Products Intended for Storage below

Drug products intended for storage below -20°C should be treated on a case-by-case basis. When available long-term stability data on primary batches do not cover the proposed shelf life granted at the time of approval, a commitment should be made to continue the stability studies postapproval to firmly establish the shelf life. 

Where the submission includes long-term stability data from three production batches covering the proposed shelf life, a postapproval commitment is considered unnecessary. Otherwise, one of the following commitments should be made  

A systematic approach should be adopted in the presentation and evaluation of the stability information, incorporating, as appropriate, results from the physical, chemical, biological, and microbiological tests, including particular attributes of the dosage form (e.g., dissolution rate for solid oral dosage forms). 

The purpose of the stability study is to establish, based on testing a minimum of three batches of the drug product, 

Where the data show so little degradation and so little variability that it is apparent from looking at the data that the requested shelf life will be granted, it is normally unnecessary to go through the formal statistical analysis providing a justification for the omission should be sufficient. 

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Shelf Life Estimation for Drug Substances or Drug Products Intended for Storage below -20°C... 

For drug substances and products intended for storage below -20°C, the retest period or shelf life should be based on the real-time data obtained at the proposed long-term storage condition and should be assessed on a case-by-case basis. 

Data from products intended to be stored in a refrigerator should be assessed according to the same principles described throughout this document for the general case pertaining to products intended for room temperature storage, except where explicitly noted in the section below. A decision tree is provided in Appendix A as an aid to the guidance below. 

Rapid growth of nuclear power has brought to a head the problem of storage and burial of radioactive waste products. Now, more than 250,000 tons of exhausted nuclear fuel has accumulated in the world. In light of this, creation of new radioactive-resistant structural materials intended for protection, storage, and burial of radioactive waste products is necessary. Application of RubCon for protection against radiation in enclosed radioactive waste product storehouses is discussed below. 

The charge is now given a neutralizing wash at 40-50 C with a warm sodium carbonate solution, until alkaline to phenolphthalein. When the nitrobenzene is intended for aniline production, this may be followed by a wash with aniline water from the reducer house if any has to be worked up. Otherwise, a final washing with a small quantity of warm water is made. The nitrobenzene is then delivered to its storage tanks, where it is again settled to remove final traces of water. The crude product can now be distilled for commerce or used directly for the preparation of aniline. In some plants where the nitrobenzene is used almost exclusively in the aniline plant, the neutralizing and subsequent washes are omitted. The nitrobenzene delivered to the reducer houses is consequently acid. No harmful effects on the equipment are noticeable, provided the acidity is kept below 0.5 per cent. 

Development of the Environmental Policy Integrated Climate (EPIC) model and its predecessor, the Erosion Productivity Impact Calculator, began in the early 1980s.69 70 The first version of EPIC was intended to evaluate the effects of wind and water erosion on plant growth and food production. More recent versions also evaluate factors important to other environmental issues. EPIC is a onedimensional model however, it can estimate lateral flow in soil layers at depth. All versions of EPIC estimate surface runoff, PET, AET, soil-water storage, and PRK below the root zone—these complete the hydrologic water balance for an ET landfill cover. 

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