HPE Drug stability: What do we need to know? | Page 16

SOURCES
Where to find extended
stability data?
Information on extended stabilities is essential for hospital pharmacists involved in the preparation
of medications for advance preparation
Elise D’Huart PharmD
Jean Vigneron PharmD
Pharmacy Department,
Centre Hospitalier
Régional Universitaire,
Hôpital Brabois Adultes,
France
Extended stability data are essential for
advance preparation and are particularly vital
not only in the field of oncology (mainly for dose
banding) but also for antibiotics or medications for
intensive care units in central intravenous additive
services. The preparation of non-injectable drugs
such as eye-drops or oral solutions also needs
extended stability. This information allows efficient
and cost-effective preparation.
The challenge for hospital pharmacists is to
find information on extended stability for their
daily practice. Information can be found from
manufacturers, in pharmaceutical journals or,
conveniently, in stability databases. Precautions have
to be taken when using these data.
Stability data provided by manufacturers
Stability information provided by manufacturers is
established as part of the marketing authorisation
application. In this case, usually short stabilities are
assigned for microbiological reasons and stability
data are usually limited to a few hours at room
temperature and for 24–48 hours between 2°C
and 8°C. However, when the drug’s status changes
from originator to generic or biosimilar, stability
studies become a part of the marketing process and
extended stability data are often available.
Until the marketing of generics or biosimilars,
hospital pharmacists have to perform their own
stability studies for their daily practice if they want
extended stability data. In France, the official text
of the Good Preparation Practices specifies that
the shelf life of products can be determined either
by literature study and review or by carrying out
stability studies, which represents a legal exercise
for the hospital pharmacist. 1
Extended stability data performed by hospital
pharmacists or academics
Hospital pharmacists are required to perform
stability studies. 2,3 International Conference of
Harmonisation Guidelines (ICH) have been written
for the EU, US and Japanese pharmaceutical
industries 4 but these recommendations are
When the drug’s status changes from
originator to generic or biosimilar,
stability studies become a part of the
marketing process and extended
stability data are often available
16 | 2019 | hospitalpharmacyeurope.com
not always applicable for hospital pharmacy.
Adapted guidelines have been written by learned
societies including the French Society of Oncology
Pharmacists (SFPO) with the collaboration of
European pharmacists, 5 the French Society of
Clinical Pharmacy (SFPC), GERPAC 6 and the National
Health Service. 7,8
In oncology, advance preparation is essential
to reduce patient waiting times. The concept of
dose banding requires extended stability studies.
For example, extended stability studies had been
performed to demonstrate long term stability over
35 days for bortezomib, 9 six months for rituximab, 10
three months for carboplatin, 11 or one month at
-20°C for azacitidine, a drug that is very temperature
sensitive. 12
In the field of ophthalmology, extended
stability has been demonstrated for the
antibiotics ceftazidime 13 and cefuroxime 14 for
intravitreal injections to treat endophthalmy,
and for bevacizumab in syringes to treat macular
degeneration with three-month and six-month
stabilities. 15,16
Where to find extended stability data outside
the SPC
Extended stability studies for injectable drugs
Relevant data are frequently published in
pharmaceutical journals (for example, the European
Journal of Hospital Pharmacy, International Journal of
Pharmaceutical Compounding, Pharmaceutical Technology
in Hospital Pharmacy, American Journal of Health System
Pharmacy, Canadian Journal of Hospital Pharmacy,
Hospital Pharmacy, Journal of Oncology Pharmacy
Practice, etc).
These data are retained in various databases.
Outside of Europe, the most established US database
is the Handbook on Injectable Drugs; 17 The King Guide to
Parenteral Admixtures is another. 18 Bing et al published
the Extended Stability for Parenteral Drugs, which is
primarily focused on home infusion therapy and
contains more than 160 monographs. 19
In Europe, to the best of our knowledge, three
databases are available:
• Stabilité des médicaments injectables en perfusion/
stabiliteit van geneesmiddelen voor intraveneuze
infusie (Belgium, edited in French and Dutch by
Professor Jean Daniel Hecq)
• A DKA STABIL Datenbank (Germany, edited
by Professor Irene Krämer and Dr J Thiesen) for
anticancer drugs
• Stabilis ® (published by the French non-profit
association INFOSTAB; www.stabilis.org).
The Stabilis ® database provides stability data
on injectable and non-injectable drugs. It uses