下圖中這里所謂的物品可變，更多的實踐是滅菌物品數量可變（滅菌物品本身以及擺放位置不可變），今天分享的是PDA Journal上的一些思路。

Flexible Loading Pattern Approach in Overkill Steam Sterilization Based on the Physical Properties of Steam and Thermodynamics of Sterilization

基于蒸汽的物理特性和滅菌熱力學的過度殺菌蒸汽滅菌中的靈活裝載模式方法。

ABSTRACT: Because overkill steam sterilization processes in autoclaves are considered critical, they are highly scrutinized, and the use of autoclaves in fixed loading patterns is a common approach to the interpretation of regulatory requirements. Many such regulations are attributed to tradition and a buildup of restrictions that aim to improve the levels of assurance of the process and minimize risk. However, these measures complicate the operation and qualification of autoclaves, becoming cumbersome, time-consuming, and costly. In actuality, overkill sterilization is one of several processes in the pharmaceutical industry that provides the highest levels of sterility assurance. This method provides a minimum reduction of highly durable spore populations of 12 logs, achieving a probability of a nonsterile unit (PNSU) of 10-6. The physical properties of steam and the thermodynamics of steam sterilization constitute a predictable and repeatable process that can be monitored and verified. The high assurance level of overkill sterilization, combined with the properties of steam, actualizes a high safety margin that encompasses nearly every load type and load configuration when the cycle is performed under certain basic rules. The aim of this article is to present data that advocate and favor an approach that allows greater freedom and variability in arranging items in an autoclave when running overkill cycles, without the need to qualify each configuration.

摘要：因為高壓蒸汽滅菌過程在滅菌器中被視為關鍵過程，它們受到嚴格的審查，使用固定裝載模式的滅菌器是解釋監管要求的常見方法。許多這樣的規定歸因于傳統和限制的積累，旨在提高過程的保證水平并將風險降至最低。然而，這些措施使滅菌器的操作和確認復雜化，變得笨重，耗時，昂貴。實際上，過度殺滅法是制藥工業中提供最高無菌保證水平的幾個過程之一。這種方法至少能將非常耐用的孢子群體減少12個logs，從而實現非無菌單元（PNSU）的概率為10−6。蒸汽的物理性質蒸汽滅菌的熱力學構成了一個可預測和可重復的過程，可以監控和驗證。過度殺菌的高保證水平結合蒸汽的特性，在遵循一定基本原則的情況下，實現了一個高安全邊際，幾乎涵蓋了所有類型的裝載和裝載配置。本文的目的是提出數據，支持并傾向于一種方法，該方法在運行過度殺菌周期時，允許在高壓蒸汽滅菌器內安排物品時有更大的自由度和可變性，無需對每種配置進行驗證。

 

1、在安全邊際的更安全一側

 

On the Safe Side of Safe Side

 

Overkill Cycles  過度殺滅周期

 

Steam sterilization is one of the most common and important practices in parenteral manufacturing, bound by many rules and regulations. In a routine inspection, the validation, maintenance, and operation of an autoclave are usually examined thoroughly. Without downgrading the criticality of steam sterilization, many requirements are derived from the definition of “critical”, even when there is no scientific basis for the requirements. In other cases, the requirements are extended far beyond what is really needed to be “on the safe side”.

蒸汽滅菌是輸液制造中一種最常見且重要的實踐，受到許多規則和法規的約束。在常規檢查中，通常會對高壓蒸汽滅菌器的驗證、維護和操作進行徹底的檢查。在不降低蒸汽滅菌關鍵性的前提下，許多要求源自“關鍵”一詞的定義，即使這些要求沒有科學依據。在其他情況下，為了“更安全”，要求被擴展到了真正需要的范圍之外。

The rationale of the overkill cycle was that it would allow more flexibility in sterilization, due to the high safety margins that it provides to compensate for potential variation in this process. The premise of overkill cycles is that the bioburden population and its resistance can be ignored, because they are irrelevant to the outcome. This genuine benefit is eliminated, because in actuality, overkill sterilization cycles are restricted by additional regulatory requirements and “expectations” to inflate the safety margin. The requirement for fixed loading patterns is one of the most burdensome of these principles.

過度殺菌周期的原理是，由于它提供了很高的安全邊際來彌補過程中可能出現的變化，因此它將允許在滅菌中有更多的靈活性。過度殺菌周期的前提是，可以忽略生物負荷的種群數量和其抗性，因為這些與結果無關。這種真正的好處被消除了，因為在現實中，過度殺菌周期受到額外的監管要求和“期望”的限制，這些要求和期望增加了安全邊際。固定裝載模式的要求是這些原則中最繁重的一個。

 

2、固定裝載模式的要求

 

Requirements of Fixed Loading Patterns

 

In a fixed loading pattern, the items that are to be sterilized are arranged according to a scheme or depiction that shows their exact number, size, position, and orientation in the chamber. This arrangement is validated, and if all the acceptance criteria are met, the load is approved for production. If a new item is added to a validated load, the load is considered to be new, and the validation must be repeated. The same process applies to items that have been validated in other loads and, due to changing production requirements,must now be sterilized with other items in a different load

 

在固定裝載模式中，待滅菌的物品根據方案或圖示所展示的它們的確切數量、大小、位置和方向在腔室內進行排列。這種排列方式經過驗證，一旦滿足所有接受標準，裝載量就會被批準用于生產。如果向經過驗證的裝載量中添加了新物品，則該裝載量被視為新的裝載量，必須重新進行驗證。同樣的過程也適用于那些在其他裝載量中已經經過驗證的物品，由于生產需求的變化，現在必須與其他物品一起在不同的裝載量中進行滅菌。

The roots of this method date back to the 1970s, when many practices that were related to large-volume parenteral (LVP) sterilization were universally adopted by the small-volume parenteral (SVP) industry, regardless of their use in a different setting (5). At that time, when gravity displacement autoclaves were used in many facilities, this principle was justified. Since then, autoclave design has evolved considerably, with the advent of vacuum and steam pulses to remove air from porous loads and greater control over temperature and pressure in the chamber. In contrast, validation practices have remained almost unchanged.

這種方法的根源可以追溯到20世紀70年代，當時許多與大容量腸外（LVP）滅菌相關的實踐被小容量腸外（SVP）行業普遍采納，而不管它們在不同設置中的使用情況。當時，許多設施使用的是依靠重力置換的滅菌器，這一原理在當時是合理的。從那時起，隨著真空和蒸汽脈沖技術的出現，用于從多孔負載中去除空氣，以及對腔室內溫度和壓力的更嚴格控制，滅菌器的設計已經發生了顯著的演變。相比之下，驗證實踐幾乎沒有任何變化。

In certain firms, only exact, validated loads are allowed to be run—if for example, just 1 of the 20 items that are validated in the full load is needed, the entire load must be prepared (i.e., washed, bagged, and arranged) and sterilized. To this end, some firms use maximal and minimal load cycles (Max-Min approach), which provides more flexibility. But, when a new item isrequired or validated loads must be combined, the new load needs to be validated again before use

在某些公司，只允許運行確切經過驗證的裝載量——例如，如果只需要運行已在完整裝載量中驗證的20個項目中的1個，那么必須準備整個裝載量（即，洗滌、包裝并排列）并進行滅菌。為此，一些公司使用最大和最小裝載周期（最大-最小方法），這提供了更多的靈活性。但是，當需要一個新的項目或必須組合經過驗證的裝載量時，新的裝載量在使用前需要重新驗證。

The requirement for fixed loading patterns is triggered by the belief that there is an interaction between items, that one item can influence or interact with an adjacent item, and that the item per se might not be sterilized in a different area in the autoclave—that is, that items can “steal” steam from other items, creating a cold spot or restricting steam flow to other items. For example,heavy items could be believed to be “steam-consuming” items that reduce the supply of steam to other items. This suspicion then leads to the requirement that many loading patterns be validated and maintained through revalidation activities.

固定裝載模式的要求源于這樣一種信念：物品之間存在相互作用，一個物品可能會影響到相鄰物品，或者物品本身在高壓蒸汽滅菌器的不同區域可能不會被滅菌——也就是說，物品可能會從其他物品那里“搶奪”蒸汽，從而制造出冷點或限制蒸汽流向其他物品。例如，人們可能認為重量較大的物品是“消耗蒸汽”的物品，它們減少了對其他物品的蒸汽供應。這種懷疑隨后導致了要求對許多裝載模式進行驗證，并通過對重新驗證活動來維持。

The standard validation procedure that is used by certain firms is to run three distribution cycles and three penetration cycles for each new load, rendering the workload and downtime of the facility to be significant and costly. Reducing nonvalue-added validation activities can create significant savings for facilities, with no adverse impact on patient safety.

某些公司使用的標準驗證程序是對每個新裝載量運行三個分布周期和三個穿透周期，這使得設施的工作量和停機時間都相當大且成本高昂。減少不增加價值的驗證活動可以為設施創造顯著的節省，且不會對患者安全產生負面影響。

This article will attempt to challenge this difficult question with data and convincing arguments, suggesting an approach that allows greater freedom and variability in arranging items in an autoclave when running overkill cycles, without the need to qualify each configuration or any adverse impact on patient safety or the required sterility assurance levels.

這篇文章將嘗試用數據和有說服力的論點挑戰這個難題，提出一種方法，允許在運行過度殺菌周期時，在高壓蒸汽滅菌器內安排物品時有更大的自由度和可變性，而無需對每個配置進行驗證，也不會對患者安全或所需的無菌保證水平產生任何負面影響。

 

3、飽和蒸汽的物理性質和滅菌熱力學

 

Physical Properties of Pure Saturated Steam and the Thermodynamics of Sterilization

 

Steam sterilization relies on the physical properties of pure saturated steam and the thermodynamics of the sterilization process. Any claim that relates to the ability of steam to sterilize should be evaluated in light of its properties, as described following.

 

蒸汽滅菌依賴于飽和純蒸汽的物理特性和滅菌過程的熱力學原理。任何與蒸汽滅菌能力相關的主張都應該基于其特性來評估，具體特性如下

 

1. Steam releases a large amount of energy relative to its weight when it condenses. A small amount of steam can heat a large load, as well as the metal structure of the autoclave. As it condenses, 1 kg of saturated steam releases 2200 kJ, which, when condensed, can heat over 40 kg of stainless steel (SS) from 20?C to 121?C ; thus, heating “heavy” metal items does not require large amounts of steam.

 

1.蒸汽在凝結時相對于其重量釋放出大量的能量。少量的蒸汽就能加熱大量的負載，包括滅菌器的金屬結構。當1公斤的飽和蒸汽凝結時，它釋放出2200千焦的能量，這足以將40公斤以上的不銹鋼從20 ?C加熱到121 ?C；因此，加熱“重”金屬物品并不需要大量的蒸汽。

2. When saturated steam is condensed, its volume decreases significantly (1 L of saturated steam turns into approximately 1.2 mL of condensate) .

Whenever condensation occurs (when steam makes contact with cold areas and condenses), the reduction in volume will bring more steam to cold sections due to the decrease in pressure until the item reaches the same temperature as the steam and no further heating is needed.

2.當飽和蒸汽凝結時，其體積顯著減少（1升飽和蒸汽大約轉變為1.2毫升的凝結水）。每當發生凝結（即蒸汽接觸到冷的區域并凝結時），由于壓力降低，體積的減少會將更多蒸汽帶到冷的區域，直到物品加熱到與蒸汽相同的溫度，此時不再需要進一步加熱。這一過程有助于確保蒸汽滅菌過程中所有物品都能均勻地達到滅菌所需的溫度。

3. There is a 1:1 correlation between saturated steam pressure and its temperature in an enclosed space with constant volume. After the pressure stabilizes, temperatures in the chamber become steady and will be maintained throughout the chamber as a result of the stabilization of pressure.

3.在恒定體積的封閉空間內，飽和蒸汽的壓力與其溫度存在1:1的相關性。壓力穩定后，腔室內的溫度變得穩定，并且由于壓力的穩定，腔室內的溫度將保持一致。

4. Steam that is under pressure in an enclosed space does not flow like air; thus, there are no steam flow patterns in the autoclave. Items do not obstruct steam or prevent it from entering other objects. Providing a load does not block the passage of steam completely—steam will reach all items. As indicated in Point 2, whenever condensation arises, the steam that is nearest to the condensation point will move toward it. These movements occur on a molecular level and are thus rapid; consequently, steam molecules are not influenced by the other items. Combining this inherent property of steam with the property in Point 3 ensures that wherever items are positioned in the chamber, each element will be subjected to the same sterilization conditions. The only interaction that might occur between items is the condensate, which can drip from heavy nonporous items onto lower items; this situation can be resolved easily by placing the former on the lower shelf of the autoclave.

4.在封閉空間中加壓的蒸汽不會像空氣那樣流動；因此，在高壓蒸汽滅菌器內不存在蒸汽流動模式。物品不會阻礙蒸汽或阻止其進入其他物體。即使裝載了物品，也不會完全阻塞蒸汽的通道——蒸汽能夠到達所有物品。如第2點所述，每當發生凝結時，最接近凝結點的蒸汽會向其移動。這些運動發生在分子層面上，因此速度很快；因此，蒸汽分子不會受到其他物品的影響。結合蒸汽的這一固有屬性和第3點所述的屬性，可以確保無論物品在腔室內如何定位，每個元素都將受到相同的滅菌條件。物品之間可能發生的唯一交互是凝結水，它可能從重量較重的非多孔物品滴落到下方的物品上；通過將前者放置在高壓蒸汽滅菌器的下層架上，可以輕松解決這種情況。

5. Heat can be transferred between objects only when there is a difference in temperature. Once the items in the autoclave attain the temperature of the steam, no more energy is transferred to the item, and further condensation stops—an equilibrium is reached. Additional small quantities of steam enter the autoclave only to compensate for the heat loss to the doors and chamber walls (even when the jacket is heated, because the temperature of the jacket is lower than that of the chamber).

5.只有在存在溫度差時，物體之間才能傳遞熱量。一旦滅菌器內的物品達到蒸汽的溫度，就不會再向物品傳遞更多的能量，進一步的凝結就會停止——達到了平衡。少量的蒸汽進入滅菌器只是為了補償對門和腔室壁的熱損失（即使滅菌器的外層被加熱，因為外層的溫度仍然低于腔室的溫度，腔室內的蒸汽仍需補充，以確保滅菌過程中溫度的均勻性和一致性）。

6. After an equilibrium is reached (after the heating phase and at the outset of the sterilization phase), pressure across the chamber will be equal, according to Pascal’s law.

6.達到平衡后（在加熱階段之后和滅菌階段開始時），根據帕斯卡定律，腔室內的壓力將是均勻的。

7. Steam and air (primarily nitrogen and oxygen) are small molecules (>1 nm); thus, air removal and steam penetration can also be achieved through narrow channels or gaps. Large quantities of steam require wider passageways, but even with small gaps, steam will eventually penetrate all parts of an object.

7.蒸汽和空氣（主要是氮氣和氧氣）都是小分子（直徑大于1納米）；因此，即使通過狹窄的通道或縫隙，也能實現空氣的移除和蒸汽的滲透。大量的蒸汽需要更寬的通道，但即使存在小的縫隙，蒸汽最終也會滲透到物體的所有部分。

With regard to load, other physical properties are involved in steam sterilization. Table I lists the load properties of items and their effects on sterilization. Combining these properties simplifies the decision over which items are easy or more challenging to sterilize. Table II lists examples of common items. Note that the table merely compares items and does not definitively state whether an item is challenging for an overkill cycle.

在蒸汽滅菌中，與裝載量相關的其他物理屬性也起著重要作用。表I列出了物品的裝載屬性及其對滅菌的影響。結合這些屬性可以簡化判斷哪些物品容易或更具挑戰性進行滅菌的決策過程。表II列出了一些常見物品的例子。需要注意的是，該表僅比較了物品，并沒有明確指出某個物品對于過度殺菌周期是否具有挑戰性

 

 

 

In summary：總結如下

1. Steam can heat a heavy load at low quantities due to high latent heat of condensation (Point 1). Fresh steam will fill the low-pressure zones that are created due to condensation (Point 2), supplying more energy. Heavy loads might elongate the heating phase, but this extra time is not included in the sterilization phase time. Eventually, after the load reaches the sterilization temperature, there is no difference between heavy and light loads, because there is no further transfer of energy to the load (Point 5). Mass should not be the chief parameter for selecting challenging items. The results of the tests in Pavell and Hughes (9) also showed that the more challenging items were the filter and the cleaning hose with a valve on one end, neither of which was among the heaviest items.

1.蒸汽的高凝結潛熱使其即使在數量較少的情況下也能加熱質量大的負載。新鮮的蒸汽將填補由于凝結而產生的低壓區域，提供更多的能量。沉重的負載可能會延長加熱階段，但這個額外的時間不包括在滅菌階段的時間之內。最終，在負載達到滅菌溫度后，重負載和輕負載之間沒有區別，因為對負載沒有進一步的能量傳遞。質量不應是選擇具有挑戰性物品的主要參數。Pavell和Hughes的測試結果也表明，更具挑戰性的物品是過濾器和一端帶閥門的清潔軟管，這兩者都不是最重的物品。

2. One of the most common myths that concern steam sterilization is that the high lethality of steam is attributed to the high energy transfer to the sterilized object during condensation (13): “Direct steam contact with the surface of the object to be sterilized is required for the steam to transfer its stored energy to the object.” Direct contact is definitely required, because the moisture in the steam must make contact with the item, but the last section of this statement becomes irrelevant when the setpoint temperature has been attained by all load items. As indicated in Point 5, energy transfer occurs only during the heating phase; throughout the sterilization phase, there is no energy transfer, and microorganisms are eradicated by maintaining the temperature and water molecules contact for the required time

2.關于蒸汽滅菌的一個常見誤解是，蒸汽的高致命性歸因于在凝結過程中對被滅菌物體的高能量傳遞：“蒸汽必須與被滅菌物體的表面直接接觸，才能將其儲存的能量傳遞給物體。” 直接接觸絕對是必需的，因為蒸汽中的水分必須與物品接觸，但當所有負載項目達到設定溫度時，這一說法的后半部分就變得無關緊要了。能量傳遞僅在加熱階段發生；在整個滅菌階段，沒有能量傳遞，微生物是通過維持溫度和水分子接觸所需時間來根除的。

3. From Points 2, 4, 6, and 7, I conclude that there is no impact of the location of items in the autoclave with regard to achieving the same extent of sterilization. The only parameter that requires attention relates to the prevention of condensate dripping. This conclusion was also the outcome of Pavell and Hughes (9)

3.從觀點2、4、6和7，我得出結論，物品在滅菌器中的位置對于實現相同程度的滅菌沒有影響。唯一需要關注的參數是防止凝結水滴落。這也是Pavell和Hughes研究的結論。

 

4、空氣去除和蒸汽滲透

 

Air Removal and Steam Penetration

 

Steam sterilization is based on the use of pure steam. When air or other noncondensable gases (NCGs) are present, they will affect the sterilization on several levels

 

蒸汽滅菌基于使用純蒸汽。當存在空氣或其他不可冷凝氣體（NCGs）時，它們會在多個層面上影響滅菌效果

1. Steam will follow the physical properties described above only when it is pure. When it is impure, the outcome is not predicted as easily.

1.只有純蒸汽才會遵循上述描述的物理屬性。當它不純凈時，結果不容易預測

2. Effective steam sterilization is predicated on the steam being in contact with the item. NCGs create isolation and can limit the destructive effectiveness

of steam.

2.有效的蒸汽滅菌基于蒸汽與物品的接觸。不可冷凝氣體（NCGs）會造成隔離，可能限制蒸汽的破壞性效果。

3. Steam lethality is attributed to the presence of water molecules. NCGs reduce steam lethality because they do not include water molecules.

3.蒸汽的致命性歸因于水分子的存在。不可冷凝氣體降低了蒸汽的致命性，因為它們不包含水分子。

Steam purity is influenced by how steam is produced and transferred and by efficient air removal from the chamber and load. Assuming that steam is tested on a regular basis for low levels of NCGs2, proper air removal should be ensured before starting the sterilization phase. In most cases, air removal is more important than additional sterilization time and increased temperature. The PNSU calculations in the first section are valid only with efficient air removal so that the full lethality of steam is applied.

蒸汽的純度受其產生和轉移的方式以及從腔室和負載中有效去除空氣的影響。假設蒸汽會定期檢測低水平的不可冷凝氣體(NCGs)，那么在開始滅菌階段之前應確保適當的空氣去除。在大多數情況下，空氣去除比增加滅菌時間和提高溫度更為重要。第一部分中的PNSU計算僅在有效去除空氣的情況下才有效，以便發揮蒸汽的全部致命性。

Air removal and steam penetration are complementary, because the same channel that allows air to be removed from internal voids allows steam to enter these voids.

空氣去除和蒸汽滲透是相輔相成的，因為允許空氣從內部空隙中排出的相同通道也允許蒸汽進入這些空隙。

The level at which air is not considered to be harmful depends on the load. Small air bubbles that are dissolved in steam are not a problem, but their accumulation in closed packs or pockets can become an issue(16).

空氣無害的水平取決于負載。溶解在蒸汽中的小氣泡不是問題，但如果它們在封閉的包裝或口袋里積聚，可能會成為問題。

Effective air removal and steam penetration are achieved by the repeated evacuation and entrance of steam into the voids. Collectively, this process entails dilution of the air in steam and subsequent extrusion of the mixture. The efficacy of the process is dictated by two factors:

通過反復抽出和進入蒸汽到空隙中實現有效的空氣去除和蒸汽滲透。總的來說，這個過程包括蒸汽中空氣的稀釋及其后混合物的擠出。這個過程的效果由兩個因素決定：

1.Values of pressure for the vacuum and steam pulses

 

1.真空和蒸汽脈沖的壓力值。

 

2. Pulse time. Slow pulses are more effective in removing air from challenging items, such as long lumens, porous loads, and packed items, because physical restrictions slow the evacuation and steam penetration. This property is the chief reason that a minimal load is required in an overkill cycle. In minimal loads, the evacuation time and steam pulse are shorter, impeding the air removal from and steam penetration of challenging items. In certain autoclaves, pulses duration can be set and be equal, regardless of load size, but in many autoclaves, this option does not exist. In such cases, this issue can be overcome through redundancy by adding more pulses or increasing the difference between the vacuum and steam pressures, rendering even shorter pulses sufficiently effective.

2.脈沖時間。慢速脈沖在去除具有挑戰性的物品中的空氣方面更有效，例如長通道、多孔負載和包裝緊密的物品，因為物理限制減慢了抽氣和蒸汽滲透的速度。這種特性是過度殺菌周期中需要最小負載的主要原因。在最小負載中，抽氣時間和蒸汽脈沖時間較短，阻礙了從具有挑戰性的物品中去除空氣和蒸汽的滲透。在某些滅菌器中，可以設置脈沖持續時間并使其相等，不管負載大小如何，但在許多滅菌器中，并不提供這種選項。在這種情況下，可以通過增加脈沖次數或增加真空和蒸汽壓力之間的差異來實現冗余，使即使是更短的脈沖也足夠有效。

In an overkill cycle, air removal is the main parameter when determining whether an item is simple or difficult to sterilize. When air removal is conducted properly, steam will penetrate all voids, eliminating “hard-tosterilize or challenging items.” Item Preparation, Wrapping, and Orientation Preparation, wrapping, and orientation are significant factors in the success of the sterilization cycle, because they impact air removal, steam penetration, and condensate removal (8). An item that is validated after being prepared, wrapped, and oriented in the chamber according to specific instructions should always be sterilized in the manner that it was validated. For example, a tube coiling of a specific length should be inserted into a double bag and placed flat on the autoclave shelf. A validated item includes its preparation, wrapping, and orientation.

在過度殺菌周期中，空氣去除是決定物品是簡單還是難以滅菌的主要參數。當空氣去除進行得當，蒸汽將滲透到所有空隙中，消除了“難以滅菌或具有挑戰性的物品”。物品的準備、包裝和方向 準備、包裝和方向是滅菌周期成功的重要因素，因為它們影響空氣的去除、蒸汽的滲透和凝結水的排出。根據特定說明在腔室中準備好、包裝好并定位好的物品應該始終按照其經過驗證的方式進行滅菌。例如，特定長度的管圈應插入雙層袋中，并平放在滅菌器架上。經過驗證的物品包括其準備、包裝和方向。

Data Collection and Interpretation Data were collected from actual validation runs that were performed at a specific facility from 2017 to 2019, as presented in Table III. The data are used to assess differences between maximal and minimal load results.

數據收集與解釋：數據收集自2017年至2019年在特定設施進行的實際驗證運行，如表III所示。這些數據被用來評估最大裝載量和最小裝載量結果之間的差異

The maximal load is prepared by collecting the more challenging items (items with a minimal F0 value) from all validated loadings.

最大裝載量是通過從所有經過驗證的裝載中收集更具挑戰性的物品（即具有最小F0值的物品）來準備的。

The minimal load usually includes one item that is found to be more challenging during the run of the maximal load

最小裝載量通常包括在最大裝載量運行過程中發現的更具挑戰性的一個物品。

Data were collected from 數據收集自：

 

6 autoclaves, varying in size and age

 

6臺不同尺寸和使用年限的高壓蒸汽滅菌器

 

4 types of loads—garments, gloves, tools, and rubber stoppers

 

4種不同類型的裝載物品：服裝、手套、工具和橡膠塞

 

4 types of air removal processes

 

4種不同的空氣去除過程

 

Cycles from 2017, 2018, and 2019

 

2017年、2018年和2019年的循環數據

 

 

5、從收集的數據里得到以下幾點看法

 

There are several insights from the data collection

 

1. Minimal load F0 values were within the values that were obtained in the maximal load (the highest and lowest F0 values were found in the maximal load cycles) (Figure 4). These data indicate that faster air removal and faster heating, which characterize the minimal cycle, do not necessarily provide the lowest lethality values.

 

1.最小裝載量的F0值在最大裝載量周期內獲得的值范圍內（最大和最小的F0值出現在最大裝載量周期中）。這些數據表明，最小周期特征的更快的空氣去除和更快的加熱，并不一定提供最低的致命性值。

2. In certain cases, the differences in F0 values between the hottest and coldest points in a specific cycle might appear to be significant, but when CT values are considered, the differences are small .

2.在特定周期中，最熱點和最冷點之間的F0值差異可能看起來很顯著，但當考慮到CT值時，這些差異很小。

3. Because the thermocouples that are used for the PQ study are calibrated to ±0.5?C, some differences can be related to calibration tolerances; when this factor is considered, the results indicate excellent temperature uniformity inside all of the loads.

3.由于用于PQ研究的熱電偶校準精度為±0.5?C，一些差異可能與校準容差有關；當考慮到這個因素時，結果表明所有裝載內部的溫度均勻性都很好

4. The correlation was low (0.26) between the equilibration time and correlated temperature differences. It would be expected that a short equilibration time indicates faster heating of the items, thus reducing temperature differences, but the low correlation does not support this relationship. Pavell and Hughes (9) also observed this finding. It would be interesting to understand the reason, scientifically. Practically speaking, the lack of correlation has no effect on the overall conclusions that are related to the overkill cycle

4.平衡時間與相關溫度差異之間的相關性很低（0.26）。人們可能會預期，較短的平衡時間表明物品加熱更快，從而減少溫度差異，但低相關性并不支持這種關系。Pavell和Hughes（9）也觀察到了這一發現。從科學上理解這一原因將是有趣的。實際上，缺乏相關性對與過度殺菌周期相關的總體結論沒有影響。

The results of the data collection and analysis show clearly that the differences in lethality between loads and between items in the load are small. The large differences in the mass or density of arrangement of the items between the maximal and minimal loads did not have any effect or direction that was related to the lethality that was gained by the items.

數據分析和收集的結果清楚地表明，裝載量之間以及裝載量內物品之間的致命性差異很小。在最大裝載量和最小裝載量之間，物品的質量或排列密度的大差異并沒有對物品獲得的致命性產生任何相關的影響或趨勢。

When evaluating the results for an overkill cycle, the differences are negligible. No item can be considered “hard to sterilize” or “challenging”, because all items achieved lethality values far beyond the initial requirements of the overkill cycle (F0 ≥ 15 min, which also covers the EU requirements) and the sterility assurance level that was required.

在評估過度殺菌周期的結果時，差異是可以忽略不計的。沒有任何物品可以被視為“難以滅菌”或“具有挑戰性”，因為所有物品的致命性值都遠遠超過了過度殺菌周期的初始要求（F0 ≥ 15分鐘，這也符合歐盟的要求）以及所需的無菌保證水平。

 

6、結 論

 

Conclusions

 

Overkill cycles, as currently used in industry, are excessive, attaching overly conservative safeguards to safeguards. The approach of allowing flexible loads for validated items, if implemented with the principles following, will result in safe and effective sterilization cycles at far lower cost to industry and the environment.

 

過度殺菌周期，按照目前工業中的使用方式，是過度的，它在保護措施上增加了過于保守的防護措施。如果按照以下原則實施允許已驗證物品的靈活裝載的方法，將能夠在大幅降低工業和環境成本的同時，實現安全有效的滅菌周期

The overkill cycle provides safe and robust sterilization for any load configuration if certain simple and basic principles are always followed:

過度殺菌周期，如果始終遵循一些簡單和基本原則，可以為任何裝載配置提供安全和可靠的滅菌

1. The cycle should be an extended overkill cycle. To allow load flexibility, more robust overkill cycles, with a calculated F0 value >25 minutes, are recommended to ensure the destruction of Geobacillus stearothermophilus BIs.

1.周期應為擴展的過度殺菌周期：為允許裝載靈活性，推薦使用計算出的F0值大于25分鐘的更強大的過度殺菌周期，以確保能夠破壞嗜熱脂肪芽孢桿菌（Geobacillus stearothermophilus）生物指示劑（BIs）

2. A validated item is one that has been validated by three penetration cycles (using thermocouples and BIs that are inserted into adjacent locations inside of the item) in any loading pattern. The term “item” includes the specific wrapping that is used when validated.

2.驗證物品：經過驗證的物品是指在任何裝載模式下，通過三次穿透周期（使用插入物品內部相鄰位置的熱電偶和生物指示劑）進行驗證的物品。“物品”一詞包括在驗證時使用的具體包裝方式

3. The item must be placed in the same orientation in which it was validated and in a manner that will not block air or steam passage to other items.

3.物品的放置：物品必須以其驗證時相同的方向放置，并且不得阻礙空氣或蒸汽流向其他物品。

4. Due to greater condensation from heavy metal items, they should be placed on the lower shelves to avoid dripping onto another item

4.重物的放置：由于重金屬材料會產生更多的凝結水，應將它們放置在較低的架子上，以避免水滴落到其他物品上。

5. The air removal stage should be designed to provide redundancy, such that even with fast pulses, it will be efficient. (If the autoclave is capable of controlling the timing of the pulses to be equal for maximal and minimal loads, the minimal load cycle validation is no longer relevant, and it could be skipped or be performed only once to ease regulatory questions [19]).

5.空氣去除階段的設計：應設計具有冗余性的空氣去除階段，以便即使在快速脈沖的情況下也能保持高效率。如果滅菌器能夠控制脈沖時間，使最大和最小負載的脈沖時間相等，那么最小負載周期驗證就不再相關了，可以省略或僅執行一次以便于監管問題的解答。

6. Revised or new loads are created under a change control procedure or a detailed SOP that includes full documentation and pictures of the revised or new load

6.新裝載或修訂裝載的創建：新裝載或修訂裝載應在變更控制程序或詳細標準操作程序(SOP)下創建，包括完整的文檔記錄和修訂或新裝載的圖片。

 

7、總體結論可以總結如下

 

The overall conclusion can be summarized as follows

 

If the preceding principles are followed, an item that has been validated in a specific overkill cycle will be effectively sterilized in any other load configuration using the same sterilization cycle parameters (including the air removal phase parameters), wrapping, and orientation. No additional validation is required to ensure that the combination of such items will be sterilized properly.

 

如果遵循前述原則，那么在一個特定的過度殺菌周期中經過驗證的物品將在任何其他使用相同滅菌周期參數（包括空氣去除階段參數）、包裝和方向的裝載配置中被有效滅菌。為了確保這些物品的組合能夠被正確滅菌，不需要額外的驗證。（這意味著，一旦物品在特定的過度殺菌周期中被驗證，就可以在不同的裝載條件下信任其滅菌效果，而無需為每種新的裝載配置重復驗證過程。這為滅菌過程提供了靈活性和效率，同時保持了所需的無菌保證水平。）

Consequently, several options are created when applying the preceding principles, such as the following:

應用前述原則后，會創建幾種選擇，例如：

1. A new item can be tested alone, running 3 penetration cycles, after which it can be multiply or combined with any other validated item.

1.單獨測試新物品：新物品可以單獨進行測試，運行3次穿透周期，之后它可以被多次使用或與其他經過驗證的物品組合。

2. A combination of any validated item in any number is allowed

2.任何數量的經過驗證的物品組合：允許將任何數量的經過驗證的物品組合在一起。

The two options are demonstrated in Figure 6. Allowing facilities to use the preceding approach will provide flexibility in their operation and can significantly reduce the validation workload without any adverse impact on patient safety

圖6展示了兩種選項。允許設施采用前述方法將為其運營提供靈活性，并且可以在不犧牲患者安全的前提下顯著減少驗證工作量。這種方法有助于提高滅菌過程的效率，同時確保滅菌效果滿足安全標準。