This series of articles will review the state of Container Closure Integrity Testing (CCIT) today and the various methods currently available, the factors for choosing the most optimal method and current regulatory guidelines under development.

Dye and microbial ingress testing have long been employed for assessing the integrity of container closure systems. However, research and experience as shown such tests are limited in their ability to provide accurate, sensitive and reliable data for definitive container closure integrity verification, especially for packages that demand the highest degree of product protection.

With the advent of new technologies, various sensitive and data-producing test methods have been developed to bring package integrity testing into the 21st century. The development of these new and improved methods over the past 10 years has led to regulatory agencies taking a fresh look at how to best guide industry. Within the next few months the United States Pharmacopeia will publish new General Chapter 1207 that deals specifically with container integrity and will outline in detail the various methods that industry can use. These new and improved Container Closure Integrity Tests have been successfully used to

  • characterize packages and materials,
  • optimize sealing parameters,
  • evaluate package storage temperature impact,
  • replace sterility tests for product stability batches,
  • screen production lots for faulty packages, and
  • support regulatory submission applications for product commercialization around the world.

The new USP 1207 chapter will prove to be a useful guide for companies that are in need of CCI testing. As this area of qualification is often misunderstood, the initial draft of the general chapter has taken a basic approach and will dedicate a section to each of the methods that may be employed. In addition, the chapter will discuss all the factors that must be considered when choosing the most optimal method. Key factors test method selection include package type, chemical make-up of product, type of seal and storage conditions.

With so many variables under consideration, there will not be one method that will satisfy all the CCIT needs of a company. Over time, the industry will need to have the ability to employ all the various methods if they are to insure that their products and package systems meet the stringent GMP regulatory requirements.