Eye drops of human origin—Current status and future needs: Report on the workshop organized by the ISBT Working Party for Cellular Therapies

Abstract

Background and Objectives Serum eye drops (SEDs) are used to treat ocular surface disease (OSD) and to promote ocular surface renewal. However, their use and production are not standardized, and several new forms of human eye drops have been developed. Materials and Methods The International Society for Blood Transfusion Working Party (ISBT WP) for Cellular Therapies held a workshop to review the current types of eye drops of human origin (EDHO) status and provide guidance. Results The ISBT WP for Cellular Therapies introduced the new terminology ‘EDHO’ to emphasize that these products are analogous to ‘medical products of human origin’. This concept encompasses their source (serum, platelet lysate, and cord blood) and the increasingly diverse spectrum of clinical usage in ophthalmology and the need for traceability. The workshop identified the wide variability in EDHO manufacturing, lack of harmonized quality and production standards, distribution issues, reimbursement schemes and regulations. EDHO use and efficacy is established for the treatment of OSD, especially for those refractory to conventional treatments. Conclusion Production and distribution of single‐donor donations are cumbersome and complex. The workshop participants agreed that allogeneic EDHO have advantages over autologous EDHO although more data on clinical efficacy and safety are needed. Allogeneic EDHOs enable more efficient production and, when pooled, can provide enhanced standardization for clinical consistency, provided optimal margin of virus safety is ensured. Newer products, including platelet‐lysate‐ and cord‐blood‐derived EDHO, show promise and benefits over SED, but their safety and efficacy are yet to be fully established. This workshop highlighted the need for harmonization of EDHO standards and guidelines.

Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery

“…The first example of a move from an autologous to an allogeneic product is seen with the preparation of serum eye drops (SEDs) and other eye drops of human origin (EDHOs), including HPLs, for treatment of dry-eye syndrome and other ocular surface disorders [ 30 , 31 , 84 , 212 , 213 ]. This situation can be explained by the fact that blood establishments producing SEDs realized the limit and logistical constraints of autologous serum production, and the incapacity of frail patients, or those unable to travel to a blood donation or apheresis center, to donate blood [ 85 ].…”

“…This variability in composition may potentially impact the effectiveness of the resulting treatment. Finally, the volume of blood collected from each individual patient is limited, which can impact the overall cost of the production process, including expenses associated with individual patient’s blood processing, monitoring, and customization [ 31 ]. These reasons make production from allogenic donations more cost-effective and better standardized and compliant with GMPs [ 83 , 86 , 213 ].…”

“…Experimental studies demonstrated the possibility of performing S/D virus inactivation treatment of SEDs without substantially affecting their functional properties [ 215 ]. Further research can be conducted to establish whether any virally inactivated pooled HPLs from outdated PCs can be a therapeutic alternative for treating ocular surface disorders [ 31 , 216 ]. Such research will need to consider various aspects to demonstrate feasibility, efficacy, and safety through well-designed preclinical and clinical studies aiming at assessing the effects on corneal epithelial healing, wound closure, inflammation reduction, and an overall improvement in ocular surface health [ 31 , 217 ], with reference to existing guidelines [ 218 ].…”

“…The successful use of allogeneic PRP has been previously documented in the treatment of chronic skin wounds, diabetic foot ulcers [ 17 , 18 , 25 – 27 ], and osteoarthritis [ 28 ]. Similarly, allogeneic serum has shown therapeutic value for dry eye syndrome and other ocular surface pathologies [ 26 , 29 – 31 ] especially in situations where autologous materials was unsuitable or inconvenient. Notably, there is a growing interest in the use of allogeneic PCs obtained from healthy donors who meet stringent donation criteria and are processed by blood establishments following licensed monitoring procedures adhering to good manufacturing practices (GMPs) principles and meeting consistent quality criteria [ 9 , 32 ].…”

Allogeneic Serum Eye Drops: A Randomized Clinical Trial to Evaluate the Clinical Effectiveness of Two Drop Sizes

“…Allogeneic serum eye drops (SEDs), which are obtained from donor serum, are increasingly being used to treat patients with dry eye disease (DED). Until now, autologous SEDs have mostly been used, but have a number of hindrances with respect to collection, production, and standardization [ 1 , 2 ]. From a clinical perspective, the definition of DED, as formulated by global DED experts is: “Dry eye disease is a multifactorial disease characterized by a persistently unstable and/or deficient tear film causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation, and neurosensory abnormalities” [ 3 ].…”