Shelf life and expiration dates

Most matrix reference materials are regarded stable for their application within a certain time frame see also Section 2.2. They are usually produced in large batches designed to ensure that the same material is available for a number of years as well as to spread the high cost of production over as many units as is possible. The stability is closely monitored from initial production by the producer lot numbers or even individual unit numbers are allocated and the producers closely monitor, by regular analysis, the condition and quality of their reference materials over time. Because of such careful control, and to minimize waste, the tendency has been for producers to give a usable life from receipt to the customer, commonly 12-24 months. However, the producers can give this shelf life expectancy only for unopened units. 

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The effect of the stability data on the retest period, shelf life, and expiration date and recommendations for the storage statement should also be presented and be consistent with stability guidance docmnents relevant to the appropriate regulatory agency. 

However, an understanding of the reaction kinetics in hydrolysis, oxidation, and photodegradation may increase the knowledge of the degradation mechanism and often provide elegant alternatives to prevent instability and an accurate determination of the product shelf life (the expiration date). 

A stability report is written to document the retest period, shelf life or expiration dates, and a storage statement for the registration batches for the formal stability studies. It is also used to document the shelf life for formulations that are being used in the clinic. In this case, the expiration date is generally a date when the product usage should be discontinued or that additional data are required to extend the retest period. A more detailed discussion of the information included in the stability report is given in Section lI.E. 

Limited life items should be identified so as to indicate their useful shelf life. The expiry date should be visible on the container and provisions should be made for such items to be removed from stock when their indicated life has expired. 

Quite often the containers of an adhesive or sealant will bear a special label stating the safe upper limit of temperature during storage. Containers should be checked when received to see if such a label is present. As soon as the container is received, the user should place an additional label on it, stating the date received and the date when the shelf life will expire. This will provide useful information when it comes to scrapping old product or maintaining the freshest product in inventory. A record should also be kept of the manufacturer s lot number for possible future reference. Containers should be kept tightly closed, and labels should be kept clean for proper identification. 

The design of the stability study is to establish, based on testing a minimum of three batches of the drug product, a shelf-life and label storage instructions applicable to all future batches of the dosage form manufactured and packed under similar circumstances. The degree of variability of individual batches affects the confidence that a future production batch will remain within specification until the expiration date. 

The outer packaging was evaluated for the presence of an expiration date, suggesting a remaining shelf life, and the implants were classified as either expired or nonex-pired components. It was unexpected that certain manufacturers would enter components with expired packaging into the survey, especially when it was explicitly framed as a competition for business with a high-volume regional orthopedic hospital. Perhaps these manufacturers considered that their expired implants were expendable and thus only suitable for scientific study. 

Note A new applicator must be used for each test and the test solutions have a specific shelf life and should not be used after the expiration date. 

Stabihty studies ate developed to assure a desirable shelf-life period. These also estabhsh limits of acceptabiUty for impurities and degradation compounds, when present, and determine acceptable storage conditions for raw materials and the manufactured products. Stabihty studies are thus important to the deterrnination of expiration dates for dmg products. 

The statistical interpretations are there is a 5% chance that the extrapolation is below 90% at f = 26 and there is a 5% chance that a further measurement at / = 26 months will yield a result below y 89% of nominal. Every batch in the stability program is subjected to this procedure the batch that yields the shortest shelf-life sets the expiration date. Possible solutions are as follows ... 

Under usual circumstances, most manufactured products require a shelf-life of 2 or more years to ensure their stability at the time of patient consumphon. Commercial products must bear an appropriate expiration date. This date identifies the time during which the product may be expected to maintain its potency and remain stable under the designated storage condihons. The expiration date limits the hme during which the product may be dispensed by the pharmacist or used by the patient. 

Minimum Approach for Multiple Batches When the hypothesis for equality of slopes is rejected at the 0.25 significance level, the minimum approach should be implemented. This is because the degradation lines of individual batches cannot be considered the same since they have different degradation rates. In this situation the FDA guideline establishes that the overall expiration dating period has to ensure that the product will remain within acceptable limits regardless of the batch from which it comes. Thus, the shelf life for each batch is calculated and the expiration dating period is based on the lowest of all shelf lives. Mathematically, this can be expressed as... 

Assuming a common slope and a common intercept for all batches, a single shelf life is computed as the expiration dating period of that package. 

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