內容來源：Julia法規翻譯
Update on the European Pharmacopoeia policy on elemental impurities – Excipients of natural origin
EP元素雜質政策更新—天然來源輔料
European Pharmacopoeia
Ph. Eur. Commission
News
31 March 2020
Strasbourg, France
InJanuary 2017, the EDQM published an update on the European Pharmacopoeia (Ph. Eur.) policy on elemental impurities in which the special case of excipients of natural origin was highlighted. At the time, andbased on feedback gathered from stakeholders during workshops and conferences, the Ph. Eur. Commission decided to make an exception for these substances and keep the specific elemental impurity tests in the corresponding individual monographs. This was considered particularly necessary since the intrinsic nature of elemental impurities in natural-origin excipients is such that they are amongst the major potential sources of elemental impurities in medicinal products. Continued elemental impurity testing was therefore seen as critical to quality control. However, it was also made clear that as new data became available, opportunities for revision of the set of individual metal tests in monographs would be examined. The success of this initiative would be heavily reliant on support from stakeholders.
2017年1月，EDQM發布了EP元素雜質政策更新，其中強調了要將天然來源輔料作為特殊情況。現在，根據培訓和會議期間從干係人處收集的反饋，EP委員會決定將這些物質作為例外，在相應的各論中保留特定的元素雜質檢測。因為天然來源的輔料中固有的元素雜質使得其成為製劑產品中元素雜質的主要來源，因此有必要對其進行特殊考量。鑑於此，對元素雜質進行持續檢測被認為是質量控制所必須的。但是也清楚要求當出現新數據時，會檢查是否需要對各論中的單個金屬檢測系列進行修訂。本提議的成功將很大程度上依賴於干係人的支持。
Since 2017, the group of experts dealing with inorganics– Group 9 – has therefore continued to work on the individual monographs for excipients of natural origin. Their first step was to collect batch data from stakeholders and compare it with the corresponding individual monographs. Each case was scrutinised closely and, where necessary, the individual elemental impurity tests were revised to reflect more closely the actual quality of substances available on the European market. The Group deleted specific elemental impurity tests when the contaminant was found to be process-related or where batch data showed that it was not actually present in the substance. On the other hand, specific tests were kept for elemental impurities that continued to be detected in production batches or were added for any new elemental impurities found. In both cases, appropriate limits were set based on available batch data.
2017年以來，負責無機物的專家組（第9組）一直在開展天然來源輔料各論方面的工作。他們工作的第一步是收集干係人處的批數據，將之與相應的各論進行比較。他們仔細審查了每個各案，必要時對單個元素雜質檢測進行了修訂，以求反映出更接近歐洲市場上現有物質的實際質量。專家組在發現汙染物與工藝有關，或者批數據顯示實際在物質中並不存在時，則會刪除特定的元素雜質檢測。另一方面，保留了在生產批次中一直檢出的元素雜質檢測，或者增加了新發現的元素雜質。這兩種情況下都根據現有批數據設定了適當的限定。
While assessing individual elemental impurities,Group 9 took into consideration the control threshold of 30% of the established permitted daily exposure (PDE) for oral dosage forms laid down in the ICH Q3D guideline. Parenteral intake was considered where appropriate. If batch data showed levels consistently higher than the control threshold, specification limits were either kept or updated in the case of existing elements and introduced in the monograph for new elements.
在評估單個元素雜質時，第9組考慮了ICH Q3D指南中為口服製劑設定PDE值的30%作為控制閾。適當時還考慮了注射給藥。如果批數據顯示雜質水平持續高於控制閾，則要麼保持了標準限度，要麼更新了現有元素，並在各論中引入新元素。
The individual monographs concerned now show atailored list of existing and new elemental impurities (where applicable) together with their limits, to facilitate their control. A certain degree of flexibility in the choice of method to be used has been allowed by including a simple reference to general chapter2.4.20 Determination of elemental impurities.This allows manufacturers to use any method that fulfils the validation requirements described in the general chapter.
相關各論現在顯示的是現有元素雜質和新元素雜質（適用時）的定製清單，以及其限度，以便於對其進行控制。通過簡單引用通則2.4.20「元素雜質檢測」，現在在方法選擇方面允許有一定程度靈活性。這樣生產商可以使用滿足通則中所述驗證要求的任何方法。
When completed, draft revised monographs on excipients of natural origin are published in Pharmeuropa for public consultation. To date, 11 monographs describing new elemental impurities and two showing updated limits for existing impurities have been published. Group 9 still has 17 monographs left on its work programme to be discussed in the framework of the Ph. Eur. policy on elemental impurities.
待修訂後的天然來源輔料各論草案完成時，將會發布在藥典在線公開徵求意見。截止現在，已發布了11篇各論有新的元素雜質，2篇更新了現有雜質的限度。第9組還有17篇各論在其工作計劃中，需要在EP元素雜質政策框架中進行討論。