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6. Repackaging Pharmaceuticals in institutional practice
Introduction
Historically, pharmacists were responsible for packaging process as the end result of formulation and
preparation of medications. As manufacturers began to prepare, package and distribute medications the
role of practitioner changed from formulator and packager to repackager. First, was the “unit-of-use
packaging” which is a drug package that contains the amount of medication necessary for the period of
treatment. This type of packaging (from bulk containers into patient-specific containers) marked as the
beginnings of the “unit dose” concept. Unit of use packaging, sometimes referred to as “prepackaging”
is suitable for inpatient and outpatient dispensing. Then, the development processes to unit-of-use
packaging leaded to the unit dose concept. In the unit dose system, single-unit packages are prepared
containing a single and separate dosage form such as one tablet, one teaspoonful, one syringe, or 2 g of
ointment. The third type of package is the “unit” or “single-dose package”. The difference between the
single-unit package and the single-dose package is that the later always contains the dose of drug for a
given patient. It may contain two tablets or two capsules in one package. However, the new
developments in automated packaging machines and in packaging materials coupled with the financial
incentives gained through in-house packaging program versus purchase of the drug already packaged
by the manufacturer, have given greater importance to establishing institutional repackaging programs.
Extemporaneous Versus Batch Repackaging
“Extemporaneous repackaging” is the process of repackaging medications on a day-to-day basis that
will be used over a short period of time. This applies to specific medications that have limited or
unknown stability in the package or that infrequently prescribed.
“Batch repackaging” is the repackaging of a specific medication at a given time by assigned operator in
sufficient quantity to last a predetermined amount of time. This applies to medications that are stable
over an extended period of time in the package material and those prescribed frequently in the
institution. Production controlled process are more likely to be performed in batch repackaging.
General Repackaging Guidelines and Good Manufacturing Practices (GMP)
ASHP technical assistant bulletin on single unit and unit dose packages must fulfill four basic
functions: (1) identify their contents completely and precisely; (2) protect their contents from
deleterious environmental effects (e.g. photodecomposition); (3) protect their contents from
deterioration resulting from handling (e.g. breakage and contamination); (4) permit their contents to be
used quickly, easily and safely.
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These guidelines have as their basis the Good Manufacturing Practices for Finished pharmaceuticals
(GMP). The USP list several key areas that define GMP’s and the requirements needed to meet these
key areas. The key areas are as the following:
1- Organization and Personnel
There shall be a quality control unit. In hospital, a pharmacist may check a single product or
completely dedicated to quality control. Each person engaged in the manufacturer, processing,
packaging or holding of a drug product shall have education, training and experience to enable the
person to perform the assigned functions.
2- Facilities
Any building used in the manufacturer, processing, packaging or holding of a drug product shall be of
suitable size, construction, and location to facilitate cleaning, maintenance, and proper operations.
3- Equipment
Equipment used in the manufacturer, processing, packaging or holding of a drug product shall be of
appropriate design, adequate size, and location suitable to facilitate operations for its intended use and
for cleaning and maintenance.
4- Control of Components and Drug Product Containers and Closures
Components and drug product containers and closures shall all times be handled and stored in a
manner to prevent contamination.
5- Production and process controls
There shall be written procedures for production and process control designed to assure that the drug
products have the identity, strength, quality, and purity that they purport or are represented to possess.
6- Packaging and Labeling Control
There shall be written procedures describing in sufficient detail the receipt, identification, storage,
handling, sampling, examination and/or testing of labeling and packaging materials.
7- Holding and Distribution
Written procedures describing the warehousing of drug products shall be established and followed.
8- Laboratory Controls
For each batch of drug product, there shall be appropriate laboratory determination of satisfactory
conformance to final specifications for the drug product, including the identity and strength of each
active ingredient, prior to release.
9- Records and Reports
Records shall be maintained for all components, drug product containers, closures, and labeling for at
least 1 year after the expiration date.
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Specific Guidelines for Repackaging Programs
Repackaging Material
Repackaging materials and the package itself must posses the characteristics to protect drug from light,
heat, moisture, air and in the case of sterile products, microbial contaminants. Packages should be
lightweight and made of materials that do not interact with the drug. The package type most often used
in practice for:
Oral solids: they may be packaged in blister or in pouch packages.
Oral liquids: always repackaged into rigid or semi-rigid containers: vials, cups, and oral syringes
Injectables: require sterile, pyrogen-free containers: glass and plastic syringes, empty evacuated vials
Topical medications: can be repackaged into glass or plastic jars or vaginal syringes for vaginal use
Respiratory medications: should be sterile and free from pyrogen: respiratory syringes
Repackaging Equipment and Filling Devices
The two most important components in ensuring a quality package are the packaging materials and the
closures system. Repackaging equipments can be categorized as manual, semiautomated or fully
automated. Manufacturer of repackaging materials and equipments described their products based on
the type of package that is achievable- class A, B, C, or D- with class A being the best and class D the
worst. Generally, class A and B are needed to extend the stability of repackaged product beyond the
few days following repackaging.
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