As changes in pharmacokinetic parameters (incremental recovery, half-life, area under the curve, clearance and mean residence time) could give a clue Barasertib in vivo about the occurrence

of weak inhibitors, the same patients had to be retested for the same pharmacokinetic parameters after 6 months, using the same dose as in the initial study; Clinical efficacy and overall safety should be reported in a minimum of five haemophilia A patients undergoing at least 10 surgical procedures; At least 50 PTP should be followed up for at least 50 exposure days or 6 months for FVIII inhibitors (determined every 3 months); A paediatric trial should be initiated before product submission for licensing and should include a minimum of 12 patients under the age of 6 years regardless of prior treatment. They had to be followed up for clinical Venetoclax mw efficacy, immunogenicity and safety parameters until they had received at least 50 exposures to the product or had been treated for 6 months (whichever came first); The protocol of a post-marketing surveillance study should be submitted together with the licensing product file. The aforementioned 1995 European guidelines dealt with regulatory requirements regarding

both FVIII and factor IX, but it was subsequently decided to have separate protocols for FVIII and factor IX products. EMA/CHMP/BPWP/144533/2009 was devoted to clinical investigations required for FVIII, and dealt with both plasma-derived and recombinant

products. The 2009 guidelines took into account the conclusions of an EMA expert meeting on the risk of inhibitor development, held in 2006 and gathering specialists from EU, MCE USA, Japan, Canada, representatives from the ISTH, the World Health Organization, patient organizations and manufacturers. As compared to previous guidelines, the main changes were as follows: Pharmacokinetic data were now required for 12 paediatric patients under the age of 6 years; Pharmacokinetic and safety data were also required for paediatric patients between 6 and 12 years age; Clinical, immunogenicity and safety data were required for 50 haemophilic children, allocated in two cohorts of 25 patients each, one under the age of 6 years and the other between 6 and 12 years; Still expected to include a total of 200 patients, the post marketing study should include 60 paediatric PTPs under the age of 12 years; There was a new shift regarding PUPs, because: clinical pre-approval study was now presented as necessary in this population, including 50 patients and post approval follow-up was required in a total of 100 patients (allowing the inclusion of those investigated in the pre-approval study).