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Comparability Protocols 2008.11.26   

2008-11-26 14:07:16|  分类: DMF |  标签: |举报 |字号 订阅

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Guidance for Industry

Comparability Protocols —

Chemistry, Manufacturing, and

Controls Information

行业指南

可比拟性变更协定

化学,制造,和控制资料

 

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

Center for Veterinary Medicine (CVM)

February 2003

CMC

美国健康和人类服务部

食品和药品监督管理局

药物评审和研究中心(CDER)

生物药评审和研究中心(CBER)

兽药中心(CVM)

2003年3月

CMC

TABLE OF CONTENTS

目录

I. INTRODUCTION................................................................................................................. 1

绪论

II. BACKGROUND ...................................................................................................................2

背景

A. What is a Comparability Protocol?..............................................................................................3

可比拟性变更限定是什么?

B. What is the Benefit of Using a Comparability Protocol? ...........................................................3

使用可比拟性变更协定的好处是什么?

C. Why is a Guidance on Comparability Protocols Being Provided?............................................4

为什么关于可比拟性变更的指南陆续被制定出?

D. Where Can More Information on Postapproval Changes and Demonstration of Equivalence

Be Found?.......................................................................................................................................4

关于批准后变更和等同性证明的更多资料,哪里可以找到?

III.  WHAT TO CONSIDER IN PLANNING  A COMPARABILITY PROTOCOL.......... 5

计划进行可比拟性变更协定需要考虑的内容

A. How Does a Comparability Protocol Affect the Reporting of CMC Changes? .......................5

可比拟性变更协定如何影响CMC变更的上报?

B. When Might a Comparability Protocol Be Useful for a CMC Change? ..................................5

可比拟性变更何时会有助于CMC变更

C. When Might a Comparability Protocol Be Inappropriate?.......................................................6

可比拟性变更协定在何时是不适用的?

IV. PROCEDURES FOR COMPARABILITY PROTOCOLS.............................................. 7

可比拟变更协定的方法

A. How Should a Comparability Protocol Be Submitted?..............................................................7

如何递交可比拟性变更协定?

B. How Are Changes and Study Results Submitted After a Comparability Protocol is

Approved? ......................................................................................................................................8

在可比拟性变更协定批准后,变更和研究结果如何递交

C. What If Study Results Do Not Meet the Criteria Specified in the Approved Comparability

Protocol?.........................................................................................................................................8

如果研究结果不符合可比拟变更协定中规定的标准,该怎么办?

D. When Does a Comparability Protocol Become Obsolete?..........................................................8

可比拟变更协定何时会过时?

E. How is an Approved Comparability Protocol Modified?...........................................................8

如何修改已批准的变可比拟变更协定

V. CONTENT OF A COMPARABILITY PROTOCOL....................................................... 9

可比拟变更协定的内容

A. What are the Basic Elements of a Comparability Protocol?......................................................9

可比拟变更协定的基本要素是什么?

B. Does FDA Have Specific Concerns About Changes in the Manufacturing Process That

Should Be Addressed in a Comparability Protocol? ................................................................13

FDA是否特别关注应在可比拟协定中叙述的制造工艺的变更?

C. Does FDA Have Specific Concerns About Changes in Analytical Procedures That Should Be

Addressed in a Comparability Protocol?...................................................................................14

FDA是否特别关注应在可比拟变更协定中叙述的分析方法的变更

D. Does FDA Have Specific Concerns About Changes in Manufacturing Equipment That

Should Be Addressed in a Comparability Protocol? ................................................................14

FDA是否特别关注应在可比拟变更协定中叙述的制造设备的变更?

E. Does FDA Have Specific Concerns About Changing Manufacturing Facilities That Should

Be Addressed in a Comparability Protocol? .............................................................................15

FDA是否特别关注应在可比拟变更协定叙述的制造厂房的变更?

F. Can a Comparability Protocol Be Used for Container Closure System Changes?................15

可比拟性变更是否可以用于容器密闭系统的变更?

G. Can Implementation of or Changes in Process Analytical Technology (PAT) Be Addressed

in a Comparability Protocol?......................................................................................................15

过程分析技术的运用或变更是否可以在可比拟变更协定中叙述?

Can a DMF or VMF Be Cross-Referenced in an Applicant’s Comparability Protocol? ......16

DMF或VMF是否可以和申请人的可比拟变更协定交叉引用?

I. Can a Comparability Protocol Be Included in a DMF or VMF? ............................................16

可比拟变更协定是否可以包含在DMF或VMF中?

I.                    INTRODUCTION

绪论

This guidance provides recommendations to applicants on preparing and using comparability

protocols for postapproval changes in chemistry, manufacturing, and controls (CMC).  The

guidance applies to comparability protocols that would be submitted in new drug applications

(NDAs), abbreviated new drug applications (ANDAs), new animal drug applications (NADAs),

abbreviated new animal drug applications (ANADAs), or supplements to these applications,

except for applications for protein products.

本指南给申请人提供了关于制定和使用用于化学,制造和控制(CMC)中的批准后变更的可比拟变更协定的建议。

Well-characterized synthetic peptides submitted in these applications are included within the scope of this guidance.  This guidance also applies to comparability protocols submitted in drug master files (DMFs) and veterinary master files (VMFs) that are referenced in these applications. The FDA is providing this guidance in response to requests from those interested in using comparability protocols. 

在这些申请中递交性质完好的合成肽包含在本指南的范围中。本指南也适用于用于递交DMF, VMF可比拟性变更协定,其可以被这些申请引用。FDA未响应那些对使用可比拟变更协定感兴趣的人而制定的本指南。

FDA guidance documents, including this guidance, do not establish legally enforceable responsibilities.  Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited.  The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

FDA指南文件,包括本指南,并不具有法律上的强制义务。相反,这些指南叙述了FDA对此问题当前的看法,应仅作为建议,除非被具体的法规或法令要求引用。FDA指南中should的适用的意思是某些东西是建议或推荐的,并不要求。

II.                 BACKGROUND

背景

As an applicant, you are responsible for assessing, prior to distribution of a product, the effect of any postapproval CMC changes on the identity, strength, quality, purity, and potency of the product as these factors relate to the safety or efficacy of the product (section 506A(b) of the Federal Food, Drug, and Cosmetic Act (the act)).  Such an assessment often includes demonstration that the pre- and postchange products (i.e., products manufactured prior to and subsequent to a change) are equivalent.  Postapproval CMC changes must be reported to FDA in one of four reporting categories (Section 506A of the Act):

作为申请人,在产品销售前,你有责任评估关于产品同一性,剂量,质量,纯度和功效的批准后的CMC变更,因为这些因素对产品的安全性或有效性相关。评估通常包括证明变更前和变更后的产品是等效的。批准后CMC变更必须以如下四种上报形式之一上报

?  Annual Report (AR)

年报

The annual submission to the approved application reporting changes that FDA has identified as having minimal potential to adversely affect the identity, strength, quality, purity, or potency of a product as they may relate to the safety or effectiveness of the product.

已批准申请的年度递交,上报FDA已经确定为对产品的同一性,剂量,质量,纯度,或功效有较小的不利影响的变更。因为这些变更可能对产品的安全性或有效性有关。

?  Change-Being-Effected Supplement (CBE)

正在受影响变更的补充申请

A submission to an approved application reporting changes that FDA has identified as having moderate potential to adversely affect the identity, strength, quality, purity, or potency of a product as they may relate to the safety or effectiveness of the product.  A CBE supplement must be received by FDA before or concurrently with distribution of the product made using the change.

已批准申请的递交申请,上报FDA确定的对产品的同一性,剂量,质量,纯度或功效有中等程度的不利影响的变更。这些变更可能会对产品的安全性或有效性相关。FDA必须在在采用变更制备的产品销售前或同步于销售收到CBE补充申请。

?  Change-Being-Effected-in-30-Days Supplement (CBE-30).

30天内正在正在受影响的变更的补充申请(CBE-30)

A submission to an approved application reporting changes that FDA has identified as having moderate potential to adversely affect the identity, strength, quality, purity, or potency of a product as they may relate to the safety or effectiveness of the product.  A CBE- 30 supplement must be received by FDA at least 30 days before distribution of the product made using the change.

已批准申请的递交申请,上报FDA确定的对产品的同一性,剂量,质量,纯度或功效有中等程度的不利影响,这些变更可能和产品的安全性或有效性相关。FDA必须在采用变更制备的产品销售前30天收到CBE-30补充申请。

?  Prior Approval Supplement (PAS)

批准前的补充申请(PAS)                                                                                                                                                           

A submission to an approved application reporting changes that FDA has identified as having a substantial potential to adversely affect the identity, strength, quality, purity, or potency of a product as they may relate to the safety or effectiveness of the product.  A PAS supplement must be received and approved by FDA prior to distribution of the product made using the change. In many cases, using a comparability protocol will facilitate the subsequent implementation and reporting of CMC changes, which could result in moving a product into distribution sooner than if a protocol were not used.

已批准申请的递交申请,上报FDA确定的对产品的同一性,剂量,质量,纯度或功效有十分重要的不利影响的变更。这些变更可能对产品的安全性或有效性相关。FDA必须在用变更制造的产品的销售前

This guidance describes the general principles and procedures associated with developing and submitting a comparability protocol to the FDA.  The guidance also describes the basic elements of a comparability protocol and specific issues to consider when developing comparability protocols for changes in:

本指南叙述了和开发和递交给FDA可比拟变更协定相关的总体原则和方法。本指南也从如下方面叙述了可比拟变更协定的基本要素和在开发可比拟变更协定时需要具体考虑的问题

?  the manufacturing process

制造工艺

?  analytical procedures

分析方法

?  manufacturing equipment

制造设备

?  manufacturing facilities

制造厂房

?  container closure systems

容器密闭系统

?  process analytical technology (PAT)

过程分析技术(PAT)

 

The guidance also discusses submitting comparability protocols in master files.

本指南也讨论了在主文件中递交可比拟变更协定

A. What is a Comparability Protocol?

可比拟变更协定是什么?

A comparability protocol is a well-defined, detailed, written plan for assessing the effect of specific CMC changes in the identity, strength, quality, purity, and potency of a specific drug product as these factors relate to the safety and effectiveness of the product.  A comparability protocol describes the changes that are covered under the protocol and specifies the tests and studies that will be performed, including the analytical procedures that will be used, and acceptance criteria that will be achieved to demonstrate that specified CMC changes do not adversely affect the product.  The submission of a comparability protocol is optional.

可比拟变更协定是用于评估具体产品的同一性,剂量,质量,纯度和功效的具体的CMC变更的确定的,详细的,书面的计划,这些因素和产品的安全性和有效性相关。可比拟变更协定叙述了此协定覆盖的变更,说明了需要做的检测和研究,包括将要使用的分析方法,和将要获得的认可标准以证明具体的CMC变更不对对产品有不利的影响。可比拟变更协定的递交是自愿的。

B. What is the Benefit of Using a Comparability Protocol?

使用可比拟变更协定的好处是什么?

At the time the application containing the comparability protocol is approved, the FDA can designate, where appropriate, a reduced reporting category for future reporting of CMC changes covered by the approved comparability protocol (see III.A).  Furthermore, because a detailed                                             

plan will be provided in the comparability protocol, the FDA is less likely to request additional information to support changes made under the protocol (see IV.D for a potential exception).

在包含可比拟变更协定的申请被批准时,适当的话FDA可以指明用于上报批准的可比拟变更协定中包含的CMC变更简化的上报目录(见III.A).再者,由于详细的计划在可比拟变更协定中提供了,FDA很少会要求其他的资料来支持在此协定下的变更(见IV.D,用于潜在的例外情况)

The use of a comparability protocol could allow an applicant to implement CMC changes and place a product in distribution sooner than without the use of a comparability protocol.

可比拟变更协定的使用可以允许申请人执行CMC变更并比未使用可比拟变更协定更快地将产品投入市场.

C. Why is a Guidance on Comparability Protocols Being Provided?

为什么关于可比拟变更协定的指南逐步被制定出

For many years, applicants have used protocols to implement certain types of CMC changes, such as to extend an expiration dating period or to demonstrate the interchangeability of certain plastic containers.  More recently, there have been many improvements in the techniques for characterizing products, production methods, process controls, and release testing.  Because of these improvements and because we are able to better assess the potential effect of CMC changes on a product, protocols are now being used with other types of CMC changes (e.g., manufacturing process, analytical procedure).  We have received a number of requests for guidance from applicants interested in using comparability protocols for these other types of changes.

很多年来,申请者申请者已经使用此协定执行具体类别的CMC变更,如延长有效期或证明具体塑料的可交换性.最近, 叙述产品的技术,生产方法, 工艺控制和放行检测有了叫多的改进. 由于这些改进,以及我们可以更好地评估产品CMC变更的潜在影响, 协定正在被用于其它类型的CMC变更(如,制造工艺,分析方法).我们已经收到了对使用变更协定用于其它类型的变更感兴趣的申请人的许多请求.

D. Where Can More Information on Postapproval Changes and Demonstration of Equivalence Be Found?

关于批准后变更和等效性证明的更多资料,哪里可以找到?

This guidance, once finalized, is not intended to supersede other FDA guidance documents, rather it supplements them with information on using comparability protocols to implement postapproval CMC changes.  We recommend that applicants consult all relevant guidances for information relating to postapproval changes.  The following guidances provide especially relevant information on (1) demonstrating equivalence, (2) documentation to be provided to support postapproval changes, and (3) the recommended reporting categories.

本指南, 一旦定案, 并不是旨在取代其它FDA指南文件,而是使用可比拟变更协定对其补充从而实现批准后的CMC变更. 如下的指南提供了紧密相关的资料,关于(1)证明等同性,(2)需提供的文件以支持批准后的变更,和(3)推荐上报类型

?  Changes to an Approved NDA or ANDA

已批准NDA或ANDA的变更

?  Changes to an Approved NADA or ANADA (draft)

已批准NADA或ANDA(草案)的变更

?  Various SUPAC documents

各种不同的SUPAC文件                                               

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