The Colorado firm announced the move this week, explaining that an unnamed CRO contracted to run the Phase III study had notified it that stocks of the knee osteoarthritis drug had been exposed to lower than permitted temperatures.
If exposed to low temperatures, Ampion - which derived from human serum albumin (HSA) - may lose potency and, according to Ampio CEO Michael Macaluso, there were several instances of the in-package monitor falling below the 15°C minimum required.
He said: “Although our entire trial drug supply was housed, packaged, and shipped in early January by a specialized drug shipment vendor contractually obligated to maintain pre-determined temperature requirements under all conditions, our CRO discovered much of the drug product received at the clinical sites had been below the temperature requirement and may have been frozen for some period of time.”
Ampio’s share price of the company dropped 19% to its lowest in three months following the announcement.
Macaluso added the firm is “frustrated” at these shipping and receiving deviations, and Ampio has been forced to pursue alternative solutions to meet the BLA requirements and file on schedule.
Last month, the company opened a new manufacturing facility ready to produce the first batches of Ampion necessary to accommodate the BLA application.
Compensation?
According to independent quality expert Peter Murray, this product - being a derivative from serum albumin complex - would depend either wholly or partially on the 3 dimensional shape they adopt when in use, and extreme temperature can destroy this.
He told Biopharma-Reporter.com “traditionally, suspension vaccines were the main members of this class but increasingly, medium and high molecular weight molecules from biotech sources are coming into use and have the same transport problems as vaccines.”
Murray , an ex-Quality Director at GSK, also suggested that Ampio could be entitlked to compensation from the unnamed CRO and any logistics subcontractor it used.
“Within most contracts, there will be some mechanism for dealing with claims arising from Physical Loss,” he said, though consequential loss (the estimated loss of predicted revenue) “are more problematic to estimate.”
Too hot, too cold
Biopharma-Reporter.com also spoke with Sue Lee from distribution company World Courier - not the logistics company involved in this case - who said that cold chain mismanagement “happens far too frequently,” despite regular updates of good distribution practice regulations.
“If you lose the opportunity to dose a patient because you have lost the contents of a shipment, or a fridge, and they get removed from a trial then you lose all their data,” Lee told us. “You can throw away years of work when you fail to have the drug there ready and correct for administration.”
Furthermore, a biologic or vaccine which has been kept in heated or frozen conditions may not work she said (adding this is a common problem in both trial and commercial distribution in the developing world), but could in the worst case scenario kill a patient.
We also asked Lee about distribution methods specific to large molecule drugs.
“The big problem is normally freezing which particularly for a biologic causes dissolved compounds to precipitate out and you cannot get them to redissolve. Therefore when dosing the patient they will not be getting the drug in the correct format.
“Take a piece of paper and crumple it up then flatten it out again. You can never get it smooth. You might be able to if you ironed it but that adds in an extra process which the doctor or patient cannot do.”