Integrity Testing and Selecting the Best Closure for Your Lyo Product

By: Bryan Braxton, Ph.D., Senior Director, Aseptic R&D

Many approach the container closure systems as part of the formulation. It must be compatible with the formulation. Container closure systems provide an integral barrier to protect stability and sterility of the drug product during the shelf-life against microorganisms, reactive gases, and moisture. This is why most regulators are moving quickly toward a mandatory 100% Closure Container Integrity Testing (CCIT) for all parenteral products. It is widely accepted that CCIT will be extended to all containers and all pharmacopeias.¹

Choose and design the container and its closure system in such a way that they can guarantee the required stability and integrity not only after manufacturing, but for the whole shelf life of the product. It is essential to check and choose all the materials involved, their stability, and their mutual interactions over time and under expected environmental conditions. Interaction with the drug to be manufactured must also be considered and checked.¹

There are several factors involved in the design and validation of a good Container Closure System¹:

The material used for the container must be stable in time and in contact with the product inside without affecting its features, safety (i.e. sterility) and medical efficacy.
It must stop external gases, liquids, microorganisms and other foreign material to enter and get in contact with the product or the product to leak outside.
In case of photosensitive products, the container must be able to block most of the light, and specially its high-frequency component such as blue and ultraviolet to protect the product.
It must be also able to withstand the changes in temperature and mechanical handling, shacking and movements expected throughout the whole shelf life of the product including manufacturing, packaging, shipping, storage and use periods and phases.
The closure system of the container must be able to provide a similar level of integrity after product filling and final assembly.
Additionally, all interactions between container-closure and closure-product must be similarly analyzed and confirmed over the whole shelf life and range of storage and use of the product.
Both the container and the closure system should be economic to produce and manage, easy to inspect for quality assurance, easy and safe to operate even by common people without special skills or knowledge and finally easy and safe to dispose after use.

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ABOUT Pii

Pharmaceutics International, Inc. (Pii), A Jabil Company, is a US-based contract development and manufacturing organization (CDMO) located in Hunt Valley, Maryland. The experienced scientists, engineers, and staff at Pii pride themselves on adroitly employing a phase appropriate method of drug development for the prudent use of their customer’s resources as they solve challenging problems. In addition to offering end-to-end development services, Pii manufactures a variety of dosage forms to include complex parenteral drugs and has a wealth of analytical testing capabilities. Its Hunt Valley campus has four aseptic suites with lyophilization capabilities. Our talented professionals stand ready to help!

Bryan Braxton, Ph.D.
Senior Director, Aseptic R&D

Bryan Braxton joined Pii in October 2018 as Senior Director of Aseptic R&D. Bryan has 30 years of experience in the pharmaceutical industry.

Bryan held roles of increasing responsibility in sterile products at both Unither, AMRI, Pfizer, Abbott, and Glaxo, in the areas of Formulation Development, Process Transfer, Quality by Design, Technical Services, Contract Services, and Project Management.

Bryan earned a Ph.D. in Pharmaceutical Chemistry from the University of Kansas and is a registered pharmacist.