HPE Drug stability: What do we need to know? | Page 3

INTRODUCTION
Stable or not stable – the question
in good preparation practice
Irene Krämer PhD
Pharmacy Department,
University Medical Center,
Johannes Gutenberg-
University, Mainz,
Germany
Reference
1 Resolution CM/Res(2016)1 on
quality and safety assurance
requirements for medicinal
products prepared in pharmacies
for the special needs of patients.
www.edqm.eu/sites/default/files/
resolution_cm_res_2016_1_
quality_and_safety_assurance_
requirements_for_medicinal_
products_prepared_in_
pharmacies.pdf (accessed August
2019).
Preparation of medicinal products is a key task
for pharmacists, especially in hospital
pharmacies. Although most of the medicinal
products are now manufactured by the
pharmaceutical industry, according to the EU
Resolution CM/Res(2016)1, 1 the preparation of
unlicensed products in pharmacies is crucial in
accommodating any special needs of individual
patients. Pharmaceutical preparations prepared
under the responsibility of the pharmacist must
correspond to the specifications of the
Pharmacopoeia and ‘Good Preparation Practice’
guidelines. The standards and methods for the
control of chemical, pharmaceutical, and
microbiological quality of the medicinal products
must be taken into consideration and appropriate
quality assurance systems established in the
pharmacy. Preparation of medicines for parenteral
use with high reconstitution risks should also be
performed in the pharmacy. 1 According to the risk
assessment, products having a high risk for
microbiological contamination because of a complex
reconstitution method, safety risks for the staff
performing reconstitution, and a high risk related to
the pharmacological activity, should be prepared in
the pharmacy. In general, the reconstitution of
hazardous drugs should take place in an
environmentally controlled area in the pharmacy.
While pharmacy-based cytotoxic preparation
services are widespread in European and UK
hospitals, central intravenous additive
services for non-cytotoxic drugs are
less common and the
development is heterogeneous
among different countries.
Albeit the preparation of
patient-individual
admixtures for total
parenteral nutrition are the
most complicated and
challenging tasks, many
hospital pharmacies offer this service.
The main advantage of the pharmacy-based
preparation is increased patient safety.
The main disadvantages are the costs for
implementation and running the service
and the limited physico-chemical and
microbiological stability of the
preparations. In order to increase the
efficiency of the preparation services,
the implemetation of automation and
advance preparation in series or batches
is necessary.
Good preparation practice
implies that prior to the
preparation, a risk assessment covering criteria
including type of preparation (especially dosage
form) and type of preparation process should
be performed. The product dossier should cover
among other topics ‘stability considerations’.
Each pharmacy product is to be labelled with the
date of preparation, the shelf life of the intact
package (that is, expiration date for industrially
manufactured medicinal products) and the usage
period after first opening. The shelf lives and the
usage periods of the pharmacy products should
be evaluated regarding the chemical, physical and
microbiological stability of the products. Due to
the wide variety of dosage forms, numerous active
substances, and varying concentrations of the
active substances, the evaluation of shelf-lives
is a considerable challenge. A literature search
is usually undertaken, and databases are checked
for stability information, which can be transferred
to the eligible product.
In general, the ready-to-administer parenterals
are prepared with industrially manufactured
medicinal products as starting material. However,
stability data provided by the manufacturer in
the Summary of Product Characteristics (SPC) are
limited and seldom refer to the physico-chemical
stability of the product. Recently, the license holders
of biosimilar monoclonal antibodies realised that
the declaration of the physico-chemical stability
(concentrated solutions and diluted infusion
solutions) in the SPCs carries a competitive
advantage. Subsequently, the SPCs
of the originator products were
also updated accordingly.
If stability data are not
available in the literature
and the product is prepared
on a regular basis, the user(s)
should design and perform
their own stability studies.
This is another time- and
cost-intensive undertaking
that is limited by the capability
and capacity of sophisticated
analytical methods in most hospital
pharmacies.
The aim of this handbook is to
consolidate and broaden our knowledge
of evaluating stability data, design and
performing practical stability studies,
and the assignment of shelf-lives.
Thereby it will support pharmacists in
answering the question ‘stable or not
stable’ and, furthermore, ‘for how
long stable?’
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