Post‐expiry stability of freeze‐dried plasma under field conditions – Can shelf life be extended?

Abstract

Background This prospective study evaluated the effect of routine, uncontrolled, Israeli field storage conditions on the safety and efficacy of Lyo‐Plas N Freeze‐Dried Plasma (FDP) at the end of the manufacturer's shelf life, and up to 24 months post expiry. Clotting factors V, VIII and XI, proteins S, C, fibrinogen, PTT, ATIII, VWF, and INR as well as TEG, DDM, residual moisture, pH, and sterility of FDP returned from field units after uncontrolled storage were evaluated. Study Design and Methods Parameters measured at the end of manufacturer shelf life, as well as 6, 12, 18, and 24 months after expiry, were compared to those of freshly supplied FDP doses. Results Changes were found when comparing freshly supplied FDP to all field‐stored groups in INR, PT, PTT, pH, fibrinogen, and factor VIII. A significant change was also seen in Factor XI in the 12, 18, and 24 months post‐expiry samples, Factor V and R in the 24 months post‐expiry samples, MA in the 12, 24 months post‐expiry group, and Protein C in the 18 months post‐expiry group. An increase in the residual moisture from 0.90% in freshly supplied FDP to 1.35% in 24 months post‐expiry FDP.; all p < .05. No growth was found in sterility analysis. Conclusion Despite uncontrolled field storage conditions, the findings demonstrate that the safety and efficacy of FDP units, stored in uncontrolled conditions are only slightly affected, even beyond their expiration date. This information allows consideration of possibly extending the shelf life.

Ex vivo hemostatic and immuno‐inflammatory profiles of freeze‐dried plasma

“…83 TEG has been used to evaluate post-expiry stability of FDP under field conditions. 81 The current findings demonstrating that the relatively low concentrations of immuno-inflammatory proteins present in FP were preserved in FPD, are consistent with the literature suggesting that freeze-drying or lyophilizing processes do not greatly enhance or disrupt the macromolecular stability of commonly detectable inflammatory cytokines, chemokines and other bioactive mediators. 21,84,85 Similarly, results from experimental animal models, administering dried or lyophilized plasma, indicate that FDP likely does not exacerbate existing harmful immune-inflammatory dysregulation after trauma and may in fact, confer beneficial anti-inflammatory effects that result in less blood loss and subsequent organ dysfunction.…”

“…There are a few in vitro studies of FDP using viscoelastic hemostatic tests in particular TEG 79‐81 . Our ROTEM results showed similarities of TFDP to plasma pools in all measures.…”

“…54 There are a few in vitro studies of FDP using viscoelastic hemostatic tests in particular TEG. [79][80][81] Our ROTEM results showed similarities of TFDP to plasma pools in all measures. This is in agreement with no significant modification in the TEG parameters (reaction time, α angle, and maximum amplitude) for the same plasma before and after lyophilization and treatment with amotosalen and ultraviolet light for pathogen reduction.…”

“…The clotting factor and inhibitor activities of LyoPlas from different lots were evaluated over 6 days after reconstitution and storage at 4°C, and still met required quality standards 83 . TEG has been used to evaluate post‐expiry stability of FDP under field conditions 81 …”

Retention of hemostatic and immunological properties of frozen plasma and COVID‐19 convalescent apheresis fresh‐frozen plasma produced and freeze‐dried in Canada

“…14 Although these products have been reported to lose 20%-25% of the labile coagulation factor activity of the starting plasma, they maintain these levels for at least 15 months of storage at ambient temperature. [13][14][15][16] Whether these in vitro losses impact clinical efficacy is unclear; meta-analyses of the relative benefits of FDP and traditional frozen plasma have either found that no conclusions can yet be drawn, 17 or that there is no difference between them with respect to mortality or allogeneic blood product transfusion requirements. 18 Canadian Blood Services and the Canadian Armed Forces are collaborating with Terumo BCT to develop a system by which blood suppliers can manufacture Terumo BCT FDP (TFDP) units from pools of frozen plasma (FP) or apheresis fresh-frozen plasma (AFFP) units in lightweight plastic containers amenable to rapid rehydration in the field.…”