Reconstitution time testing

Reconstitution time testing. Reconstitution time testing should be provided for all parenteral products that require reconstitution. 

Reconstitute the lyophilized caked powder by adding clear and particulate-free distilled water to the vials one by one. Amount of water to be used should be per the product reconstitution requirement prior to use. Note the reconstitution time for each vial from the addition of water to obtaining a clear solution. Reconstitution time should not be more than the specification limit. Record the reconstitution time on the attached format. Calculate the average. Test should be carried out on 20 vials. Shake to dissolve and check as described in the procedure for visual inspection of solutions. 

Powders for Oral Solutions and Suspensions Water content, reconstitution time, and reconstituted solutions and suspensions should be tested as above for oral solutions and suspensions. 

The design of the validation testing and the composition of the protocol reflect the circumstances under which the study is conducted. For retrospective validation the test may be statistical analysis of batch release data, such as assay, pH, physical appearance, residual moisture, reconstitution time, and constituted solution appearance. This retrospective process validation would be intended to demonstrate that the product is of consistent quality. A critical review of the processing conditions in a retrospective validation may consist of a test comparing actual processing conditions during lyophilization with ideal parameters. This not only shows adherence to the defined processing conditions, but also demonstrates process reproducibility. 

In contrast with routine QC where a very limited number of samples are tested, a large number of product containers of each batch should be tested for critical analytical properties such as assay, activity or bioactivity, purity, degradation products, residual moisture, and reconstitution time. The purpose of extensive testing is to show that each pellet is typical and representative of the rest of the batch, which is a guarantee of product safety and efficacy as the patients are usually injected with the contents of a single container. 

Testing of drug product for reconstitution at dispensing time and reconstituted time. 

Testing of drug products for reconstitution at the time of dispensing (as directed in the labeling) as well as after they are reconstituted. 

The dwell time was 200 msec for the analytes and 100 msec for the IS. At least 500 extracted samples were injected onto each column without any column regeneration. No solvent evaporation and reconstitution steps were involved. Ethyl acetate was preferred over methyl t-butyl ether (MTBE) because MTBE caused pulp-up of the mat. Six blank plasma lots were tested for matrix interference and none was detected in the analyte or IS region. When 100 ng/mL of the analytes were spiked into the blank plasma samples, the relative standard deviations were 1.0 and 1.5% for omeprazole and its metabolite, respectively. Precision and accuracy figures are given in Table 1.9. 

Figure 2 Cytokine gene expression in immunopotentiating reconstituted influenza virosomes (IRIV) stimulated peripheral blood mononuclear cells (PBMC). PBMC were cultured in the presence or absence of IRIV. On days 1 and 2, culture cells were harvested and total cellular RNA was extracted and reverse transcribed. The cDNAs thus obtained were tested in real time polymerase chain reaction assays in the presence of primers specific for the indicated cytokine genes. Source From Refs. 6 and 9.

A few minutes before the end of the incubation time prepare the working solutions The kit contains two working solutions. Solution 1 contains the catalyst. When using the assay kit for the first time, it is necessary to reconstitute the lyophilizate for 10 min by adding 1 mL of aquadeion into bottle 1 and mixing it thoroughly. The reconstituted catalyst may be stored at 4°C for several weeks. Bottle 2 contains the dye solution and is ready to use. To prepare reaction solution for 100 tests, mix 11.25 mL of dye solution (bottle 2) with 250 pL of catalyst (bottle 1). This reaction mixture should not be stored, so prepare it immediately before use (see Note 10). 

Real time stability tests based upon the identity tests for the active ingredient(s), physio-chemical and biological tests nota aggregation, degradation, modifications etc.I Stability of product after reconstitution tests under stress, e.g. heat, light, humidity. 

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