HPE Drug stability: What do we need to know? | Page 28

drafted for evaluation of stability of anticancer
drug infusions, although the principles and
methodologies discussed are applicable to infusions
beyond anticancer agents.
In the UK, the NHS Pharmaceutical Quality
Assurance Committee has published a two-part
Standard Protocol for stability studies on aseptic
preparations: Part 1 (small molecules) and Part
2 (biopharmaceuticals). 4,5 These publications are
updated regularly and are a valuable resource not
only for specialist laboratories conducting infusion
stability studies, but also for those assessing and
evaluating stability studies in the literature to
assign shelf-lives and to identify the robustness and
limitations of published studies.
Evaluating stability studies in the literature
Any evaluation must consider the following points:
• Appropriateness of the study – does it relate to the
requirements of the practice situation?
• Is the study design appropriate and robust?
• Are the methodologies used acceptable and have
methods been properly validated?
• Are the results robust, reproducible and reliable?
• Have the results been correctly interpreted and are
conclusions on infusion stability realistic?
The reference sources noted above will assist in the
evaluation of published literature and, in addition,
the quality of the journal and the review process used
will also be a guide on the reliability of the study and
significance of any shelf-life recommendations made.
The following information is intended to augment,
and not replace, these sources.
Appropriateness
The study must replicate closely the conditions
to which the stability data will be applied in
practice. This would include the drug or drugs,
the formulation of the drugs to be used, drug
concentration, diluent, temperatures at which
stability has been assessed, container and
container material, protection from light and
the duration of the study. It may be acceptable
if the study used drug from a different
manufacturer to that to be used in practice
providing there is documented evidence in the
SPC 1 that the formulation is equivalent.
Study design
Stability studies may be carried out at a single
temperature, usually the storage temperature, or
in the case of more recent studies, at both storage
and in-use temperatures. Typically, the storage
temperature will be 2–8 o C, replicating pharmacy
refrigeration temperatures, and in-use temperatures
will be 20 or 25 o C, reflecting room temperature.
Where infusions are to be administered using an
ambulatory infusion pump, the in-use temperature
is usually 35–37 o C to take account of body heat
on an infusion device worn under the patient’s
clothing.
Where more than one temperature is
investigated, most stability studies have used a
‘parallel temperature’ design, where separate
batches of infusions are stored at each study
temperature, and stability at each temperature is
assessed independently. More recently, ‘sequential
temperature’ designs have been used, 6 where
infusion containers are incubated under storage
conditions (usually refrigeration) for set time
periods, subjected to testing and assay, then undergo
further incubation under ‘in-use’ conditions
followed by further assay and testing. There may
even be a further cycle where the infusions are
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