HPE Drug stability: What do we need to know? | Page 8

IN PRACTICE
In-use stability studies:
an important added value
Independent In-use stability studies demonstrate that drugs are very often more stable than
indicated by the manufacturers in the Summary of Product Characteristics, which do not always
reflect the real needs for most practical situations
Alain Astier PharmD PhD
Honorary Head of the
Department of Pharmacy,
Henri Mondor University
Hospitals, Creteil, France;
Member of the French
Academy of Pharmacy,
and the Belgian Royal
Academy of Medicine
The concept of practical stability (or in-use
stability) is more extensive than just stability
of a drug in its primary container, and takes into
account its stability determined under conventional
situations and also encompassing variations
routinely observed in clinical practice (such as
long-term infusion, advance preparation) or
observed unexpectedly (such as temperature
variations during storage).
For anticancer drugs, in-use stability is of
paramount importance in daily practice. Indeed, in
a number of countries, centralised preparation of
these drugs by pharmacy departments has greatly
impacted the technical aspects of the handling
processes, compared with the traditional method
of preparation, as needed at the bedside. Indeed,
immediate preparation for an individual patient
following prescription, as was the traditional
way, is not feasible in centralised units. Advance
preparation optimises the workload. Moreover, a
patient might be unable to receive the drug at a
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specific time for a number of reasons (for example,
low neutrophil count, inability to attend the clinic).
If a previously prepared bag is not administered
to a patient, the question is: might it be possible to
store it until the biological parameters normalise
or until the patient arrives? These unpredictable
situations could lead to possible loss of the
preparation if the available stability data indicate
inadequate storage times. A financial impact is
also important considering the very high cost of
new anticancer drugs, such as antibodies. Another
problem is the possibility to use the remnants of
several vials of these costly drugs if only part of the
vial contents is used. As an example, the anti-CTLA4
monoclonal antibody ipilimumab, which is used in
first- and second-line treatment for inoperable stage
III melanoma, is available in vials of 50mg (5mg/ml;
10ml) and 200mg (5mg/ml; 40mg) and the standard
dose regimen is 3mg/kg. Thus, for an individual of
70kg, the total dose will be 210mg. The dose will
comprise the contents of a 200mg vial plus 2ml