PB0579 - Approaches to assure similarity of pharmaceutical preparations of unfractionated heparin

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Francisco Felipe Bezerra, PhD

Post doctoral
Federal University of Rio de Janeiro
Rio de Janeiro, Rio de Janeiro, Brazil

Co-Author(s)

SO

Stephan Oliveira

Post doctoral
Federal University of Rio de Janeiro
Rio de Janeiro, Rio de Janeiro, Brazil
AP

Adriana Piquet

Laboratory technique
Federal University of Rio de Janeiro
Rio de Janeiro, Rio de Janeiro, Brazil
EV

Eduardo Vilanova

Post doctoral
Federal University of Rio de Janeiro
Rio de Janeiro, Rio de Janeiro, Brazil
AT

Ana Tovar

Professor
Federal University of Rio de Janeiro
Rio de Janeiro, Rio de Janeiro, Brazil
RS

Rodrigo Sales

Master degree student
Federal University of Rio de Janeiro
Rio de Janeiro, Rio de Janeiro, Brazil
NC

Nina Capille

Laboratory technique
Federal University of Rio de Janeiro
Rio de Janeiro, Rio de Janeiro, Brazil
PA

Paulo A. S. Mourão

Professor
UFRJ
Rio de Janeiro, Rio de Janeiro, Brazil

Background: Studies on similarity of pharmaceutical preparations of heparin are much more complex in comparison with those of other biological molecules. The emergence of biosimilar preparations of LMWH over the past decade required similarity studies, which led to the elaboration of specific guidelines. However, there are no guidelines aiming similarity studies of preparations of unfractionated heparins (UFH). This is particularly relevant as we have preparations of UFH available in the past (from bovine lung), in the present (from porcine intestine) and in development for future use (ovine intestine).

Aims: Notwithstanding such lack of guidelines, we established a set of criterions and methodologies to carry out comparison studies with basis: 1) the current guidelines for comparing LMWHs; 2) assessments required by pharmacopeias and 3) in-depth analytical procedures from scientific studies. This analytical framework includes both classic/routine methods employed to analyze heparins and state-of-the-art innovative approaches.

Methods: Table 1 summarizes the criterium for the analysis and the main methodologies employed to clarify specific aspects of UFH structure and activity.

Results: The results obtained were divided into five topics, according to the particularities of the methods: 1-) biochemical, 2-) chromatographic, 3-) spectroscopic, 4-) enzymatic and 5-) biological activities. This set of results ensures the physical-chemical and biological similarity of the batches of porcine sodium UFH from two manufacturers. The preparations of sodium heparin meet all the characteristics of products obtained from porcine intestine, which are clearly distinct from those of heparins obtained from bovine and ovine intestine or bovine lung.

Conclusion(s): In conclusion, this comprehensive and detailed study ensures the similarity between the porcine intestinal sodium UFH preparations from two manufacturers. As an outcome of this structural and biological similarity, we also foresee that the therapeutic action of the bovine heparins from these two manufacturers in humans should be similar.