Anaheim, Calif. — When Clariant International Ltd. brought a twin-screw compounding extruder on line at its facility in Lewiston, Maine, earlier this year, the materials supplier wrapped up a years-long expansion project aimed at producing larger batches of its Mevopur brand compounds.
The Lewiston plant is one of three sites where the Swiss specialty company produces materials for medical devices and pharmaceutical packaging. Changes coming to the industry were behind some of the reasons for the “multimillion-dollar” expansion project.
The footprint of the facility was increased by 40 percent to accommodate the high throughput compounding line, which was built around a new 70 millimeter extruder, as well as materials handling, weighing stations, a maintenance area and additional water-cooling capacity.
“People know Clariant masterbatches but in fact we've always done compounds as well. The new capability lets us compound from 50 pounds up to 12,000 and higher so this is a bigger line,” said Steve Duckworth, global head of Clariant's Healthcare Polymer Solutions, at Medical Design & Manufacturing West, held Feb. 6-8 in Anaheim.
Lewiston was selected to house the compounding line partly to meet current needs of customers for larger batch sizes of rapidly produced pre-colored Mevopur.
“Some customers were taking our concentrates and sending them to a compounder on the corner,” Duckworth said. “We could see that they didn't know Clariant could do compounds or we didn't have the capacity. With the added capability to handle much bigger lot sizes, we really have a complete solution to the customer.”
Demand for Mevopur also is expected to increase as manufacturers meet stricter regulations for pharmaceutical packaging and drug delivery devices over the next couple years.
To prepare for the changes, which go into effect in May 2020, Clariant officials say they have completed testing on the ingredients in the Mevopur and Remafin-EP product lines and both comply with the new standard called U.S. Pharmacopeia (USP) 661.1. Duckworth said the new requirements call for a significant update of packaging test methods and a more robust process for risk assessment.
The new standard aims to go further in reducing the risk of an ingredient in the packaging from interacting with the drug. For example, food-contact materials have been used historically to package drugs taken orally in the form of tablets but that won't satisfy the new standard.
“The FDA has come out and said, if in May 2020 you have a material and the only declarations you can do is food contact, it is insufficient. They're saying you need to have done the tests to the new standard in addition, and that's a fundamental change,” Duckworth said.
The stricter standard requires data from in-vitro tests and for cytotoxicity on packaging materials used for all categories of drugs from solid oral doses to injectables, nasal doses and ophthalmic solutions. Some of the data will be obtained from extraction and leachables testing.
“For the leachables testing, the actual drug is placed in contact with the packaging material for shelf-life stability testing. They're looking for a time period up to 2-3 years of contact with the drug. They do accelerated testing with increased temperature and can get the results in 6 months.
You don't want to find anything. By doing the tests on the raw materials, we really help the pharmaceutical manufacturer and people making the packaging to reduce the risk they'll find something.”
The biggest challenge to meet the new standard is in the U.S., Duckworth added. Internationally, packaging producers have already been getting requests from pharmaceutical companies to submit under the new standard.
“I think there's some catch-up to do in the US industry,” Duckworth said. “Go to your pharmacy store and every package on those shelves needs to be compliant to the new standard. All those materials need to be retested. It's a huge burden on the industry and the later they leave it, the more problems they will have.”
The standard was supposed to go into effect in 2017 but the Federal Drug Administration granted a transition period. Duckworth said it's time to get ahead of the regulatory changes and “future-proof” packaging.
“Today you have a choice to file under the old legislation and all the test methodology that comes with that; or, you can file under the new,” Duckworth said. “Because we completed our test program for the new standard for all of our materials, people can go into this with the new standard and not worry about 2020. That's future proofing.”
Clariant started testing the packaging ingredients in its Mevopur and Remafin-EP product lines in 2017 and completed the process this year.
The company also has data to meet stricter International Council for Harmonisation (ICH) guidelines for assessing risk of elemental impurities in drugs, Duckworth said. The guideline (ICH-Q3D) calls for the evaluation of not only the pharmaceuticals, but also the packaging to ensure it isn't a source of elemental impurities in drugs.
In addition to the new compounding line, Clariant will continue to operate its smaller Mevopur lines in Lewiston and at other facilities. Duckworth said small- and medium-sized lots are in demand from medical manufacturers because many resin producers have discontinued or scaled back their custom-color offerings for orders less than a railcar or full-truck load.
In Lewiston, Clariant also recently installed a smaller line to meet processing requirements for fluoropolymer resins, such as FEP, ETFE and PVDF. Fluoropolymers are being used more frequently in medical catheters and diagnostic devices because of their flexibility, lubricity and chemical resistance.
“They can require special processing equipment and manufacturing techniques, and that's exactly what we have put in place in Lewiston,” said Eric Rohr, Clariant's North America segment manager for medical and pharmaceutical.