Laboratory of Pharmaceutical Technology, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Pharmaceutical Care Unit, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Orphanet J Rare Dis. 2019 Aug 1;14(1):186. doi: 10.1186/s13023-019-1154-x.
Pharmaceutical compounding of orphan active ingredients can offer cost-effective treatment to patients when no other drug product is available for a rare disease or during periods of drug product shortages. Additionally, it allows customized therapy for patients with rare diseases. However, standardized compounding formulas and procedures, and monographs are required to ensure the patients' safety.
Standardized formulas and compounding procedures were developed for seven orphan active ingredients (L-arginine, sodium benzoate, sodium phenylbutyrate, L-carnitine, chenodesoxycholic acid, primaquine phosphate, pyridoxal phosphate) and one non-orphan molecule (sodium perchlorate) regularly compounded by hospital pharmacists for extemporaneous use. The stability of these formulations was evaluated over 3 months at refrigerated (5 °C) and standard storage conditions (25 °C/60%RH) using HPLC-based assays and a suitable shelf life was assigned to the formulations. Additionally, suitable analytical methods for quality control of formulations of pyridoxal phosphate and sodium perchlorate were developed as monographs for these components were not available in the European Pharmacopeia or United States Pharmacopeia.
Availability of compounding formulas and protocols, as well as stability information, for orphan active ingredients can improve patients' access to treatment for rare diseases. Such data were collected for seven orphan active ingredients to treat patients with rare diseases when no other treatment is available. More efforts are needed to develop standardized formulas and compounding procedures for additional orphan active ingredients whose clinical efficacy is well-known but which are not available as products with a marketing authorization. Additionally, a legal framework at EU level is required to enable the full potential of pharmaceutical compounding for orphan active ingredients.
当没有其他药物可用于治疗罕见病或在药物短缺期间时，对孤儿原料药进行药物配制可以为患者提供具有成本效益的治疗方法。此外，它还可以为患有罕见病的患者提供定制疗法。然而，需要标准化的配方和配制程序以及专论来确保患者的安全。
为经常由医院药剂师临时配制的七种孤儿原料药（精氨酸、苯甲酸钠、苯丁酸钠、左旋肉碱、鹅去氧胆酸、磷酸伯氨喹、磷酸吡哆醛）和一种非孤儿分子（高氯酸钠）制定了标准化配方和配制程序。使用基于 HPLC 的测定法在冷藏（5°C）和标准储存条件（25°C/60%RH）下评估了这些制剂的稳定性，为制剂分配了适当的保质期。此外，还为磷酸吡哆醛和高氯酸钠的制剂开发了合适的质量控制分析方法，因为这些成分在欧洲药典或美国药典中都没有专论。
为孤儿原料药提供配制配方和协议以及稳定性信息，可以改善患者获得罕见病治疗的机会。为了在没有其他治疗方法的情况下治疗患有罕见病的患者，收集了针对七种孤儿原料药的此类数据。需要进一步努力制定标准化的配方和配制程序，以满足那些临床疗效明确但没有上市许可产品的其他孤儿原料药的需求。此外，需要在欧盟层面建立法律框架，以充分发挥药物配制在孤儿原料药方面的潜力。
