Ensuring Sound Bioanalytical Methods Transfer

Medicilon is the first CRO company to provide a full set of pre-clinical trial services and our company meet chinese GLP a nd the USA GLP standards at the same time.Our company is the only one China CRO company to build cooperation with the foreign large CRO company.Medicilon provides biology, chemistry and preclinical research,our animal experiment facility has won international assessment of experimental animals and recognition(AAALAC) and chinese food and drug administration GLP certificate,and has reached the United States food and frug administration GLP standard.

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The pharmaceutical industry is highly regulated and regulatory authorities normally offer guidance documents that describe best practices for the validation and subsequent application of bioanalytical methods. The fundamental parameters of a method that require being in control include accuracy, precision, selectivity, sensitivity, reproducibility, and stability. The quality of an analytical method is normally assessed by the performance of standards and quality control samples (QCs). Current guidance recommends an acceptance criterion of 15% for accuracy, precision of all standards, and QCs, with the exception of the lower limit of quantitation (LLOQ), where the acceptance criterion is increased to a 20% deviation. However, standards and QCs may not adequately reflect the composition of study samples from dosed subjects (i.e., incurred samples). The limitation of using spiked control samples to assess 'real' samples is known, and there is general acceptance that confirmatory reanalysis of incurred samples can be used to assess the reproducibility of a method.

Method transfers are very common and, in fact, the majority of regulated bioanalysis is now performed at CROs. A method may be validated either in-house or at another CRO company, and because of resource or quality constraints the sponsor might request that a new CRO use the previously validated method with minimal additional work. It is important to note that a regulator expects to be able to verify all aspects of the method validation during an inspection at the site performing regulated bioanalysis. If all raw data generated during method validation are available on-site for review, and the regulator can verify that the original method is being executed in the same validation manner, this would eliminate the need for repeating the method validation at a new CRO company. Unfortunately, it is rare that all raw data are transferred to the receiving CRO, when what typically is provided is only the validation report. Moreover, it is difficult to assure a regulator that the method is being executed in exactly the same manner as might be documented in a validation report. The path of least resistance is to revalidate the method in its entirety to assure that all source records are available in the event of a regulatory audit.

A regulator will also typically require some assessment of comparability between methods, particularly if two or more methods are used within the same study. Comparability can be performed by using samples of known concentration (i.e., QCs and standards), and/ or existing study samples. The acceptance criterion for comparability is commonly 20% relative error for small molecules and 30% for large molecules (e.g., protein therapeutics). BP