Product file shelf life

Situation A cream that contains two active compounds was investigated over 24 months (incomplete program if today s ICH standards are applied, which require testing at 0, 3, 6, 9, 12, 18, and 24 months). The assays resulted in the data given in file CREAM.dat. Program SHELFLIFE performs a linear regression on the data and plots the (lower) 90% confidence limit for the regression line. For each full time unit, here months, it is determined whether this CL drops below levels of y = 90% resp. y = 95% of nominal. Health authorities today require adherence to the 90% standard for the end-of-shelf-life test, but it is to be expected that at least for some products the 95% standard will be introduced. 

For products approved globally, API retest period and finished product shelf-life can be extended through a type IB (major) variation. One of the conditions for shelf-life changes is that the change not be due to stability concerns therefore, shortening and then re-extending product shelf-life would need to be filed via a Type II variation. 

C3 Be able to draw up drug-preparation protocols and product files that meet the technical, biopharmaceutical and other relevant quality standards C4 Be able to design, set up and validate (including shelf-life tests) non-sterile, aseptic and sterile preparation processes and implement them... 

For a standardised preparation the product file may be quite extensive. There is need for a more elaborate evaluation of the topics discussed above, and the product file should also include information on the validation of the preparation and on the stability and shelf life of the preparation. The product file of pharmacy preparations that are distributed on a relatively large scale should be the most extensive. The various topics of the product file in its most extensive form will be discussed in detail in the following subsections. At the end of each section an example of 12.5 mg diclofenac suppositories is used, assuming that diclofenac is not available in this strength as licensed medicine. 

This section of the product file should give information about the stability of the product and the choices that have led to its shelf life and the storage conditions. In most cases a shelf life for the unopened package is defined, as well as for the container after opening. Also the storage temperature is specified, and if applicable special conditions, for example protect from light or in a well closed container . 

For infrequently prepared products the analysis of some expired batches may also provide usefiil support for the shelf-hfe of a preparation. A more detailed product file should include data from a thorough stability study. Stability testing should ideally be performed prospectively, but it can also be performed concurrently by following the first batches produced, this can be particularly useful if accelerated storage at an elevated temperature is included in the study. The product shelf life can be increased during the study as more data becomes available. The design of a stability study is described in Sect. 22.5. 

The quality requirements are described in a separate section of the product file. These quality requirements include the specifications during preparation (in process controls), immediately after preparation (release specifications) and that at the end of shelf life of the product (shelf-life specifications). The specifications must be relevant to the respective dosage form and should be chosen in a such a way that they characterise the product quality within strict limits, while simultaneously ensuring that sufficient margin is left so that small batch-dependent variations can be accepted. 

For products described in a pharmacopoeia, the official specifications can and should be used for the product file, with referral to the official source. The same applies to preparations from standard formulatimis, in which quality requirements are included. For in-house formulations, the quality requirements have to be set by an appropriately competent person internally. Useful information can be found in the formulatimi or validatimi studies. The results of stability studies may be useful when setting the quality requirements for the product, because the premise is that a preparation should comply to the quality requirements throughout the whole shelf life. An overview of the applicable quality requirements, including supporting information, has to be included in the product file. In addition it should be specified how the packaging and labelling are checked, and how and with what analytical method the product quality is controlled. Additionally the validation of the analytical methods is included in this section of the product file. 

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