Stoppers and syringe plungers are not the only primary packaging components undergoing change. Many new drugs, especially
those used for oncology, are sensitive to the glass used to manufacture vials and syringe barrels. Contaminants from the glass
might leach into the drug product which in some instances can be worth thousands of dollars per dose. This new generation
of high-value biopharmaceutical therapies requires equally high-value packaging and administration systems to maintain the
drug's biological integrity and to maximize its therapeutic benefits.
Some manufacturers are switching their products from glass vials and syringe barrels to products manufactured from cyclic
olefin copolymers (COC) and cyclic olefin polymer (COP) materials. These resins are inert and have properties such as extremely
low extractables, high heat resistance, excellent low-temperature characteristics, excellent drainability, and low-moisture
permeability that are favorable for high-potency, high-value drugs.
A deliberate evolutionary process
The transformation to today's primary pharmaceutical packaging environment, with an emphasis on quality and cleanliness, proceeded
deliberately with the focus on creating a CGMP environment. From the manufacturing floor and into a company's day-to-day operating
procedures, CGMP regulations represented a huge shift in thinking. They required improved traceability of the raw-materials
chain; the introduction of new systems for quality control and quality assurance testing of raw materials, work in progress,
and finished goods; and a tightening of manufacturing and operating procedures and product specifications to achieve new levels
of quality.
Today's plant has the cleanliness one would expect in pharmaceutical manufacturing. Employees in manufacturing and processing
areas wear protective clothing appropriate for the work space's classified environment to keep particulate and fibers out
of the manufacturing area, and they are trained thoroughly in CGMP requirements. The quest for quality begins even before
raw materials are received at the plant. Materials are purchased on the basis of a supplier's ability to meet tight tolerances
and strict quality standards.
Moreover, incoming raw materials are sampled and tested; the lots are not released for production until the laboratory determines
that specifications have been met. Today's elastomeric formulations are blended from fewer materials that are less extractable.
The formulations used 30 years ago would not be acceptable for new drug products today because of concerns over extractables
and leachables and because some of the materials used in the 1970s would not meet current industry guidelines. In addition,
the properties of today's elastomers, including coring and resealing properties, help pharmaceutical manufacturers meet shelf-life
requirements and provide better performance during administration. Further, today's elastomers have helped improve the manufacturing
process. As a result, molding yields fewer rejected parts.
Today, mixing equipment used to blend the ingredients that go into elastomeric formulations is closed to minimize contamination.
The calendaring and extrusion processes can achieve tight dimensional tolerances for the sheeting that is used to mold the
components. Improved equipment and quality systems such as in-process metal detectors help ensure the highest quality finished
components.
Molded sheets of components move from molding to trimming, where a die trims the individual parts from the sheet. Today's
trim dies operate at a high level of precision. The result is components with very little dimensional deviation from the standard
and fewer instances of particulate from the trimming process.
Postmanufacturing processes also have advanced significantly. In today's manufacturing environment, downstream processing
frequently includes washing in a pharmaceutical-grade washer to yield ready-to-sterilize components that are shipped to manufacturers.
Final rinse processes use water-for-injection and final packing is conducted in a Class 100 cleanroom. The bags used to pack
the washed components are suitable for direct entry into a sterilizer.
The contrast with 1970s processing is striking. Three decades ago, most components were trimmed and dropped into a poly bag.
The bag was secured with a twist tie and shipped to the customer in a corrugated box. Component washing was rudimentary compared
with today's process; the wash did little more than remove lubricants applied during the trimming operation.
The impact of regulatory guidances
Guidances issued by the US Food and Drug Administration have had a strong influence on the drive to cleanliness and ultrahigh
quality.
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