Ampoules testing

The Delvotest-P-Multitest is a modification of the original Delvotest-P test (50). This is not an ampoule test but a polystyrene plate-based test with cups similar in principle to the original version. Its main advantage is that it permits up to 96 test cups to be used at one time. Following a collaborative study (51), both tests have been adopted by the Association of Official Analytical Chemists (AOAC) as official tests for the detection of -lactams in milk and milk products. 

A very extensive study of xanthan stability at elevated temperatures was carried out by Seright and Henrici (1986). They developed ampoule tests in which undetectable levels of dissolved oxygen could be established (less than 2 ppb). A range of experiments were carried out to examine the relative importance of different pathways for xanthan degradation, including... 

Each interferon preparation was ultracentrifuged at 20,000 revolutions per minute for one hour to remove tissue debris and inactivated virus. The supernatant was dialyzed against distilled water (1 400) for 24 hours at4°C. The material was then freeze-dried. The dried product was reconstituted in one-tenth of the original volume in distilled water and dispensed into ampoules. Reconstituted solutions were assayed for interferon activity, examined for toxicity, and tested for sterility. 

Once a suitable strain is available, the prachce is to grow, often ftom a single organism, a sizeable culture which is distributed in small amounts in a large number of ampoules and then stored at 70°C or freeze-dried. This is the seed lot. From this seed lot, one or more ampoules are taken and used as the seed to originate a limited number of batches of vaccine which are first examined exhaustively in the laboratory and then, if found to be satisfactory, tested for safety and efficacy in clinical trials. Satisfactory results in the clinical trials validate the seed lot as the seed from which batches of vaccine for routine use can subsequently be produced. 

Adiabatic calorimetry. Dewar tests are carried out at atmospheric and elevated pressure. Sealed ampoules, Dewars with mixing, isothermal calorimeters, etc. can be used. Temperature and pressure are measured as a function of time. From these data rates of temperature and pressure rises as well as the adiabatic temperature ri.se may be determined. If the log p versus UT graph is a straight line, this is likely to be the vapour pressure. If the graph is curved, decomposition reactions should be considered. Typical temperature-time curves obtained from Dewar flask experiments are shown in Fig. 5.4-60. The adiabatic induction time can be evaluated as a function of the initial temperature and as a function of the temperature at which the induction time, tmi, exceeds a specified value. 

The quantity requested should be sufficient to allow for all the pre-testing required and the preparation of a stock of vials or ampoules which will last for several years. 

Implementation of this procedure precludes the necessity of giving expiry dates for these substances. However, no studies are undertaken to test the stability of the substance in opened vials or ampoules nor the substances in solution. Users of reference substances should not store solutions of chemical reference substances or opened vials. 

Sample Preparation. Liquid crystalline phases, i.e. cubic and lamellar phases, were prepared by weighing the components in stoppered test tubes or into glass ampoules (which were flame-sealed). Water soluble substances were added to the system as water solutions. The hydrophobic substances were dissolved in ethanol together with MO, and the ethanol was then removed under reduced pressure. The mixing of water and MO solutions were made at about 40 C, by adding the MO solution dropwise. The samples for the in vivo study were made under aseptic conditions. The tubes and ampoules were allowed to equilibrate for typically five days in the dark at room temperature. The phases formed were examined by visual inspection using crossed polarizers. The compositions for all the samples used in this work are given in Tables II and III. 

Process controls include daily testing of water for injection (USP), conformation of fill doses and yields, checking and approving intermediate production tickets, and checking label identity and count. Finished product control includes all the tests necessary to ensure the potency, purity, and identity of the product. Parenteral products require additional tests, which include those for sterility, pyrogens, clarity, and particulate analysis, and for glass-sealed ampoules, leaker testing. 

The interpretation of sterility results is divided into two stages by the USP relative to the type of sterility failure if one occurs. If sterility failure of the test samples occurred because of improper aseptic technique or as a fault of the test itself, stage 1 may be repeated with the same sample size. Sample size is doubled in a stage 2 testing, which is performed if microbial growth is observed in stage 1 and there is no reason to believe that the test was invalid. The only absolute method to guarantee the sterility of a batch would be to test every vial or ampoule. 

Ampoules that have been sealed by fusion must be tested to ensure that a hermetic seal was obtained. The leaker test is performed by immersing the ampoules in a dye solution, such as 1% methylene blue, and applying at least 25 in. (64 cm) of vacuum for a minimum of 15 minutes. The vacuum on the tank is then released as rapidly as possible to put maximum stress on weak seals. Next, the ampoules are washed. Defective ampoules will contain blue solution. 

The ampouled solid exploded violently on melting. Distillation at ambient pressure and impact tests had not previously indicated instability. 

Certain equipment configurations allow for the use of Dewar flask testing at elevated pressures. Several arrangements have proved successful such as a sealed glass ampoule in the Dewar flask, a steel pressure vessel in the flask, a Dewar flask in an autoclave under inert gas pressure, and a stainless steel Dewar flask. Dewar flasks provided with an addition line can also be used to study chemical reactions. In Figure 2.21, typical temperature-time curves of Dewar flask experiments are shown. 

This reaction was therefore negligible when C6D12/Zn(CH3)2 = 13. The rates of reactions (1) and (14) are strongly dependent on the nature of the surface. In an ampoule coated with tar from decomposition of a large quantity of dimethyl zinc, the rate of both reactions is only J-i the rate observed in unconditioned vessels (tested at 348 °C with fraction Zn(CH3)2 reacted in conditioned vessel = 0.035). It has also been shown that in 90 min at 290 °C, the overall decomposition of dimethyl zinc in the absence of cyclohexane is 94 % complete if a zinc oxide surface is used, but only 4.5 % complete in a conditioned vessel. Decompositions carried out in conditioned vessels were assumed to be homogeneous. 

The performance qualihcation of vial/ampoule washer is to be performed on all sizes of vials/ampoules. The tests are to be performed on X ml vial/ampoules size for pyroburden analysis on washed vials/ampoules, particulate reduction challenge test on washed vials/ampoules, and soil test to ensure vial/ampoule washer efficacy. 

This test is to assess the efficacy of the vial/ampoule washer in producing washed vials/ampoules that have low pyroburden. The X ml vials/ampoules are to be washed according to the operational parameters described for each vial/ampoule size. The results of endotoxin for each vial/ampoule size are to be entered in Table 1. 

Pyrogen Test No. of Vials Acceptance Criteria X ml Vials/Ampoules... 

This test is to assess the efficacy of the vial/ampoule washer in reducing the particulate level in contaminated vials. Particulate matter to be determined in eight vials/ampoules, each spiked with approximately 500 particles of 40- im glass beads. A sample is to be taken from each individual needle at the end of vial/ampoule washing at set operational parameter of vial/ampoule washer and analyzed to determine the reduction in particulate level. The X ml vials/ampoules are to be washed according to the operational parameters described for each vial/ampoule size. The results are to be compared with negative and positive controls. The test results for each size of vial/ampoule are to be entered in Table 2. 

In the three studies performed on vial/ampoule washer using X ml size, the vial/ampoule washer should meet soil test acceptance criterion, i.e., negative (free from precipitates). 

The sterile solutions are filled in different sizes of ampoules/vials under aseptic conditions. For this purpose, all operations and conditions require validation according to the approved protocols and subsequent requalification on an annual basis by one heat penetration study and microbial challenge test using a B. stearothermophilus strip. 

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