Experts say FDA enforcement remains unchanged, use of alternative tools to grow

The U.S. Food and Drug Administration (FDA) will continue to focus on data integrity practices and closely examine OTC companies’ testing programs, either through on-site inspections or by using other inspection tools in fiscal year 2022, according to experts who spoke with Regulatory guidance on short-term enforcement trends.

Additionally, industry should expect to continue to respond to requests for electronic records as the agency’s use of this alternative inspection tool is expected to grow. Pending user fee legislation would codify this tool and extend its use to device inspections, a legal watcher said.

Experts discussed these trends in the context of a significant decrease in the number of FDA inspections, a consequent drop in warning letters for Good Manufacturing Practices (GMP) violations, and the growing reliance of the agency to the use of alternative tools to carry out inspections.

Overall drop in execution letters

In March 2020, the FDA announced that it would end all domestic and foreign on-site inspections, except for critical inspections, as pandemic-induced travel restrictions prevented personnel from traveling to sites in the whole world. (RELATED: Coronavirus prompts FDA to cancel trips, postpone inspections and meetingsRegulatory guidance March 10, 2022).

For all regulated products, the number of domestic inspections increased from 14,725 in fiscal year 2017 to approximately 4,500 so far in fiscal year 2022, and the number of overseas inspections fell from 3,166 in fiscal year 2017 to 135 so far in fiscal year 2022, according to FDA inspections. Data Dashboard.

This resulted in a similar drop in warning letters. In fiscal year 2021, the FDA issued 42 drug GMP warning letters, a significant decrease from the 106 letters issued in fiscal year 2020, according to an analysis of drug GMP warning letters. FDA Drug GMPs for fiscal years 2021 and 2021 conducted by consultant Barbara Unger.

OTC focus will continue

Despite declining warning letters, the FDA will continue to focus on data integrity breaches and testing programs at OTC businesses, whether through on-site or remote inspections. predicts the experts.

Unger’s analysis found that in fiscal year 2021, nearly 80% of warning letters sent to drug manufacturers, excluding compounding pharmacies and contracting facilities, were been sent to OTC companies. She predicted that going forward, OTC firms will continue to receive the bowl of warning letters.

“With over-the-counter drugs, everyone has a medicine cabinet full of them, so they affect everyone, it’s not like prescription drugs, which have a narrow subset, so if you look at the public health, they affect many more people. A few years ago the FDA inspected a few of these sites and it was like “oh my god, they’re out of control”. I guess the profit margin of these drugs is quite narrow. They don’t have a lot of things that prescription drugs have, like a quality system, that would develop those requirements.

Unger said lack of testing of incoming raw materials, inadequate qualification of suppliers, and failure to establish the validity of suppliers’ certificates of analysis are some of the major GMP violations cited in the letter. warning to OTC manufacturers. She said it was “basic stuff” and added that “prescription drugs were in this place 20 or 30 years ago, and the over-the-counter manufacturers are right behind the game.”

wolf step out the door

Robert Pollock, consultant at Lachman Consultants, said data integrity will be an area of ​​continued focus for the FDA.

“If you narrow down the issues, the data integrity will be very high. In my opinion, the natural course is for people to get a little lax when the wolf isn’t at the door, and the wolf hasn’t been been on the door for a few years. He added: “I don’t think it was intentional because it may have to do with a drop in training and things of that nature.”

The number of warning letters with data integrity issues has increased over the past three years, from 47% of warning letters issued in fiscal year 2019, to 51% in fiscal year 2019. fiscal 2020 and 65% in fiscal 2021, according to Unger.

Attorney Anne Walsh of Hyman, Phelps and McNamara agreed that data integrity will continue to be a priority during inspections.

“I think that’s definitely an area that we will continue to focus on from the FDA. They know what to look for now, data integrity issues will continue to come up.”

She added: “Even if there is no outright fraud, we will continue to see data integrity issues… I don’t see this going away, where you can see it on the spot, you can see it see on paper, the agency was able to do both.”

“Gone are the days when you would see papers being thrown out of the dumpster behind the facility, this stuff probably doesn’t happen anymore as pharma companies are hopefully better trained in data integrity” , she said.

Cross contamination: a persistent problem

Another recurring theme seen by Pollock in the warning letters is cross-contamination issues. “There were sterility issues and the clean rooms weren’t as clean as they should be. This has been prominent themes in warning letters issued over the past two years.

Pollock said some of the fiscal 2021 warning letters showed failures to prevent cross-contamination and issues he had “not seen in a while,” such as companies not paying attention to facility maintenance, such as cleaning air ducts. The FDA’s June 11 warning letter to Lupin’s subsidiary Novel Laboratories revealed inadequate equipment cleaning and maintenance procedures, including inspection of air ducts. (RELATED: The FDA warns the subsidiary of Lupin, aesthetic practiceRegulatory guidance June 29, 2021).

The FDA also continues to focus on compounding pharmacies, Pollock said. “There have been a ton of warning letters” sent to compounding pharmacies. “There have been issues with sterility and all sorts of things, like clean rooms not being as clean as they should be.”

Of the 42 warning letters issued by the FDA in fiscal year 2021, 12, or about 25%, were directed to compounding pharmacies, according to Unger’s analysis.

Remote reviews aren’t going away

Walsh said the industry should expect more inspections through electronic record requests, as proposed House user fee reauthorization legislation would further codify the FDA’s authority to request recordings or other information in the context of remote monitoring.

Walsh said that under the legislation, “they codify their authority for this, it would be a permanent tool in the FDA’s bag of tricks.”

The proposed legislation also directs the FDA to issue guidance “concerning circumstances under which the Secretary intends to issue requests for records or other information before or in lieu of an inspection under the Section 704(a)(4) of the Federal Food Drug and Cosmetic Act. The legislation directs the FDA to issue draft guidance on the matter within one year of its adoption.

The guidance would address processes for responding to requests, either electronically or in physical form, and the factors used to assess “whether such records and other information is provided in a timely, reasonable manner and in a reasonable manner, depending on resources. and other limitations that may exist, including for small businesses.

Walsh said remote inspections have advantages because they “give [FDA] the ability to peek at more sites, and for industry seeking drug approval, having a drug reviewed remotely by inspectors can get a drug approved sooner than if you had to wait that the FDA inspects on the spot.

Walsh advises retraining

With the resumption of on-site inspections by the FDA, Walsh advised the industry to step up training efforts on how to conduct internal audits and guest inspections.

“Because the regulatory teams lack a bit of practice during inspections, they have had a break for the past two years. Retraining on how to conduct inspections and respond to the FDA could be timely not only for the FDA but also for subject matter experts at the facility. This could be useful to ensure they have their A game when FDA inspectors come on site.

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