Sabatini S, Ferguson R M, Helderman J H, Hull A R, Kirkpatrick B S, Barr W H
Texas Tech University Health Sciences Center, Lubbock, USA.
Am J Kidney Dis. 1999 Feb;33(2):389-97. doi: 10.1016/s0272-6386(99)70318-5.
Specific safeguards to guide the approval process and substitution practices for generic immunosuppressive agents are necessary for the effective delivery of patient care. Currently, the Food and Drug Administration (FDA) requires the demonstration of bioequivalence of generic drugs to innovator drugs in normal healthy subjects, a criterion that may be insufficient for critical-dose drugs. For generic equivalents of critical-dose drugs and for innovator critical-dose drugs, there should be a requirement for replicate studies measuring intrasubject variability and subject-treatment interactions to establish that bioequivalence holds true. Extensive testing of generic drugs in all target patient types is impractical and should not be required. However, when evidence suggests that the bioavailability of a critical-dose drug may vary substantially in certain subgroups, the FDA should require a demonstration of bioequivalence of generic versions to innovator products in these representative target populations. Changes in the approval process for generics should be accompanied by more consistent substitution practices. Pharmacists should notify the prescribing physician and patient whenever a critical-dose drug (generic or brand name) is dispensed in a different formulation from the one the patient has been taking. Therapeutic substitution for such drugs should not be made unless the prescribing physician has granted approval. The health care provider should consider instituting appropriate monitoring whenever patients are switched between generic formulations or between innovator drugs and generic formulations. Patients should be well informed about generic substitutes so that they can participate in treatment choices.
为有效提供患者护理，需要有特定的保障措施来指导通用免疫抑制剂的审批流程和替换做法。目前，美国食品药品监督管理局（FDA）要求在正常健康受试者中证明通用药物与创新药物的生物等效性，这一标准对于关键剂量药物可能并不充分。对于关键剂量药物的通用等效物以及创新关键剂量药物，应该要求进行重复研究，测量个体内变异性和个体-治疗相互作用，以确定生物等效性是否成立。在所有目标患者类型中对通用药物进行广泛测试是不切实际的，不应予以要求。然而，当有证据表明关键剂量药物的生物利用度在某些亚组中可能有很大差异时，FDA应要求在这些有代表性的目标人群中证明通用版本与创新产品的生物等效性。通用药物审批流程的变化应伴随着更一致的替换做法。每当为患者配药的剂型与患者一直服用的剂型不同时（无论是通用剂型还是品牌剂型的关键剂量药物），药剂师都应通知开处方的医生和患者。除非开处方的医生已批准，否则不应进行此类药物的治疗性替换。每当患者在通用剂型之间转换，或在创新药物与通用剂型之间转换时，医疗服务提供者应考虑进行适当的监测。应让患者充分了解通用替代药物，以便他们能够参与治疗选择。
