首页 > 资讯 > 半年之内FDA再次修订帕利哌酮长效注射剂BE指南

出自识林

2016-07-05 Lachman CONSULTANTS

我们之前曾报道过FDA于2015年12月发布对用于肌肉注射的棕榈酸帕利哌酮长效注射剂混悬液生物等效性指南（BE）的修订【识林资讯-FDA修订帕利哌酮长效注射剂BE指南】。FDA于今年6月又发布了另一修订版本（2016年6月修订版草案）。

我们注意到有一些有趣的变化。之前我们介绍过2015年12月的那版BE指南的变化包括使用仅接受稳定156mg药物剂量的患者，而在2016年6月的修订版中，FDA现在建议受试者应包括“患有精神分裂症或分裂情感障碍的，已接受通过肌肉注射的棕榈酸帕利哌酮缓释混悬液稳定方案的男性和非妊娠女性患者。那些已经接受每个月棕榈酸帕利哌酮注射剂任何剂量方案的患者有资格通过继续其已建立的维持剂量参与到研究中。”这里去掉了对156mg药物剂量的要求。

另外，FDA仍不建议在不同的抗精神病药物中使用健康志愿者或受试者。同时为了充分的注射部位代表性以支持研究结果，需要将两个注射部位（臀部和三角肌）纳入研究设计。2016年6月的修订版中，FDA还指出：“所有规格的受试产品需要来自相同的原料药，以便用于在药代动力学BE研究中所有规格的试验。”这意味着原料药悬浮产品必须来自单一批次，分装进不同尺寸的小瓶。

这些要求将如何影响潜在的ANDA申请人尚不清楚。目前该产品还没有列在FDA的第IV段声明数据库中，也就是目前还没有ANDA提交。

Lachman CONSULTANTS - Bob Pollock先生
编译：识林-椒
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Paliperidone Palmitate BE Guidance Revised Again
By Bob Pollock | July 1, 2016 原文地址

Back in January 2016, we posted a blog that described a revision in the bioequivalence (BE) Guidance for Paliperidone Palmitate extended-release suspension for intramuscular use (here). That draft Guidance revision was dated December 2015, just a few months ago. Now another revision takes its place.

Some interesting changes are noted. We reported that the December 2015 changes included using only patients on a stable 156 mg dose of the drug, while in the June 2016 revision, FDA now recommends that subjects should include “male and nonpregnant female patients with schizophrenia or schizoaffective disorder who are already receiving a stable regimen of paliperidone palmitate extended release suspension via the intramuscular route. Patients who are already receiving any dosage regimen of paliperidone palmitate injection every month would be eligible to participate in the study by continuing their established maintenance dose” (emphasis added).

Again, the FDA does not recommend using healthy volunteers or subjects on a different antipsychotic medication, that both injection sites (gluteal and deltoid) be included in the study design. FDA also states that: “All strengths of the test product need to be from the same bulk in order for all strengths of the test to be administered in the PK BE study.” This implies that the bulk suspension product must be from a single lot that was filled into differing vial sizes.

As previously noted, the innovator has submitted a petition requesting certain requirements to establish BE of a test product to their reference listed drug. That link can be found in our previous post above. A copy of the revised June 2016 BE Guidance can be found here. How this will impact potential ANDA applicants is unclear. There is currently no listing on the FDA Paragraph IV database for this product.