分析方法转移程序(USP草案))--美国药典usp1224(中英对照)

1、BRIEFING<1224Transfer of Analytical Procedures.分析方法转移After publication of the Stimuli article Transfer of Analytical Procedures: A Proposal for a New General Information Chapter" in PF 35(5) Sept.-Oct. 2009 and based on comments received, the General ChaptersPhysical Analysis Expert Committe

2、e proposes this new general information chapter. The proposed chapter is intended to become one of a series of general chapters that provides guidanee for generation of data (i.e., qualification, validation, and verification) in support of compendial analytical procedures While the concepts presente

3、d in the proposed chapter are related to the verification processes described in general chapter Verification of Compendial Procedures 1226 , the verification process is focused primarily on the drug product and associated matrix effects or other potential interferenee issues In contrast, the proced

4、uretransfer process focuses on Qualifying the receiving laboratory to Derform an analytical procedure that was developed and validated in ano the 门 aboratory 分析方法转移程序的目的是为了确认接收的实验室是否可以进行在另一个实验室中研发并经过验证的 检验方法。(GCPA: H. Pappa.) Correspondence NumberC74516Comment deadline: March 31,2011Add the followin

5、g:1224 TRANSFER OF ANALYTICAL PROCEDURES分析方法转移程序INTRODUCTION 前言Testing to the specificatio n of an an ciliary material, i ntermediate, an d/or in gredie nt and product is critical in establishing the quality of a finished dosage form. The transfer of analytical procedures (TAP), also referred to as

6、method transfer, is the documented process that qualifies a laboratory (the receiving unit) to use an analytical test procedure that originated in another laboratory (the transferring unit, also referred to as the sending unit), thus ensuring that the receiving unit has the procedural knowledge and

7、ability to perform the transferred analytical procedure as intended对辅料.中间体、和/或药物成分和产品进行检验确定是否符合质虽标准对确定制剂成品的质虽是非常重要 的。分析方法转移程序（TAP）,通常也称作方法转移，该程序就是记录一个实验室（接收方）能够使用 由另一个实验室（转移方，也称作转出方）所开发检验方法的过程，并确保接收的实验室知道检验的程序 并有能力按规定进行检验。The purpose of this general informational chapter is to summarize the types of

8、 transfers that may occur, in eluding the possibility of waiver of any verificati on, and to outli ne the pote ntial compone nts of a tran sfer protocol. This chapter does not provide statistical methods and does not encompass the transfer of microbiological or biological procedures 该节内容的忖的是总结可能存在的分

9、析方法转移的类型，包括可能不需要进行任何确认，概述转移方案中 需包含的内容。该节不包括统计方法，也不包含对微生物和生物检验方法的转移。TYPES OF TRANSFERS OF ANALYTICAL PROCEDURES 分析方法转移类型TAP can be performed and dem on strated by several approaches The most comm on is comparative testing performed on homogeneons lots of the target material from standard product!on b

10、atches or samples intentionally prepared for the test （e.g., by spiking relevant accurate amounts of known impurities into samples）. Other approaches in elude covalidation between laboratories, the complete or partial validation of the analytical procedures by the receiving unit, and the transfer wa

11、iver, which is an appropriately justified omission of the transfer process The tests that will be transferred, the extent of the transfer activities, and the implementation strategy should be based on a risk analysis that considers the previous experienee and knowledge of the receiving unit, the com

12、plexity and specifications of the product, and the procedure In early development phases the procedure understanding may be limited. In those cases, the transfer process is more challenging because of incomplete knowledge about the variables of the procedure, particularly its robustness This may com

13、plicate the transfer process by adding more variables to a system that should be as simple as possible 进行分析方法转移有好儿种方法。其中最常用的方法是：对从生产批次取出的同批次样品或为检验专门制 备的样品（例如：将相对准确的一定屋的已知杂质添加到样品中），两个实验室同时进行检验并进行对比。 其他的方法包括：实验室间一起进行验证；接收方进行完整的或部分的分析方法验证；或者有充分理由证 明不需进行分析方法转移。将要转移的方法，需进行的转移工作的程度以及执行的方法应根据风险分析来 进行，需考虑到之

14、前的经验，接收方得情况、产品的复杂性和规格标准以及相应的方法等内容。在早期研 发阶段，对分析方法的理解也是有限的，转移过程会更具挑战性，因为对方法中心在的变动因索认识不充分，尤其是否方法的耐用性。因为对本应该尽可能简单的系统增加了更多的变动因索，所以使转移过程变 得更复杂。Comparative Testing 对比试验Comparative testing is the most comm on method for TAP and requires the an alysis of a predetermi ned nilmber of samples of the same lot by

15、 both the sending and receiving units. Other approaches may be valid, e.g., if the receiving unit meets a predetermined acceptance criterion for the recovery of an impurity in a spiked product. Such analysis is based on a preapproved transfer protocol that stipulates the details of the procedure, th

16、e samples that will be used, and the predetermined acceptance criteria, in cludi ng acceptable variabilit y. Meeti ng the accepta nee criteria and comparing data gen erated by both parties are ways of assuring that both sending and receiving units are similarly qualified to run the procedure 进行对比试验是

17、分析方法转移时嚴常用的方法，需要转出方和接收方同时对同一批次的样品进行检验（需 要进行的检验批次数应预先规定）。其他的方法也可能足有效的，例如：对于一个掺了杂质的产品，接 收方测定的杂质回收率符合预先规定的标准。所进行的分析应根据预先批准的转移方案来进行，方案中 规定的程序的具体细节，应使用的样品，和预先规定的标准，包括可接受的变异性。检验结果符合标准 规定并且将转出方和接收方的所得的结果进行比较，可以保证双方都能进行检验，能力相当。Covalidation Between Two or More Laboratories两个实验室或多个实验室间的共同验证The laboratory that

18、 performs the validation of an analytical procedure is qualified to run the procedure Manufacturers can involve the receiving unit in an interlaboratory covalidation, including them as a part of the validation team and thereby obtaining data for the assessment of reproducibility. This assessment is

19、made using a preapproved transfer or validation protocol that provides the details of the procedure, the samples to be used, and the predetermined acceptanee criteria General chapter Validation of Compendial Procedures 1225provides useful guidanee about which characteristics are appropriate for test

20、i ng.进行了分析方法验证的实验室是可以使用检验方法的。生产企业可以让接收方参与多个实验室的共同验证 工作，将接收方作为验证小组的成员，因此需要进行乘现性的评估并获得相关数据。该评估按照预先批准 的转移或验证方案来进行，方案中规定了该程序的具体细节，应使用的样品，和预先规定的标准。通则1225 “约典方法的验证”就需对哪些项目进行验证提供了非常有用的指南。Revalidation 再验证The revalidation or partial revalidation is another acceptable approach for transfer of a validated proc

21、edure This approach is more time consuming than comparative testing, and manufacturers also may find it more difficult to observe bias between different sites, operators, and instruments 进行再验证或部份验证是分析方法转移中使用的另一个可行的方法。这种方法比仅作对比试验要耗费时间, 生产商更难发现不同场地、不同操作人员和不同仪器之间的偏移。Transfer Waiver转移豁免（不需要进行分析方法转移的情况）T

22、he conventional TAP may be omitted under certain circumstances In such instances, the receiving unit is considered lo be qualified lo use the analylical test procedures wilhoul comparison and generalion of in terlaboratory comparative data. The following examples give in cidences that may justify th

23、e waiver of TAP:在某些特定的情况卜，不需要进行常规的分析方法转移。在这种情况下，不需要进行对比，也不需要获得 实验室间的对比数据，就可认为接收方是有资格进行分析方法的。下而的悄况不需要进行方法转移。The new procucfs composition is comparable to that of an existing product and/or the concentration of active ingredient is similar to that of an existing product and is analyzed by procedures w

24、ith which the receiving unit already has experienee.新产品的成份与已有的品种的成份类似和/或活性药物的浓度与已有产品的浓度类似，并且对于使 用的分析方法，接收方有经验。 The analytical procedure is the same or very similar to a procedure already in use.检验方法与已使用的方法相同或非常相近。 The personnel in charge of the development, validation, or routine analysis of the pro

25、duct at thesending unit are moved to the receiving unit.负贵方法开发、验证或产品日常检验的人员有转出方调到接收方。ELEMENTS RECOMMENDED FOR THE TRANSFER OF ANAYTICAL PROCEDURES进行分析方法转移建议需考虑的因素Several elements, many of which are interrelated, are recommended for a successful TAP using thecomparative testing approach. When appropr

26、iate and as a part of pre-transfer activities, the sending unit should provide training to the receiving unit, or the receiving unit should run the procedures and identify any issues that may need to be resolved before the transfer protocol is signed. Training should be documented 在使用对比检验来进行成功的方法转移时

27、，建议应考虑到一些因素（其中很多内容是相互关联的）。作为 方法转移询的准备活动，转出方应对接收方进行培训或者在转移方案签字询，接收方应使用一下将转移的 方法并确认存在哪些问题。进行的培训应记录。The Iransferring unit, often lhe development unit, is responsible for providing lhe analytical procedure, lhe referenee standards, the validation reports, and any necessary documents, as well as for prov

28、iding the necessary training and assistance to the receiving unit as needed during the transfer. The receiving unit may be a quality control unit, ano ther in tracompany facility, ano ther compa ny, or a con tract research organization. The receiving unit provides qualified staff or properly trains

29、the staff before the transfer, ensures that the facilities and instrumentation are properly calibrated and qualified as needed, and verifies that the laboratory systems are in complianee with applicable regulations and in-house general laboratory procedures Both the transferring and receiving units

30、should compare and discuss data as well as any deviations from the protocol. This discussion addresses any necessary correct!ons or updates to the final report and the analytical procedure as necessary to reproduce the procedure 转出方，通常是研发部门，负贵提供分析方法，对照品，验证报告，必要的文件，并且须提供必要的培训， 在方法转移的过程中给予接收方必要的帮助。接收方

31、可能是质屋控制部门、公司内部的其他部门、其他公 司或委托研发机构。在方法转移前，接收方应确保具有适当资质的人员或在方法转移前对人员进行适当的 培训，确保设施也仪器都根据需要进行合适的饿校正和确认，并确定实验室的体系足符合相应法规和内部 的实验室管理程序要求的。转出方和接收方都应对数据进行比较并讨论，包括与方案发生的偏差。经讨论 决定对最终的报告和检验方法需要进行哪些更改或更新，这些内容对帝新起草检验方法是必要的。A single lot of the article may be used for the transfer because the aim of the transfer is

32、not related to the manufacturing process but rather to the evaluation of the analytical procedure's performanee at the receiving site If two or more different lots are used, the lot-to-lot variability should not be computed 对于方法转移可能选择一个批次，因为方法转移的目的与生产工艺无关，而足为了评估检验方法在接收方 是否可行。如果选择两个批次或更多的批次的话，不需计

33、算批与批间的差异。PREAPPROVED PROTOCOL预先批准的方案A well-designed protocol should be discussed, agreed upon, and documented before the implementationof TAP. The document expresses a consensus between the parties, indicating an intended execution strategy, and should in elude each party's requireme nts and res

34、p on sibilities The protocol should describe the objective, the scope, the responsibilities of the transferring and the receiving units, and the materials and instruments that will be used, as well as the analytical procedure, the experimental design, and the accepta nee criteria for all the tests a

35、n d/or methods in eluded in the tran sfer. Based on the validati on data, and the procedural knowledge, the transfer protocol should identify the specific analytical performanee characteristics （see 1225 ） ） that will be verified and the analysis that will be used to evaluate acceptable outcomes fro

36、m the transfer exercise设计好的方案在执行方法转移询经过人家讨论并获得一致同意并形成文件。文件能表明对将要采取的执行 策略各方已达成一致意见，其应包含各方的要求和职贵。方案中应说明目的、范阳、转出方和接收方的职 责、使用的仅帶和试剂以及分析方法、试验的设计和转移中使用的所有检验和/或方法的可接受的标准。根 据验证数据和检验方法，在转移方案中规定需对哪些项目进行确认（见1225）以及对方法转移进行评估可 接受结果的方法The transfer acceptanee criteria, which are based on method performanee and his

37、torical data from stability and release results, if available, should in elude the comparability criteria for results from all study sites These criteria may be based on the differenee between mean values and established ranges and should be accompanied by an estimation of the variability e.g., perc

38、ent relative standard deviation （%RSD） for each site, particularly for the in termediate precision %RSD of the receivi ng unit an d/or a statistical method for the comparison of the means for assay and content uniformity tests In instances of impurity testing, where precision may be poorer, a simple

39、 descriptive approach can be used Dissolution can be evaluated by a comparison of the dissolution profiles using the similarity factor h or by comparison of data at the specified time points. The laboratories should provide a rationale for any analytical performa nee characteristic not in eluded, as

40、 well as any tran sfer waiver. The materials, refere nee standards, samples, instruments, and instrumental parameters that will be used should be described 依据方法性能及稳定性和放行历史数据（如有的话）制定的分析方法转移可接受的标准，应包括在所有场 地获得的数据之间的可比性标准。这些标准的制定可依据平均值和标准规定间的总异来制定，并应考虑变 异性（例如：每个场地的相对标准偏差），尤其应包括接收方的中间精密度和/或含暈和含暈均匀度检验方 法的

41、对比用的统计学方法。就杂质检验而言，梢密度会差些，可使用简单描述的方法。溶出可通过对比溶 出曲线（使用相似因子f2）来评佔，或将在规定点获得的数据来比较。实验室对于没有进行的项目和不进行方法转移的情况应说明理由。对使用的物料.对照品.样品、仪器和仪器参数应说明。Expired or aged samples should be carefully chosen and evaluated to identify potential problems related to differences in sample preparation equipment and to evaluate th

42、e impact of potential aberrant results on marketed products The docume ntation secti on of the tran sfer protocol may in elude report forms to ensure con sistent recording of results and to improve consistency betwee n laboratories This section should contain the additi onal info rmati on that will

43、be in eluded with the results, such as example chromatograms and spectra, along with additional information in case of a deviation. The protocol should also explain how any deviation from the acceptance criteria will be managed Any changes to the transfer protocol following failure of an acceptanee

44、criterion must be approved before collect!on of additional data. 应慎重选择并评估过期或久置的样品，以确定与样品配制仪器间的差异相关的潜在问题，并评估异常值对己销您产品的影响。转移方案的文件部分应包括报告的格式，以确保可以持续地记录检验结果并提高不同 实验室间的一致性。该部份还应包含结果及其他附带信息，例如：样品的色谱图和光谱图，如果发生偏差 的话还应包含其他的信息。方案中述应说明如果与可接收的标准发生偏差的话应采取哪些措施。当不符合 标准规定的情况后，对转移方案发生的任何变更，必须在获得其他额外的数据前获得批准。THE ANAL

45、YTICAL PROCEDURE 分析方法The procedure should be written with sufficient detail and explicit instruct!ons so that a trained analyst can perform it without difficulty A pre-transfer meeting between the transferring and receiving units is helpful to clarify any issues and answer any questions regarding th

46、e transfer process. If complete or partial validation data exist, they should be available to the receiving unit, along with any technical details required to perform the test in question. In some cases it may be useful for the individuals who were involved with the initial development or validation to be on site during the transfer. The number of batches, replicates, and injection sequences in the case of liquid or gas chromatog