Author’s Reply to Petersen: “Differences in In Vitro Properties of Pancreatin Preparations for Pancreatic Exocrine Insufficiency as Marketed in Russia and CIS”

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 preparations as well as enzyme activity and optimal dissolution characteristics.