Top Analytical Method Problems in INDs and BLAs Include Not Enough Detail for FDA Replication and Inadequate Suitability Controls

Insufficient detail to allow FDA to replicate an analytical method, and failure to include appropriate system suitability controls, are two prominent analytical method problem areas that FDA is finding in reviewing investigational new drug (IND) and biologic license application (BLA) submissions.

Other common deficiencies in analytical method submissions include not submitting the actual test instrument output, using a compendial method for a non-compendial product without sufficient validation, and not evaluating linearity.

At an IBC “Well Characterized Biologicals” conference in Washington, D.C. in late October, CBER Division of Biological Standards and Quality Control Analytical Chemistry Team Leader Alfred Del Grosso reviewed the “top ten” analytical method inadequacies in IND and BLA submissions and what companies need to submit to smooth out the application clearance process.

The FDA reviewing official stressed that such deficiencies are resulting in information requests and can delay application clearance.

These analytical concerns do not generally result in a “refuse to file” status or a rejection letter, as the agency is usually “able to iron out most issues regarding quality in a submission,” Del Grosso commented.  However, paying attention to the agency’s expectations for these analytical method submissions will “ease the process for everybody” involved.

Based on his extensive method reviewing experience, Del Grosso provided valuable insights into FDA’s expectations and details around how to avoid agency questions for each of the ten problem areas.

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