From Professor M. C. Allwood, FRPharmS and Professor G. J. Sewell, MRPharmS
SIR,—A recent meeting of the Joint Pharmaceutical Analysis Group (on June 24 at the Royal Pharmaceutical Society’s headquarters) considered the current state of intravenous pharmaceuticals with particular respect to stability in clinical practice. Assignment of shelf-lives was a key issue, especially in the light of the rapid growth in the provision of pharmacy-prepared ambulatory and other home-delivery parenterals in an expanding range of devices and containers.
Further complicating the issue is the increasing number of home care companies providing services requiring these relatively “high tech systems”.
The assignment of shelf lives requires both detailed laboratory evaluation through extensive stability studies, for which considerable expertise and facilities are required, and a thorough understanding of all the pharmaceutical issues associated with maintaining drug stability (chemical, physical and microbiological) in each device. Assigning shelf-lives to each drug/ delivery reservoir combination is therefore dependent on detailed evaluation by someone with extensive experience and expertise.
We are increasingly concerned that many shelf-lives are now being recommended by home care companies with no evidence of pharmaceutical input. Brochures are produced listing drug/device combinations with extended shelf-lives for which there is little, if any, evidence of support. At best, data are derived by extrapolation from previous studies, often in different devices. Important factors which often directly influence degradation rates, in particular drug concentration and vehicle, are ignored.
We are also aware that customers are influenced by the length of the shelf-life offered by a company in making their purchasing or contracting decisions. This particularly concerns us as it is clear that product shelf-lives are being offered which fall outside normal stability criteria accepted by experts, which are based on maximum degradation prior to administration and/or minimal risk of toxicity from degradation products. One important example is the antibiotic ceftazidime. While shelf-lives may be extended, based on degradation rates, the appearance of pyridine as a degradation product must also be taken into account in reaching a decision, particularly in view of the high drug concentrations and duration of infusion used. In our view, caution must be exercised in such situations and advice sought from independent experts before purchasing decisions are made. We would stress the need for great caution and emphasise the paramount importance of patient safety in the use of home care parenterals. Independent expertise should be sought where any doubt exists, especially when shelf-lives are based entirely on extrapolations from published studies which do not mimic the particular situation, or on in-house reports lacking independent evaluation.
Mike Allwood
University of Derby
Graham Sewell
University of Bath