Products Packaged in Semipermeable Containers

Aqueous-based products packaged in semipermeable containers should be evaluated for potential water loss in addition to physical, chemical, biological, and microbiological stability. This evaluation can be carried out under conditions of low RH, as discussed below. Ultimately, it should be demonstrated that aqueous-based drug products stored in semipermeable containers can withstand low-RH environments (Table 2.5). Other comparable approaches can be developed and reported for nonaqueous, solvent-based products. 

Aqueous-Based Drug Products Stored in Semipermeable Containers 

Minimum Time Period Covered by Data at Submission (months) 

A 5% loss in water from its initial value is considered a significant change for a product packaged in a semipermeable container after an equivalent of 3 months of storage at 40°C and not more than (NMT) 25% RH. However, for small containers (1 mL or less) or unit-dose products, a water loss of 5% or more after an equivalent of 3 months of storage at 40°C and NMT 25% RH may be appropriate if justified. 

An example of an approach for determining water loss follows  

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Marketed Drug Product Packaged in Semipermeable Containers ... 

Laminated aluminum foils are increasingly being used to protect drug products packaged in semipermeable containers (e.g, low-density polyethylene... 

If the drug product is packaged in a semipermeable container, appropriate information should be provided to assess the extent of water loss. Data from refrigerated storage should be assessed according to details given below (Table 2.7). 

For liquid (e.g., solution, suspension, elixir) and semisolid (e.g., creams, ointments) dosage forms in permeable or semipermeable container closure systems, a change to an ink and/or adhesive used on the permeable or semipermeable packaging component to one that has never been used in a CDER-approved product of the same dosage form, same route of administration, and same type of permeable or semipermeable packaging component (e.g., low density polyethylene, polyvinyl chloride). 

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