FDA’s New Inspection Protocol Begins to Have Impact

The FDA’s new Inspection Protocol Project is expected to increase the likelihood of a drug manufacturing facility undergoing a pre-approval inspection from the current 30 percent to a target of 50 percent.

“As a pharma company if you’re going to submit a new drug, instead of a 30 percent chance of getting a pre-approval inspection, it’s now 50/50,” said John Avellanet, managing director & principal of Cerulean Associates. “So now instead of threatening your management and saying we might get an inspection, it’s more like we’re going to get inspected unless they were just here.

“No more are you going to have a situation where a company has submitted a drug for approval and the agency pops by six or nine months later and finds out they can’t even spell the drug, which is something you can see today.”

In addition to pre-market inspections, the protocol will help with inspection uniformity, as different inspectors may look at different aspects of facility operations. A drug company may receive a warning letter from an inspector who looks at big picture factors, such as sterility methods and cleanliness, or from one who puts an emphasis on paperwork.

That has created a rift between investigators and the industry in the past, but now investigators will be directed at what to look for, which will give facilities and companies a better idea of what to prepare for.

“Another issue this solves is that companies never know based upon who’s conducting the inspection whether they will get it and go along with the shades of grey or if they’re going to be nitpicky and issue a warning letter because someone forgot to sign a training letter from seven years ago,” Avellanet said. “The industry has just about had it with that type of inspection. The goal of this is also to eliminate as much of this annoyance stuff as possible.”

Now, inspections will put more emphasis on the written quality controls a firm has in place, the actual behaviors in the day-to-day operations and transition agency inspections to a risk-based inspection plan.

The project also aims to standardize the FDA’s inspection process world-wide and to allow for increased reliance on inspections by sister agencies such as Health Canada and the European Medicines Agency.

The data that the FDA will rely on “is pretty intense and incorporates information from the original product submissions for market approval, subsequent submissions, and adverse events reported by the firm versus reported directly to FDA,” Avellanet said. “It will also use data from previous inspection results from both FDA and sister regulatory agencies.”

The protocol is expected to be fully operational 2018. The next two years will be used to get FDA investigators trained and acclimated to the new standards and also to “provide time for feedback from investigators as they slowly go out and conduct these inspections — what’s working, what isn’t and what could be better, — and then incorporate that to continuously improve the program.” Avellanet said.

Although Avellanet believes the new protocol is an improvement to handling inspections and keeping the public safe, it may be some time before the industry can see how much better it will be.

“They’ll get all the investigators trained within the next couple of years and everybody will be implementing it and using it, but the real proof in the pudding of is this working really won’t be available until 2020.”

Check out this webinar CD: Special Protocol Assessments: Decoding FDA’s SPA Program and Revised Guidance. How has the revised guidance changed the process? Get in the know with an overview of the SPA program and a discussion of the impact of the FDA’s new draft guidance on sponsors and regulatory affairs professionals, and key opportunities and challenges for sponsors.