The New South Wales (NSW) racing authority in Australia identified testosterone in a vial of BOVA’s long acting omeprazole injection in mid-June 2019. Supply of the product ceased in Australia and BOVA immediately initiated investigations.
Following on from the racing NSW findings, the BHA contacted Bova in the UK to find out if the UK product was likely to be affected. Bova UK sent samples to the BHA for analysis which showed the issue did extend to the UK. Both Bova Aus and Bova UK had been using the same source for the excipient that was responsible for the traces of testosterone. Both companies have now switched their supplier of this excipient. All testing done on the new supplier has shown no traces of testosterone, even with the new extra sensitive method of analysis which is capable of reaching picogram levels.
Nick Bova, managing Director of BOVA UK said: “We had no explanation for how contamination could have occurred at that time as we do not handle testosterone.
“The Omeprazole active pharmaceutical ingredient (API) is subject to ID testing on arrival at our licensed manufacturing facilities as well as material approval checks and compliance checks to set specifications in order to ensure that it complies with international standards.”
He continued: “We have been in contact with our suppliers both in the UK and Australia and have commissioned extensive testing of our products and those of our suppliers. We have also been in continual discussion with both the British Horseracing Authority (BHA) and the Federation Equestrian Internationale (FEI). Through this independent testing process, we determined that one of our excipient raw ingredients contained testosterone at levels that are well within accepted international standards for impurities.”
To put the international standard into perspective, it is an accepted standard that when producing monograph raw materials (APIs and excipients) that impurities present at less than 0.1%, need to be monitored but don’t need to be identified. 0.1% of 1g would be 1mg. The impurities found to be present were in picograms which are 1 billionth of a mg. There are grams, then mg, mcg, ng and then pg. Each with a factor of 1000 between them.
The levels of testosterone in the end product were confirmed by external laboratories to be 400-700 pg/ml, which is less than one millionth of the internationally accepted standard for impurities (1 picogram being equal to one billionth of a milligram). The international standards being referred to is the veterinary international conference on harmonization documents (VICH).
https://vichsec.org/en/guidelines/pharmaceuticals/pharma-quality/impurities.html
Nick Bova continued: “We have consulted veterinary
pharmacologists and sports medicine
specialists who have given their opinion that these levels
are within accepted standards and could neither have
a clinical effect nor result in a positive blood or urine
test for testosterone in competition horses.
“The levels of testosterone within the product are inconsequential compared to endogenous production in mares and geldings as well as stallions and higher levels are found frequently in feed and water sources; testosterone being a common compound produced by humans and animals from multiple organs.”
“Whilst we hope to reassure you that the use of long acting injectable omeprazole will not have had adverse implications for your patients or clients we can also reassure you that we are not complacent about the presence of impurities in any of our products, particularly an impurity that is of such significance to equestrian sport.
“Although the level of impurities is well within the accepted international standard, we have changed the supplier of the excipient in question. We have established an analytical method capable of testing down to picogram levels, which has been used to test the end product to ensure there are no further concerns with future batches.
“We sincerely apologise for any inconvenience this issue may have
caused. Many vets and horse owners now rely on long acting injectable
omeprazole for horses that do not respond to oral treatment and we can
reassure anyone who has used the product in recent months, or has product that
they are due to use, that they can do so safely. However, we would draw
attention to the recent statement from the BHA that they do not wish the
product to be used in horses in training currently.”
Visit www.bova.co.uk for further information.
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