In the fall of 2014, the United States Pharmacopeia (USP) released its proposed revisions to General Chapter 1207, Sterile Product Packaging—Integrity Evaluation. [1] The expanded chapter provides detailed information on container closure integrity (CCI) testing methods, categorizing them as either deterministic (quantitative, verifiable) or probabilistic (qualitative, subject to human judgment). The chapter also evaluates nondestructive leak-testing methods, a new and notable inclusion. [2]
While the USP Package Integrity Expert Panel evaluates all of these methods for their usefulness and suitability to the pharmaceutical industry, the proposed revisions strongly recommend deterministic methodology to assure CCI. The new chapter should become operational next year. [3]
Industry Buzz
Oliver Stauffer is the chief operating officer at Packaging Technologies & Inspection (PTI) a New York–based company that manufactures nondestructive package inspection technologies for the pharmaceutical, medical device, and food industries. The “revision” of USP Chapter 1207, he says, is not a revision at all. It’s more like a massive overhaul, and long overdue.
“The original Chapter 1207 document was just a few pages,” he notes. “The revision is over 40 pages. The changes do not change testing methodology, but should change how organizations relate to test methods.”
The end result, Stauffer says, is that organizations will have to test their packaging using more reliable and quantitative test methods. Ultimately, he concludes, they’ll have to take “a more patient-centric, quality-oriented approach to assuring that pharmaceutical packaging is of the highest quality, [and] based on quantitative measures.”
The resulting buzz in the pharmaceutical packaging arena is linked directly to industry “culture of quality” discussions.
“The revisions are a response to a long-standing lenient approach to primary package testing as an afterthought,” says Stauffer, referring to the many FDA recalls related to primary package integrity.
In recent years, both pharmaceutical packaging and regulatory changes have had to respond to new delivery systems and new drug products. These require the FDA to adapt in oversight — a driver of change in the pharmaceutical industry.
“It’s not a one-way street,” explains Stauffer. “The regulatory agencies and drug manufacturers are continuously evolving to adapt to new primary packaging trends, and both need to respond to the challenges of new package formats using better testing solutions.”
Delicate Biologics
Some estimates point to biologics as making up more than 60 percent of the drugs currently in clinical development and predict that 50 percent of all pharmaceuticals will be biologics by 2020. [4] This growth is certain to affect pharmaceutical packaging. Biologics are often delivered by prefilled auto injectors, a unique packaging format that has been growing at a rate of 20 percent per year. [5] This makes CCI even more difficult, due to the nature of biologics, which Stauffer calls “delicate.”
“Testing auto injectors is not an easy task because of the products’ content and the device characteristics,” he continues. “Container closure issues require unique methodology for this delivery system. Other inspection solutions, such as automated visual inspection techniques, may not be suitable due to the delicate nature of the product. If you cannot agitate the vials for visual inspection, testing may require thinking that is out of the box. Very few solutions can be applied blindly as the new drugs and delivery systems continue to evolve.”
Quality Culture
As a large number of brand-name drug patents expire over the next few years, generic manufacturers may increasingly turn to contract packaging operations when they lack packaging capacity or expertise. [6] When this happens, Stauffer worries that lower margins in the generic space may affect packaging quality if a “compliance culture” rather than a “quality culture” prevails. This is especially problematic if testing methods are grandfathered in from package format to package format without considering the unique characteristics of each product and delivery system.
“I think that pharmaceutical packaging in general is making great progress in assuring that new delivery systems and new drug products are better and safer for consumers,” Stauffer says, citing the importance of the International Society of Pharmaceutical Engineering’s (ISPE) efforts in quality metrics. But he warns that “you cannot achieve a state of quality if you don’t have measurement of quality.”
Echoing the many discussions on “culture of quality” held at ISPE meetings, other industry events, and in boardrooms, Stauffer also emphasizes that when quality issues are identified, they must be referred up the management chain, and when testing reveals quality gaps, organizations must respond accordingly and appropriately.
“Raising quality concerns should not be synonymous with whistleblowing,” Stauffer concludes. “Achieving a state of quality requires an open and collective approach to addressing any deviations. Rather than let quality issues fester, it’s better to address them.”
Co-located with PACK EXPO Las Vegas (Las Vegas Convention Center, Las Vegas; September 28-30, 2015) and making its Las Vegas debut, Pharma EXPO will serve as a resource to pharmaceutical manufacturers seeking packaging solutions, practices and resources to enhance quality, handle delicate biologics and assess their formats to ensure product protection.
Pharma EXPO is co-produced by PMMI, The Association for Packaging and Processing Technologies, and The International Society for Pharmaceutical Engineering (ISPE). Together, the two shows, for the first time ever in Las Vegas, will present aisles of innovation in action, educational programming and opportunities to cross-pollinate ideas between industries and to network with peers and suppliers.
Visit Pharmaexpo.com to register and learn more.
References
[1] United States Pharmacopeia. “<1207> Sterile Product Packaging—Integrity Evaluation (USP38-NF33 2S).” USP Pharmacopeial Forum 40, no.5 (September 2014). www.usppf.com. [2] Sagi, Hemi. “USP <1207> Updates Leak Testing Recommendations for Pharmaceutical Companies.” Pharmaceutical Online (June 4, 2015). http://www.pharmaceuticalonline.com/doc/usp-updates-leak-testing-recommendations-for-pharmaceutical-companies-0001 [3] Forcinio, Hallie. “Evaluating Package Integrity.” Pharmaceutical Technology 39, no. 4 (April 2, 2015). http://www.pharmtech.com/evaluating-package-integrity [4] Strain, Alandra. “Current Challenges in Pharmaceutical Packaging,” Pharmaceutical Engineering Packaging Supplement, October 2014: 7. http://www.ispe.org/pharmaceutical_engineering/2014-packaging-supplement. [5] Zadbuke, Nityanand, et al., “Recent Trends and Future of Pharmaceutical Packaging Technology,” Journal of Pharmacy and BioAllied Sciences 5, no. 2 (April–June 2013): 98–110. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697200. [6] Berghahn, Walter. “Growth Prospects for Pharmaceutical Contract Packaging,” Contract Pharma June 2015. https://www.google.com/webhp?sourceid=chrome-instant&ion=1&espv=2&ie=UTF-8#q=%E2%80%9CGrowth+Prospects+for+Pharmaceutical+Contract+Packaging%2C%E2%80%9D.
About ISPE
ISPE, the International Society for Pharmaceutical Engineering, is the world’s largest not-for-profit association serving its Members through leading scientific, technical and regulatory advancement throughout the pharmaceutical lifecycle. The 20,000 Members of ISPE are building solutions in the development and manufacture of safe and effective pharmaceutical and biologic medicines and medical delivery devices in more than 90 countries around the world. Founded in 1980, ISPE has its worldwide headquarters in Tampa, Florida, USA. Visit: www.ISPE.org or more information.
