Reference standards storage/stability

Hodgson DW, J.F. Thompson, Watts, RR. 1982. Accuracy of pesticide reference standard solutions. Part II Chemical stability under four storage conditions. J Assoc Off Anal Chem 65 94-102. 

As it is imperative that the plant-derived hiopharmaceutical product must be obtained repeatedly and on a consistent basis, a master cell culture bank, seed bank for transgenic plants, or virus seed stock for transient expression systems must be constantly maintained. Storage conditions must therefore he optimized to prevent contamination and ensure viability. Both transgene stability (e.g., reversion to wild type or sequence drift of plant virus expression vectors) and protein expression levels must be monitored in a representative plant of a given bank or stock to minimize any possible variation in expression levels that may affect safety and consistency of the hnal product. A program that monitors lot-to-lot consistency of the hiochemical and biological properties by comparing the product with appropriate in-house reference standards could he implemented as a fundamental component of product development. 

Reference Standard and Critical Reagents Source records should document lot numbers, date of receipt or preparation (as appropriate), the identity, purity, and stability at the time of use, expiration date (as applicable), storage location (e.g., equipment identifiers), and temperature conditions. 

A reference standard should be developed and appropriately quahfied for defined physico-chemical characteristics, specificity, and potency [34, 35]. Storage under conditions that maximize stability (e.g., -80 °C as appropriate) and periodic testing will document the reference standard s continued physico-chemical integrity and justify its continued use. The reference standard should be used for lot-to-lot comparisons performed for product release and stability studies [34, 35]. Major manufacturing changes often warrant estabhshment and qualification of new reference standards. 

In terms of residues in food, stability is an important parameter as it relates to (1) residues in biological matrices during storage, (2) analytical reference standards, (3) analytes in specified solvents, (4) samples prepared for residue analysis in an interrupted assay run such as might occur with the breakdown of an analytical instrument, and... 

Method performance in air analysis involves terms such as accuracy, storage stability, capacity, sampling rate, recovery, and sensitivity. To evaluate the performance of a developed method, certified reference materials for particulate matter, such as urban dust SRM 1649a particulate matter from NIST (Gaithersburg, MD, USA) can be purchased. In addition, a standard reference material has been recently developed for the determination of organic compounds in house dust the SRM 2585 is intended for using in method validation for the analysis of PAHs, PCBs, chlorinated pesticides, and PBDEs (Poster et al. 2007). 

A crucial property of the analyte (and thus of the analytical standard) is its stability, both in the purified form and in solution. Relevant information pertaining to the stability of the pure compound, though not necessarily of the compound in solution in the chosen solvent, may be found on the Certificate of Analysis (Sections 2.2.2 and 9.4.4c). In many instances, instead of an expiration date a re-assay date will be provided. An extreme form of instability is the propensity of the analyte to explode or be set afire such properties should be available in the MSDS information and the Certificate of Analysis that should specify the appropriate storage conditions under which the stated expiration or re-assay date is valid. In any event, the reference standard should be stored under the same conditions that were used to establish stabdity and should not be used past the expiration or re-assay date unless other documentation is provided to substantiate the stability of the analyte under the storage conditions used. 

Documentation of preparation of stock and sub-stock solutions must start with receipt of the reference standard, its Certificate of Analysis, assigned purity (and possibly chiral purity) and its history of storage and use after receipt (Section 9.4.4). Procedures for preparation and subsequent dilution of stock solutions are described in Section 9.5.4 and stability testing for these solutions in Section 10.4.Ih. Some of the relevant documentation might be included in general laboratory SOPs but full documentation of all study-specific procedures and data regarding preparation, storage and validation of stock solutions is required. 

For studies of more than four weeks in experimental duration, a reserve sample of each batch of the test, reference (analytical reference standard) and control substance must be retained. As this archive sample may be retained by either the sponsor or the contract facility, the responsibility should be addressed in the protocol. Additionally, a sample of the chemical should be collected prior to each application and immediately frozen for possible analysis for "storage stability of the test, reference and control substance at the test site". If the sponsor s storage stability data are inclusive of the storage conditions recorded at the test site, the GLP requirement will have been met and the above storage stability samples will not have to be analyzed (10). It should be noted that all test substance containers must be retained for the duration of the study i.e., until the study director signs the final report. A conditional exception for disposing of the containers may be obtained by writing to the OCM (11). OCM will set forth certain documentation requirements that will be required to account for the test substance containers. 

For biopharmaceuticals, storage conditions are critical to maintain activity. Normal ICH stability studies are conducted with reference to global climatic zones under standard and accelerated conditions over time periods of up to 5 years. For biopharmaceuticals, this may not be appropriate, and specific coohng conditions (2-8°C, <-20°C) may have to be provided to keep the product intact (see Section 1.4.6). Furthermore, the container and the closure system used for final market presentation (e.g., vial with mbber) must be investigated for interaction potential. Last -but not least - the stability of the reconstituted solution in the case of lyophilisate, or diluted solutions in the case of infusion therapy, must be characterized. 

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