Background

Since 2009 we provide serum eye drops for the treatment of ocular surface diseases. In Austria serum eye drops are considered as medicinal products, therefore a stability program is mandatory to monitor product compliance with specifications and shelf life. Our stability program consisted in measuring growth factors EGF, PDGF-BB and Fibronectin as surrogate markers. In 2021, total protein was validated and is used since then. In addition, sterility testing is performed on each batch.

Methods

Three batches of serum eye drops are manufactured according to SOP. Serum samples are tested before freezing and then thawed at 3, 6, 9 and 12 months of storage. Growth factors as well as total protein concentration proof the stability of the product, sterility verifies the integrity of the applicators, both are therefore used as quality parameters. Additional in-use stability tests are performed after 3 months of storage and 24 and 48 hours of usage. Growth factors are tested with ELISA, total protein with CMIA. Sterility testing was performed by direct inoculation, changing to BacTAlert 3D mid 2020. A loss of growth factor, respectively total protein concentration of no more than 50% is accepted and sterility testing must be negative.

Results

From 2017 to 2021, EGF and Fibronectin passed the acceptance criteria in the 6 and 12 months testing, for PDGF-BB two results were OOS (-55.9 % and -54.2 % after 12 months). Overall, there are notable batch variations in initial and follow-up growth factor values. In contrast, total protein (in use since 2021) has very stable initial values and a deviation of -5.8 % to 3.0 % for 6 months and -4.2 % to 3.0 % for 12 months storage. Sterility was performed before freezing and after 6 and 12 months and was negative for all batches. In-use stability testing was done at 24 and 48 hours. All results passed the acceptance criteria, except one for sterility where human failure and contamination was likely.

Conclusion

Serum eye drops stability can continuously be demonstrated for 12 months at -20°C. Furthermore, total protein concentration is an efficient and preferable surrogate marker for serum eye drops with minimal deviations. Serum eye drops quality can also be retained in the opened applicator for 24 to even 48 hours at 2-8°C and the application is safe, provided that the patient handles it carefully (e.g. without touching the applicator tip).

Offenlegung Interessenkonflikt:

The authors declare that there is no conflict of interest.