HPE Drug stability: What do we need to know? | Page 18

FIGURE 2
Bibliographic reference of the rituximab monograph
Extended stability studies for non-injectable
drugs
These concern mainly oral solutions and eye drops.
Stabilis ® is the only database which gives stability
data for all dosage forms (injectable drugs, oral
solutions, eye-drops, aerosol, capsule, mouthwash
etc).
Oral solutions are mainly used for patients
who have difficulties in swallowing (for example,
paediatric and geriatric patients). For these
preparations, many stability studies using simple
syrup and aroma or special excipients such OraPlus ® ,
OraSweet ® , OraBlend ® and Inresa ® have been carried
out over one, two, or sometimes three, months,
allowing advance preparation and the delivery for
outpatients. In Stabilis ® , as of May 2019, 216 oral
solutions monographs were available, most of which
include extended stability data.
Eye drops require a long shelf life to allow
delivery for ambulatory patients. In Stabilis ® , 29
monographs are currently available (as of May 2019).
Some of them include stability of frozen solutions
for very unstable drugs at room temperature or
in the refrigerator. Injectable drugs used for the
preparation of eye drops are usually off-label.
Stability studies of these preparations cannot be
performed by the pharmaceutical company that
References
1 Bonnes Pratique de
Préparation. AFSSAPS, arrêté du
3 décembre 2007. https://ansm.
sante.fr/ (accessed August 2019).
2 Vigneron J. Stability studies: A
scientific mission of the hospital
pharmacist. Pharm Technol Hosp
Pharm 2017;2(4):143–4.
3 Vigneron J, D’Huart E,
Demoré B. Stability studies in
oncology: A marketing tool for
pharmaceutical companies, a
scientific mission for hospital
pharmacists. EJOP 2019;2:e12.
4 ICH Guidelines. www.ich.org/
products/guidelines/quality/
article/quality-guidelines.html
(accessed August 2019).
5 Bardin C et al. Guidelines for
the practical stability studies of
anticancer drugs: A European
consensus conference. Ann
Pharm Fr 2011;69:221–31.
6 Methodological guideline
for stability studies of hospital
pharmaceutical preparation,
edition 2013. This guideline has
been written in collaboration
between the French Society
of Clinical Pharmacy (SFPC)
and the Group of Evaluation
and Research for protection in
areas under control (GERPAC.)
www.gerpac.net/platform/
course/index.php?categoryid=8
(accessed August 2019).
7 NHS Pharmaceutical Quality
Assurance Committee. Standard
protocol for stability assessment.
Part 1: Aseptic preparation
(small molecules) 3rd edition,
December 2015. https://pasg.
nhs.uk/downloads.php?did=288
(accessed August 2019).
8 NHS Pharmaceutical Quality
18 | 2019 | hospitalpharmacyeurope.com
produces the drug and are therefore carried out by
hospital pharmacy teams.
How to use these data
Extended stability data provided by the
manufacturers in the SPC of generics or biosimilars
can be taken into account as they are legal
information. This kind of information is usually not
available for originators.
The extrapolation of information from one
generic to another is only possible if the qualitative
and quantitative composition is strictly the same.
For biosimilars, stability data cannot be extrapolated
and should be demonstrated for each new
biosimilar.
For data provided by international publications
and databases, users have to compare the product
used for the stability study and the product used
in their daily practice in terms of composition, and
to compare the concentration, the container, the
storage temperature and the excipients, and make
a decision on how to use these data. Extrapolation
of published data should always be justified. Trissel
noted in the preface of the Handbook on Injectable
Drugs that: “Users of the Handbook information
should always keep in mind that the information in
the Handbook must be used as a tool and a guide to
the research that has been conducted and published.
It is not a replacement for thoughtfully considered
professional judgment.”
A ‘level of evidence’ function was implemented in
2017 to provide information on the quality of each
publication of stability of anticancer drugs. This
function was then extended to antifungal, antiviral
drugs, and then to some antibiotics. Four levels were
created (A, B, C and D), A being the most robust. The
definition of chemical stability (90% or 95% of the
initial concentration) was indicated. This criterion
is essential for selecting stability studies for dose-
banding. 20
The Stabilis ®
database provides
stability data on
injectable and
non-injectable
drugs. It uses
pictographic
information and
is translated into
29 languages Conclusions
Information on extended stabilities is essential for
hospital pharmacists involved in the preparation
of medications for advance preparation. These data
reduce outpatient waiting times, mainly in oncology.
It also allows preparation and delivery of oral
solutions or eye-drops with a compatible shelf life
for ambulatory patients. The published stability data
should only be taken into account if the assurance
of sterility is maintained for injectable drugs in
accordance with Good Manufacturing Practices.
Stabilis ® is the most comprehensive database
for providing extended stability data for all
pharmaceutical forms.
Assurance Committee. A
Standard protocol for deriving
and assessment of stability -
Part 2: Aseptic preparations
(Biopharmaceuticals)
Edition 3, April 2017. www.
sps.nhs.uk/wp-content/
uploads/2017/03/Stability-part-2-
biopharmaceuticals-v3-April-17.
pdf (accessed August 2019).
9 Walker SE, Charbonneau LF,
Law S. Stability of bortezomib
2.5 mg/mL in vials and syringes
stored at 4°C and room
temperature (23°C). Can J Hosp
Pharm 2014;67:102–7.
10 Paul M et al. Long-term
stability of diluted solutions of the
monoclonal antibody rituximab.
Int J Pharm 2012;436:282–90.
11 Kaestner S, Sewell G. A
sequential temperature cycling
study for the investigation of carboplatin infusion stability to
facilitate ‘dose-banding’. J Oncol
Pharm Practice 2007;13:119–26.
12 Balouzet C et al. Stability of 25
mg/mL 5-azacitidine suspension
kept in fridge after freezing.
Pharmaceut Technol Hosp
Pharm 2017;2:11–16.
13 Daul A et al. Stability of frozen
ceftazidime in polypropylene
syringes for intravitreal injection.
Poster at the EAHP Congress,
Paris 2013.
14 Fleury-Souverain S,
Sadeghipour F, Bonnabry P.
Development of ready-to-
use cefuroxime syringes for
use in ophthalmology. EJHP
2014;21:34–8.
15 Paul M et al. Long-term
stability of bevacizumab
repackaged in 1 mL
polypropylene syringes for
intravitreal administration. Ann
Pharm Fr 2012;70:139–54.
16 Khalili H et al. Storage
stability of bevacizumab in
polycarbonate and polypropylene
syringes Eye 2015;29:820–7.
17 AHFS Drug Information ®
Handbook on Injectable Drugs,
20th Edition. ASHP, 2018.
18 King Guide to parenteral
admixtures. www.kingguide.com
(accessed August 2019).
19 Bing CD, Nowobilski-Vasilios
A. Extended Stability for
Parenteral Drugs, Sixth Edition
ASHP, 2017.
20 D’Huart E et al. Evolution of
the Stabilis ® Database: Creation
of a level of evidence for stability
studies. Pharm Technol Hosp
Pharm 2018;3:3–12.