Shelf-life limits

In contrast to the extreme reactivity of the monomeric PX (1) generated from it, the dimer DPX (3) feedstock for the parylene process is an exceptionally stable compound. Because of their chemical inertness, dimers in general do not exhibit shelf-life limitations. Although a variety of substituted dimers are known in the Hterature, at present only three are commercially available DPXN, DPXC, and DPXD, which give rise to Parylene N, Parylene C, and Parylene D, respectively. 

The total exclusion of air from vessels and equipment containing peroxide formers, and the establishment and observing of strict shelf life limitations, are basic strategies for managing peroxide-forming hazards. 

Loucas et al. studied the stability of procaine hydrochloride in a buffered cardioplegic solution [154]. The time required for procaine to degrade to the lower shelf-life limit of 90% of its initial concentration was extrapolated to be approximately two days at room temperature, and eleven days under refrigeration. 

CuDAL Approach. The CuDAL approach is specifically written for tablets or capsules. This approach is recommended in the PDA paper [1] for final product testing. For content uniformity, when the potency limits are not symmetrical about 100% of label claim, the USP 25 content uniformity test allows the individual results to be expressed as either a percentage of the label claim, the found mean, or the average of the upper and lower potency specifications, depending on the value of the sample mean. Acceptance limits have not been constructed for the more complicated situation in which the potency shelf life limits are not symmetric about 100%. One approach to this problem is to evaluate the content uniformity results twice. First express the sample mean as a percentage of label claim and then express the mean as a percentage of the average of the potency specifications. To pass the acceptance limits, both means must meet the acceptance criteria. To use the dissolution acceptance limit tables, the value of Q is required. 

Simulation. One approach is to assume the sample mean and standard deviation are the true population mean and standard deviation, to provide a best estimate of the true probability of passing. This has the advantage that it can provide estimates of the probability of passing at any stage and can handle the nonsymmetric potency shelf life limits in the content uniformity test. The disadvantage is that it does not provide a bound on the probability with high assurance and is not a function of sample size. It can provide a good summary statistic of the content uniformity data, however. 

The SNS Program ensures that the medical materiel stock is rotated and kept within potency shelf-life limits. This involves quarterly quality assurance/quality control checks on all 12-hour Push Packages, annual 100% inventory of all 12-hour Push Package items, and inspections of environmental conditions, security, and overall package maintenance. 

The concept of release limits versus shelf-life limits may be applied where justified. This concept pertains to the establishment of limits that are tighter for the release than for the shelf life of the DS or DP Examples where this may be applicable... 

Changes in moisture content affect charged species in foods that are not part of the chemical equation, but that may impart their own effects upon reaction rate. Reactions that involve proton and electron transport, which include hydrolysis, Maillard browning, oxidation, and almost every critical shelf-life-limiting reaction in foods, will be affected by the presence of ions. This is part of the theory behind the Debye-Hiickel equation. This model describes the effect of ionic strength on the reaction rate constant in dilute solutions ... 

For first order reactions, the loss of API or formation of degradation product follows a logarithmic function, which is different from the linear degradation one expects for zero-order reactions. Similarly, other order reactions will have different functional forms. As it turns out, for the situation of relatively low conversions (as will be the case for shelf-life limitations), the differences between these functions are less significant than they appear at first. This can be seen in Fig. 6.1 for formation of a degradation product (up to 30% of the API). 

Once a set of stability smdies are conducted at elevated temperatures, an Arrhenius plot (i.e.. In k versus 1/T) can be made. This in turn can be used to predict the rate of formation of a degradation product (or loss of starting API) at the storage condition. The shelf-life will then correspond to the time needed to hit the shelf-life limiting level of degradant (loss of starting API) using Equation (6.9) ... 

A mathematical model for deriving specifications based on the manufacturing capability and stability data is given below. The parameters for the shelf-life limits are estimated by the equation... 

LR = Shelf-life limit or Lower registration limit... 

Shelf life limitations that can be controlled by low temperature storage (below 60°F/15°C) of the resin component... 

Shelf life limitation of the resins require refrigerated storage below 60°F/15°C to extend its useful life... 

Long shelf life - limited by slow diffusion of iodine through the electrolyte along grain boundaries. 

The same polyester resins are used to formulate mortars and grouts as are used to formulate monolithic surfacings and polymer concretes. Carbon and silica fillers are used in the formulations. Polyester resins have a shelf life limitation and should be stored below 60 F (15°C). Any of the polyester-type resins provide suitable resistance to normal atmospheric corrosion (see Table 10.3). 

Both manually and automatically activated zinc/silver oxide batteries were developed to meet highly stringent requirements with regard to performance and reliability. The time and temperature of storage prior to use are of importance, and records should be maintained to ensure use within allowable limits. Special care must be exercised to ensure that the proper amount of the specified type of electrolyte is added to each cell of a manual-type battery and that, after activation, the unit is discharged within the shelf-life limitation at the proper temperature. Some battery containers have pressure-relief valves or heaters, or both, and these must be carefully maintained and monitored. 

Shelf life limiting attribute (SLLA) An attribute which will breach its limit when stored at fixed conditions at a point predetermined by CSA (s) (e.g., degradation product... and would be measured on stability). 

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