Package integrity evaluation

Sterile Product Packaging—Integrity Evaluation (1207), USP 29-NF 24 United States Pharmacopeia Rockville, MD, 2006 3035-3037. 

This review is necessarily selective, and is divided into several sections. Initially we give an overview of the availability of supercomputers in the U.K., and summarise the experience gained in the implementation of various quantum chemistry packages. Optimization of Quantum Chemistry codes on the CRAY-1 is considered, with integral evaluation, self-consistent-field and integral transformation phases of quantum chemical studies being considered together with some aspects of the correlation problem. 

There was also the development of a vectorised version of GAMESS, implemented on the CRAY by Martyn Guest, that provided an outstandingly flexible and efficient package for LCAO-MO-SCF work in which the integral evaluation code went about 20 times as fast as it did on the IBM 360/195. For a time then, the UK was ahead of the field, for these kind of speeds could simply not be matched on minis (not even on the very popular VAX machines) that had been opted for by so many workers in the United States. Of course this did not last, for there was a rapid development of supercomputer centres in the United States funded by both Federal and State resources. On the whole, the United States machines had much larger fast-store than did the UK machines and so the United States workers again drew ahead in full Cl calculations. The work of Charlie Bauschlicher at NASA Ames on the CRAY-2 exemplifies this trend. ... 

Physical Test Methods. Some of the physical test methods have been available for many years as published ASTM standards. Recently, industry has taken a closer look at the validity and effectiveness of these methods and has developed new methods for evaluating package integrity. 

Figure 44 Package constructions used to evaluate the thermal transfer properties of the die attachment materials and substrates. TO-3 steel package is composed of steel case la, OFHC copper 2a, nickel film 3, soft solder 4a, and integrated circuit 5. TO-3 aluminium package is formed of aluminium header lb plated with nickel 3 on the top of which a silver-filled epoxy adhesive 4b is employed to bond the semiconductor device 5. The 24-lead CERDIP package is based on nickel-plated alumina substrate Ic with soft solder bonded silicon chips. In 40-lead plastic package, integrated circuits 5 are bonded to leadframes 2b by using silver-filled epoxy adhesive 4b and then encapsulated in moulding...

Tools developed in the previous section will be utilized to analyze some of the different integral evaluation schemes. The mathematics, however, stops at this point, or as Boys states after having the analytic expressions for the simplest ERI ... we can easily derive the formulae for the general class. .. . From this point onwards the principal matter is to make the most efficient use of the tools as possible. The methods covered will involve most of those available in the standard quantum chemistry packages today. The Pople-Hehre method is included for historical reasons as it constituted the first efficient integral code. The early versions of GAUSSIAN owe much of their success to this integral evaluation scheme. 

Some of the integral packages and the techniques used to evaluate the integrals are described in ... 

In fact, the Coulomb integrals discussed in Section IV.C are available in contemporary quantum chemistry packages. We do not really need to develop our own method to calculate them. However, it is necessary to master the algebra so that we can calculate the matrix elements of the derivatives of the Coulomb potential. In the following, we shall demonstrate the evaluation of these matrix elements. 

Production Test. In a small-scale production test, tinplate containers with two commercially available enamels and two end-sealing compounds, which were selected from the results of this study, performed satisfactorily when packed with beef and ham. Beef was irradiated with 4.5-5.6 Mrad at 5, —30, and —90°C ham was irradiated with 3-4 Mrad and 6-7.5 Mrad at —30°C. For this production test, beef and ham were packaged in round tinplate containers and ham in Pullman tinplate containers, frozen and refrigerated products were shipped 1,200 miles by truck, and were gamma irradiated at various doses and temperatures. Irradiated products were shipped 1,200 miles in a non-refrigerated truck and stored at selected temperatures and humidities. The integrity of the cans was evaluated after storage for 10 days, 3 months, and 6 months. 

These objective, quantitative tests have shown that nitrile containers should protect the taste and odor of packaged foods and beverages. But the primary consideration in judging overall package performance, once safety is assured, rests on the subjective evaluations of taste, odor, and appearance. It is well known that the animal senses, in many instances, are far more sensitive than the best instruments and also are capable of integrating the individual effects of the several influences on product quality. 

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