ARLINGTON, Va. – The Product Quality Research Institute (PQRI) forwarded its first recommendation to the Food and Drug Administration (FDA) for review. The recommendation proposes that in-process dosage unit analysis (of tablet cores, hard gelatin capsules or other solid dose forms) be considered as an alternative to routine blend sampling analysis to satisfy the agency’s good manufacturing practices (GMP) requirement to demonstrate “adequacy of mixing to assure uniformity and homogeneity.”
The recommendation, “The Use of Stratified Sampling of Blend and Dosage Units to Demonstrate Adequacy of Mix for Powder Blends,” represents an extensive effort by PQRI’s Blend Uniformity Working Group to address the gap between scientific principles and regulatory policy related to blend uniformity analysis and content uniformity of solid oral dosage forms.
The working group process included identification of the issues associated with blend uniformity analysis as currently performed, i.e., sampling and analysis of powder blends prior to manufacture of the final oral dosage form, evaluation of the scientific literature on the topic of blend uniformity and careful evaluation of various alternatives to blend analysis. The group also analyzed data obtained from pharmaceutical companies, which confirmed that blend analysis is not always predictive of the desired amount of drug content in the final dosage form.
Based on the working group’s evaluation, PQRI recommended that FDA allow stratified sampling and testing of in-process dosage units to demonstrate blend uniformity in all production batches as an alternative to blend analysis following a science-based process development described in the PQRI proposal. PQRI also recommended that FDA revise its guidances and policies to reflect the proposed changes.
In an agreement between FDA and PQRI and as stated in the PQRI by-laws, the FDA will evaluate the recommendation and either adopt it or, if it chooses not to adopt it, provide a scientific explanation to PQRI where the recommendation is lacking.
About PQRI
PQRI brings together for the first time the innovator and generic pharmaceutical industry, academia and the FDA (specifically the Center for Drug Evaluation and Research) to address issues related to pharmaceutical product quality. In addition to academic and industry members, the Blend Uniformity Working Group of PQRI included FDA representatives from the Office of New Drug Chemistry, the Office of Generic Drugs and the Office of Compliance. Several other working groups are in the process of conducting research to provide scientific evidence for assisting FDA in evaluating its policies and guidances.
For additional information on PQRI visit http://www.pqri.org. Calls and questions may be directed to the institute office at 703-248-4719.