Change control analytical methods validation

The majority of 21 CFR 211.160 (laboratory controls) and subsections can be applied in the same manner for clinical supplies as for commercial products. An exception, in many cases, is the time by which analytical methods validation is required. For new chemical entities or significant formulation changes, new analytical methods may need to be developed. As with manufacturing processes, until such methods are robust it is difficult (or impossible) to validate them to the full extent that is expected for commercial products. 

Approaches to Process Validation Process Validation Program Periodic Review of Validated Systems Cleaning Validation Validation of Analytical methods Change Control, Rejection, and Reuse of Materials Rejection Reprocessing Reworking... 

In practice, the sheer nature of the dynamic validation process results in a substantiation of the original validation throughout the useful life of the method. As previously mentioned, a well-developed and-written method includes system suitability that must be met each time the method is performed. Additionally, the pharmaceutical industry has standardized on the need of formal method transfer exercises whenever an analytical method is to be performed by a different laboratory or in another facility. Also, change control procedures may require the revalidation of part or all of the method in the event of changes to the method, the process, or the formula of a drug product. The QAU should therefore have a system to formally monitor the... 

The corporation must have an SOP that combines the method development and validation activities. Also, SOPs for the preparation of analytical method and validation protocols must stress change control and procedural deviations. The SOPs must allow the analytical chemist to revise methods and protocols to reflect changes encountered during the drug development process. Additionally, an accurate audit trail of changes must exist to track all changes and modifications. 

A stringent change control system must be developed and implemented to provide a complete history of the analytical method and validation protocol. This system must fully document each of the changes made to a method and whether or not the change affects previous validation results. Often the... 

All stability studies on clinical trial materials must be carried out in full accordance with cGMPs, even if a research department carries out the studies. All studies must be carried out by adequately trained personnel under adequate work conditions. The personnel must use properly qualified and calibrated stability chambers, instruments, reagents, and standards. They must follow validated analytical methods and approved written procedures, and they must properly document all work. There must be proper sample and data traceability, change control, and go on. 

As part of the validation procedure, as well as examining such properties as accuracy, precision, linearity, selectivity, we looked for a design that would enable us to verify the ruggedness of the analytical method to minor changes in the operating conditions, and where necessary to identify factors requiring tighter control. 

On the other hand, is it worth fighting for a change of the following well-known and accepted situation A deadline is fixed and therefore a vahdation must be finished in two weeks. Later, the burden of subsequent, substantial costs for a repeat of the measurements, complaints, out-of-spec situations, etc., which inevitably result because an analytical method can hardly be validated within two weeks under real conditions, is not placed on us but on quality control, and as testing costs they have been accepted since decades in the absence of overall considerations. The reader may imagine the consequences, or viewed more positively, the possibilities for improvement. 

Together, these studies contributed to the development of validated procedures to measure brain-tissue levels of endocannabinoids and related lipids. In light of the considerable variability among quantitative regional estimates of endocannabinoids with different sample preparation techniques and analytical methods, assessment of relative changes with intrastudy controls provided the most reliable information on their... 

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. 

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