目的:血清滴眼液缓解干燥综合征等眼部症状,或慢性移植物抗宿主病。本研究旨在对我们的标准制造进行良好的制造实践验证,自体和同种异体SED的储存和运输过程。缺乏质量参数的规格,旨在定义。
方法:使用无菌收集,凝固的全血,通过离心分离血清并装入一次性滴眼液涂药器小瓶中。质量控制测试包括目视检查,不育,白细胞浓度,pH值,维生素A,TGF-β和VEGF-A。在制造后和冷冻储存(_20°C)24小时和6个月后收集样品。在以规定的间隔打开SED施用器之后进行无菌测试。对于传输验证,将SED包装在绝缘运输袋中,并在20-24°C和30-32°C下储存8小时。
结果:维生素A,TGF-β和VEGF-A测定显示新鲜和24小时冷冻血清之间的浓度没有差异。满足pH(目标7.4)和细胞污染的所有规格,微生物污染测试均为阴性。保质期定义为在-20°C下6个月。一旦打开,产品必须在24小时内使用,以避免细菌生长。证明了在最多4小时内通过当地药房将来自制造商的冷冻SED运输到患者。
结论:我们的生产符合GMP,成功验证了自体和同种异体SED的储存和运输过程.一次性使用的涂药器中的100%血清滴眼液可以在打开后安全使用长达24小时。
OBJECTIVE: Serum eye drops alleviate ocular symptoms of diseases such as sicca syndrome, or chronic graft-versus-host disease. This study was designed for good manufacturing practice validation of our standard manufacturing, storage and transport processes for both autologous and
allogenic SEDs. Specifications of quality parameters are lacking and were aimed to be defined.
METHODS: Using sterile collected, coagulated whole blood, serum was separated by centrifugation and filled into single-use eye drop applicator vials. Quality control tests included visual inspection, sterility, leukocyte concentration, pH, vitamin A, TGF-ß and VEGF-A. Samples were collected after manufacture and after 24 h and 6 months of frozen storage (-20°C). Sterility testing was performed after opening the SED applicators at specified intervals. For transport validation, SEDs were packed in insulated transport bags and stored at 20-24°C and 30-32°C for 8 h.
RESULTS: Vitamin A, TGF-ß and VEGF-A assays showed no difference in concentration between fresh and 24 h frozen serum. All specifications for pH (aim 7.4) and cellular contamination were met and microbiological contamination tests were negative. Shelf-life was defined as 6 months at -20°C. Once opened, the product must be used within 24 h to avoid bacterial outgrowth. Transporting frozen SEDs from the manufacturer via a local pharmacy to the patient within a maximum of 4 h was demonstrated.
CONCLUSIONS: The GMP compliance of our production, storage and transport processes for autologous and
allogenic SEDs was successfully validated. 100% serum eye drops in single-use applicators can be safely used for up to 24 h after opening.