Referring to the publication by Maev et al. [1], it can be agreed with the authors that particle size, label claim-compliant lipase activity, high batch-to-batch conformity, gastric resistance and quick enzyme release in the intestine are relevant parameters for successful treatment of pancreatic exocrine insufficiency with pancreatic enzyme-replacement therapy (PERT). However, the authors’ claim that the particle size of PERT should be smaller than 2 mm appears debatable, and it should be emphasized that particle size distribution (PSD) is also relevant. After measuring particle sizes, the authors concluded that only Kreon and not other PERTs available in Russia or CIS (Commonwealth of Independent States: Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Uzbekistan) fulfilled the criterion of a suitable particle size of 2 mm. Ermytal, Pangrol and Panzytrat displayed a significantly larger particle size than Kreon when using the selected parameter Feret max X50. Unfortunately, the authors provided no data regarding the PSD or X10 and X90. For Ermytal, Pangrol and Panzytrat, the PSD was small because of the production process (sieved microtablets). This is not necessarily true for pellet-based products such as Kreon. Thus, evidence is lacking that the average diameter is not caused by the combination of two particle fractions with diameters either too big or too small to empty simultaneously with the meal. For a complete evaluation, data regarding the length/width ratio of the cylinder-shaped pellets would also be needed (Feret min X50 data missing). The authors pointed out that the critical dimension of the particle is the length of the cylinder, but it has been shown that particles of that shape can leave the pylorus lengthwise [2]. Given that, for Kreon, the Feret max is already quite small, it is possible that quite a high number of particles have a width small enough to leave the pylorus before the chyme, especially as even 2 mm enteric-coated pancreatin microspheres have been shown to do so [3]. Even if all Kreon particles showed a very narrow PSD and a rather round shape, it is questionable whether the particle size difference of 1 mm compared with Ermytal, Pangrol and Panzytrat in any way affects the efficiency of the PERT. It is true that the European guideline [4] recommends particles smaller than 2 mm, but it has only recently been demonstrated that there is no scientifically sound evidence for this cut-off value, which needs serious re-evaluation [5]. This criticism includes the fact that the cited guideline has failed to provide clinical evidence for the claimed advantage of smaller-sized particles. Instead, that document cited a study that, rather than reporting a trial comparing different pellet sizes for gastric emptying and efficacy, provided evidence for 2 mm particles emptying faster (not slower) than a pancake meal from the stomach of patients with chronic pancreatitis [3]. Finally, Maev et al. [1] themselves conceded that there was no evidence to suggest an impact on clinical outcome of particle size differences in the discussed range. So, we agree with the author that studies with direct comparisons are lacking.

中文翻译：

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评论：“在俄罗斯和独联体上市的用于治疗胰腺外分泌功能不全的胰酶制剂的体外特性差异”

参考 Maev 等人的出版物。[1]，与作者一致认为，颗粒大小、符合标签要求的脂肪酶活性、高批次间一致性、胃耐受性和肠道内酶快速释放是成功治疗胰腺外分泌功能不全的相关参数。胰腺酶替代疗法（PERT）。然而，作者声称 PERT 的粒径应小于 2 mm 似乎值得商榷，应该强调的是，粒径分布 (PSD) 也是相关的。在测量颗粒大小后，作者得出结论，在俄罗斯或独联体（独联体：亚美尼亚、阿塞拜疆、白俄罗斯、哈萨克斯坦、吉尔吉斯斯坦、摩尔多瓦、俄罗斯、塔吉克斯坦、乌兹别克斯坦）满足 2 毫米合适粒径的标准。使用选定的参数 Feret max X50 时，Ermytal、Pangrol 和 Panzytrat 的粒径明显大于 Kreon。不幸的是，作者没有提供有关 PSD 或 X10 和 X90 的数据。对于 Ermytal、Pangrol 和 Panzytrat，由于生产过程（筛分微片），PSD 很小。对于 Kreon 等基于颗粒的产品，情况不一定如此。因此，缺乏证据表明平均直径不是由直径太大或太小而无法与膳食同时排空的两个颗粒部分的组合引起的。为了进行完整的评估，还需要有关圆柱形颗粒的长/宽比的数据（Feret min X50 数据缺失）。作者指出，颗粒的关键尺寸是圆柱体的长度，但已经表明这种形状的颗粒可以纵向离开幽门 [2]。鉴于，对于 Kreon，Feret max 已经非常小，有可能相当多的颗粒具有足够小的宽度以在食糜之前离开幽门，特别是即使已经显示了 2 mm 肠溶包衣的胰酶微球这样做 [3]。即使所有 Kreon 颗粒都显示出非常窄的 PSD 和相当圆的形状，与 Ermytal、Pangrol 和 Panzytrat 相比，1 mm 的粒径差异是否会以任何方式影响 PERT 的效率是值得怀疑的。确实，欧洲指南 [4] 推荐小于 2 毫米的颗粒，但直到最近才证明，对于这个临界值没有科学上可靠的证据，需要认真重新评估 [5]。这种批评包括这样一个事实，即引用的指南未能为声称的较小尺寸颗粒的优势提供临床证据。相反，该文件引用了一项研究，该研究没有报告比较不同颗粒大小的胃排空和功效的试验，而是提供了证据表明 2 毫米颗粒排空比慢性胰腺炎患者胃中的煎饼餐更快（而不是更慢）[3 ]。最后，Maev 等人。[1] 自己承认，没有证据表明所讨论范围内的粒度差异对临床结果有影响。因此，我们同意作者的观点，即缺乏直接比较的研究。