Particularly sensitive injectable drugs, including monoclonal antibodies and recombinant proteins, require additional stabilization to help ensure effectiveness. Lyophilzation, or the process of freeze-drying drug products, can help sensitive drugs that are unstable in an aqueous solution while increasing the drug’s temperature tolerance and potential shelf life.
 
Worldwide, lyophilized products account for nearly 2 billion drug product units, with a volume growth from 2010 to 2014 of nearly 60 percent.¹ Top therapies using the lyophilization process include antiulcerants, blood coagulations, expectorants, Chinese medicines, hepatic proct lipotropic drugs and corticosteroids.
 
In order to lyophilize a drug product, operations must be sterile to ensure that the drug, which undergoes extreme physical and chemical changes during the process, can be reconstituted effectively. The process itself must be monitored closely, to ensure that proper conditions are in place for product consistency.² In addition, a primary container closure system that not only suits the drug product but also ensures optimal operations should be selected to overcome challenges associated with the lyophilization process. Such challenges include glass breakage, and the risk of the lyophilization stopper popping up during the waiting phase prior to capping.
 
A proper primary containment system should consider the needs of the drug first and foremost, but also ensure effective and consistent fill-finish operations. Primary drug containment for freeze-drying applications typically consists of a vial (glass or engineered polymer), elastomer stopper and seal. Currently, aluminum seals are the standard in the industry; however, rising concerns regarding particulates and issues associated with crimping of the seal on the vial after lyophilization have resulted in a new trend – the use of plastic caps for aseptic crimping.
 
Good manufacturing process guidelines suggest that capping/crimping shortly after lyophilization process, as well as minimizing human intervention prior to capping, should be used to overcome challenges associated with the lyophilization process.³ Immediate capping within the lyo chamber with a medical grade polypropylene cap, such as the LyoSeal cap from West would reduce unwanted interactions – with both humans and between the elastomer and the lyo shelf, which can cause catastrophic (and costly) problems should the elastomer adhere to the shelf.
 
Designed for processability in the lyo chamber, a plastic cap, such as the LyoSeal cap, consisting of a button, lock and shell would enable filling, stoppering, freezing and closing to be done aseptically. In addition, the use of a medical grade polypropylene ensures that the cap can withstand a variety of variations within the process itself, including chamber pressure and shelf temperature, without sticking to the shelf.
 
A container closure integrity study targeted for 24 months at storage conditions of 2°C and 25°C is currently being conducted to show that vacuum is maintained.
 
Plastic seals offer a wide range of benefits for lyophilized drug products and the fill-finish process. Plastic caps present a potentially unique value for pharmaceutical R&D projects, allowing for easy manual crimping during the drug development process, as well as operational efficiencies during the lyophilization process that allows immediate vial closure within the chamber. Use of plastic caps potentially could eliminate the use of aluminum used for current vial closures, thus reducing a source of particulate and the challenges associated with non-aseptic crimping.
 
Products made with new materials and components often face challenges when introduced to the healthcare industry. While plastic caps will have to prove their usefulness through performance, they are a viable solution to the myriad challenges of the current fill-finish processes associated with drug product lyophilization. Through ease of use, efficiency in manufacturing processes, and successful trials, plastic caps may soon become the industry standard for lyophilized drugs.

References:
¹IMS Health
 
²Genetic Engineering & Biotechnology News. (2005, September 15). Lyophilization: Growing with Biotechnology. Retrieved from https://www.genengnews.com/gen-articles/lyophilization-growing-with-biotechnology/1083
 
³EC EMA Guide EUROPEAN COMMISSION; EudraLex; The Rules Governing Medicinal Products in the European Union; Volume 4: EU Guidelines to Good Manufacturing Practice, Medicinal Products for Human and Veterinary Use; Annex 1: Manufacture of Sterile Medicinal Products, Annex 1, clause 118, 119, 122

---

Sylvia Marzotko joined West in October 2013 and has recently taken on the role of Senior Manager Product Management within West’s Vial, Containment & Delivery area, where she is managing the product, service and brand portfolio. Before joining West, Sylvia worked as Marketing Manager for a Market Research agency specializing in the Health Care Market.