Analytical method transfer process

The old adage if it isn t written, it isn t done certainly applies to analytical transfer. The expectation of the health authorities is that a final report will be issued documenting the analytical method transfer process and associated results. Two types of records are subject to PAI Primary records that demonstrate safety, purity, and efficacy of the drug (e.g., batch records, test data) and supporting documentation such as equipment verification records, change control and development and validation reports that demonstrate the cGMP compliance status of the facility. The method transfer report is categorized vmder the latter set of documentation. 

The transfer of analytical methods may be a component of the overall process of technology transfer involving transfer of several methods simultaneously, or it may be limited to transfer of an existing method to qualify an additional testing site (see Chapter 14). In simplest terms, the analytical method transfer is conducted to ensure the following ... 

The process for the transfer of analytical methodology is, on the surface, a relatively simple operation. In its most common form, analytical method transfer is the verification that a method or test procedure works in an equivalent fashion at two or more different sites or laboratories and meets all acceptance criteria. This process is driven by compliance and governed by a statistical treatment of the resulting data. This interlaboratory transfer aspect of the overall transfer process has been covered comprehensively by McGonigle, who stressed that successful transfers are linked to the method validation process. Method transfer was defined in this case as the introduction of a validated method into a designated laboratory so that it can be used in the same capacity for which it was originally developed. The second portion of the technology transfer... 

Both method validation and transfer are important pieces in the drug development puzzle. Without reliable analytical data it is not possible to make informed decisions during product development, and it complicates batch disposition decisions whether for the clinic or the market. Ultimately it is clear that the effort spent on developing and validating robust methods will be time well spent, especially as a product moves through the pipeline toward commercialization. Similarly, the method transfer process should not be seen as a check-the-box activity but rather the transfer of knowledge from a laboratory perspective and an extension of the method development/validation process since the better a method is designed the easier it will likely be for new analysts to perform it well. 

The process for the transfer of analytical methodology is, on the surface, a relatively simple operation. In its most common form, analytical method transfer is the verification that a method or test procedure works in an equivalent fashion... 

This chapter highlights the important aspects of the analytical transfer processes as they relate to process, compliance, analytical data, and documentation. Types of method transfers and the timeline of transfer activities are discussed. The risk assessment prior to initiation of transfer activities is also described. The chapter describes content and utility of the transfer protocol and final report, as well as documents that govern analytical method transfers (i.e., SOPs and master plan). The importance of selecting appropriate method transfer acceptance criteria and use of statistical methods to evaluate results are described. The significance of the inclusion of an adequate level of detail in the methods, protocol(s), and other documents cannot be overly stressed. Last of all, the process for transfer of technical ownership of the analytical methods is discussed. Other chapters in this text should be consulted for elaboration on the various important facets of technical transfer, including method development, method validation, documentation, and stability. 

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. 

Simplified environmental fate estimation procedures are based on the predominant mechanisms of transport within each medium, and they generally disregard intermedia transfer or transformation processes. In general, they produce conservative estimates (i.e., reasonable upper bounds) for final ambient concentrations and the extent of hazardous substance migration. However, caution should be taken to avoid using inappropriate analytical methods that underestimate or overlook significant pathways that affect human health. 

For the equihbrium properties and for the kinetics under quasi-equilibrium conditions for the adsorbate, the transfer matrix technique is a convenient and accurate method to obtain not only the chemical potentials, as a function of coverage and temperature, but all other thermodynamic information, e.g., multiparticle correlators. We emphasize the economy of the computational effort required for the application of the technique. In particular, because it is based on an analytic method it does not suffer from the limitations of time and accuracy inherent in statistical methods such as Monte Carlo simulations. The task of variation of Hamiltonian parameters in the process of fitting a set of experimental data (thermodynamic and... 

Manufacturers publish their product s performance characteristics as specifications, which are often used by the customer for comparison during the selection process. Table 1 shows the specifications of an Agilent 1100 Series Quaternary Pump, which is quite representative of other high-end analytical pumps. Note pulsation is particularly detrimental to the performance of flow-sensitive detectors (e.g., mass spectrometer, refractive index detector). Differences in dwell volumes and composition accuracy between HPLC systems might cause problems during method transfers. 

It is important to include the receiving lab early in the development process of analytical methods. In this way, the receiving lab can provide critical input that may be primordial for a successful application in QC. In return, the receiving lab will be familiarized with the resulting method description and can receive proper training of analysts to perform the method, prior to final validation of the method. As a result method transfer activities are bound to be successful. This concept is essential for new technologies such as CE to be introduced in the QC environment. 

Increases in processor speeds and storage capacity allowed these system to acquire and process data rapidly. Many fourth-generation systems became nodes in laboratory computer UMS networks. They communicate with host computers to receive instructions for analyses and for transferring results. Programs and values of parameters for specific analytical methods can be stored in memory and recalled by the analyst as needed. While the analyst found interaction with these systems easier, he or she became further removed from the system components and often more dependent on the vendor s software. Tailoring requirements to individual user requirements was often not viable with this approach. 

These liner exchange systems make feasible yet another analysis mode direct thermal desorption (DTD). Here the liner or an insert is packed with the solid sample. The liner exchange system can then be used in place of a conventional autosampler. The liner is automatically inserted into the PTV and the volatiles thermally desorbed onto the column. Some analysts may feel uneasy about such desorption from the solid phase how does one know that all of the volatile analytes have been released from the sample crystal lattice However, where applicable, this approach may not be as difficult to validate as one might imagine. For instance, the PTV can be cooled after the analyte transfer, and then, at the end of the chromatographic temperature programme, reheated to repeat the process. Ideally all of the analyte should transfer in the first cycle and none in the second, demonstrating that complete desorption occurs in the method. 

Analytical potency method development should be performed to the extent that it is sufficient for its intended purpose. It is important to understand and know the molecular structure of the analyte during the method development process, as this will facilitate the identification of potential degradation impurities. For example, an impurity of M + 16 in the mass spectrum of a sample may indicate the probability of a nitrogen oxide formation. Upon successful completion of method development, the potency method will then be validated to show proof that it is suitable for its intended purpose. Finally, the method validated will be transferred to the quality control laboratory in preparation for the launch of the drug substance or drug product. 

A pilot production is at about a lOOx level in general, the full scale-batch and the technology transfer at this stage should comprise preformulation information, product development report, and product stability and analytical methods reports. This is the time to finalize the batch production documentation for the lOOx level. The objectives of prevalidation trials at this stage are to qualify and optimize the process in full-scale production equipment and facilities. 

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