Welcome to our new website! If this is the first time you are logging in on the new site, you will need to reset your password. Please contact us at firstname.lastname@example.org if you need assistance.
Your membership opens the door to free learning resources on demand. Check out the Member Knowledge Center for free webcasts, publications and online courses.
This comprehensive resource covers product change evaluation, postmarket surveillance, audit/inspection compliance, and various other laws and regulations pertaining to maintaining a product on the market.
Hear from leaders around the globe as they share insights about their experiences and lessons learned throughout their certification journey.
| 11 October 2013 | By Alexander Gaffney, RAC
EU officials with the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) have confirmed their initial assessment of hydroxyethyl starch (HES) solutions, saying the blood loss stabilization products' safety risks could outweigh their respective benefits.
HES products have long been used to stabilize patients experiencing hypovolemia-low blood volume, most often the result of blood loss following trauma-and have been extensively used during combat engagements by military forces.
A website for one of the largest manufacturers of HES products, BioTime, explains that the product "creates oncotic pressure, which would normally be provided by blood proteins, and permits retention of intravascular fluid." FDA notes it has approved three HES products-manufactured by Fresnius Kabi (Voluven), BioTime, Inc. (Hextend) and B. Braun Medical (Hespan)-the first of which was licensed before 1985.
However, the product has been under intense scrutiny by US and EU regulators in recent years.
In June 2013, the European Medicines Agency (EMA) announced that its Pharmacovigilance Risk Assessment Committee (PRAC) had recommended suspending marketing authorizations for HES products in light of their conclusion that the benefits of the products "no longer outweigh their risks."
Explained EMA: "The review of infusion solutions containing HES was triggered … following three recent studies that compared HES with other products used for volume replacement called crystalloids in critically ill patients. The studies showed that patients with severe sepsis treated with HES were at a greater risk of kidney injury requiring dialysis. Two of the studies also showed that in patients treated with HES, there was a greater risk of mortality."
That recommendation was followed days later by FDA, which issued a safety communication saying that it had concluded that HES solutions "should not be used in critically ill adult patients," and that a boxed warning should be affixed to the product's labeling.
FDA's warning added that patients could experience "excessive bleeding" as a result of the products-a dangerous situation for any patient to be in, let alone one who has already lost a considerable volume prior to the initiation of treatment.
Now EMA's PRAC has confirmed its initial findings, saying that "HES should no longer be used in patients with sepsis or burn injuries or in critically ill patients."
PRAC explained in its statement that it had considered new evidence since its 13 June 2013 preliminary recommendation "that was not available at the time … including new studies." It has also assessed proposals to introduce new risk mitigation measures, "including restrictions on use and a commitment from the companies to conduct additional studies."
However, those measures were rejected, with PRAC concluding that "there was clear evidence for an increased risk of kidney injury and mortality in critically ill and septic patients, and that therefore HES should no longer be used in these patients."
However, PRAC did concede one point, saying the product could still be used in patients with hypovolemia caused by acute blood loss in instances where alternate treatment with crystalloids would not be considered effective. In such cases, the product should not be used for more than 24 hours, and the patient's kidney condition should be monitored for three months after treatment.