Pharmaceutical Manufacturing Handbook: Production and

178 PACKAGING AND LABELING
If the product is sensitive to photolysis, then opaque materials may be required.
Most secondary packaging materials (e.g., cartons) do not transmit light, but in
some cases specialized primary packaging designed to limit light transmission is
employed.
The package must also prevent the entry of organisms; for example, packaging
of sterile products must be microorganism proof — hence the continued use of glass
ampules. For nonsterile products the preservative provides some protection, but
continual microbial challenge will diminish the effi cacy of the preservative, and
spoilage or disease transmission may occur.
The packaging material must not interact with the product either to adsorb substances
from the product or to leach chemicals into the product. Plastics contain
additives to enhance polymer performance. PVC may contain phthalate diester
plasticizer, which can leach into infusion fl uids from packaging. Antimicrobial preservatives
such as phenylmercuric acetate are known to partition into rubbers and
plastics during storage, thus reducing the formulation concentration below effective
antimicrobial levels.
A complication of modern packaging is the need for the application of security
seals to protect against deliberate adulteration and maintain consumer confi dence.
The active products used must also be stability tested in the proposed packaging
material.
The FDA guidance for industry suggests considering consistency in physical and
chemical composition. Using a few simple tests, the quality of components and ultimately
the container closure system can be monitored.
Physical Characteristics The physical characteristics of interest include dimensional
criteria (e.g., shape, neck fi nish, wall thickness, design tolerances), physical
parameters critical to the consistent manufacture of a packaging component (e.g.,
unit weight), and performance characteristics (e.g., metering valve delivery volume
or the ease of movement of syringe plungers). Unintended variations in dimensional
parameters, if undetected, may affect package permeability, drug delivery performance,
or the adequacy of the seal between the container and the closure. Variation
in any physical parameter is considered important if it can affect the quality of a
dosage form.
Physical considerations such as water vapor transmission to evaluate seal integrity,
thermal analysis such as DSC to monitor melting point and glass transitions of
plastics, and IR scanning to prove identity should be part of an ongoing quality
control monitoring program.
Chemical Composition The chemical composition of the materials of construction
may affect the safety of a packaging component. New materials may result in new
substances being extracted into the dosage form or a change in the amount of known
extractables. The chemical composition may also affect the compatibility, functional
characteristics, or protective properties of packaging components by changing rheological
or other physical properties (e.g., elasticity, resistance to solvents, or gas
permeability).
The chemical composition should also be evaluated by performing the simple but
informative USP physicochemical tests using water, drug product vehicle, and
alcohol extractions of plastic components. Specifi cations should be set for nonvola-