药学热点话题：复配难题——有效期解析：何为BUD，BUD非指什么

欢迎收听ASHP官方播客，我们将为您解读与药物使用、公共卫生及药学专业相关的议题。

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

大家好，感谢各位参与本期《复配难题》节目，我们将与无菌复配专家探讨当前药学领域最受关注的话题。

Hello, thank you all for joining us in 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住院医疗从业者复配实践咨询小组成员制作的三部曲系列中的第二部。

This is the second 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·隆德。

My name is Jim Lund.

我曾任复配实践咨询小组主席，现为维桑特咨询公司医院与卫生系统事业部高级总监。

I'm the immediate past chair of the SAG on Compounding Practice, and I'm currently a senior director in the Hospital and Health System Division at Vissant Consulting.

很荣幸再次与三位优秀同事共同参与，他们在全国各地负责复配业务的不同环节，同时也是部门咨询小组成员。

Again, I'm fortunate to be joined by three wonderful colleagues, some that have some aspect of compound operations throughout the country and are also members of the Section Advisory Group.

今日再次与我同台的是：Premier公司503B项目总监凯文·汉森、俄亥俄州哥伦布市全国儿童医院家庭药学经理泰瑞·拉里拉，以及阿肯色州斯普林代尔市阿肯色儿童西北医院运营经理凯莉·汤普森。

Again, joining me today is Kevin Hansen, who is the Director of 503B Programs at Premier, Terri Larilla, who is the Homecare 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.

感谢各位再次参与我们播客系列的第二期节目。

So thank you all for joining me again in the second part of our podcast series.

上期讨论中我们决定从基础概念切入，涵盖了复配的基本定义，以及《食品、药品和化妆品法案》503A与503B条款下合规复配实践的细则。

In our previous podcast discussion, we said we wanted to start with the very basics and we covered the basic definition of compounding and some of the details around what qualifies compounding practices under section 503A or 503B of the Food, Drug and Cosmetic Act.

我认为上期的讨论非常精彩，为后续探讨复配领域最新动态奠定了良好基础，这些内容我们将在未来几期播客中逐步展开。

I thought this was a great discussion last episode, and it really set the stage for some ongoing discussion around some recent updates in the compounding world that we wanted to start to touch on in these future podcast episodes.

今天我想重点讨论超越使用期限（BUD）的相关细节，包括如何设定BUD及其在不同复配产品中的应用。

So today I wanted to discuss some detail around Beyond Eustating or BUD, how we assign them and how they apply to various types of products in our compounding practice.

希望今天我们能通过从简单案例入手逐步增加复杂度的方式，系统阐述BUD在产品中的应用体系。

So hoping today we will outline the application of BUDs to products, starting with the simplest examples and then increasing complexity throughout our discussion.

那么我们从定义开始吧。

So let's start with definitions.

凯文，上期节目你最后就是用定义结束的。

Kevin, you let us off with definitions in the last episode.

所以节目一开始我又要请教你了，能否为我们解释一下'超使用期'和'失效日期'的相关定义？

So I'm gonna pick on you again here at the start, but could you break down the relevant definitions that relate to beyond use date and expiration date for us?

听起来不错。

Sounds good.

非常感谢你，吉姆。

Thank you so much, Jim.

深入探讨这些定义，我认为对展开对话很有帮助。

So really getting into these definitions, I think will be great to start this conversation.

我们使用的术语包括：失效日期、超使用期、输注时间、悬挂时间、使用中时间、弃用时间。

And so we have terms that we use such as expiration date, beyond use date, infusion time, hang time, in use time, discard time.

最好先理解每个术语的应用场景以及由谁来设定这些期限。

And so it would be good to start with understanding the application of each of these and who is assigning it.

我们就从失效日期开始吧。

So let's start with the expiration date.

失效日期适用于常规生产的药品、原料药、添加剂等，通常由生产商根据大量分析和性能测试结果设定，这些测试方法需符合CGMP规范并经过验证。

Expiration dates are assigned to conventionally manufactured products, APIs, added substances, and these are generally assigned by the manufacturer and are based on extensive analytical and performance testing, usually with validated methods following CGMP.

在考虑失效日期时，这点非常重要。

So that's really important as we think about expiration date.

让我们思考常规生产产品在启用前的储存使用时限问题。

Let's think about those conventionally manufactured products as far as that time of use for storage before it can be used there.

现在，当我们考虑使用期限时，显然会看到关于适用于化合物的定义，并由药房或负责配制这些无菌制剂的人员（如USP 797标准下的情况）来指定。

Now, when we think about beyond use date, we obviously see the definition about applying to compounds and having it being assigned by the pharmacy or whoever's compounding these compounded sterile preparations in the case of USB seven ninety seven.

这个禁止使用、储存或运输的时间是根据制剂配制的日期和时间来确定的。

And is that time that it must not be used, stored or transported is determined from the date and the time that preparation is compounded.

因此，对于配药人员来说，深入理解使用期限状态的定义将非常重要。

So that will be really important for compounders is to lean in to that definition of beyond use state.

正如我们讨论过的其他定义，还需要理解我们现有标准的适用范围。

Now, as we talked about some of these other definitions is also to understand the scope of the standards that we have.

例如，USP 797标准是关于什么的标准？

So USP seven ninety seven, for example, is a standard on what?

它是关于配药的标准。

It's a standard on compounding.

因此，一旦开始给药，比如说无菌制剂的使用，本章节的适用范围就结束了。

And so once administration begins, let's say of a compounded sterile preparation, the scope of the chapter ends.

我认为这是重要的背景信息，当我们考虑输液时间和悬挂时间时，因为这超出了本章节的范围。

So I think it's important context as we start thinking about our infusion time and hang time because that is beyond the scope of the chapter.

这部分通常由我们的护理同事负责，针对医疗环境中使用的细胞制剂。

So this is generally assigned by our nursing colleagues for compounded cell preparations that are used within healthcare settings.

我们可以从输液护士协会、CDC等机构获取相关指导。

And we can get guidance on this from Infusion Nurse Society, the CDC, for example.

还有其他一些组织也能提供这方面的指导。

And there's some other organizations that can give some guidance about this.

但本质上，这是指输液在使用前允许的时长，超过这个时间就必须撤下或更换。

But essentially, it's that time, that allowable length of time for an infusion to be used before it must be taken down or exchanged.

因此我们当然要考虑更换管路和穿刺液体时的无菌因素。

And so we think about, of course, sterility factors from exchanging and taking out lines and spiking those fluids.

关键在于最后的无菌混合或对袋装液体的操作。

It's really that last aseptic admixture or manipulation of that bag.

我们还需要考虑这些成分的稳定性。

We do have to factor in the stability of those components as well.

在药房端，我们在确定超期使用状态时需要考虑很多因素，比如这种疗法将持续使用多长时间？

So on the pharmacies end, as we can do a lot to consider when we assign a beyond use status to factor in, well, what's the length of time that this therapy is going to be used?

我们是否需要考虑这种制剂存在稳定性问题，从而影响其超期使用日期或分发策略？

And do we have stability concerns for this preparation that we need to factor in to that beyond use date or maybe the dispensing strategy?

或许不应一次性分发多日用量，而是制备更小份的分装。

Maybe not dispensing multiple days at a time worth, but creating a smaller aliquot.

最后一个术语类别是使用中时限或弃置时限。

And the last bucket of terms is this in use time or maybe this discard time.

你会注意到修订版USP797中完全没有使用这个术语。

So you'll see that this term is not used in the revised USP seven ninety seven at all.

但在FDA传统制造产品的包装说明书中，仍常见于获批标签。

However, it is still used a lot in approved labeling that you'll see within FDA package inserts for these conventionally manufactured products.

许多人仍称之为超期使用状态。

Many do still call this beyond use state.

这是恰当的。

It is appropriate.

但需要考虑的是，具体用途有所不同，对吧？

However, the one thing to think about is that the use is different, right?

通常我们会考虑使用后的状态，使用即意味着给药的开始。

Generally, we think about beyond use state, the use is the start of administration.

当我们讨论使用时间或丢弃时间时，指的是常规生产的产品——我们正在接触的容器密封系统，其中装有无菌药品或可能需要重新配制的药品。

When we talk about in use time or discard time, we're talking about a conventionally manufactured product that we're accessing that container closure system that contains that sterile drug product or maybe reconstitution.

计时器启动的时机大约是在你需要使用该容器内药品时，这种使用是为了配制复合无菌制剂，而不应用于限制最终制剂的后续使用状态。

And that timer starts about when you need to use the contents of that container and that use is for compounding a compounded sterile preparation and should not be used to limit the beyond you state of whatever that final preparation is.

以上就是我认为能为后续讨论奠定基础的主要定义。

So that's really the main definitions that I think will set the context for the rest of this conversation.

那么我把话筒交还给你，吉姆。

So I'll yield it back to you, Jim.

很好。

Great.

谢谢你，凯文。

Thank you, Kevin.

像往常一样，一开始就回顾这些定义很有帮助。

As always helpful to kind of review the definitions right off the bat here.

有些事看似简单，但当你开始全面比较时，可能会让情况变得稍微复杂些。

Some things seem so simple, but yet as you start to compare them all, could make it a little bit more complicated.

希望通过我们的讨论，这些问题能逐渐明朗起来。

So hopefully as we walk through this, some of this will become more clear.

如我之前提到的，我们将从最简单的产品案例开始，讨论如何应用有效期规定。

As I mentioned earlier, we'll we'll kinda start with maybe the simplest examples of products and how BUDs are applied.

然后我们会逐步增加复杂度。

We'll we'll increase in complexity.

我在这里快速过一遍最简单的场景，我们或许可以从原料产品或常规制造产品开始讲起。

I'll quickly here just go through the simplest scenarios, and we'll start maybe with source products or conventionally manufactured products.

简单回顾一下，单剂量小瓶可能是最典型的例子。

And a quick review here, single dose vials are probably the simplest example.

对于单剂量小瓶，希望大家都比较熟悉。

So for single dose vials, hopefully we're all familiar.

它们必须在ISO五级或更洁净的空气环境中穿刺使用。

They must be punctured in an ISO five or cleaner air environment.

只要满足规定的储存条件，穿刺后可使用长达12小时。

And if doing so, they're able to be used up to twelve hours as long as the required storage conditions are met.

这与2008版或现行USP第797章规定的6小时使用期限有所不同。

And that's a change from the 2008 or the currently enforceable version of chapter USP seven ninety seven where that timeline is a six hour BUD.

类似地，我们还有单剂量安瓿瓶，但处理方式会大不相同。

Similarly, we have single dose ampoules, but we will think of these very differently.

单剂量安瓿瓶一旦折断瓶颈，自那一刻起就不允许再储存了。

So single dose ampoules, once you, you know, crack the neck of that ampoule per se, those products, there's no longer storage time allowed once that initial entry point is made.

如果考虑更复杂的情况，我们会涉及到多剂量小瓶。

If we go a little bit more complex, we get into multi dose vials.

这类小瓶的设计允许多次抽取内容物。

So these are vials formulated for removal of portions of contents on multiple occasions.

它们含有抗菌防腐剂以实现这一功能。

They contain antimicrobial preservatives to allow for that.

除非制造商另有说明，否则这些产品可使用28天。

And these can be used for twenty eight days unless otherwise stated by the manufacturer.

最后，从原包装的角度来看，我们有药房大包装，这些是供配药使用的无菌产品容器，内含多个单次剂量，但不适用于直接输注。

And then lastly, from a source container perspective, we have pharmacy bulk packages and these are containers of sterile products used for parental use that contain multiple single doses, but they're not intended for direct infusion.

它们必须仅在ISO五级空气环境中进行开封或穿刺操作。

They must be entered or punctured again, only in an ISO five air environment.

不允许在ISO五级环境之外使用这些产品，且必须按照制造商的标签说明使用。

It's not permissible to use these outside of that ISO five environment, and they must be used according to the manufacturer's labeling.

这类产品的常见例子包括某些抗生素。

So some examples of of these, commonly, there's some antibiotics out there.

比如万古霉素、萘夫西林等，它们都装在标有PVP或大包装字样的容器中。

I think vanco, naficil, and they all come in a container that's labeled as a PVP or bulk package.

许多人可能熟悉标为PVP的10克装万古霉素小瓶这类例子。

Many folks are probably familiar with, like, a 10 gram vanco vial as an example that's labeled as a PVP.

其制造标签注明，例如重构后的小瓶内容物应在四小时内用完。

Its manufacturing labeling indicates that the contents of the vial after reconstitution should be removed within four hours, for example.

因此这些内容大多并非新信息。

So most of this is not new information.

如前所述，修订版第797章的最大变化是将单剂量小瓶在ISO五级空气条件下的使用时限从6小时延长至12小时。

As mentioned previously, the one big change in the revised chapter seven ninety seven is the extension for single dose vials going from six hours to twelve hours in that ISO five air condition.

新章节中多剂量小瓶和药房大包装的标准保持不变。

The standards for multidose vials and pharmacy bulk packages remain the same with the new chapter.

如前所述，关键条款之一是：根据制造标签说明，单剂量小瓶使用12小时或药房大包装使用更长时间的前提是——这些产品需在ISO五级空气条件下穿刺并保存。

So as mentioned, one of, the key provisions of using single dose vials for twelve hours or using pharmacy bulk packages for longer durations as indicated by the manufacturing labeling is the expiration that these products or the expectation that these products are punctured and maintained within ISO five air conditions.

但若未满足这些条件，产品在ISO环境外被穿刺，则需立即适用第797章规定的即刻使用条款。

However, if those conditions are not met and products are punctured outside of the ISO environment, venture into the immediate use provision outlined at seven ninety seven.

我们稍后会在这里讨论这个问题。

We'll talk about that in a moment here.

但最后，我想我们经常听到一个常见问题，特别是在SAG中，我们通过连接板看到这个问题，也听到关于将单剂量小瓶从ISO五级环境中移除的疑问。

But lastly, one common question I think we often hear, particularly in the SAG, I think we see this coming through some of the connect boards as well as we hear questions around removing the single dose vial from that ISO five environment.

我认为在旧章节中，关于这一点是否明确存在很多疑问。

And I think in the old chapter, there were a lot of questions around whether this was clear or not.

在修订后的第797章中，现在允许将产品从ISO五级环境或您的主要工程控制中移除。

In the revised chapter seven ninety seven, you're now allowed to remove products from the ISO five environment or from your primary engineering control.

只要您按照制造商批准的标签存储产品，就可以维持12小时的使用期限（BUD）。

And you can maintain that twelve hour BUD as long as you store the product according to the manufacturer's approved labeling.

例如，如果您有一个冷藏的单剂量小瓶在ISO五级主要工程控制下穿刺，您可以将其从ISO五级环境中移除，并保持在标签批准的冷藏存储条件下。

So for example, if you have a refrigerated single dose vial that you puncture on the ISO five primary engineering control, you can remove it from the ISO five environment and keep it within the refrigerated storage condition as approved by the label.

您仍然可以从它在ISO五级主要工程控制下首次穿刺的时间开始计算12小时的使用期限。

And you can still tie that twelve hour BUD from the time it's initially punctured in the ISO five primary engineering control.

但再次强调，您必须达到批准的标签存储条件才能继续使用这12小时的使用期限。

But, again, you must achieve those approved labeling storage conditions to continue using that twelve hour BUD.

那么，Terry，您能否带我们回顾一下我提到的关于即时使用CSPs的标准？

So, Terry, could you perhaps walk us through I mentioned the standards around immediate use CSPs.

所以，如果我们开始进入在主工程控制之外穿刺小瓶的情况，您能否为我们概述从2008年章节到新修订章节中关于即时使用CSPs的变化？

So, again, if we start to get into the world where we're puncturing vials outside outside of the primary engineering control, could you outline for us what's changed from the 2008 chapter to the newly revised chapter as it applies to immediate use CSPs?

谢谢你，Jim。

Thank you, Jim.

即时使用CSPs适用于直接且立即给药的CSPs配制。

Immediate use CSPs applies the compounding of CSPs for direct and immediate administration.

若满足特定条件，则不受第一、第二或第三类CSP要求的约束。

It is not subject to the requirements for category one, two, or three CSPs if certain criteria are met.

首先，我们需要确保使用无菌技术和流程，并有书面政策和程序或标准操作规程作为支持。

First off, we need to ensure that aseptic techniques and processes are being used, and these are backed up by written policies and procedures or SOPs.

现有流程必须最大限度减少来自非无菌表面、颗粒物或生物体液的潜在污染，并防止与其他生产产品或CSP混淆。

The process in place has to minimize the potential contamination from non sterile surfaces, particulate matter, or biological fluids, as well as to prevent mix ups with other manufactured products or other CSPs.

这意味着要在尽可能清洁的区域进行操作。

What this means is to work in an area as clean as possible.

使用酒精棉片等消毒剂清洁操作部位或工作台。

Use disinfectants like alcohol swabs to clean sites or work trays.

建议佩戴口罩以防止呼吸颗粒造成污染。

You may want to wear a mask to prevent contamination from breath particles.

配药区域应保持有序以防止配药错误。

The compounding field should be organized to prevent errors in compounding.

第二点，配药人员（包括药剂师、技术人员或护士）需接受相关无菌操作培训，并具备验证其操作能力的资质。

The second point, compounding personnel, either pharmacists, technicians, or nurses, need to be trained in the aseptic processes that they are doing and have a competency that validates that they can do it.

第三点，混合、稀释和配制过程需基于说明书或其他稳定性/相容性参考文献等循证信息。

The third point, the mixing, diluting, and preparation is grounded by evidence based information, such as package insert or other stability or compatibility references.

第四点，即时使用产品涉及不超过三种不同无菌产品。

The fourth point, the immediate use product involves not more than three different sterile products.

第五点，单剂量容器仅供一名患者使用，CSP配制完成后即弃置。

Five, single dose containers are only used for one patient, and it is discarded after CSP preparation is complete.

第六点，给药必须在配制过程开始后四小时内进行。

Six, administration has to begin within four hours following the start of the preparation process.

若四小时内未开始给药，则该制剂必须立即、妥善且安全地废弃。

If administration is not started within four hours, then that preparation must be promptly, appropriately, and safely discarded.

最后第七点：若即用产品非由配制者给药，则必须进行标签标注。

And finally, the seventh point, if immediate use product is not administered by the person who prepared it, then it must be labeled.

或者，若配制者未亲眼见证产品给药过程，则必须进行标签标注。

Or, well, if the person that prepared it does not see the product being administered, then it must be labeled.

标签标注要求包括：活性成分名称及用量、制剂者姓名或首字母缩写，以及必须开始给药的具体四小时时限。

By labeled, it means to have the names and amounts of the active ingredients, the names or initials of the person who made the preparation, as well as the exact four hour time when administration has to begin.

非常好。

Excellent.

谢谢你，特里。

Thank you, Terry.

这个回顾总结得很到位。

That was a great review.

你刚才在概述中提到不应涉及超过三种不同的无菌产品。

You mentioned not involving more than three different sterile products in that outline there.

能否具体说明这三种不同无菌产品的含义？

Can you tell us more about what the three different sterile products mean specifically?

这与之前的即用标准相比有何不同？

And then how does that compare to the previous immediate use standards?

感谢这个需要澄清的问题。

Thank you for that clarifying question.

此前，公司即用流程的表述包含容器、针头穿刺容器等术语，且产品不得具有危险性。

Previously, the immediate use company process included language like containers, needle sticks into the containers, and the products could not be hazardous.

请注意，这里变更为三种不同的无菌产品。

Notice that the change to three different sterile products.

在家庭护理中，由于稳定性考虑，英夫利昔单抗由护士在家中进行混合配制。

In home care, because stability, infliximab is a home mix by a nurse.

他们需要重新配制，比如六瓶100毫克的英夫利昔单抗，抽取后加入生理盐水袋中。

They reconstitute, let's say, six vials of infliximab one hundred milligrams and withdraw that and add to a bag of saline.

这样总共需要6×2+1=13个容器，但实际上只有三种无菌产品。

So that would be six times two plus one for 13 containers, but it's really just three sterile products.

有意思。

Interesting.

那么从1小时时限改为4小时，在这种情况下如何适用？

So how would the change from a one hour limit to four hours apply in a situation like this?

假设家庭护士先建立了静脉通路，然后重新配制并准备好英夫利昔单抗。

So let's say that that nurse in the home started an IV and then reconstituted and prepared the infliximab.

等到他们准备给药时，静脉通路可能已经失去通畅性。

By the time they went to administer the IV, that IV access could have lost patency.

以前我们只有1小时的时间窗口来开始输注英夫利昔单抗。

Before, we would only have one hour window to get that infliximab started.

现在我们有4小时。

Now we have four hours.

如果需要，我们可以呼叫另一名护士重新建立静脉通路完成输注。

And if needed, we can call another nurse to get another IV placed and that infliximab infused.

需要说明的是，虽然最长使用时限是4小时，但这并不意味着必须用满4小时。

Now that being said, even though the beyond use time is four hours, that does not mean that the four hour limit has to be used.

想想那些为护士或麻醉师制定的标准化流程，甚至是手术室里的程序，还有家庭输液患者被教导如何在配置全肠外营养液（TPN）和输液泵时添加多种维生素等操作。

Think about the standardized processes that have been put in place for nursing or anesthesiologists or in the OR or even how home infusion patients have been taught to add, like, multivitamins to a TPN when setting up with the TPN and pump for administration.

仅仅因为你能做到，并不意味着你必须挑战极限。

Just because you can does not mean that you have to push the limit.

有意思。

Interesting.

谢谢特里为我们概述这些内容。

Thanks Terry for outlining that for us.

让我们回到药房内部配置的产品话题。

Let's shift back to products compounded within the pharmacy.

我们已经讨论过如何为常规生产的原料产品（包括西林瓶、安瓿瓶和预充式注射器）分配使用期限的问题。

We covered the use of conventionally manufactured products on how to assign BUDs to these source products, vials, ampoules, PVPs.

我认为药房通常还会制备储备溶液，或者特殊稀释浓度的大袋装/大瓶装产品，作为将来配置其他无菌制剂的原料。

I think it's also common practice for a pharmacy to create a stock solution or perhaps a bulk bag or bulk vial of a special dilution to be used as a source for compounding other sterile products in the future.

凯莉，或许该请你来谈谈这个问题。

Kaylee, maybe I'll ask you to jump in here.

你能为我们概述一下797标准对这种情形有哪些规定吗？

Could you outline what the seven ninety seven standards say about this scenario for us?

当然。

Sure.

谢谢吉姆给我机会讨论这个话题。

Thank you, Jim, for the opportunity to discuss this topic.

复合储备溶液是一种用于制备其他无菌制剂的复合无菌产品，在为新生儿和儿科患者提供配置服务的机构中相当常见。

A compounded stock solution is a compounded sterile preparation utilized to prepare other CSPs and is pretty commonplace in facilities that compound for neonate and pediatric populations.

这一流程通常需要将多个单剂量瓶装的常规生产产品混合，有时会配制出大容量的储备溶液袋。

This process typically involves combining sometimes multiple single dose vials of a conventionally manufactured product to make a compounded stock bag sometimes a very large volumes.

该流程确实缩短了患者专用剂量的周转时间，并减少了需要进行的稀释次数。

This process does decrease turnaround time for patient specific doses and decreases the number of dilutions that have to be made.

为每位患者专用剂量单独配制稀释液会导致药物浪费增加、时间浪费，以及每剂所需操作显著增多。

Making a dilution for each patient specific dose would lead to increased drug waste, wasted time, and significantly more manipulations per dose.

现行可执行的USP797版本中未涉及储备溶液的相关规定。

Stock solutions are not addressed in the current enforceable version of USP seven ninety seven.

不过在更新版USP指南第16节中，提供了关于使用CSP作为原料来配制最终CSP的一些信息。

However, in section 16 of the updated USP guidance, there is some information on the use of CSPs as components to prepare final CSPs.

谢谢你凯莉的解释和背景说明。

Thank you, Kaylee, for that explanation and that background.

那么更新版指南对使用这些储备溶液的配制者提供了哪些关于Beyond You声明的指导？

And what kind of guidance for Beyond You stating does the updated version provide for compounders using these stock solutions?

当CSP作为原料使用时，我们必须非常谨慎，以最大限度降低起始原料CSP和最终CSP的污染风险。

So when a CSP is used as a component, we have to be very careful to minimize the risk of contamination of both the starting component CSP as well as the final CSP.

用于配制最终CSP的原料CSP必须根据第14节规定设定有效期，并在未使用时按其有效期要求储存。

The component CSP that we're using to make a final CSP must be assigned a BUD that is consistent with section 14 and must be stored under conditions for its assigned BUD when not in use.

当配制单剂量CSP和CSP储备溶液作为原料用于配制其他CSP时，只要原始原料CSP是在ISO5级或更洁净环境中穿刺或开封，并按其有效期要求储存，就可视为常规生产的单剂量容器。

When a compounded single dose CSP and a CSP stock solution is used as a component to compound additional CSPs, the original component CSP is treated as a conventionally manufactured single dose container as long as it is punctured or entered into in an ISO class five or cleaner air and stored under the conditions which its BUD is based.

因此正如我们之前讨论的，根据稳定性不同，有效期通常为12小时或更短。

So for this, and as we've previously discussed, this would typically be twelve hours or shorter depending on stability.

如果原料CSP符合多剂量CSP标准，则实际上可以适用不同的有效期规定。

Now, if a component CSP meets the criteria for a multiple dose CSP, then different BUDs actually can be applied.

大多数机构可能不太会配制多剂量CSP，因为这些通常含有防腐剂，需符合抗菌效果测试标准，并且必须通过容器密封完整性测试。

Most facilities are probably unlikely to be compounding multiple dose CSPs as these usually contain a preservative, meet the criteria for antimicrobial effectiveness testing, and must be tested and conform to container closure integrity test.

然而，如果有机构使用组分CSP，且已通过各项复杂程序并能将其作为多剂量CSP使用，则可赋予其28天有效期（BUD），或可能更短。

However, if there is a facility that is utilizing a component CSP, that they have jumped through these hoops and are able to use it as a multidose CSP, then it would be assigned a twenty eight day BUD or potentially shorter.

谢谢凯莉的详细区分。

Thanks, Kaylee, for that distinction.

我认为一个常见问题是：这如何影响最终CSP产品的有效期？

A question I think that commonly comes up is how does this impact the BUD of the final CSP product?

更新后的USP七月版本是否对此提供了指导？

Does the updated USP July version provide guidance on this?

确实提供了。

It does actually.

根据修订后的USP指南，只要原液储存条件适当且在隔离器洁净空气中操作，对组分CSP穿刺或启封的时间限制并不旨在约束最终CSP的BUD。

So per the revised USP guidance, time limit for entering or puncturing of the component CSP, provided the stock solution was stored under appropriate conditions and entered in isofiber cleaner air, it is not intended to restrict the BED of the final CSP.

我们来看个例子。

So let's look at an example.

某医院用常规生产产品配制40毫克/毫升的头孢曲松1000毫升袋装原液，在洁净室中使用，并赋予该原液冷藏条件下10天有效期。

A hospital compounds a ceftriaxone forty milligram per mil, one thousand mil bag from conventionally manufactured products to use as a stock solution in a clean room suite and assigns that stock bag a ten day BUD at refrigerated temperature.

该头孢曲松原液袋在48小时后被穿刺，穿刺后标记12小时有效期。

That ceftriaxone stock bag is then punctured forty eight hours later and labeled with an appropriate twelve hour BUD once punctured.

用该CSP原液配制的最终CSP产品，其有效期可沿用原液剩余的有效期天数。

Final CSPs made from the stock CSP may be assigned a BUD of what's remaining on the original ten day BUD from the CSP stock.

就本例而言，技术上可以说还有8天剩余有效期。

And for our example here, we could technically say it would have eight additional days.

目前存在一些讨论，关于将复合CSP临时储存一段时间后再次使用是否是最佳实践，这会进一步增加微生物污染的风险。

Now there is some discussion about whether this would be considered best practice as the compounded CSP is stored for an interim period of time, then accessed again, further increasing the risk of microbial contamination.

不过根据指南，这种做法是被允许的。

For the guidelines though, this would be allowed.

我认为这为各机构留下了讨论空间，可以制定最适合其场所的政策。

I do believe this leaves open some discussion within facilities to write policies that would be best for their site.

我们在讨论储存时间时，另一个需要考虑的因素是评估制备的储备溶液体积。

An additional point to consider when we're talking about storage times would be to evaluate the volume of stock solution prepared.

美国药典(USP)没有针对这个具体问题提供指导。

USP does not provide guidance on this particular issue.

然而，如果配制者制作一个3000毫升的储备袋，并在接下来12小时内为患者特定剂量取用75到100次，就会引发许多合理的担忧。

However, many valid concerns are raised if a compounder is making, say, a 3,000 mil stock bag and accessing that bag 75 to a 100 times over the next twelve hours for patient specific doses.

替代方案是考虑使用多个较小的储备溶液袋或小瓶，以降低污染风险。

The alternative approach would really be to consider multiple smaller stock solution bags or vials to decrease that risk of contamination.

有意思。

Interesting.

谢谢你，卡丽。

Thank you, Carrie.

这是个很好的例子。

That's a great example.

我们确实经常用这个来思考和考虑很多问题。

And certainly we use this a lot to think about and a lot to consider.

感谢你涵盖了这些考虑因素。

So thank you for covering those considerations.

每个人都提出了非常棒的观点。

Excellent points made by everybody.

我要感谢在座的各位今天精彩的讨论。

And I wanna thank the group here for the great discussion today.

遗憾的是，我们今天的时间就到这里了。

Unfortunately, it's all the time we have today.

我要感谢凯文、特里和海莉再次加入我们，并回顾BUDs的建立及其在当前实践中的应用。

I wanna thank Kevin, Terry and Haley for joining us again and to review the establishment of BUDs and how these apply to current practice.

这是第二次非常棒的讨论。

This is a great second discussion.

我期待继续推进我们的《复合难题》播客。

I'm looking forward to continuing our Compounding Conundrum podcast going forward.

在下期播客中，我们将更深入地探讨并回顾新的一类、二类和三类分类及其对实践的意义。

In our next podcast, we're gonna focus a little bit more and review the new category one, two, and three classifications and what they mean for practice.

非常期待下次再聚首进行讨论。

So definitely looking forward to getting together again for that discussion.

我还要感谢今天参与我们节目的听众。

I also wanna thank our audience for joining us today.

如果之前没有了解过，我建议大家去看看ASHP的在线资源，包括我们都很期待的新更新的复合资源中心。

If If you haven't before, I would encourage you all to check out ASHP's online resources, including the newly updated Compounding Resource Center that we're all very excited about.

ASHP还新建了一个关于复合的Connect社区，这是一个在线论坛，鼓励成员们就无菌与非无菌复合以及危险药物安全相关的问题提问和解答。

ASHP also has a new Connect Community on Compounding, which is an online forum where members are encouraged to ask and answer questions related to sterile and non sterile compounding, as well as hazardous drug safety.

这个Connect社区非常活跃，我建议大家去看看。

This has been a very active Connect Community and something I would encourage everybody to check out.

再次感谢您收听本期《药学热点话题》。

Thanks again for joining us on this episode of Hot Topics of Pharmacy.

如果您喜欢今天的对话，请务必订阅ASHP官方播客，获取更多精彩内容。

And if you enjoyed today's conversation, be sure to subscribe to the ASHP official podcast for more 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获取更多精彩剧集、查看节目备注并下载文字稿。

Be sure to visit ashp.org/podcast to discover more great episodes, access show notes, 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 want to hear more, be sure to subscribe, rate, or leave a review.

下次ASHP官方节目再见。

Join us next time on ASHP official.