Social Distancing Doesn't End At Door: Pandemic Precautions During Onsite Drug GMP Inspections

“Any practices that limit the social interaction between the investigator and the firm are always good,” says FDA ORA official Rachel Harrington. Donald Ertel, of FDA’s Center for Biologics Evaluation and Research, encourages firms to “try to maintain a one-way flow through the facility” for investigator plant walkthroughs.

Onsite inspections pharmaceutical manufacturers host during the coronavirus pandemic should be as remote as possible, US Food and Drug Administration officials suggest.

The advice stated at the recent Parenteral Drug Association/FDA conference comes as the agency gains experience with domestic site inspections, which it resumed in July in areas of reduced COVID-19 infection rates.

A UK Medicines and Healthcare products Regulatory Agency official described a similar approach, while noting that the UK has been slower to resume site inspections.

Limit Social Interactions

“Any practices that limit the social interaction between the investigator and the firm are always good,” said Rachel Harrington, a consumer safety officer with the FDA’s Office of Regulatory Affairs, during an ask-the-regulators session at the virtual conference.

“For example,” Harrington said, “instead of having the subject matter expert come with the investigator on the walk-through, maybe you could have them participate by phone. If you have the ability to set up a video call, so even if the person’s onsite, maybe they could be in a separate room.”

Another idea she shared: do some of the work outside, where viral transmission is reduced. “I have heard of firms setting up an outdoor room where they will have discussions and even document review.”

Avoid Paper

Another idea is to avoid paper. “Providing documents electronically to limit the back-and-forth handling of paper is also a good practice,” Harrington said. That can mean sharing computer files or, as one company did, “projecting documents on a large screen in a conference room for the investigator to review onsite.”

Donald Ertel, of the FDA’s Center for Biologics Evaluation and Research, encouraged companies to “try to maintain a one-way flow through the facility” for investigator plant walkthroughs.

Ertel, a senior reviewer and lead inspector in CBER’s compliance office, said companies should minimize the number of people in each room during these tours and make sure there are masks, hand sanitizers and opportunities for frequent hand washing available throughout the facility.

One best practice Ertel shared was from a manufacturer that had everyone wear plastic face shields in the conference room.

A Slow Return To The ‘New Normal’

Even after global pandemic travel restrictions largely grounded the agency’s inspection operations in March, FDA investigators have traveled to domestic and foreign facilities to conduct drug good manufacturing practice inspections the agency considers mission-critical, at least to the extent possible. In many cases, quarantine restrictions and travel bans make it difficult or impossible.

Since 20 July, the agency has been selectively conducting routine domestic surveillance inspections in localities where COVID-19 infection and hospitalization rates are low and travel restrictions are limited. (Also see "US FDA Restarting Domestic Inspections, Prioritizing Areas With Low Covid-19 Rates" - HBW Insight, 13 Jul, 2020.)

Harrington provided some insight into considerations involved in deciding when and where to risk surveillance inspections during the pandemic.

The agency still uses a model that factors risks such as inspection history and dosage form to help it decide which sites to inspect. But now it also uses an advisory tool that adds other factors to the risk analysis such as travel restrictions and disease prevalence. “We’re trying to avoid areas of high community spread,” Harrington explained. The focus is on facilities in low- or medium-spread areas, or near investigators’ homes.

The agency has relied heavily on remote assessment of documents in lieu of inspections but has not embraced remote video “virtual inspection” alternatives like some other inspectorates have, at least not yet, even though industry has clamored for the option. (Also see "What The FDA’s Inspections Q&A Guidance Really Means: It’s Time To Offer Virtual Inspections" - HBW Insight, 11 Sep, 2020.) 

A Hybrid Approach In The UK

“FDA’s experience of the return to onsite inspections is that little bit further ahead than MHRA because the US started back onsite a little bit earlier,” said MHRA’s David Churchward, deputy unit manager, Inspectorate Strategy and Innovation.  

MHRA is taking a hybrid remote/onsite approach to inspections that will likely continue after travel restrictions end. 

In his remarks at the PDA/FDA meeting, Churchward stressed the importance of early industry engagement. For example, he said the MHRA shared its plans and guidance for inspections during the pandemic with industry trade associations in advance.

“We said, ‘Look, this is what we’re thinking of doing, these are some commonsense elements that we thought of. Do you want to build on this? What else can we put in?’ It was very much a collaborative effort, because it’s in everybody’s interest to keep people safe. ... Now we’re in the process of actually testing that work to see how practical it is. But so far, it's looking pretty good.”

Similar Precautions Taken

The MHRA is following many of the same measures as the FDA ,as well as others to protect against viral transmission during inspections. 

Churchward emphasized the agency does as much as it can remotely before it visits a site. “We’re making pre-requests for information. We’re reviewing as much as we can back in the office, so we’re minimizing the amount of time we spend onsite.”

The site visits focus on activities that are difficult to do remotely, he said. The expectation is that companies hosting MHRA inspections will not have the customary back room. Corporate experts who normally travel to a plant for an inspection will not be there; instead they might be phoning in.

MHRA will send a minimal number of inspectors; they may interview people by video, even if they are at the plant. But by being onsite, the inspectors can expect to get documents to review much more quickly, he said. But the documents should be submitted electronically.

During walkthroughs, subject matter experts may be providing support via cell phone rather than in person.

Churchward said MHRA is looking into enhancing inspections with “remote or semi-remote facility tours using technology such as video or augmented reality.” Such technology could be used to get around travel restrictions or simply to prevent viral transmission on the shop floor by allowing investigators to tour the plant virtually from a conference room at the site.

It’s important to develop such alternatives because, he said, especially for international travel, “these restrictions are likely to stay for some time yet, and we need to operate an effective inspection surveillance program.”

This article previously was published in Informa Pharma's Pink Sheet newsletter.