USP通則<711>溶出(out)度試驗更新解讀

2023-04-23 10:28:16

在(exist)2022年11月USP發布的(of)PF48(6)中，對通則<711>進行了(Got it)修訂，經過開放評議後，新修訂的(of)USP<711>通則将會在(exist)2023年5月1日正式生(born)效。

生(born)效後會使用(use)新的(of)标準物質，即USP溶出(out)試驗性能驗證标準物質-潑尼松标準物質（Prednisone RS）取代USP标準物質潑尼松片（USP Prednisone Tablets RS）。同時(hour)與此标準物質相關的(of)《The Dissolution Procedure—Development and Validation ?1092?》也将會一(one)同修訂。

修訂後的(of)通則将使用(use)新的(of)USP溶出(out)試驗性能驗證标準品潑尼松标準物質（DPVS-潑尼松片）取代現有的(of)USP标準物質潑尼松片，用(use)以(by)确認溶出(out)試驗裝置1（籃法）和(and)溶出(out)試驗裝置2（槳法）。


在(exist)此，我(I)們(them)對現階段使用(use)的(of)USP Prednisone Tablets RS及新發布的(of)Prednisone RS做了(Got it)總結對比如下：


01

全新的(of)标準物質與現行标準物質之間的(of)區别

1、全新DPVS-潑尼松片仍然含有潑尼松作(do)爲(for)分析标記物，調整後的(of)形狀爲(for)球體形狀，在(exist)籃法及槳法測試時(hour)能夠始終保持在(exist)容器底部，對儀器設置的(of)操作(do)和(and)機械變量更加敏感。



2、現行的(of)标準物質對介質脫氣較爲(for)敏感，實驗時(hour)溶出(out)介質氧濃度應不(No)超過6ppm（如下圖）。

新的(of)DPVS-潑尼松片标準物質對介質脫氣不(No)那麽敏感，而且可重複性更高。


3、包裝配置也已改變，每盒6片的(of)吸塑包裝被裝在(exist)一(one)個(indivual)鋁袋中，以(by)提供防潮保護。


02

全新的(of)标準物質與現行标準物質之間的(of)區别

目前USP已發布的(of)潑尼松片标準物質批次R154P0，将是(yes)最後一(one)批批次，預計在(exist)2023年4月底停産，其有效使用(use)日期(VUD)爲(for)2023年7月31日。在(exist)新版<711>正式生(born)效後将不(No)能再使用(use)。
1、官方發布的(of)有效使用(use)日期：


2、測試條件及标準：

2、PVT限度值


下表爲(for)Prednisone Tablets RS R154P0批PVT限度值，USP Prednisone Tablets RS每批對應一(one)個(indivual)PVT限度，在(exist)更換批次時(hour)需要(want)注意限度也在(exist)随之改變。

4、标準物質标簽


下圖爲(for)Prednisone Tablets RS Lot：R154P0标簽



03

即将生(born)效的(of)新版标準物質


新版的(of)标準物質已發布，詳細信息如下：


1、新版标準品信息

官方發布的(of)新标準品的(of)第一(one)個(indivual)批次批号爲(for)F161Y0，第一(one)批次的(of)有效使用(use)日期至2024年11月14日：



 2、測試條件及标準：

*如果設備僅專用(use)一(one)種槳法或者籃法，則僅需要(want)對該法設備進行驗證。



3、PVT限度值

下表爲(for)Prednisone RS R161Y0批PVT限度值


通過與Prednisone Tablets RS R154P0批實驗條件及驗證标準對比，PVT程序本身沒有發生(born)變化，新标準物質的(of)GM有所提高，%CV減小，結果将會更穩定。



4、标準物質标簽



下圖爲(for)Prednisone RS Lot：F161Y0标簽



04

其他(he)更新内容

在(exist)修訂版通則<711>正式生(born)效之前，USP對溶出(out)度工具包同時(hour)進行了(Got it)升版，由原來(Come)的(of)2.0升版至3.0，工具包中包含裝置1及裝置2的(of)機械驗證及性能驗證測試程序指南。可複制以(by)下網址進行查看：

static/file/dissolution-toolkit-version3.pdf



05

現在(exist)需要(want)做哪些工作(do)？

現在(exist)官方發布的(of)全新DPVS-潑尼松片标準物質，我(I)們(them)需要(want)詳細閱讀官方發布的(of)常見問答，了(Got it)解在(exist)官方發布修訂的(of)通則<711>生(born)效後是(yes)否需要(want)馬上重新進行性能驗證？全新的(of)标準物質是(yes)否可以(by)立即訂購？同時(hour)需要(want)更新公司内部文件，如溶出(out)儀的(of)性能驗證以(by)及機械驗證的(of)相關文件及記錄，保證在(exist)官方發布後能夠按時(hour)執行。


06

新舊标準物質常見問題的(of)問答

USP-NF對新舊标準物質更替過程中容易出(out)現的(of)一(one)些常見問題發布的(of)問答，詳見如下：
1.Is the new reference standard (USP Dissolution Performance Verification Standard- Prednisone RS catalog #1222818) available for sale?
新的(of)标準物質(USP溶出(out)度性能驗證标準物質-潑尼松标準物質目錄#1222818)是(yes)否可供銷售?
Yes, please refer to the product page on the USP Store for up-to-date information on the release of the new reference standard.
是(yes)的(of)，請參考USP商店的(of)産品頁面，了(Got it)解有關新标準物質發布的(of)最新信息。
The associated revisions to General Chapter <711>Dissolutionare targeted to become official on 01-May-2023, at which time the new reference standard will be the only reference standard which can be used to meet the requirements of <711> Dissolution. The release of the new reference standard prior to the General chapter <711> Dissolution targeted official date would provide an opportunity for users to update internal documents and obtain experience with the new reference standard.
通則<711>溶出(out)度的(of)相關修訂定于(At)2023年5月1日正式生(born)效，屆時(hour)新标準物質将成爲(for)唯一(one)可用(use)于(At)滿足<711>溶出(out)度要(want)求的(of)标準物質。在(exist)通則<711>溶出(out)度的(of)目标生(born)效日期之前發布新的(of)标準物質，将爲(for)用(use)戶提供一(one)個(indivual)更新内部文件和(and)獲得新标準物質經驗的(of)機會。

2.Why was a new reference standard released?

爲(for)什麽要(want)發布一(one)個(indivual)新的(of)參考标準？

The release of the new USP Dissolution Performance Verification Standard – Prednisone RS catalog #1222818 is a part of USP's commitment to continuous enhancement of our products and services. The introduction of this new reference standard and the associated revisions to General Chapter <711>Dissolution are being recommended based on discussions with, and feedback from, various USP stakeholders.

新的(of) USP 溶出(out)度性能驗證标準 - 潑尼松 RS 目錄 #1222818 的(of)發布是(yes) USP 對持續改進我(I)們(them)産品和(and)服務的(of)承諾的(of)一(one)部分。根據與USP各利益相關者的(of)讨論和(and)反饋，我(I)們(them)建議引入這(this)一(one)新的(of)參考标準以(by)及對<711>溶出(out)度的(of)相關修訂。

3.What is the difference between the new reference standard (USP Dissolution Performance Verification Standard – Prednisone RS catalog #1222818) and the current reference standard (USP Prednisone Tablets RS catalog #1559505)?

新的(of)标準物質（USP溶出(out)度性能驗證标準--潑尼松片RS（産品編号1222818））與現行标準物質（USP潑尼松片RS（産品編号1559505））之間有什麽區别？

Based on the internal USP studies that have been performed, the new reference standard is considered more sensitive to operational and mechanical variables of instrument setup, less sensitive to media degassing, and more reproducible. The packaging configuration has also been changed. Each blister pack of 6 tablets is packaged in an aluminum sachet to provide additional protection against moisture.

根據已經進行的(of)USP内部研究，新的(of)标準物質被認爲(for)對儀器設置的(of)操作(do)和(and)機械變量更加敏感，對介質脫氣不(No)那麽敏感，而且可重複性更高。包裝配置也已改變。每盒6片的(of)吸塑包裝被裝在(exist)一(one)個(indivual)鋁袋中，以(by)提供額外的(of)防潮保護。

4.Will the Valid Use Date (VUD) for each lot of the new reference standard continue to be provided on the USP Certificate?

USP證書上是(yes)否會繼續提供每批新标準物質的(of)有效使用(use)日期（VUD）？

Yes, the Valid Use Date (VUD) will be included on the USP Certificate for the new reference standard (USP Dissolution Performance Verification Standard – Prednisone RS catalog #1222818).

是(yes)的(of)，有效使用(use)日期（VUD）将包括在(exist)新标準物質的(of)USP證書上（USP溶出(out)性能驗證标準-潑尼松RS（産品編号1222818））。
5.Will USP Prednisone Tablets RS catalog #1559505 be discontinued?
USP潑尼松片RS（産品編号：1559505）是(yes)否會停産？

Yes, the current reference standard (USP Prednisone Tablets RS catalog #1559505) will be discontinued on or about 28-Apr-2023 in anticipation of the associated revisions to General Chapter <711> Dissolution becoming official. The target official date for the proposed revisions is 01-May-2023. These revisions include the replacement of the USP Prednisone Tablets RS with the USP Dissolution Performance Verification Standard – Prednisone RS. USP has released Lot R154P0, which will be the last lot of the USP Prednisone Tablets RS and has an assigned Valid Use Date (VUD) of 31-July-2023.

是(yes)的(of)，目前的(of)标準物質（USP潑尼松片RS（産品編号：1559505））将在(exist)2023年4月28日前後停止發行，因爲(for)預計通則<711>溶出(out)度的(of)相關修訂将正式生(born)效。拟議修訂的(of)目标生(born)效日期是(yes)2023年5月1日。這(this)些修訂包括用(use)USP Dissolution Performance Verification Standard – Prednisone RS取代USP Prednisone Tablets RS。USP已經發布了(Got it)R154P0批次，這(this)将是(yes)USP潑尼松片RS的(of)最後一(one)個(indivual)批次，其指定的(of)有效使用(use)日期（VUD）爲(for)2023年7月31日。

6.Can I still use the current reference standard (USP Prednisone Tablets RS catalog #1559505) after the official date of the revised documentary standard?

在(exist)修訂後的(of)文件标準的(of)生(born)效之後，我(I)是(yes)否還能使用(use)目前的(of)标準物質（産品編号爲(for)1559505的(of)USP潑尼松片RS）？

No, Lot R154P0 cannot be used to meet the requirements of General Chapter <711> Dissolution after the revisions are official (Target Official Date: 01-May-2023).

不(No)可以(by)，批号R154P0不(No)能用(use)于(At)滿足通則<711>在(exist)修訂後溶出(out)度的(of)要(want)求（計劃生(born)效日期：2023年5月1日）。

7.Can I use the new reference standard (USP Dissolution Performance Verification Standard – Prednisone RS catalog #1222818) to meet the requirements of the currently official version of General Chapter <711> Dissolution?

我(I)是(yes)否可以(by)使用(use)新的(of)标準物質（USP溶出(out)度性能驗證标準--潑尼松RS(産品編号:1222818)）來(Come)滿足目前官方版本的(of)通則<711>溶出(out)度要(want)求？

No, USP Dissolution Performance Verification Standard – Prednisone RS (catalog #1222818) cannot be used to meet the requirements of General Chapter <711> Dissolution where the use of USP Prednisone Tablets RS (catalog #1559505) is specified. It has been provided prior to the official date of the <711> revisions only to ensure users have sufficient time to prepare for compliance by the official date (Target Official Date: 01-May-2023). Early adoption will not be allowed (see next question).

不(No)可以(by)，USP溶出(out)性能驗證标準物質-潑尼松片RS（産品編号1222818）不(No)能用(use)于(At)滿足<711>溶出(out)的(of)要(want)求，因爲(for)該章節規定使用(use)USP潑尼松片RS（産品編号1559505）。在(exist)<711>修訂版的(of)生(born)效日期之前提供，隻是(yes)爲(for)了(Got it)确保用(use)戶有足夠的(of)時(hour)間在(exist)生(born)效日期（目标生(born)效日期：2023年5月1日）之前做好合規準備。将不(No)允許提前采用(use)（見下一(one)個(indivual)問題）。
8.Will the revisions to General Chapter <711> Dissolution be eligible for early adoption?
對通則<711>溶出(out)度的(of)修訂是(yes)否可以(by)提前采用(use)？
The new standard (USP Dissolution Performance Verification Standard – Prednisone RS catalog #1222818) has been made available for purchase before the revision to General Chapter <711> Dissolution is targeted to become official in order to allow users to update internal documents and obtain experience with the new reference standard. However, the <711> Dissolution revisions is not eligible for Early Adoption (refer to General Notices 3.10). The new reference standard (USP Dissolution Performance Verification Standard- Prednisone RS catalog #1222818) is a unique formulation and has a different dissolution profile compared to the USP Prednisone Tablets RS (catalog #1559505). USP is not allowing early adoption in order to minimize ambiguity on compendial compliance.  
新标準物質（USP 溶出(out)度性能驗證标準 - 潑尼松 RS （産品編号：1222818））已在(exist)通則 <711> 溶出(out)度修訂版正式生(born)效之前提供給大(big)家購買，以(by)便用(use)戶更新内部文件并獲得使用(use)新參考标準的(of)經驗。但是(yes)，<711>溶出(out)度修訂版不(No)符合早期采用(use)的(of)條件（參見凡例3.10）。新的(of)标準物質（USP溶出(out)性能驗證标準-潑尼松片RS（産品編号：1222818）是(yes)一(one)種獨特的(of)配方，與USP潑尼松片RS（産品編号：1559505）相比具有不(No)同的(of)溶出(out)情況。USP不(No)允許提前采用(use)，以(by)盡量減少對藥典合規性的(of)歧義。
9.Is Performance Verification Testing (PVT) performed before the revision to General Chapter <711> Dissolution still valid after the revision becomes official?
在(exist)修訂通則<711>溶出(out)度前進行的(of)性能驗證測試（PVT）在(exist)修訂版本正式生(born)效後是(yes)否仍然有效？
The <711> Dissolution revision will not require customers to reevaluate an instrument that underwent Performance Verification Testing (PVT) prior to the official date. <711> Dissolution indicates that the apparatus suitability test must be performed “periodically” (without indication of a definitive time-period). USP recommends six-month intervals in the PVT Toolkit: https://www.usp.org/reference-standards/dissolution.pvt. 
<711>溶出(out)度修訂版不(No)會要(want)求客戶重新評估在(exist)正式日期之前已經進行了(Got it)性能驗證測試（PVT）的(of)儀器。<711>溶出(out)度指出(out)，儀器适用(use)性測試必須“定期”進行（沒有指出(out)明确的(of)時(hour)間段）。USP在(exist)PVT Toolkit中建議每六個(indivual)月進行一(one)次：https://www.usp.org/reference-standards/dissolution.pvt。
10.What advantages does the use of the USP Performance Verification Test (PVT) present over mechanical calibration?
與機械校準相比，使用(use)USP性能驗證測試（PVT）有什麽優勢？
static/file/20240626150605_0351
PVT驗證用(use)戶獲得準确的(of)溶出(out)度結果，以(by)确保病人(people)的(of)安全并避免因質量問題而導緻的(of)昂貴的(of)召回。單純的(of)機械校準并不(No)能提供足夠的(of)證據證明儀器的(of)性能是(yes)令人(people)滿意的(of)。PVT評估整個(indivual)組件的(of)操作(do)，以(by)驗證不(No)同的(of)組件是(yes)否正常工作(do)。機械校準和(and)PVT都是(yes)必要(want)的(of)，以(by)确保溶出(out)度儀器是(yes)完全合格的(of)。有關PVT的(of)更多信息和(and)好處，請參考以(by)下有關溶出(out)度測試儀驗證的(of)論文：
static/file/usp-pvt-dissolution-test.pdf
11.What stakeholder engagement tools does USP plan to use when the revisions to General Chapter <711> Dissolution become official?
當通則<711>溶出(out)度的(of)修訂版本正式生(born)效時(hour)，USP計劃使用(use)哪些利益相關者參與工具？
USP will have a number of informational tools, including but not limited to a product factsheet, webpage, video(s), webinar(s), and a white paper, available to users regarding the new reference standard and General Chapter <711> revisions. Additional information will be provided here when available.

USP将提供一(one)些信息工具，包括但不(No)限于(At)産品說明書、網頁、視頻、網絡研讨會和(and)白皮書，供用(use)戶了(Got it)解新的(of)标準物質和(and)通則<711>的(of)修訂情況。如有其他(he)信息，将在(exist)此提供。

12.Does using tweezers affect the integrity of the tablets? – USP Dissolution Performance Verification Standard - Prednisone RS (catalog #1222818) is stronger than USP Prednisone Tablets RS (catalog #1559505). Due to the changes in size and formulation of the new reference standard, the new tablets require a significantly higher tablet breaking force compared to the current product. We have not observed any issues with crushing or scratching the tablet surface when using metal forceps to handle the tablets in our lab. Of course, as with any analytical method, best practices for handling and testing a product are likely to be product-specific and can always be improved. Please refer to the following video for additional information on DPVS – Prednisone packaging and handling: https://www.youtube.com/watch?v=ou_qjeXXsVg

使用(use)鑷子是(yes)否會影響藥片的(of)完整性？- USP溶出(out)度性能驗證标準物質-潑尼松片 RS（産品編号：1222818）比USP潑尼松片RS（産品編号：1559505）硬度更大(big)。由于(At)新标準物質的(of)尺寸和(and)配方發生(born)了(Got it)變化，與目前的(of)産品相比，新藥片需要(want)的(of)破片力要(want)高得多。我(I)們(them)在(exist)實驗室中使用(use)金屬鑷子處理片劑時(hour)，沒有觀察到(arrive)任何壓碎或刮傷片劑表面的(of)問題。當然，與任何分析方法一(one)樣，處理和(and)測試産品的(of)最佳做法很可能是(yes)針對具體産品的(of)，而且總是(yes)可以(by)改進。關于(At)溶出(out)度性能驗證标準-潑尼松包裝和(and)處理的(of)其他(he)信息，請參考以(by)下視頻：

https://www.youtube.com/watch?v=ou_qjeXXsVg


作(do)者：常曉偉

審核：王孝東、魏巍、王亞蕊

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