How To Host Onsite Drug GMP Inspections Without Spreading The Coronavirus
Executive Summary
US FDA suggests meeting with investigators onsite by video instead of in person, moving document rooms outside, avoiding paper and more. UK MHRA shares similar recommendations.
Pharmaceutical companies hosting onsite inspections during the coronavirus pandemic should make them as remote as possible, US Food and Drug Administration officials suggested at the recent Parenteral Drug Association/FDA conference.
The advice 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, said 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
Yet another idea is to avoid paper. “Providing documents electronically to limit the back-and-forth handling of paper is also a good practice,” she 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 inspectorate in March, FDA investigators have traveled to domestic and foreign facilities to conduct drug good manufacturing practice inspections that 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 Announces Plans To Resume Domestic Inspections" - Pink Sheet, 10 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 "US FDA Assesses Over 500 Biopharma Plants Remotely Via Records Review; Refines Process" - Pink Sheet, 17 Sep, 2020.)
A Hybrid Approach In The UK
The UK MHRA’s David Churchward observed that “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.”
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 taking many of the same measures as the FDA to protect against viral transmission during inspections, as well as some others.
Churchward stressed that 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.”