Feasibility study: internal production and controls of autologous serum eyedrops (ASED)

Context
ASED is a magistral preparation derived from human serum, indicated for the long-term treatment of severe keratoconjunctivitis sicca unresponsive to first-line therapies. The ophthalmology department requested the implementation of an internal production process for ASED to treat a cohort of 10 patients.

Objectives
To assess the feasibility of ASED production at our hospital and describe the manufacturing and quality control steps.

Materials and Methods
We first conducted a literature review to evaluate the relevance of ASED, its regulatory status, posology, stability data, and necessary controls.
To draft the manufacturing and quality control procedure, we compared existing ASED production methods and consulted seven hospital centers regarding blood collection and control practices.
Simulations of the process, along with discussions with stakeholders (laboratory, ophthalmologists,technicians…), enabled us to adapt the procedure to our resources.
A media-fill test was conducted to validate the method, alongside a fertility test using the six strains required by test 2.6.1 of the European Pharmacopoeia, inoculated into a separate unit from a fourth series.

Results
Based on our research, we developed a draft operating procedure for producing 24 vials of 5 mL (plus 20 mL for quality controls). A needle-free device will be used to improve operator safety. The additional 20 mL will be used to inoculate two BACTEC® aerobic/anaerobic bottles for routine sterility testing. Three production runs were performed in an isolator as part of the media-fill test, with an average production time of 1 hour and 20 minutes per batch. After 14 days of incubation at 30°C, no signs of bacterial contamination were observed. Additionally, after 72 hours, all six vials inoculated with the six different strains showed macroscopic signs of bacterial growth, while the negative control remained sterile.

Conclusion
The success of our mediafill and fertility test allows us to validate our production method. So, our unit could technically incorporate this kind of production into its activities, allowing patients to benefit from a new therapeutic option close to home.

Discussion
The next step will involve meetings between all stakeholders (laboratory, clinical units, pharmacy department, etc.) to finalize the workflow, with particular attention to establishing a robust traceability system due to the biological origin of the raw material. These meetings will also serve to clearly define the responsibilities of each party involved in the ASED circuit.

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