Moeti Lerato, Litedu Madira, Joubert Jacques
South African Health Products Regulatory Authority (SAHPRA), Kirkness Street, Arcadia, Pretoria, 0007, South Africa.
School of Pharmacy, University of the Western Cape, Robert Sobukwe Road, Bellville, Cape Town, 7535, South Africa.
Ther Innov Regul Sci. 2022 Mar;56(2):276-290. doi: 10.1007/s43441-021-00359-9. Epub 2021 Dec 2.
This research study aims to determine the qualitative and quantitative common deficiencies included in the API section of dossiers submitted to SAHPRA. The study was conducted retrospectively over a 7-year period (2011-2017) for non-sterile generic products that were finalised by the Pharmaceutical and Analytical pre-registration Unit. In this period, the restricted part of the CTD was evaluated when needed therefore this was not conducted on all applications. The requirement to evaluate the restricted part for all applications was initiated in January 2020, thus, a separate study has been conducted to identify the common deficiencies in the restricted part.
There were 2089 applications finalised between 2011 and 2017 and in order to attain a representative sample for the study, the multi-stage statistical sampling called the 'stratified systematic sampling' was selected as the method of choice. Sample size was obtained using the statistical tables found in the literature and confirmed by a sample size calculation with a 95% confidence level, resulting in the selection of 325 applications. Subsequently, all the deficiencies were collected and categorised according to CTD subsections. For the restricted part study, all new applications evaluated between January to May 2020 were used.
A total of 1130 deficiencies were collected from 325 applications sampled. The majority of the identified deficiencies were from Module 3.2.S.3.1 (19.38%) on characterisation, Module 3.2.S.1.3 (19.11%) on general properties, Module 3.2.S.4.1 (10.44%) on specifications and Module 3.2.S.4.3 (8.32%) on validation of analytical methods. The study on the restricted parts included the five most common deficiencies that SAHPRA has identified, which are similar to those observed from the 2011-2017 applications. This confirms that the quality of the evaluations has been maintained over the years. Comparison of the deficiencies with those reported by other agencies such as the USFDA, EMA, WHOPQTm and TFDA are discussed with similarities clearly outlined.
The most common deficiencies observed by SAHPRA were extensively discussed. These findings could serve as a guidance for API manufacturers to submit better quality APIMFs which will improve turnaround times for registration and accelerate access to medicines for patients.
本研究旨在确定提交给南非卫生产品监管局（SAHPRA）的档案中原料药（API）部分存在的定性和定量常见缺陷。该研究对制药与分析预注册部门在7年期间（2011 - 2017年）完成的非无菌仿制药产品进行了回顾性研究。在此期间，必要时对CTD的受限部分进行了评估，因此并非对所有申请都进行了此项评估。2020年1月开始要求对所有申请的受限部分进行评估，因此，已开展一项单独研究以确定受限部分的常见缺陷。
2011年至2017年间有2089份申请完成，为获得该研究的代表性样本，选择了称为“分层系统抽样”的多阶段统计抽样作为首选方法。使用文献中的统计表获取样本量，并通过95%置信水平的样本量计算进行确认，最终选择了325份申请。随后，收集所有缺陷并根据CTD子部分进行分类。对于受限部分研究，使用了2020年1月至5月期间评估的所有新申请。
从抽取的325份申请中总共收集到1130个缺陷。所确定的大多数缺陷来自3.2.S.3.1模块（19.38%）的特性描述、3.2.S.1.3模块（19.11%）的一般性质、3.2.S.4.1模块（10.44%）的规格以及3.2.S.4.3模块（8.32%）的分析方法验证。受限部分的研究包括了SAHPRA确定的五个最常见缺陷，这些缺陷与2011 - 2017年申请中观察到的缺陷相似。这证实了多年来评估质量一直得以保持。还讨论了与美国食品药品监督管理局（USFDA）、欧洲药品管理局（EMA）、世界卫生组织预认证计划（WHOPQTm）和台湾食品药品管理局（TFDA）等其他机构报告的缺陷的比较，并清晰地概述了相似之处。
对SAHPRA观察到的最常见缺陷进行了广泛讨论。这些发现可为API制造商提交质量更高的原料药主文件提供指导，这将缩短注册周转时间并加快患者获得药品的速度。
