Public Health England (PHE) and the Medicines and Healthcare products Regulatory Agency (MHRA) are in the final stages of their investigations into the outbreak of Bacillus cereus in the implicated intravenous liquid (Total Parenteral Nutrition, TPN).
Since the last 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 4 possible cases). This baby has sadly died and our thoughts are with the family. This is the third confirmed case to have died and all 3 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.
The strain of Bacillus cereus identified in the 19 cases confirmed as infected, 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 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 2014 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, there is sufficient evidence to indicate an isolated incident. 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.
A public health investigation that compared 18 confirmed cases with a comparison group of babies who did not have the outbreak strain of Bacillus cereus demonstrated a highly significant association between receiving TPN manufactured on 27 May 2014 and being infected by the outbreak strain.
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 Total Parenteral Nutrition (TPN) supplies during manufacture in a particular sterile manufacturing area at ITH Pharma on the 27 May 2014.
There is no evidence to suggest that individual ingredients, components or materials used for the manufacture of TPN on 27 May 2014 were the cause of the contamination. However, what we do know from our investigation is that the strain of Bacillus cereus which infected the babies has also been identified at ITH Pharma’s manufacturing facility and within some of the unopened TPN supplies manufactured 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.
Notes to editors
- There have been no new infections since 2 June 2014. As we continue to work with clinicians to review information on children in hospital, the number of cases linked to this cluster may fluctuate, as previously unrecognised cases may come to light or investigations may enable us to exclude cases previously thought to be part of the outbreak.
- Bacillus cereus is a common bacteria found widely in the environment in dust, soil and vegetation. Bacillus cereus produces very hardy spores, which make it persistent in the environment. Under certain conditions, the bacteria produces a number of toxins which can cause illness.
||1 July 2014
|Chelsea and Westminster Hospital NHS Foundation Trust
|Guy’s and St Thomas’ NHS Foundation Trust
|The Whittington Hospital
||1 confirmed, 1 possible
|Brighton and Sussex University Hospital NHS Trust
|Luton and Dunstable University Hospital
|Peterborough City Hospital
|Southend University Hospital – this possible case had signs of the infection while at Chelsea and Westminster but is now being cared for at Southend University Hospital
||1 confirmed, 1 possible
|Stoke Mandeville Hospital
|Basildon University Hospital
|Harley Street Clinic
Read the press release – 13 June 2014
Read the statement – 12 June 2014
Read the statement – 6 June 2014
Read the statement – 5 June 2014
Read the press release – 4 June 2014
Other findings and information from the MHRA:
It’s 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.
Companies manufacturing medicines are required to comply with Good Manufacturing Practice (GMP) to ensure the quality of the products they produce and for the protection of public health. The MHRA undertake inspections to assess the compliance of manufacturing facilities to the standards of GMP and the frequency of these inspections will depend on a many factors, but will be determined by a risk-based approach. As such, ITH Pharma will be subject to an increased level of monitoring by inspection.
The MHRA continues to work closely with ITH Pharma to monitor their activities and to ensure their manufacturing processes meet the requirements of Good Manufacturing Practice.
The MHRA press office can be contacted on 020 3080 7651, at firstname.lastname@example.org or on our out-of-hours number 07770 446 189.