12 research outputs found
Dissimilar ferric derisomaltose formulations : in vitro comparisons between an originator and its intended similars
No full textBackground
The complex nature of intravenous (IV) iron formulations makes manufacturing and characterising similars challenging. This study examined whether simple in vitro tests can distinguish the high-dose IV iron formulation, Monofer® (ferric derisomaltose [FDI]), from the first intended copies of FDI, Rapifer® (FDI intended similar A [FDIIS-A]) and Tosiron® (FDI intended similar B [FDIIS-B]), approved in India and Pakistan, respectively. Neither intended similar is available in Europe or the United States.
Methods
Iron content, pH, density, non-volatile residue, carbohydrate content, molecular weight distribution, complex robustness (measured using acid hydrolysis half-life [t½]) and free (dialysable) iron content were examined. Mean results from three batches of FDIIS-A were compared with mean values calculated from three batches of Monofer®. Due to product withdrawal, only one batch of FDIIS-B was available for comparison with Monofer®.
Results
Iron content was similar for all formulations (∼100 mg/mL). The chromatograms (obtained using gel permeation chromatography) of FDIIS-A and FDIIS-B differed from that of Monofer®. FDIIS-A was substantially less robust than Monofer® (t½: 15 h versus 40.3 h); t½ for FDIIS-B was not tested. Free iron content was substantially higher in FDIIS-A (0.091 % w/v) and FDIIS-B (1.0 % w/v) versus Monofer® (<0.003 % w/v). Where tested, remaining parameters varied between the formulations (insufficient sample quantities prevented all tests being conducted for all intended similars). For all tests, greater inter-batch variability was seen for FDIIS-A versus Monofer®.
Conclusions
Simple in vitro tests demonstrated that, aside from total iron content, the first intended similars of FDI bear little resemblance to their originator drug. It is clear that the efficacy and safety profile of Monofer® cannot be extrapolated to the two intended similars. The results call for increased regulatory scrutiny of intended IV iron similars
Valgancyclovir‐induced encephalopathy in a child after hematopoietic stem cell transplant
No full textHaploidentical bone marrow transplants in a pediatric and young adult population: A tertiary centre experience
No full textHaploidentical bone marrow transplants in a pediatric and young adult population: A tertiary centre experience
No full textSubsequent donation requests among 2472 unrelated hematopoietic progenitor cell donors are associated with bone marrow harvest
No full textApproximately 1 in 20 unrelated donors are asked to make a second donation of hematopoietic progenitor cells, the majority for the same patient. Anthony Nolan undertook a study of subsequent hematopoietic progenitor cell donations made by its donors from 2005 to 2011, with the aims of predicting those donors more likely to be called for a second donation, assessing rates of serious adverse reactions and examining harvest yields. This was not a study of factors predictive of second allografts. During the study period 2591 donations were made, of which 120 (4.6%) were subsequent donations. The median time between donations was 179 days (range, 21-4016). Indications for a second allogeneic transplant included primary graft failure (11.7%), secondary graft failure (53.2%), relapse (30.6%) and others (1.8%). On multivariate analysis, bone marrow harvest at first donation was associated with subsequent donation requests (odds ratio 2.00, P=0.001). The rate of serious adverse reactions in donors making a subsequent donation appeared greater than the rate in those making a first donation (relative risk=3.29, P=0.005). Harvest yields per kilogram recipient body weight were equivalent between donations, although females appeared to have a lower yield at the subsequent donation. Knowledge of these factors will help unrelated donor registries to counsel their donors.</p
Total body irradiation in a case of thalassemia major with source to axis distance based planning: A case report
No full textBackground: The use of total body radiation (TBI) before hematopoietic stem cell transplantation (HSCT) would increase the engraftment without transplant-related morbidity or mortality among Thalassemia major (TM) cases. Case presentation: A 2-year-old female child, diagnosed with TM was scheduled for haploidentical allogenic transplant-based protocol, and after that, based on protocol she was scheduled to undergo a single session of TBI as a conditioning regimen before haploidentical allogenic hematopoietic stem cell tranplant. A total dose of 4 Gy was administered.. The incidence of graft failure was reduced as TBI was used before allogeneic stem cell transplantation. TBI provided a uniform dose of radiation to the entire body, penetrating areas such as the central nervous system (CNS) and testes. Conclusion: Total Body Irradiation with the SAD technique is the most effective way of treatment. As it is comfortable for the patient to undergo, easily reproducible, and it helps to achieve a uniform dose distribution
Standardization and validation of PCR-fragment analysis based assay for detection of mixed donor chimerism following bone marrow transplant
No full text
