Do you know the difference between remote/virtual and hybrid GMP inspections and which may be applicable to your facility and situation?

At the 48th annual International GMP Conference held in early March 2024 at the University of Georgia in Athens, Georgia, Health Canada Acting Associate Director of Health Products and Licensing Divisions Teresa Forlini explained the difference between the various GMP inspection types as defined by her agency, how they were developed, and how it chooses which to conduct at various sites.

She revealed that during the pandemic, one of Health Canada’s areas of focus was a reanalysis of how it performs drug GMP inspections.

“There are some products and categories of products and activities that are considered lower risk,” she explained. For example, wholesaling is a lower risk than sterile manufacturing. “We did a lot of work to review all that, to make sure that we were being risk-based and that inspectors were being used for the highest-risk issues.”

Remote and Hybrid GMP Evaluations

During the pandemic, Health Canada performed pilot projects involving remote evaluations. “Our stakeholders were aware that it was part of a pilot,” she said. “I think everybody recognizes that you cannot replace an onsite GMP inspection, but that there is a place” for other inspection types. She characterized the results of the pilot as “successful.”

Early this year, the agency issued a “DEL bulletin” on the topic. A DEL, or Drug Establishment License, is a license issued by Health Canada that is required for a facility to operate as part of a Canadian drug supply chain.

Broad communication by the agency with DEL holders and other stakeholders is accomplished through DEL bulletins. A January bulletin outlined the agency’s strategy for using remote or hybrid inspections and defined the following inspection types:

Remote inspections: Using technology to communicate, share, and review documentation without the need for an on-site visit.
Hybrid inspections (domestic): Using technology to communicate, share, and review documentation remotely, with a short on-site visit to evaluate critical aspects that could not be assessed remotely.
Hybrid inspections (foreign): Consisting of both remote and on-site inspections involving a minimum of 2 regulators inspecting the same site (1 on-site and 1 remotely).

Remote / Hybrid GMP Inspection Eligibility

Forlini summarized the differences between the inspection types as follows (see Figure 1, Remote/Virtual GMP Evaluations and Hybrid Inspections).

Remote or virtual inspections do not include an on-site visit, whereas a hybrid inspection has a “targeted” on-site visit as a component.

Figure 1 | Remote/Virtual GMP Evaluations and Hybrid Inspections

Risk Factors for Remote and Virtual Inspections

Forlini reviewed the risk factors her agency looks at to determine which type of inspection to conduct and the rationale behind the choice (see Figure 2, GMP Inspection Eligibility Factors and Exclusions).

Figure 2 | GMP Inspection Eligibility Factors and Exclusions

“An initial inspection is the first time a company is asking for a DEL,” she explained. “We do not expect to see anything that has happened at the site. The company was not allowed to do any licensable activities, so they will be eligible for a virtual inspection.”

The first time the agency inspects a site – for example, a wholesaler or distributor or importer – “we do not expect to see anything except a shell of the quality system that has been put into place. We think that is a good opportunity for us to save some time – those initial inspections.”

However, if it is an initial inspection for a fabricator – Health Canada’s term for a drug manufacturer – an in-person visit is warranted to evaluate the facility and manufacturing operations.

Another determining factor is inspection frequency – for example, the last time agency inspectors were on-site. “If we did not go on-site the first time because we did not think there was anything to be seen at that point except the shell of the quality system, our policy indicates that a year after the company has been in business, we are coming in. That is why we feel that the initial inspection risk is very low in those cases.”

Also examined is the compliance history of the site. “If they have a very high level of compliance, if they have never had an issue, if they have been on our radar for two years, then we could consider them for a virtual or a hybrid inspection,” Forlini said.

However, if the company had a non-compliant rating (NC) in the past, “then normally we would go in.” Exclusions to eligibility for a remote inspection include high-risk activities, complexity, and scope, or that an onsite visit is essential. “That is where we do a virtual inspection.”

Risk Factors for Hybrid Inspections

Eligibility for hybrid inspections is similar with the addition of for cause inspections and reassessments.

“After our inspectors have gone into a site, even though they deem it to be GMP compliant, they may decide it should be re-inspected after a few years,” the Health Canada official emphasized.

“Maybe we need to go back after two years because we saw some things that could be slipping in their compliance. In those cases, then maybe they can be eligible for a remote inspection. Maybe all I want to see is how their CAPA implementation is going. Then we could put them up for a hybrid or a remote.”

She pointed out an additional exclusion for hybrid inspections. “There are some ma and pa operations that we do not want to disqualify or penalize because they may not be able to do a remote inspection” due to a lack of facilities or resources for it.

When that is the case, the company can request an in-person inspection. An additional example Forlini provided is the case of a company that is located in a very remote area with poor Wi-Fi.

“We will go in because they just cannot share their documents. Or if they are paper-based, we do not want them photocopying for weeks on end to send us the documents.”

Preparing for a Remote or Hybrid GMP Inspection

Forlini noted that Health Canada was part of a team working with the International Coalition of Medicines Regulatory Authorities (ICMRA) that developed “ICMRA Reflections on Remote Approaches Reflection Paper December 2021.”

The 15-page “reflection paper” summarizes the collective regulatory experiences of remote inspections during the pandemic and provides transparency to stakeholders on approaches taken. It includes the following sections: