Metrics poster presentation at AAPS reinforces value of internationally embraced approach
GREENVILLE, N.C. – When a core tablet proved too weak to withstand coating, scientists at Metrics Inc. made it stronger.
While that sounds simple enough, Metrics’ scientists tackled the problem using Quality By Design, which has been embraced by the International Conference on Harmonisation, as well as the U.S. Food and Drug Administration and its regulatory counterparts in Europe and Japan.
Despite finding favor with regulatory authorities worldwide, however, Quality by Design still represents for many pharmaceutical companies a challenging approach to quality control – which is why Metrics’ weak-tablet-made-strong case study was chosen for poster presentation at the annual conference of the American Association of Pharmaceutical Scientists (AAPS).
In his Oct. 17 presentation at AAPS, Joseph E. “Joe” Cobb Jr., associate director of pharmaceutical development at Metrics, explains how Quality by Design principles helped the company’s scientists improve the robustness of a core tablet destined for a modified release dosage form.
“The Quality by Design approach calls for looking at operations upstream from the compression process, such as high shear wet granulation and milling, and testing the outcomes of different parameters,” Cobb said. “Using the QbD mindset, we were able to identify the actual factors that had the greatest impact, which was a nice outcome.”
In his AAPS poster, Cobb describes how a coated tablet had been formulated to deliver 40 milligrams of an active pharmaceutical ingredient over the course of four hours. The core tablets had undesirable physical attributes such as poor breaking strength and unacceptable friability.
The Metrics scientists first established a quality target product profile for the core tablets, which required the tablets to withstand the coating process and show acceptable uniformity of dosage units. Then they determined the critical quality attributes of the core tablets.
The third step involved performing a risk assessment to identify the critical processing parameters and determining the necessity of individual upstream unit operations, including compression of the core tablets themselves. Finally, an informal design of experiments was drafted and executed to determine optimal settings for core tablets in the critical granulating step.
As a result of their Quality by Design effort, Cobb said, Metrics scientists found that by increasing granulating liquid volume by 5.5 percent and reducing post-addition wet-massing time by 50 percent, they could improve friability from a baseline of ~0.15 percent to near 0.00 percent, and increase tablet breaking strength by approximately 50 percent. Uniformity of dosage units met product quality requirements.
“By following Quality by Design principles, we were able to substantially improve the robustness of the core tablet,” Cobb said. “And therein lies the value of Quality by Design and why regulatory agencies in the United States, Europe and Japan have all embraced it and expect the pharmaceutical industry to adopt it as best practice.”
Cobb holds the highly respected Certified Pharmaceutical Industry Professional (CPIP) credential awarded by the International Society of Pharmaceutical Engineers. He manages all aspects of projects at Metrics that involve early-phase solid oral dosage development.
Metrics Inc. is one of the most respected contract pharmaceutical development and manufacturing companies in the United States today.
Started as an analytical laboratory in 1994, Metrics has evolved into a full-service provider of quality pharmaceutical formulation development; first-time-in-man (FTIM) formulations; clinical material manufacturing (CTM) for Phase I, II and III trials; commercial manufacturing; and analytical method development and validation services.
Metrics recently agreed to be acquired by Mayne Pharma Group Limited, a publicly traded pharmaceutical company in Melbourne, Australia. Metrics will operate as a subsidiary.
To learn more about Metrics Inc. and its services and facilities, visit http://www.metricsinc.com.