12. March 2015
Pharmaceutical companies spend years developing and testing their newest drugs in order to obtain the necessary regulatory approvals for drug commercialization. While developing an effective pharmaceutical is one piece of the puzzle, high-quality packaging is just as crucial in assuring patients that their drugs are delivered in their intended forms. Determining how the drug and its packaging will interact from the filling line to patient administration — which can consist of years of storage time — is crucial to a successful pharmaceutical.
The wrong packaging can render a drug unusable or potentially dangerous, triggering costly recalls. In recent years, drug and packaging manufacturers have worked in unison to systematically test containers for the risk of delamination and extracted or leached components — the most pervasive interactions between drug and packaging. Verifying that a drug can safely withstand short- and long-term storage is one of the last lines of critical testing prior to regulatory approval. Packaging manufacturers have also worked hard to improve the glass manufacturing process in order to reduce variations that can decrease the chemical durability of a container.
New guidelines, established by international regulatory agencies and the FDA, help ensure compatibility and reliability for drug compounds with their delivery and storage systems. The new regulations, which set forth a number of best practices for the design, justification, and execution of an assessment, represent the new spotlight of attention that’s been placed on these tests. These best practices act as guidelines for packaging manufacturers to ultimately determine the interaction between a drug and its packaging, and whether those interactions might be harmful throughout the life of a drug.
How specialized testing maintains drug safety
Glass delamination is the detachment of small flakes from the inner surface of glass containers due to an interaction with the drug. While most drug formulations won’t appreciably react with glass containers, testing is required to find the formulations and containers that might react. Delamination has been a concern in recent years after causing a number of recalls in 2010. The United States Pharmacopeia (USP) established new protocols in 2012 for delamination testing in the wake of those recalls. Since 2010, SCHOTT pharma services has conducted more than 300 delamination screenings for customers using well-established tests, which confirm the presence or absence of glass flakes in solutions, assess the container surface for pre-delamination features, and determine the root cause of glass attack, which can be caused by a poorly manufactured container or a drug product and glass chemistry incompatibility.
A close up of delamination.
In response to the heightened awareness of glass delamination, SCHOTT has developed Vials DC (delamination controlled), a vial produced under tightened process conditions along with a quick routine control that examines vials throughout the manufacturing process for their likelihood of delamination.
For extractables and leachables (E&Ls), manufacturers conduct testing after the container is selected and the drug’s chemistry is set, but before the drug’s registered with the FDA. These are time-consuming tests, so drug companies aim to complete E&L testing only once. USP guidance chapters 1663 and 1664, which establish a basic framework for assessment, design, and testing, have recently been released. The two-phase process of testing for E&Ls determines what molecules or compounds can be forced out of the drug’s container (extractables), and what is drawn out of the container during storage (leachables). If molecules or compounds are forced out of the container above a safety concern threshold, toxicological assessment must be conducted, and in a worst case, a new container or container closure system might be required. Additional regulations in terms of the amount of trace metals have recently been harmonized between the USP and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
A lab with the mission of safety
In 2009, SCHOTT pharma services was established as an ISO/IEC 17025 accredited laboratory staffed by former SCHOTT R&D scientists and engineers who conduct analytical testing for a range of pharmaceutical companies. The lab conducts three major tests or procedures for pharmaceutical companies: performing drug product and container compatibility testing (E&Ls and glass delamination); troubleshooting the manufacturing, processing, and filling of containers (glass breakage, defect analysis, and foreign material identification); and determining the functionality of containers (container strength, integrity, and the correct materials of construction). This independent lab acts as a testing ground both for pharmaceutical packaging and for new processes and technologies that further reduce the risk of delamination and E&Ls.
The mantra behind all of these tests and new guidelines is safety. A drug stored in the wrong container can lose its effectiveness or cause harm, so it’s critical that pharmaceutical companies and packaging manufacturers work together to prevent delamination and package leaching. Only then can they ensure that each drug safely does its job, just as prescribed.