热点话题：复合药物的困惑：何为复合药物，何非复合药物

欢迎收听ASHP官方播客，本节目将为您解读药物使用、公共卫生及药学专业相关议题。

Welcome to the ASHP official podcast, your guide to issues related to medication use, public health, and the profession of pharmacy.

感谢大家收听本期《复配难题》，我们将与无菌复配专家对话，探讨当前药学领域最受关注的话题。

Thank you all for joining us on this episode of Compounding Conundrums, where we sit down with sterile compounding experts and discuss what is currently top of mind in the world of pharmacy.

这是由ASHP住院护理医师分会复配实践咨询小组成员制作的三部曲系列的第一期。

This is the first of a three part series that is being produced by members of the ASHP Section of Inpatient Care Practitioners Advisory Group on Compounding Practice.

我是吉姆·伦德。

My name is Jim Lund.

我曾担任复配实践咨询小组的上届主席，目前是瓦桑特药房咨询公司医院与卫生系统事业部的高级总监。

I'm the immediate past Chair of the Section Advisory Group on Compounding Practice, and I'm currently a Senior Director in the Hospital and Health System Division of Vasant, a pharmacy consulting firm.

很荣幸能与三位来自咨询小组的杰出复配专家同台——他们都是极具智慧与才华的同行。

I'm fortunate to be joined by three incredibly smart and talented compounding leaders colleagues that are also members of the Section Advisory Group.

今天与我共同参与的是凯文·汉森，他在北卡罗来纳州格林斯伯勒的科恩健康担任复配服务与数据分析总监。

Joining me today is Kevin Hansen, who is the Director of Compounding Services and Data Analytics at Cohen Health in Greensboro, North Carolina.

凯文也曾担任咨询小组主席，并在数年前协助创建了这个小组。

Kevin is also a past chair of the Section Advisory Group and helped establish the SAG a few years ago.

此外还有俄亥俄州哥伦布市全国儿童医院的家庭护理药房经理泰瑞·拉瑞拉，以及阿肯色州斯普林代尔市阿肯色儿童西北分院的运营经理凯莉·汤普森。

Additionally, we have Terri Larilla, is the Home Care Pharmacy Manager at Nationwide Children's Hospital in Columbus, Ohio, and Kaylee Thompson, who is the Operations Manager at Arkansas Children's Northwest in Springdale, Arkansas.

欢迎各位的到来，感谢你们今天的参与。

Welcome everybody and thanks for joining us today.

近期复配领域发生了许多重要动态。

So there's been a lot of activity in the compounding world recently.

我们不仅看到了FDA更新指导文件，去年底还迎来了期待已久的USP第797章修订版正式发布。

We've seen recently updated FDA guidance documents and late last year the publication of the long we anticipated, revised USP Chapter seven ninety seven.

我们有很多话题可以讨论。

So there's a wide array of topics we can discuss.

不过在我们播客系列的第一集中，我们认为从最基础的内容开始会更有益——先深入探讨什么是药物配制，以及为什么它如此重要。

However, in this first episode of our podcast series, we thought it would be beneficial to start with the very basics and start by diving into the definition of what exactly is compounding and why does this matter.

这看似是个简单的问题，但我们都认同在深入研究各种法规标准细节之前，理解这个概念很重要。

It may seem like a silly question to start with, but I think we would all agree it's important to understand this before someone dives into the details of various regulations and standards.

那么凯文，我想先请你来谈谈。

So, Kevin, I'll start with you.

过去多次听到你讲解这个概念，我一直很欣赏你的见解。

I've seen you and heard you review this concept many times in the past and I've always enjoyed your review.

能否为我们概述药物配制的定义，并说明这对我们的日常实践有何指导意义？

So could you outline for us some of the definitions around compounding and provide some perspective on how this applies to our daily practice?

当然可以。

Absolutely.

非常感谢吉姆的介绍。当我们思考药物配制的难题——什么算配制、什么不算时，这是个很好的切入点。

Thanks so much, Jim, for the kind introduction And and what great way to start when we think about compounding conundrums of what even is considered compounding and what what is it not considered.

实际上追溯发展历程，我们从2008版USP797或现行可执行版本开始看，会发现并没有明确定义。

And really, when we kinda look at the evolution, we'll start with the 2008 version of USB seven ninety seven or the currently enforceable version of there's not necessarily a clear definition.

必须仔细阅读每个风险类别（低风险、中风险和高风险），并思考我们有多少产品，具体在做什么。

You have to really read through each of the risk categories, low risk, medium risk, and high risk, and think about how many products we have, what are we doing.

当然，章节中列出了需要为患者提供无菌处理的不同产品。

Of course, the chapter provides different products that are given to our patients that need to be sterile.

但什么时候算药物配制？什么时候不算呢？

But when is it considered compounding and when is it not?

重组、稀释、混合这些操作在具体情境中如何定位？

Is reconstituting, diluting, pooling, where does that fit into that context?

这不仅对配药人员是个难题，对监管机构和认证机构同样如此——当他们试图执行这些标准时，如果对‘配药’的理解与配药人员不同，你就能预见到这将是个极具挑战性的局面。

And while this is a conundrum not only for compounders, it may be for regulatory agencies, accreditation bodies as well as they think about enforcing these standards of, you know, if they have a different interpretation of what's compounding than a compounder, you can see that that is gonna be very challenging scenario.

正如我们现在思考发展进程时，吉姆提到我们即将在2023年实施USB797的可执行版本。

So as we think through now the evolution, you know, Jim mentioned we have this 2023 upcoming enforceable version of USB seven ninety seven.

其中部分内容已作修改，且在很多方面表述更加清晰。

Some of this has been changed, and in many ways, has been made more clear.

该章节现在被置于引言部分，并给出了明确定义。

The chapter now comes out within the the introduction section and defines it clearly.

其中指出：无菌配药被定义为通过混合、稀释、汇集、重组、重新包装或其他方式改变药品或原料物质以制备无菌制剂的过程。

It says sterile compounding is defined as combining and mixing, diluting, pooling, reconstituting, repackaging, or otherwise altering a drug product or bulk substance to create a sterile preparation.

对吧？

Right?

因此对于什么是配药、什么不是配药，应该完全不存在任何混淆了。

So there should be really no confusion, right, at all of what is considered compounding and what is not.

不过从难题角度来说，还有些其他要素需要讨论——这取决于你所处的立场和对话背景。

Well, there's also some other elements that we want to talk about from a conundrum aspect is it depends on what hat you're wearing and the context of the conversation.

例如FDA对配药的定义就截然不同，因为他们决策的基础是基于审批路径。

So for example, the FDA has a very different definition of what is considered compounding, and that is because the basis of their decisions on this is about the approval pathway.

对吧？

Right?

我们都知道通过FDA审批流程的药物都经过有效性和安全性验证。

We know that drugs that go through the FDA approval process are undergone efficacy and safety.

他们已经批准了标签。

They have approved labeling.

这些标签必须满足特定要求。

They have to meet certain requirements for that labeling.

因此在FDA看来，如果你遵循已批准标签上的规定，这在他们眼中就不算复配药物，因为它已经通过了FDA的审批流程。

And so really in FDA's eyes is if you're following what is prescribed in this approved labeling, that is not considered compounding in their eyes because, again, it's been through that FDA approval pathway.

对吧？

Right?

而复配药物则没有经过这种审批流程，对吗？

Whereas drugs that are compounded have not gone through that approval pathway, right?

所以当我们阅读FDA的这些指导文件时，必须选择正确的视角来理解其中的复配定义。

So when we're reading these guidance documents from the FDA and reading things, we have to put the right hat on and view what is that compounding definition in this lens.

修订后的章节确实让这一点更加清晰，我们所有医院和医疗系统组织在修订标准操作程序和政策时，这个定义将成为我们应对方式的核心。

So certainly, the revised chapter makes that a lot more clear and is something that all of our hospitals and health systems organizations, as we revise our SOPs and our policies and prepare for these revisions, that that definition really is is central to to how we approach that.

很好。

Great.

谢谢你，凯文，做了这个回顾。

Thank you, Kevin, for that review.

就像我们之前说的，这看似基础，但其中有些复杂性。

Again, something that, like we said earlier, it seems relatively basic, but there's a bit of complexity here.

我们经常会把任何与配制静脉产品相关的活动都简单地视为复配。

So, I think so frequently we think of any activity associated with preparing an IV product as simply being compounded.

但从监管角度来看，情况并非总是如此。

But from a regulatory perspective, that's not always true.

正如你为我们详细阐述的那样，不同监管机构之间存在差异。

As you've outlined so well for us, there's differences between different regulatory bodies here.

凯文，我有个后续问题要问你。

One follow-up question for you, Kevin.

你稍微提到了关于遵循药品说明书的问题，以及FDA是否将其视为复配药物或非复配药物。

You mentioned a little bit about around the idea that you're following the package inserts and whether the FDA maybe sees that or compound and is not.

这里我要提出一个有点唱反调的问题。

A bit of a devil's advocate question here.

如果有人只是遵循药品说明书操作，且可能不符合FDA对复配药物的定义，是否可以认为USP第797章在此不适用？

If someone is simply following the package insert and perhaps not meeting the definition of compounding per the FDA, could one argue that USP seven ninety seven does not apply here?

是的。

Yeah.

感谢你的后续提问。

Thanks for the follow-up question.

这个新章节真正重要的一个方面是它提到了要按照批准的标签说明来操作。

And it's really an important aspect of this new chapter is it talks about following per the approved labeling.

但我们知道并非所有批准的标签说明都具有同等效力。

But we know that all the approved labelings are not created equal.

对吧？

Right?

因此我们确实需要审视标签说明中的具体内容。

And so we really have to look at the context of what's in that labeling.

它是否包含关于复溶、稳定性、储存条件和环境要求的信息？

Does it have information on reconstitution and the stability, the storage conditions, the environment?

我们知道有些获批的标签确实如此，而其他则不然。

We know that some approved labeling does while others do not.

因此，从复配者的角度来看，需要评估这些标签以确定其适用性。

And so from a compounders aspect is evaluating that to determine where those do apply or not.

我们是为单个患者制备的吗？

Are we making it for a single patient?

我们是在批量制备作为示例吗？

Are we making it a batch for an example?

我认为可以举两个具体例子，比如选择达托霉素这种药物。

So I think to maybe call out two specific examples, let's pick a drug, Daptomycin.

这是FDA批准的药物。

It's an FDA approved drug.

药品说明书详细说明了如何稀释这种冻干粉，包括最终浓度、如何进一步稀释后通过静脉输注给药。

That package insert outlines how to dilute this lyophilized powder, you know, what the result in concentration is, how to further dilute that to administer, you know, through an IV piggyback.

它还提到了使用环境。

It talks about the environment.

里面包含大量信息。

There's there's lots of information in there.

如果你完全按照说明书指示操作，根据现行USP和FDA标准，这不被视为复配。

So if you're following that, that package insert in the way, in the directions that's there, it is not considered compounding per now USB and the FDA.

但如果你需要调整稀释方法——可能出于患者特殊需求而改变说明书要求，

Now, if you were to put a tweak on that and say, well, maybe you want to dilute it differently than what's in the package insert, maybe for a patient specific reason that's there.

一旦你偏离说明书指示操作，就会被视为复配行为。

If you're deviating from that package insert and not following the instructions, then it would be considered compounding.

再次强调，因为你没有遵循药品说明书中规定的安全性和有效性审批路径。

Again, because you're not following that approved safety and efficacy pathway that was outlined in that package insert.

这个问题中另一个需要考虑的重要事项是：当我们混合多种已获批药物时会发生什么？

One other important thing to think about in this question too is what about when we're mixing multiple approved drugs together?

一个非常常见的例子就是缓冲利多卡因。

So a really common example is buffered lidocaine.

我们有常规生产的获批注射用利多卡因小瓶，以及同样获批的碳酸氢钠注射液。

So we have a conventionally manufactured approved lidocaine for injection vial and the same of an approved injection of sodium bicarbonate.

配制人员或从业者经常会在利多卡因小瓶中加入少量碳酸氢钠进行缓冲，用于静脉穿刺等用途。

It's not uncommon that compounders or practitioners will add a little bit of sodium bicarbonate to the lidocaine vial to to buffer it for line starts and for other purposes there.

当我们思考FDA会如何看待这种情况时，虽然这两种产品都获得了FDA批准并有各自的说明书，但这种混合制剂——缓冲利多卡因——并不存在于市场上。

Well, when we think about how the FDA would view this, right, while both of those products are FDA approved and have their individual package inserts, that combined preparation, that buffered lidocaine does not exist on the market.

目前不存在常规生产的缓冲利多卡因溶液。

There is not a conventionally manufactured buffered lidocaine solution that exists.

因此FDA会将其视为配制药物，尽管你使用的是无菌的、常规生产的原料，因为这种组合从未经过安全性和有效性评估。

And so the FDA would view that as compounding, even though you're using these sterile, you know, conventionally manufactured ingredients because it has never been evaluated for the safety and efficacy.

希望通过这些例子能帮助大家理解我们的评估思路：如何判断什么是药物配制，什么不是——即使你拥有获批的药品标签。

So hopefully through some of those examples can help to provide a little bit of guidance on our thought process of, you know, evaluating what is compounding, what is not, even if you you have that approved labeling.

很好。

Great.

谢谢，凯文。

Thank you, Kevin.

这是个非常重要的区别。

That's a very important distinction.

感谢您的评论和提供的观点。

Thank you for your review and that perspective there.

我想再请教您一个问题，如果可以的话。

I guess one one additional question I have for you, if you could.

这里关于重新包装与重新包装概念存在一些差异，以及它们如何与复合制剂相关联。

There's there's some differences here with repackaging and the concept of repackaging and how does that relate, if you will, to compounding.

您能否简要为我们讲解一下重新包装的概念？

Could you cover briefly for us the the concept of repackaging?

这与复合制剂有何关联？

How does that relate to compounding?

以及它在USP第795章和第797章之间有何不同？

And and how does it differ between USP chapter seven ninety five and seven ninety seven?

好的。

Yeah.

感谢您的跟进提问。

Thank you for the follow-up.

根据我们七月份重点关注的这个定义，我们还需要参考第795章关于非无菌复合制剂的定义。

So within this definition now that we've been focused on for July, right, we also need to look at the definition for seven ninety five for non sterile compounding.

可以看到这些定义几乎逐字相同。

So we can see that these definitions, almost word for word, are the exact same.

不过还是存在一些差异。

There are some differences, however.

当我们实际考虑在797章或无菌复合制剂背景下对特定药品或制剂进行重新包装操作时，这被视为复合制剂，相关章节将适用。

When we when we actually think about the practices of repackaging, a a given drug product or preparation in the context of seven ninety seven or sterile compounding, that is considered compounding, and the chapter would apply.

当我们考虑非无菌复配或第795章时，重新包装并不属于该定义范畴。

When we think about non sterile compounding or the chapter of seven ninety five, repackaging is is not within that definition.

所以，你知道，你会问这个问题，嗯，为什么会这样？

And so, you know, you ask the question, well, well, why might this be?

嗯，在每章的引言和范围部分，你知道，它讨论了该章的目的。

Well, in that introduction and scope of each of the chapters, you know, it talks about the purposes of the chapter.

因此，我们当然关注的是，你知道，制剂稳定性问题，无论它是无菌还是非无菌的。

So, of course, we're concerned with, you know, the stability of a preparation, whether it's sterile or it's non sterile.

所以它讨论了，你知道，与预期强度的正确成分之间的变异性。

So it talks about, you know, variability from the intended strength of the correct ingredients.

但两章之间的区别在于，显然对于无菌复配，我们关注的是成品制剂的灭菌性。

But what's different between the two chapters is, obviously, with sterile compounding, we're concerned about the sterility of the finished preparation.

而在非无菌情况下，你知道，没有灭菌要求，且给药途径也不需要它们无菌。

Whereas in July, you know, there's no requirements to have those be sterile and they're given via routes of administration that does not require them to be sterile.

因此还有其他指导文件可用于帮助非无菌液体或液体重新包装工作。

And so there's other guidances that are out there to help with repackaging of non sterile, you know, liquids or repackaging liquids.

例如，USP第1178章关于良好重新包装实践的内容，就是研究这方面时很好的起点。

And so that is, for example, USP eleven seventy eight on good repackaging practices would be a great place to start when you're when you're looking into that.

所以这是一个重要的区别点，这两种情况的复配定义都明确排除了重新包装。

So that is one important differentiation and the definition of compounding for each of these is that within repackaging.

有意思。

Interesting.

非常感谢，凯文。

Thank you so much, Kevin.

这些内容非常实用，我希望观众们能认同，理解和解析这些定义对于掌握法规及其应用至关重要。

This is really helpful and I hope our audience agrees that understanding and breaking down these definitions are critical to understanding the regulations and how they apply.

凯文指出的一个有趣区别在于FDA对复配药的定义，以及在某些情况下这与USP标准可能存在的差异。

One interesting distinction that Kevin pointed out there, specifically how the FDA defines compounding and how that may differ from USP in certain circumstances.

因此显然，在解读USP发布的标准时，理解这种差异很重要，同时也要明白这些标准与FDA文件的不同之处。

So clearly, understanding that difference is important when it comes to interpreting standards published by USP and how that differs from documents made available by the FDA.

最近，FDA根据《食品、药品和化妆品法案》第503A条发布了针对医院复配药的最新指导文件，并根据第503B条为复配药设施发布了多份文件。

Recently, the FDA released their updated guidance document for hospitals compounding under Section 503A of the Food, Drug, and Cosmetic Act and multiple documents for facilities compounding under Section 503B of the Food, Drug, and Cosmetic Act.

特里和凯莉，我想讨论下这些文件如何为复配药操作者提供额外指导。

Terry and Kaylee, I'd like to talk through how these documents provide additional guidance to compounders.

特里，或许你可以先开始，能否带我们了解下FDA关于503A复配药指导中需要考虑的重要事项？

Terry, maybe you could start could you walk us through some important considerations in this regard as it applies to the FDA's guidance on 503A compounding?

首先，根据《食品、药品和化妆品法案》第503A条，复配药品可以获得哪些豁免？

Maybe to start, where are the exemptions provided to compounded drug products under Section 503A of the FD and C Act?

谢谢，吉姆。

Thanks, Jim.

符合503A条款所有条件进行复配的药品可获得三项豁免。

Drugs compounded in accordance with all of the conditions of Section 503A are exempt from three things.

一是免除CGMP要求，二是免除使用说明标签要求，三是免除上市前审批要求。

One would be the CGMP requirements, then labeling with adequate directions for use, as well as pre marketing approval.

好的，明白了。

Okay, great.

所以需要牢记的是，必须满足五零三条款规定的所有条件，才能获得你刚才提到的这些豁免。

So it's important to keep in mind that all these conditions that must be met according to five zero three to allow for these exemptions you just outlined.

特里，你能稍微详细说明一下这些条件吗？

Could you expand on those conditions a little bit, Terry?

可以。

Yes.

第一个条件是，503条款专为根据处方进行个性化配药或在预期处方情况下限量配药而设立。

The first condition, the five zero three designation was set for patient specific compounding pursuant to a prescription or in limited quantities in anticipation of a prescription.

仅根据处方配药的药房更容易遵守503条款指南。

A pharmacy that only compounds pursuant to a prescription can more easily stay within those five zero three guidelines.

预期配药系统可能更适用于大型医疗系统药房，这些药房会向区域内各医疗点（如急诊科或手术室）分发配药。

The anticipatory compounding system may be more applicable to larger healthcare system pharmacies that distribute compounds to various health system locations within their areas, such as the emergency department or operating rooms.

另一个条件是配药必须由持证药剂师在州许可药房或联邦机构进行，或由持证医师执行。

Another condition would be that compounding is performed by a licensed pharmacist in a state licensed pharmacy or federal facility or by a licensed physician.

另一个条件是必须符合USP797-795关于药房配药的章节规定，且使用的原料药应在注册设施生产并附有效分析证书。

Another condition would be that it is in compliance with the USP seven ninety seven-seven 95 chapters on pharmacy compounding and that using bulk drug substances are manufactured in a registered facility and received and accompanied by valid certificate of analysis.

另一个条件是这些药物已退市或被FDA认定为不适合配药的产品。

Another condition is that the drugs have been removed from the market or drugs that have been identified by the FDA as a product that demonstrates difficulties for compounding.

FDA有一份可用于503条款配药的药物清单。

There is an FDA list of drugs that can be used for five zero three a compounding.

FDA已制定该清单并将可用成分分为三类。

The FDA has developed that list and has three categories those ingredients that can be used.

第一类是正在评估中且具备充分支持信息的物质。

Category one are those substances that are under evaluation and have sufficient supporting information.

还有一个考虑因素是，该条件不涉及定期大量配制基本等同于该无菌化合物的产品，且对跨州分销配药存在限制（如5%规则）。

One more consideration is that the condition does not compound regularly large quantities of products that are essentially copies of that sterile compound And that there is also a limitation in the interstate distribution of compounded drugs such as the 5% rule.

另一点是，FDA有一份谅解备忘录，规定了某些药物何时可以通过503A条款进行配制并跨州运输。

Another point was that the FDA had a memorandum of understanding describing when certain drugs could be compounded by a five zero three a and shipped out of state.

但这一规定遭到了Wellness药房对FDA的质疑。

But that was challenged by wellness pharmacy versus the FDA.

因此现在FDA将根据5%规则行使执法裁量权，该规则限制配制机构跨州分销的比例不得超过其配制总量的5%。

So now the FDA will use the enforcement discretion regarding a five percent rule, which limits the facility to 5% out of state distribution from which they were compounded.

这可能更适用于位于州界附近的药房。

And this may be more applicable to a pharmacy that is located near a state border.

好的。

Okay.

很好。

Great.

谢谢你，Terry。

Thank you, Terry.

我想FDA总共列出了大约10项条件，感谢你为我们重点介绍了一些更值得注意的内容。

I think in total, there's maybe like 10 total conditions that the FDA outlines, I appreciate you outlining some of the more noteworthy ones for us there.

能否请你帮助我理解一个我认为对收听本期播客的所有人都很重要的问题？

Could you maybe help me understand one thing that's important I think for everyone to understand, listening to this podcast.

你提到了处方要求。

You mentioned the prescription requirements.

药房经常会在处方或用药订单下达前预先配制以满足患者需求吗？

Oftentimes, pharmacies compound in advance of a prescription or advance of a medication order to meet patient needs?

作为医院药房，我们如何做到这点同时仍保持503A配制机构的身份？

How are we able to do that as hospital pharmacies and still function as a 503A compounder?

谢谢，吉姆。

Thanks, Jim.

当你谈到预期性调配时，这种调配指的是你尚未拿到患者的处方，但之后会收到该处方，因为正如我们所知，开处方者将会下达医嘱，药物随后会被使用。

When you talk about anticipatory compounding, that compounding, you do not have that patient prescription yet, but you will be getting that prescription at a later time because as we know that the prescriber is going to order that and it's going to be administered.

关于预期性调配，该指南实际上严格限定了仅适用于以下情形。

When it comes to anticipatory compounding, that guidance actually describes what is strictly limited and controlled to the following circumstance.

其中之一是药物仅在该医院或医疗系统内对患者使用，且调配药物在转出调配药房后24小时内必须使用或丢弃。

One of those being that it's only administered to a patient within that hospital or health system and that the compounded drug is used or discarded within twenty four hours after being transferred out of the compounding pharmacy.

最后一项要求是药物调配必须符合其他规定，例如不得在非卫生条件下制备，也不得存在标签不当的情况。

And the final is that the drug is compounded in accordance with other requirements such as not being made under insanitary conditions nor misbranded.

很好。

Great.

谢谢你，泰瑞，为我们做的概述。

Thank you, Terry, for that overview.

理解FDA对医院及医疗系统药房在503A条款下调配操作的期望很重要，感谢你的讲解。

It's important to understand the FDA's expectations of hospital and health system pharmacies and their compounding practices under 503A, so thank you.

换个话题，或许可以与我们503A指南稍作对比。

Switching gears, maybe contrasting a little bit with our 503A guidance.

凯莉，你能为我们描述下《食品、药品和化妆品法案》第503条对调配药物产品提供的豁免条款吗？

Kaylee, can you describe for us the exemptions provided to compounded drug products under Section five zero three of the Food, Drug, and Cosmetic Act?

当然。

Sure.

谢谢，吉姆。

Thanks, Jim.

因此，根据503b条款所有条件配制的药物，需遵守《食品、药品和化妆品法案》中适用于常规药品生产的所有规定，但需排除使用说明标签和上市前审批要求，这些要求与503a条款中规定的条件相似。

So drugs compounded in accordance with all of conditions of section five zero three b are subject to all the provisions of the Food, Drug, and Cosmetic Act that apply to conventionally manufactured drug products except labeling with adequate directions for use and premarket approval requirements, which are similar, to the provisions required, admitted under five zero three a.

此外，最后一个例外是《药品供应链安全法案》的要求。

And then additionally, the last, exception is, the Drug Supply Chain Security Act requirements.

这些实际上并不在503b条款的强制要求范围内。

Those are actually not required under five zero three b.

好的。

Okay.

很好。

Great.

所以这里有些相似，也有些差异。

So some similar, some difference here.

有个值得注意的区别，我听到Terry提到503条款的豁免包括不必符合CGMP标准。

One distinction that's noteworthy, I heard Terry mention the exemptions for five zero three including not having to meet CGMP.

但是Kaylee，你提到的503条款三项豁免中并未包含对CGMP要求的豁免。

But, Kaylee, you mentioned three exemptions for five zero three which did not include an exemption from CGMP requirements.

因此，503条款需要符合CGMP标准。

So, five zero three need to meet CGMP standards.

为什么会有这种差异？

Why is there a difference?

为什么一个503条款需要符合CGMP标准，而另一个503条款却不需要？

Why would a five zero three need to meet CGMP standards but a five zero three would not?

我认为这是个很好的问题，我们需要从全局角度来审视。

I think that's a great question, and I think we really have to look kind of, you know, from the whole picture.

FDA确实承认复合药物确实满足了患者的重要需求。

The FDA really does acknowledge the fact that compounded drugs do serve an important patient need.

但正如凯文之前提到的，这些复合药物并非FDA批准的药物。

But, you know, like Kevin mentioned earlier, those drugs compounded drugs are not, you know, FDA approved drugs.

因此，它们在某种程度上缺失了某些必要的流程。

So therefore, they've kind of missed some of the process that is required.

所以我认为FDA制定503b条款并要求其符合良好生产规范的目的，就是要明确区分复合与生产之间的界限。

And so the goal, I think, of the FDA for this dis in this distinction and to ensure that five zero three b's do meet good manufacturing requirements is they're really trying to make the distinction between compounding and manufacturing.

我想我们都同意批量复合本质上对患者安全风险更高，因为一旦出现问题可能影响成百上千名患者（取决于批量大小），而非单个患者。

I think we would all agree that batch compounding is inherently more risky for patient safety because of the risk to multiple, if not, you know, thousands of patients at a time depending on the size of the batch, not just to one individual patient.

因此我认为CGMP规范中的附加要求确实试图降低这种风险，这非常重要。

So I think additional requirements of CGMP practices do attempt to mitigate that risk, and it's very important.

同时对于503a复合机构来说，CGMP的大部分要求根本不切实际。

I think it's also, you know, for five zero three a compounders, most of the requirements of CGMP are just not practical.

举例来说，需要设立完全独立的质量控制部门专门监督生产各环节。

I mean, just some examples, you know, separate independent quality control unit that their sole responsibility is to oversee various aspects of production.

虽然我们都希望拥有这样的监管人员配置，但现实是503a复合机构根本无力承担。

I think we would all love to have that kind of staffing available in oversight, but, realistically, in a five zero three a compounding facility, we we just don't have that available to us.

还有非常严格的具体设施设计要求，大多数503a复合机构也没有这样的空间条件。

I think there's very specific strict facility design requirements that, again, most five zero three a compounding facilities are not gonna have that space available.

另外某些具体要求，比如必须在建议储存条件下进行容器密封系统测试，且每次容器或密封件制造商规格变更后都要重新测试。

And then, you know, some very specifics, the container closure closure system testing that really has to be done under the proposed storage conditions and retesting each time that a manufacturer specifications of the container or the closure is changed.

我认为这些CGMP的具体要求对503a复合机构来说几乎不可能完全遵守。

I think that those, you know, specific requirements under CGMP would actually be next to impossible for a five zero three a compounder to really abide by.

这样一来，就为503B复合制剂厂商开辟了空间。

And so that kind of opens up that space for the five zero three b compounders.

很好。

Great.

非常有趣。

Very interesting.

谢谢你，凯莉。

Thank you, Kaylee.

你刚才提到从复合制剂转向生产，通常当我想到生产时，我猜会想到能够一次性生产数千个单位的大规模操作。

You mentioned a moment ago crossing over from compounding to manufacturing and typically when I think of manufacturing, guess I think of very large scale operations capable of producing thousands of units at a time.

早些时候特里讨论503A条件时，他提到一个预期是503A每次只能复合有限数量的药物。

When Terry was discussing the 503A conditions earlier, he mentioned an expectation is that 503A's compound limited quantities of drugs at a time.

FDA是否提供了更多关于什么是有限数量的指导？

Is there any more guidance provided from the FDA around what's considered a limited quantity?

是的，实际上，FDA在2016年发布的处方要求指南中确实提供了一些指导，针对作为503A复合制剂厂商的设施，关于什么是所谓的'有限数量'。

Yeah, actually, so the FDA guidance on prescription requirements released in 2016 does provide some I guess, some guidance to facilities functioning as 503A compounders as to what would be considered, you know, quote, limited quantity.

他们基本上规定，复合产品的数量不得超过30天的供应量以满足预期处方需求，而且这30天的供应量必须基于过去一年30天期间收到的有效实际处方。

So they do provide, basically, says no more than a thirty day supply of a compounded product to fill anticipated prescriptions, and that thirty day supply has to actually be based on valid actual prescriptions received in the thirty day period over the past year.

这很不错。

Now it is nice.

FDA在同一份文件中确实提供了重新评估和根据需求调整30天期限的许可。

The FDA does, in that same document, kind of provide allowance to reevaluate, and revise your thirty day period, depending on your need.

这确实为503B设施提供了一些灵活性，让他们可以真正审查内部实践，并根据自己的工作流程确定什么是可行的。

So that does give some flexibility to five zero three facilities to really review their internal practices and and see what's practical from their own workflow.

我认为FDA也意识到，复合药物产品可能会分发给任何持有有效处方的患者或处方者。

I think the FDA, you know, also realizes that the compounded drug product, you know, might be distributed to any patient or prescriber who presents a valid prescription.

因此，这再次提供了灵活性，可以随时备有所谓的三十天供应量。

So that allows, again, that flexibility to to have that, you know, quote, thirty day supply on hand.

太好了。

Great.

谢谢你澄清这一点，凯莉。

Thank you for clarifying that, Kaylee.

这些是非常非常有价值的信息。

Very, very great information there.

我想我们时间差不多了，讨论即将结束。

I guess as we are wrapping up here, we are kind of running out of time.

感谢大家提出的精彩观点和今天的出色讨论。

So thank you all for the excellent points and for the great discussion today.

我要感谢凯文、特里和凯莉今天参与我们关于无菌复合定义及其在当前实践中应用的讨论。

I want to thank Kevin, Terry, Kaylee for joining us today to discuss definitions of sterile compounding and how these apply to current practice.

这次讨论为我们开了个好头，在下期播客中我们将继续讨论，但会稍作转向，开始探讨更新的USP第797章对无菌复合的影响及其在BUDs确立中的应用。

This is a great discussion to start us off and I think in our next podcast we'll continue our discussion but shift gears a little bit and start reviewing beyond you stating and the impacts of the updated USP Chapter seven ninety seven on sterile compounding and how that applies to the establishment of BUDs.

我非常期待与大家进行那场讨论，也希望听众们能继续参与。

I'm really looking forward to that discussion with you all and hope the audience joins us for that as well.

我还要感谢今天参与我们节目的听众。

I also want to thank our audience for joining us today.

如果你还没看过，我建议大家查看ASHP的在线资源。

You haven't before, I encourage you all to check out ASHP's online resources.

您可以找到会员专享服务，如导师工具包、研究资源中心等。

You can find member exclusive offerings such as the Preceptor Toolkit, the Research Resource Center and more.

再次感谢您收听本期《复合药物难题》节目，如果您喜欢今天的对话，请务必订阅ASHP官方播客获取精彩内容。

Thanks again for joining us on this episode of Compounding Conundrums and if you enjoyed today's conversation, be sure to subscribe to the ASHP official podcast for great content.

谢谢。

Thank you.

感谢您收听ASHP官方频道——推动医疗进步的药剂师之声。

Thank you for listening to ASHP official, the voice of pharmacists advancing health care.

请访问ashp.org/podcast发现更多精彩剧集，获取节目笔记，并下载文字稿。

Be sure to visit ashp.org/podcast to discover more great episodes, access show notes, and download the episode transcript.

如果您喜欢本期节目并想收听更多内容，请务必订阅、评分或留下评论。

If you loved the episode and wanna hear more, be sure to subscribe, rate, or leave a review.

下次ASHP官方频道再见。

Join us next time on ASHP official.