There are a couple of significant challenges that pharmaceutical manufacturers may experience in selecting and implementing packaging systems. One of these challenges is posed by the growing trend toward prefilled syringes for liquid injectables. Prefilled syringes offer a much higher degree of performance than traditional vials by eliminating the dosage preparation necessary at the hospital. However, the implementation of prefilled syringes expands the validation process for the drug manufacturer.
Another challenge stems from the new standard on the qualification of materials for packaging systems with regard to extractables and leachables. Chemicals that can migrate out of the packaging materials and into the dosage form are a concern. With advancing analytics technology, there is a push from the FDA to understand what risks are posed by packaging ingredient migration. U.S. Pharmaceutical Convention (USP) is actively working on revising its standards for qualifying plastic packaging materials from the raw material to the final format. It's in the process of being finalized and it will be helpful for the industry to follow those standards. The goal is to establish standard evaluation methods and eventually, threshold limits, out of a consensus of experts.
Can you elaborate more on the revision of standards by the USP?
USP has formed an expert committee of volunteers from different reaches of the pharmaceutical and biotech sectors — including testing laboratories, drug manufacturers and component or equipment suppliers — to assess the risks and establish an updated, standardized approach to qualifying materials and packaging systems. The first two new standards published late last year addressed the qualification of component materials and final containers made from those materials. The next standards will address the process equipment side — upstream of filling the final packaging. These are currently in draft form and will be finalized by the end of this year. The next step, slated for 2017, is to generate standards for the suitability of packaging in the final dosage form.
When will drug manufacturers be expected to comply with these new standards?
No deadlines are set for compliance. These standards are voluntary. The USP sets the reference standards for the U.S. Food and Drug Administration (FDA). Therefore, pharmaceutical manufacturers that follow the USP standards will not have to go through any extra steps to meet FDA approval. However, pharmaceutical manufacturers that opt not to abide by USP standards will be held accountable by the FDA to provide other proof that the methods of analysis utilized are at least as effective. The USP's guidelines are treated as expectations. If an FDA reviewer questions a practice that complies with USP standards, pharmaceutical manufacturers have a strong scientific basis to stand on.
At this particular juncture in time, what is driving the need for these new USP standards?
Packaging systems are becoming more and more complex. I recently read about a biological that is packaged in an automatically timed, self-injection device that patients can wear on their stomachs. When a packaging system was just a vial in a box, there were far fewer components to evaluate. We're moving into a domain where the drug and the device are a package deal, but assessed by different teams at the FDA. The trend toward more complex delivery systems just doesn't always fit into the organizational structure of that agency. The FDA addressed this through the Office of Combination Products and new guidance. Creating a standardized set of expectations will make oversight of these increasingly complex packaging systems easier for all parties.
How has this trend toward complex packaging systems affected the general supply chain?
Pharmaceutical manufacturers certainly want to ensure that drugs, especially biologicals, are kept at the right temperature through the course of the supply chain. While we haven't seen many instances where temperature control of the drug has compromised the delivery device, temperature control is becoming more sophisticated with tracers that monitor the temperature and maintaining it through electronic signal so that the operators detect any deviation before the product goes bad. The added complexity is bound to necessitate greater utilization of the Internet of Things (IoT) to provide a higher sense of security and environmental control. These methods are being investigated now. On the topic of track-and-trace, sophisticated monitoring devices can help serve to authenticate original products when the threat of counterfeits loom over a drug.