Referring to the Letter to the Editor by Prof. Dr. Karl-Uwe Petersen [1] regarding our article entitled Differences in In Vitro Properties of Pancreatin Preparations for Pancreatic Exocrine Insufficiency as Marketed in Russia and CIS [2], we would like to provide further information and feedback. Our investigation has indeed focused on Feret max X50 as the selected representative parameter for particle size measurements. As explained in the publication, this was used as a representative parameter for the overall particle size diameter (PSD), for which the cumulative distribution Q3 (volume-based) assumes a value of 50%, where X50 represents the particle size at which 50% of particles in the material are smaller than this. Within the study, X10 and X90 have also been determined (data on file). For the X90 max assessments, Kreon has the lowest PSD (approximately 2000 μm) compared with all other pancreatin preparations (approximately 3000 μm). Upon evaluation of the X10 results, the preparations meeting a particle size smaller than 2000 μm are Kreon 25000, Kreon 40000, and Micrazim 25000 and 40000. All other preparations, including Ermytal (both strengths), Pangrol, and Panzytrat, still do not meet a particle size smaller than 2000 μm. Even when assessing the Feret min X50 data, only Kreon and Micrazim preparations are below 1500 μm, with averages of 1121 μm for Kreon and 1389 μm for Micrazim. The authors therefore believe that the choice of X50 is justified and supportive of the United European Gastroenterology Diagnosis and Treatment of Chronic Pancreatitis (UEG/HaPanEU) guideline consensus statement [3] and previously published comparative studies assessing the in vitro properties of different pancreatin preparations. Prof. Dr. Karl-Uwe Petersen mentions that the conclusion of the abovementioned HaPanEU guideline [3] has been challenged, particularly in his systematic review from March 2021 [4], which succeeds our publication; however, the authors would like to point out that the systematic review is based on publications currently in the public domain and is not reflective of the full dataset for our particular study and the pancreatin preparations available in Russia/Commonwealth of Independent States (CIS). Additionally, contrary to what is being postulated and as mentioned in the publication by Prof. Dr. Karl-Uwe Petersen; the pancreatin preparations assessed, including Kreon, do not have a round shape but rather a more cylindrical shape, where the Feret min diameter represents the diameter of the cylinder and the Feret max represents the maximum size of the particle in any dimension, thereby being indicative of the probability of the particle passing the pylorus together with the chyme. We also note that Prof. Dr. Karl-Uwe Petersen only addresses the PSD and the max Feret X value in his Letter to the Editor [4], and does not comment on the other differences between the specific pancreatin preparations identified in our in vitro investigation, particularly the differences observed regarding lipase activity (with Micrazim 40000 being a significant outlier at 79% of the declared lipase content) and (associated) dissolution [2] variables likely having an even greater impact on digestive potency and clinical efficacy. We therefore re-emphasize the conclusion drawn in our publication aligned with the HaPanEU guidelines and previous investigations that pancreatin preparations with a diameter of < 2 mm should be regarded as optimal for the treatment of pancreatic exocrine insufficiency (PEI), combined with clinical efficacy data generated with said This reply refers to the comment available online at https:// doi. org/ 10. 1007/ s4026802100366-z.

中文翻译：

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作者对彼得森的回复：“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 Karl-Uwe Petersen 教授 [1] 教授给编辑的信，关于我们题为“在俄罗斯和独联体销售的胰腺外分泌功能不全的胰酶制剂的体外特性差异”[2] 的文章，我们想提供进一步的信息和反馈。我们的研究确实集中在 Feret max X50 作为粒度测量的选定代表性参数。正如该出版物中所解释的，这被用作总粒径 (PSD) 的代表性参数，其中累积分布 Q3（基于体积）假定值为 50%，其中 X50 表示粒径为 50材料中的颗粒百分比小于此值。在研究中，还确定了 X10 和 X90（数据存档）。对于 X90 max 评估，与所有其他胰酶制剂（约 3000 μm）相比，Kreon 具有最低的 PSD（约 2000 μm）。在评估 X10 结果后，满足粒径小于 2000 μm 的制剂是 Kreon 25000、Kreon 40000 和 Micrazim 25000 和 40000。所有其他制剂，包括 Ermytal（两种强度）、Pangrol 和 Panzytrat，仍然不符合粒径小于 2000 μm。即使在评估 Feret min X50 数据时，也只有 Kreon 和 Micrazim 制剂低于 1500 μm，Kreon 的平均值为 1121 μm，Micrazim 的平均值为 1389 μm。因此，作者认为 X50 的选择是合理的，并且支持联合欧洲胃肠病学诊断和治疗慢性胰腺炎 (UEG/HaPanEU) 指南共识声明 [3] 和之前发表的评估不同胰腺素制剂体外特性的比较研究。Karl-Uwe Petersen 教授提到，上述 HaPanEU 指南 [3] 的结论受到了挑战，特别是在他从 2021 年 3 月开始的系统评价 [4] 中，该评价成功地完成了我们的出版；然而，作者想指出，系统评价是基于目前在公共领域的出版物，并不反映我们特定研究的完整数据集和俄罗斯/独立国家联合体 (CIS) 可用的胰酶制剂。此外，与 Karl-Uwe Petersen 教授在出版物中的假设和所述相反；评估的胰酶制剂（包括 Kreon）不是圆形，而是更呈圆柱形，其中 Feret 最小直径代表圆柱体的直径，而 Feret 最大代表颗粒在任何维度上的最大尺寸，因此具有指示性颗粒与食糜一起通过幽门的概率。我们还注意到，Karl-Uwe Petersen 教授在致编辑的信 [4] 中仅讨论了 PSD 和最大 Feret X 值，并没有评论我们体外确定的特定胰酶制剂之间的其他差异调查，特别是观察到的脂肪酶活性差异（Micrazim 40000 在声明的脂肪酶含量的 79% 处是一个显着的异常值）和（相关的）溶解 [2] 变量可能对消化效力和临床疗效有更大的影响。因此，我们再次强调在我们的出版物中得出的结论与 HaPanEU 指南和先前的调查相一致，即直径 < 2 mm 的胰酶制剂应被视为治疗胰腺外分泌功能不全 (PEI) 的最佳选择，并结合临床疗效数据用所述生成此回复是指在 https://doi 上在线提供的评论。org/ 10. 1007/ s4026802100366-z。