3.6 Compatibility:
3.2.P.2.6 The compatibility of the FPP with reconstitution diluent(s) or dosage devices (e.g. precipitation of API in solution, sorption on injection vessels, stability) should be addressed to provide appropriate and supportive information for the labeling.
Where a device is required for oral liquids or solids (e.g. solutions, emulsions, suspensions and powders or granules for reconstitution), which are intended to be administered immediately after being added to the device, the compatibility studies mentioned in the following paragraphs are not required.
Where sterile, reconstituted products are to be further diluted, compatibility will have to be demonstrated with all diluents over the range of dilution proposed in the labeling. These studies should preferably be conducted on aged samples. Where the labeling does not specify the type of containers,
compatibility (with respect to parameters such as appearance, pH, assay, levels of individual and total degradation products, subvisible particulate matter and extractables from the packaging components) should be demonstrated in glass, PVC and polyolefin containers. However, if one or more containers are identified in the labeling, compatibility of admixtures needs to be demonstrated only in the
specified containers.
In the case of infusion sets where a product formulation is added to an infusion vehicle in an intravenous administration set (giving set) immediately prior to administration, the following data would be required:
■ Physical and chemical stability data for the prepared infusion to
support the claimed in-use shelf-life and storage conditions;
■ Compatibility data to support the claimed in-use shelf-life and storage
conditions;
■ Specification control and secure sourcing of all giving set contact
materials.
Studies are usually required to cover the duration of storage reported in the labeling (e.g. 24 hours under controlled room temperature and 72 hours under refrigeration). Where the labeling specifies co-administration with other FPPs, compatibility should be demonstrated with respect to the principal FPP
as well as the co-administered FPP (i.e. in addition to the other, aforementioned parameters for the mixture, the assay and degradation levels of each co-administered FPP should be reported).
In some cases when a pharmaceutical product is developed for global marketing there may also be a need to consider alternative diluents or liquids for dispersion and/or in-use reconstitution for a product, and compatibility with these diluents or liquids may be required to be established.
Pharmaceutical Development of Multi source (generic) Finished Pharmaceutical Products – points to consider, (Annex 3, WHO Technical Report Series 970, 2012)
