Regulators suggest contamination was a manufacturing incident, not from ingredients
Public Health England (PHE) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) are in the final stages of their investigations into the outbreak of Bacillus cereus that affected several babies given the intravenous liquid Total Parental Nutrition (TPN).
Since the last PHE update on 12 June 2014, a further case has been identified and the total number of cases linked to this investigation is 23 (19 confirmed and four possible cases). This baby is the third confirmed case to have died and all three cases have been reported to the coroner. The baby most recently identified received the implicated batch of TPN from 27 May 2014 but did not immediately develop sepsis so did not fit the case definition of the outbreak at that time. However, recent microbiological tests have shown the presence of the outbreak strain.
So far the investigations have discovered that the strain of B.cereus identified in the confirmed 19 cases, has also since been identified in environmental samples collected from the day of manufacture (27 May 2014), located within the particular sterile area at ITH Pharma where the specific TPN supplies were manufactured. These specific TPN supplies were recalled by the MHRA on 4 June 2014.
There is no evidence to suggest that individual ingredients, components or materials used were the cause of the contamination
PHE says there is sufficient scientific evidence to indicate that the contamination was introduced into these specific TPN supplies during manufacture in a particular sterile manufacturing area at ITH Pharma on 27 May and MHRA’s investigations of the production process of TPN have found no evidence to suggest that individual ingredients, components or materials used were the cause of the contamination.
The MHRA has inspected ITH Pharma’s manufacturing facility and undertaken a rigorous and thorough review of the manufacturing processes and conditions within which the specific TPN supplies were manufactured. Based on the information obtained, it says there is sufficient evidence to indicate an isolated incident and that appropriate immediate action has since been taken at ITH Pharma’s facility to avoid a recurrence. The MHRA continues to allow TPN, a critical product, to be manufactured at ITH Pharma and therefore be supplied to patients.
Unopened supplies of the contaminated TPN (manufactured on 27 May 2014 at ITH Pharma) were collected from a few hospitals and these have been confirmed to contain the same strain of bacteria. Other tests on unopened TPN products manufactured by ITH Pharma after 27 May 2014 have all been clear of the bacteria.
The main findings have all pointed towards there being a single incident that occurred on one day
Professor Mike Catchpole, PHE Incident Director, said: 'There are still some elements of our investigation that need finalising but the main findings have all pointed towards there being a single incident that occurred on one day and was associated with the illness seen in the babies. We are reassured that this was a very rare occurrence as we have not seen this particular strain of bacteria in any product made since that day and there has been no further illness.'
Gerald Heddell, the MHRA’s Director of Inspection, Enforcement and Standards, said: 'At this stage, our investigation has provided sufficient evidence to indicate that the contamination was introduced into the specific TPN supplies during manufacture in a particular sterile manufacturing area at ITH Pharma on the 27 May 2014.
'From our investigation to date, we continue to believe this was an isolated incident and that appropriate immediate action has been taken at ITH Pharma’s facility to avoid a recurrence. Therefore we are allowing this critical product to be supplied to patients while our investigation continues.'
There have been no new infections since 2 June 2014
There have been no new infections since 2 June 2014 but PHE said that previously unrecognised cases may still come to light. B.cereus is a common bacteria found widely in the environment which under certain conditions can cause illness. Industry experts have recently warned of the increasing incidence of B.cereus in manufacturing situations (see Cleanroom Technology Vol 22 No.1 p75).
It is a requirement that TPN is manufactured in sterile manufacturing facilities, such as those at ITH Pharma, under strict controls to avoid contamination. These controls also include the regular collection of environmental samples from the facility to monitor the presence of any micro-organisms.
The MHRA continues to work closely with ITH Pharma to monitor its activities and to ensure its manufacturing processes meet the requirements of Good Manufacturing Practice.