Pharmaceutical Manufacturing Handbook: Production and

176 PACKAGING AND LABELING
The safety of material can be guaranteed by using appropriate analytical methods
and instrumentation to identify and quantitate extracted chemicals. Liquid and gas
chromatography and MS are powerful analytical tools that can separate and quantitate
volatile and nonvolatile chemicals along with useful structural information.
The mass spectrum or fragmentation pattern acquired for each molecule makes
these excellent and effective tools for identifying unknown impurities or degradation
products.
Toxicological evaluation of identifi ed and unidentifi ed impurities from a container
can help improve the safety index of drug products. The toxicological evaluation
should take into consideration container closure system properties, drug
product formulation, dosage form, route of administration, and dose regimen. A
close correlation between chemical and toxicological information can provide better
control on safety and compatibility of containers and closures.
Performance The fourth attribute of the suitability of the container closure system,
performance and drug delivery, refers to its ability to function in the manner for
which it was designed. There are two major considerations when evaluating performance.
The fi rst consideration is functionality that may improve patient compliance,
[e.g., a two - chamber vial or intravenous (IV) bag], or improve ease of use (e.g., a
cap that contains a counter, a prefi lled syringe). The second consideration is drug
delivery, which is the ability of the packaging system to deliver the right amount or
rate (e.g., a prefi lled syringe, a transdermal patch, a metered tube, a dropper or spray
bottle, a dry - powder inhaler, and a metered - dose inhaler).
3.2.3.2
Packaging Components
Quality control refers to the tests typically used and accepted to establish that, after
the application is approved, the components and the container closure system continue
to possess the characteristics established in the suitability studies.
To ensure consistency, protection, compatibility, safety, and performance of the
packaging components, it is necessary to defi ne QC measures that will be used to
ensure consistency in the packaging components. These controls are intended to
limit unintended postapproval variations in the manufacturing procedures or materials
of construction for a packaging component and to prevent adverse effects on
the quality of a dosage form.
The USP tests and studies for establishing suitability and QC of container closure
system and for associated component materials are summarized in Table 5 .
Hydrolysis and oxidation are the two main routes of degradation for the majority
of drugs. To gain more information, the drug could be subjected to a range of temperature
and relative humidity conditions. In addition, photostability studies could
be conducted by exposure to artifi cial or natural light conditions. Elevated temperature,
humidity, and light stress the drug and induce rapid degradation. Harmonized
guidelines are available for new drug substances and products and may provide
useful information to characterize degradation processes and selection of appropriate
packaging material.
The primary packaging must physically protect the product from the mechanical
stresses of warehousing, handling, and distribution. Mechanical stress may take a