Evaluation of blend uniformity and content uniformity based on 2003 stratified sampling guidance and 1999 blend uniformity analysis guidance: product A.

In August 1999 the FDA issued a Draft Abbreviated New Drug Application (ANDA) Guidance for Industry titled "ANDA's: Blend Uniformity Analysis" that detailed blend uniformity sampling and acceptance criteria for the determination of final blend uniformity for generic drug products. Although this guidance was written specifically to address ANDA's, the guidance was also adopted as standard practice in the development of NDA's (New Drug Applications). The proposed release criteria established for blend uniformity were to be used in addition to, and independent from, the USP finished product uniformity release requirements. Based on the Blend Uniformity Guidance, batches that failed to meet the blend uniformity acceptance criteria should be rejected regardless of the products ability to demonstrate final product uniformity. In March 2002, the Product Quality Research Institute (PQRI) issued a proposal to the FDA with respect to both ANDA's and NDA's recommending the use of stratified sampling for final blend and in-process dosage units. The proposal recommended the use of final blend uniformity and dosage unit uniformity to demonstrate overall batch uniformity, with the possibility of using dosage unit uniformity in lieu of blend uniformity during routine commercial production. Consequently, in October 2003, the FDA issued a Draft Guidance for Industry titled "Powder Blends and Finished Dosage Units-Stratified In-Process Dosage Unit Sampling Assessment" that detailed the criteria for the use of stratified sampling and acceptance criteria to demonstrate batch uniformity. In response to the PQRI proposal, Endo Pharmaceuticals conducted an impact evaluation of the proposed PQRI sampling procedures and acceptance criteria on a product-by-product basis as compared to the 1999 Draft Guidance and current USP requirements. The evaluation of Product A demonstrates the benefit of implementing the 2003 Guidance for products that demonstrate questionable blend uniformity but acceptable finished product uniformity.