Method transfer performance

Structured packings maintain mass-transfer performance with minimum penalty for pressure drop [108]. Two models are presented for calculating pressure drop (1) Bravo-Rocha-Fair [111] and (2) Stichlmair-Bravo-Fair [112]. Each method is qmte involved with rather complex equations to calculate the factor to ultimately calculate a pressure drop. The authors [108] recommend for design using... 

Lin Q, Jiang F, Wang X-Q, Han Z, Tai Y-C, Lew J, Ho C-M (2000) MEMS Thermal Shear-Stress Sensors Experiments, Theory and Modehng, Technical Digest, Solid State Sensors and Actuators Workshop, Hilton Head, SC, 4—8 June 2000, pp 304-307 Lin TY, Yang CY (2007) An experimental investigation of forced convection heat transfer performance in micro-tubes by the method of hquid crystal thermography. Int. J. Heat Mass Transfer 50 4736-4742... 

When the reaction was performed in the microreactor, the maximum conversion of 97.0 % was attained when the flow rate of Boc-AMP solution was 9 ml/min and the molar equivalents of KOH to Boc-AMP was 13 as shown in Fig. 1. Optimum operating conditions were obtained from a statistical method by using factorial design [6]. The yield decreased over the KOH equivalency of 13 in Fig. 1, since the phase separation between the t-Boc20 and the aqueous phase was observed due to the increased water content with increasing KOH equivalency. As the heat transfer performance of the microreactor was greatly improved compared with conventional reactors, higher reaction temperature could be admissible. 

We developed and applied two oxidation methods to lycopene and p-carotene. The first chemical oxidation method was performed in biphasic medium using the potassium permanganate hydrophilic oxidant. Cetyltrimethylammoniumbromide was the phase transfer agent used to achieve contact of the hydrophilic oxidant with the lycopene lipophilic carotenoid dissolved in methylene chloride/toluene (50/50, v/v). 

For any new excipients, APIs or drug products (where new does not necessarily mean novel, but new to the receiving site) there are additional testing criteria, e.g. supplier audits, third-party contract laboratory audits, analytical method transfers, sample management/tracking, etc. For those key excipients, where there is on-site historical experience, it still behoves both parties to check whether the local grade/supplier used by the CMO is equivalent to that used by the supplier (Worsham, 2010). There are many examples of differences in excipient physical properties, e.g. particle size, which have been attributed to different excipient sources that could ultimately impact on the performance of those excipients in formulated products (Frattini and Simioni, 1984 Dansereau and Peck, 1987 Phadke et al., 1994 Lin and Peck, 1994). 

Partial or complete re-validation is another precedented approach to method transfer. Those variables described in method validation guidance documents (ICH Q2B, 1996 USP, 2012c) that are likely to be impacted by method transfer, should be assessed and documented (transfer or validation protocol). Agut et al. (2011) indicated that, in the changing industry model with the increased outsourcing of R and D activities (alliances, outsourcing, etc.), method re-validation may constitute, in some cases, an efficient approach when the transfer is performed from the Analytical Development Laboratory of an external partner who does not share exactly the same environment (validation standards, analytical culture or traditions , equipment, etc.). ... 

On the basis of this risk assessment the transfer strategy is evaluated. For those transfers with lowest risk, method transfer will be limited to simple knowledge transfer as there is no added value in performing any practical transfer exercises i.e. transfer waiver. 

Gradient HPLC No Complex High Receiving site has no familiarity of the compound or method. Transferring site have indicated that resolution of two impurities is critical. Comparable performance... 

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. 

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. 

Once a method has been developed and validated, it should be transferred to each site that intends to use the method. A typical method transfer would take place between the research group that developed and validated the method and the QC group that will use the method to release the finished commercial product, although method transfer may occur at any point where knowledge moves from one group to another. As in the case of method validation, method transfer should be performed under the control of a protocol that details the steps required for the study. 

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. 

Method transfer from development side to a contractor or a production side may be challenging. For HPLC, GC, or IC such transfers are performed permanently and most of the contractors and production sites have expertise in these technologies. In many cases, building up expertise at the production side lab is required for CE. 

Recent results demonstrated the importance of an inter-laboratory comparison in order to ensure a correct method transfer. Earlier inter-company collaborations were performed for small molecules and biomolecules. ... 

HPLC methods can usually be transferred without many modifications, since most commercially available HPLC instruments behave similarly. This is certainly true when the columns applied have a similar selectivity. One adaptation, sometimes needed, concerns the gradient profiles, because of different instrumental or pump dead-volumes. However, larger differences exist between CE instruments, e.g., in hydrodynamic injection procedures, in minimum capillary lengths, in capillary distances to the detector, in cooling mechanisms, and in the injected sample volumes. This makes CE method transfers more difficult. Since robustness tests are performed to avoid transfer problems, these tests seem even more important for CE method validation, than for HPLC method validation. However, in the literature, a robustness test only rarely is included in the validation process of a CE method, and usually only linearity, precision, accuracy, specificity, range, and/or limits of detection and quantification are evaluated. Robustness tests are described in references 20 and 59-92. Given the instrumental transfer problems for CE methods, a robustness test guaranteeing to some extent a successful transfer should include besides the instrument on which the method was developed at least one alternative instrument. 

This chapter sheds light on the different validation requirements and methods to investigate them. Evaluation of the typical validation characteristics, namely accuracy, precision, specificity, DL, QL, linearity, and range in CE, has been discussed in details. Validation in CE is similar to validation in other separation techniques such as HPEC, but in CE, the capillary surface properties and namely the EOF have to be especially addressed. Eurther, the instrument performance has to be carefully considered during validation and method transfer. Here, the condition of the lamp and the thermostating system is of particular importance. 

Reproducibility represents the precision of the method between two or more laboratories and it is typically assessed during method transfer between laboratories, but may be assessed during method validation when more than one laboratory will be performing the method. Reproducibility would also be reported as the SD or RSD value of the mean results between laboratories. These data are not part of the marketing authorization application. 

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