NHS Blood and Transplant, Liverpool, UK.
BMJ Open Ophthalmol. 2022 Nov;7(Suppl 2):A12. doi: 10.1136/bmjophth-2022-EEBA.28.
NHS Blood and Transplant Tissue and Eye Services (TES) offer a serum eyedrop (SE) service to patients suffering from severe ocular surface disease. SE are prepared from serum collected at blood donation sessions; the serum is diluted 1:1 with physiological saline. Formerly, 3ml aliquots of diluted serum were aliquoted into glass bottles in a Grade B clean room. Since this service was started, Meise Medizintechnik have developed an automatic closed filling system consisting of tubing-linked chains of squeezable vials. They can be heat-sealed closed, under sterile conditions, after the vials have been filled.
TES R&D were asked to validate the Meise system to increase the efficiency and speed of SE production. Validation of the closed system consisted of a process simulation assessment, using bovine serum and simulating each step of the filling process, freezing to -80oC, checking the integrity of each vial and packing the vials into storage containers. They were then put into transport containers and shipped on a round-trip journey to simulate delivery to patients. On return the vials were thawed and the integrity of each vial re-checked visually and by squeezing in a plasma expressor.Subsequently a shelf-life study was carried out on three batches of fully consented human allogeneic SE. The serum was dispensed into vials, frozen as above and stored for set time points 0, 1, 3, 6 and 12 months in a standard domestic freezer set at -15-20oC to mimic a patient's freezer. At each time point, 10 random samples of vials were removed, and the outer containers were tested for damage or deterioration, the vials for integrity and their contents for sterility and stability. Stability was assessed by measuring serum albumin concentrations and sterility by testing for microbial contamination.
No structural damage or leakage was found in any of the vials, or the tubing evaluated, after thawing, at any time point. In addition, all samples tested negative for microbial contamination and serum albumin levels were always within the expected range (3 - 5 Dg/L) at each set time point.
These results demonstrate that Meise closed system vials can successfully dispense SE drops and the vials can be stored frozen without affecting integrity, sterility or stability. These vials have been in use in TES for 3 years saving clean room space and greatly increasing the numbers of patients that can use the SE service.
英国国民保健署（NHS）血液与移植组织和眼部服务（TES）为患有严重眼表疾病的患者提供血清滴眼剂（SE）服务。SE 是从献血时采集的血清中制备的；血清用生理盐水稀释 1:1。以前，将 3ml 等分的稀释血清分装到 B 级洁净室中的玻璃瓶中。自该服务启动以来，Meise Medizintechnik 开发了一种由管连接的可挤压小瓶组成的自动密闭灌装系统。小瓶灌装后可在无菌条件下热封密闭。
TES 研发部门被要求验证 Meise 系统，以提高 SE 生产的效率和速度。密闭系统的验证包括使用牛血清模拟灌装过程的各个步骤，对每个小瓶进行完整性检查，将小瓶冷冻至-80°C，将小瓶包装在储存容器中。然后将小瓶放入运输容器中，进行往返运输模拟，以运送至患者。返回后，小瓶解冻，目视和在等离子体挤出器中挤压检查每个小瓶的完整性。随后，对三批完全同意的同种异体人类 SE 进行了保质期研究。将血清分配到小瓶中，如上所述冷冻，并在设定的时间点 0、1、3、6 和 12 个月在标准家用冰箱中储存，温度设定为-15-20°C，以模拟患者的冰箱。在每个时间点，取出 10 个随机小瓶样本，检查外容器是否损坏或变质，小瓶是否完整，其内容物是否无菌且稳定。稳定性通过测量血清白蛋白浓度来评估，无菌性通过测试微生物污染来评估。
在任何时间点解冻后，均未发现任何小瓶或评估的管有结构损坏或泄漏。此外，所有样本均未检测到微生物污染，且血清白蛋白水平始终在预期范围内（3-5 Dg/L）。
这些结果表明，Meise 密闭系统小瓶可成功分配 SE 滴剂，小瓶可冷冻储存而不影响完整性、无菌性或稳定性。这些小瓶已在 TES 中使用 3 年，节省了洁净室空间，并大大增加了使用 SE 服务的患者数量。
