Christine Clark PhD FRPharmS FCPP(Hon)
The provision of safe injectable products is a fundamental responsibility of the pharmacy department – the use of unsafe products can have far-reaching and tragic consequences
Two items in this issue focus on safe injectable medicines (Braun symposium report, page 11 and Gerpac report, page 14) and the importance of safe injectables has never been higher. At the time of writing, 32 people have died in the US as a result of fungal meningitis linked to the use of injectable steroids from three recalled batches of preservative-free, methylprednisolone acetate distributed by the New England Compounding Center (NECC). The full horror of this episode is still unfolding.
Pharmacists in Europe have repeatedly emphasised the importance of working to GMP standards when preparing injectable products and the recent Council of Europe Resolution (CM/ResAP(2011)1) lends further weight to this. The current episode in the US is a terrible lesson in what can go wrong if appropriate standards of practice are not scrupulously maintained. According to a news release by the Food and Drugs Administration (FDA) on 26 October, FDA investigators found ‘objectionable conditions’ during their inspections of the NECC premises. Some of their findings were:
- Eighty-three vials out of a bin containing 321 one ml vials of methylprednisolone acetate (preservative free) 80mg/ml from a single batch contained what appeared to be greenish-black foreign material. Seventeen vials from this bin contained white filamentous material
- FDA analysis of samples from this batch confirmed viable microbial growth in all of the 50 vials tested
- The company provided no documentation to show that the steam autoclave cycle used to sterilise suspensions prepared using non-sterile ingredients was effective
- The company’s environmental monitoring programme recorded the presence of bacteria and moulds in the clean room used for the production of sterile drug products between January and September 2012
- No documented corrective actions were taken to remove the microbial contamination from the facility
- The air conditioning in the clean room was shut down each day from 8.00 pm until 5.00 am the following morning.
The final report from the FDA has yet to be published.
The offending organism in this case turned out to be Exserohilum rostratum (and not Aspergillus fumigatus as in the index case) – a plant pathogen that is rarely implicated in human infections. It is a tribute to the skill of the microbiologists that they were able to track this down. However, the nature of this organism only raises further questions about the hygiene standards in the compounding unit.
What does this episode tell us? It underlines and reinforces the importance of high standards of practice in the preparation or manufacture of injectable products. There is no room for short cuts. The Council of Europe Resolution provides clear guidance on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients. Although this episode inevitably raises a question mark over the activities and safety of third party compounding units, it is worth remembering that in the UK and several other European countries such units are subject to rigorous inspection and licensing procedures. Nevertheless, hospitals purchasing from third party compounders should satisfy themselves that products are prepared in appropriate conditions.