method in use meets analytical criteria or targets deemed to be appropriate for the application and to develop figures of merit (Delves 1984). 

The prerequisite that the laboratory chosen to conduct the ILV trials must not be involved in the method development and/or in its subsequent use is not applicable for multi-methods. If the applicability of a multi-method is published in an official manual, an ILV is not obligatory for this particular a.i. ILV is always required for single methods. Communications between the chosen laboratory and the method developers must be reported, provided that these communications were required to carry out the analysis successfully. Also, any subsequent amendments or modifications to the original method must be reported. Furthermore, the ILV report must contain a statement as to the applicability of the method. In contrast, it is not necessary to confirm fhe resulfs of fhe enforcement methods for soil, water, body fluids, tissues, and air by an independent laboratory validation. 

A plefhora of methods developed for the determination of triazine compounds in water, soil, crops, biological fluids, etc., have been reported in the literature, and several excellent reviews are available for the interested reader. " More method papers are published on the determination of triazines in water than for all other sample matrices combined (water > soil > crop). The majority of the water method reports relate to the determination of parent triazine compounds plus compounds from one or more other chemical classes of pesticides (e.g., phenoxy acids, carbamates, pheny-lureas, acetanilides, acetamides, organophosphorus compounds, etc.) for generalized multi-residue screening or monitoring purposes. Addressed in other more selective... 

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