Ask the Expert: Drug Approval Submissions

Could a pharmaceutical company’s regulatory affairs department become the target of a regulatory inspection? Susan J. Schniepp, distinguished fellow with Nelson Labs, and Siegfried Schmitt, PhD, vice president, Technical, at Parexel, say that it can, and companies that assume otherwise are exposing themselves to risk.

According to Schniepp, inspectors are not auditing the electronic submission mechanism itself because the eCTD system is already validated, and paper submissions are essentially obsolete in both the United States and the European Union. What's inspectable is the accuracy and completeness of the information within those submissions, and whether the company is following what it submitted. That scrutiny typically surfaces during chemistry, manufacturing, and controls (CMC)-focused inspections, such as pre-approval inspections, and becomes especially complicated when a company relies on a contract manufacturing organization (CMO) that may only have access to a fraction of the full submission.

Schmitt added that regulatory affairs departments function as a relay point: they receive condensed information, such as confirmation that an analytical method was validated per United States Pharmacopeia (USP) or European Pharmacopoeia (Ph.Eur.), rather than the full underlying validation report. That compression creates risk. If information is incomplete, inaccurate, or garbled somewhere in the handoff from manufacturing to regulatory affairs (often through quality assurance as an intermediary), the resulting submission can be wrong. Inspectors, he noted, may specifically probe how communication pathways function between manufacturing sites, CMOs, and regulatory affairs.

Schniepp pointed to concrete gaps that often go unaddressed: submissions frequently state that a compendial method is used without including verification that the method actually works under the conditions in that specific lab. Similarly, when a proprietary test method is developed at an R&D site and later transferred to a manufacturing site, the tech transfer documentation supporting that move may not be part of the submission, raising the question of whether the company’s regulatory affairs department can answer for it if asked.

The conversation also covered the reverse information flow: feedback from regulators, such as an approved label change, must be communicated back into operations—to packaging teams, for instance—and executed correctly, particularly for companies managing multiple SKUs across many countries. Both panelists emphasized that inspectors have found regulatory affairs departments operating outside the company's quality system, mistakenly believing they're exempt from standard operating procedures (SOPs). Schniepp was unequivocal that regulatory affairs must operate within the quality management system, even though quality doesn't dictate every regulatory task. Any change must go through formal change control and be supported by documentation in the submission or a subsequent update; undocumented changes put the entire validated process in question.

Schniepp raised a further liability: regulatory affairs departments receiving clinical data must have some means of confirming that data have not been falsified. Cases exist where fabricated data made it into submissions because no one cross-checked it against the reporting site, and that gap becomes a serious liability once discovered.

Schmitt closed by noting inspections of regulatory affairs typically require a trigger—inspectors generally focus their attention on operational sites first. But especially in Europe, inspectors do verify that what's stated in the license matches actual site practice. He recommends that processes be kept as simple and robust as possible, because complexity is what generates gaps. His practical recommendation for manufacturers: ensure regulatory affairs staff are properly trained, operate under clear SOPs, and understand that they are not exempt from inspection scrutiny.

Click the above video to watch Sue and Siegfried answer the following question:

“Our regulatory affairs department handles all the submissions to regulatory agencies. Is there a chance the department may be inspected?”

About the Experts

Susan J. Schniepp is distinguished fellow at Nelson Labs and a member of PharmTech's Editorial Advisory Board.

Siegfried Schmitt is vice president, Technical at Parexel and a member of PharmTech's Editorial Advisory Board.