Several U.S. Pharmacopeia packaging chapters are undergoing some sort of change, reported Dwain L. Sparks, an Eli Lilly Co. retiree and now a strategic advisor and expert consultant with YourEncore, to attendees at Pharmapack North America. These include the following chapters:

• Chapter <381> Elastomeric Closures for Injections.

• Chapter <659> Packaging and Storage Requirements.

• Chapter <660> Containers—Glass.

• Chapter <670> Auxiliary Packaging Components.

• Chapter <661> Containers—Plastics.

• Chapter <671> Containers—Performance Testing.

• Chapter <1207> Sterile Product Package—Integrity Evaluation.

• Chapter <1660> Evaluation of the Inner Surface Durability of Glass Containers.

• Chapter <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems.

• Chapter <1664> Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery 
Systems.

“It is important for pharmaceutical packaging professionals to keep an eye on new and changing packaging standards through regulatory surveillance, especially what is transpiring with USP packaging chapters through proposals published bimonthly in the free, on-line Pharmaceutical Forum,” Sparks told PMP News.

With all the pending revisions, it’s no wonder that pharma packaging engineers are consumed with material science and performance. These engineers must understand the level of risks that products face and how they can be addressed when developing every type of packaging component from plastic containers to elastomeric closures. 

“For instance, USP Chapter <381> on Elastomeric Closures is being restructured to incorporate a risk-based assessment consistent with those in the recently revised USP <661>,” explained Diane Paskiet, director of scientific affairs for West Pharmaceutical Services, to the Pharmapack North America audience. She spoke during the June 9 morning session on the USP packaging chapters. “There will be future changes related to the heavy metals section; certain elements will be reported as found since the limits in USP <232> Elemental Impurities only applies to final drug products. Applicants will need to verify risks based on their intended use,” she said.   

“Limits on components alone would not be practical,” she continued. “It is the applicant that will need to substantiate that cumulative elements do not exceed the total daily intake limits.”

For instance, “elements leached from [a]  container closure system should be based on a scientific understanding of likely interactions between a particular drug product type and its packaging; contributions of elements from other sources such as excipients will factor into the total daily intake,”  she said. “Studies to understand potential leachables from the final/actual container closure system (after washing, sterilization, irradiation) should be performed.” 

While <381.1> covers injectables and <381.2> inhaled drug products, future planned chapters are expected to cover elastomers used in manufacturing systems <381.3> and elastomers used in devices <381.4>.

Michael Ruberto, president of Material Needs Consulting, spoke about the new USP chapters pertaining to plastic packaging. “All materials can produce leachables,” he said. “Chemicals can migrate from packaging, devices, and processing equipment.” To understand what is an “actual” (a leachable; in the presence of the drug or drug components during normal use) and a “potential” (an extractable; determined in the lab to predict worst-case conditions of exposure), engineers need to design extraction studies, and then determine what is appropriate for a given application, he explained. “There’s no premarket clearance for materials used in pharmaceutical packaging,” he added.

Ruberto said USP’s vision with its <661.1>, <661.2>, <1663>, and <1664> chapters is to have engineers or scientists first characterize plastic materials or resins (covered in <661.1>), then move to packaging systems (covered in <661.2>). These subchapters will point to <1663> for extractables and <1664> for leachables, even though those latter chapters are for informational purposes since their chapter numbers are above 1000, he said. The point is to arrive at a “well-characterized system,” he explained. “If you have well-characterized materials, chances are you will have a well-characterized container that is suitable for packaging pharmaceuticals. You have the flexibility to decide based on risk.” 

What if a pharma company has a product already on the market in a particular packaging system? It is grandfathered under <661.1>. However, if the packaging system is used with a new drug, then the plastic resin and packaging system must be tested according to <661.1> and <661.2>, respectively. 

“Individual plastic materials of construction are deemed to be well characterized and appropriate for use if they are used in a packaging system that meets the relevant specifications in <661.2>,” he explained. “Materials must meet the specifications in <661.1>, and there are a variety of tests to be performed as needed for biocompatibility and physiochemical testing. However, extractables and leachables testing isn’t necessarily required for the container closure systems for all dosage forms—<1663> and <1664> allow for flexibility and a risk-based approach.” 

“On the surface, it might seem like the new and revised USP chapters will simply mean additional testing for the industry,” he tells PMP News. “However, the data and information gained from this testing will help to ensure that the materials used to package our pharmaceutical products will be suitable for use.”

Sparks encourages communication with USP. “Persistent efforts through written comments and collaboration with the Packaging, Storage, and Distribution Expert Committee (Senior Scientific Liaison, Desmond Hunt, Ph.D.; [email protected]) and industry colleagues are important and can help achieve and maintain practical and meaningful packaging standards for the future,” he says.

If you have further questions, please contact Ruberto at [email protected] and Sparks at [email protected].