When this is not possible, a pharmacist ideally consults with the manufacturer to establish a beyond use date. This is acceptable since it is not the purpose of an accelerated test to determine batch uniformity but rather to test for kinetic degradation. The Pharmaceutics and Compounding Laboratory. The ability of the product to retain its sterile condition is a function of the container-closure system. This will usually involve high temperature and high humidity.
Because of compelling patient-care needs, a pharmacist may be unable to stay within the approved labeling and product guidelines stated in the package insert. Most pharmacies have the name, address, and phone number of the pharmacy pre-printed on their prescription labels. Some firms have chosen, for economical purposes, random dates to test all stability samples of a given product. If a product was stored under controlled conditions, year 41 those actual conditions temperature and humidity should be recorded. The pharmacist should communicate the deviations from the package insert to the manufacturer when requesting stability information.
This is in contrast to incompatibilities that can be visually observed. It is commonly recommended that stability testing be performed initially, than every three months for the first year, then every six months for the second year, and then annually thereafter. For example, a product liable to degrade by light need not be stored in a lit area if it is normally packaged and stored for use in an opaque container. Beyond use dates are different from expiration dates.
When qualifying the container-closure system, sterility testing should be performed initially and at the end of the expiration dating period. The expiration dating period used would then be the sum of that justified individually at each storage condition. However, reliable, published stability information is sometimes lacking for many types of drugs. Satisfactory comparison of container-closure systems may be done by several methods, i.
In these instances, pharmacists should consult with the drug's manufacturer to establish a beyond use date. Many times the published references do not evaluate exactly the same formulation, or the study did not examine the stability for a long enough period of time. However, the repacker is subject to applicable current good manufacturing practices. However, top dating sites in kenya more frequent testing near the end of the anticipated expiration date is often likely to give better information about the actual stability of the finished product.
When the same product is marketed in more than one size, e. Stability studies should be conducted on product stored under normal storage conditions or, preferably, under exaggerated conditions. The preservative system should be monitored at the same stability testing times as other ingredients are monitored. Information obtained from old stock, not previously the subject of stability studies, may also be utilized.
As long as there is at least one test performed annually, writing the best this approach can be quite satisfactory. This indicates that the smallest marketed container is the most critical in terms of the container properties contributing to product degradation. Products sterilized in glass ampuls need not be subjected to sterility testing as part of the stability testing program. This also does not apply to repacking from bulk containers.
The Pharmaceutics and Compounding Laboratory
- Expiration dates are required on commercially manufactured products and are determined after extensive study of the product's stability.
- When accelerated stability studies are performed, one batch may be adequate in order to establish a tentative expiration date.
- Because of the uniqueness of each drug product, it is virtually impossible to provide one set of rules that can apply to all situations.
U.S. Food and Drug Administration
Once a minimally effective level of preservative is established, chemical testing for the preservative s may be performed. The use of quantitative analysis, where limits are known, such as thin layer chromatography, may be satisfactory. In other words, dating the evidence is not from a product-specific experiment. Beyond use dates are used for compounded preparations and are generally in days or months.
Expiration Dating of USP Reference Standards
The use of accelerated testing data to establish a tentative expiration dating period of greater than three years is discouraged when it is based solely on accelerated data. Most expiration dates are given in years for commercial products. The requirement that stability testing be performed in the same container-closure system as that in which the drug product is marketed has been subject to interpretation.
Expiration Dating and Stability Testing for Human Drug Products
- Beyond use dates should be in accordance with the manufacturer's approved labeling.
- The major problem for pharmacists is that the stability of compounded formulations often is not known.
- The stability indicating test does not have to be the assay method used to determine product strength.
It is not possible to use a manufacturer's expiration date and extrapolate or estimate a beyond use date for a compounded formulation. There must be separate stability studies to support each expiration date. Generally, the placing of three initial batches into the long term stability program is considered minimal to assure batch uniformity for establishing an expiration date. Combining data compiled at room temperature and at accelerated temperature is possible to justify an expiration dating period of over two years.
Likewise, repackers who rely on stability studies performed by the manufacturer must have copies of all analytical data necessary to support the expiration dating period. Products formulated to contain preservatives to inhibit microbial growth should be monitored throughout their shelf life to assure the effectiveness of the preservative system. This can be done, as an example, by taking a sample product that has been at room temperature for one year and subjecting that sample to accelerated temperature conditions.
Based on published information, it appears that C is a reasonable reference for thermal exposure at room temperature. Merely stating that a product was stored at room temperature is not sufficient for purposes of determining stability. Pharmacists should obtain a letter from the manufacturer certifying the beyond use dating period provided. Although specific methods are critical to determine product stability, they do not have to employ any specific technique. Stress testing refers to testing the product after storage under exaggerated conditions.