Figure 1, which is taken from the upcoming GlobalData report New Drug Approvals and Their Contract Manufacture – 2022 Edition, shows that all seven products that received their first EUA last year used CMOs for their manufacture. This is an increase from 2020, when 50% of EUA products had no known manufacturing outsourcing agreements.

Under an EUA, the FDA allows the use of unapproved medical products, or unapproved uses of approved medical products, in a public health emergency if there are no adequate alternatives. The use of multiple EUAs by the FDA is unique to the Covid-19 pandemic.

With the best will in the world remote inspections cannot go into sufficient detail compared to on-site audits, meaning there is a risk that something important might be overlooked. That could be something as seemingly innocuous as a cracked floor (which could present a hazard, breaching compliance) to poor levels of cleanliness or haphazard warehouse organisation (contamination risk/potential labelling mix-ups). Even in a live remote session with a video link, these transgressions could be missed if cameras are not directed into every corner.

To understand more fully how the industry has adapted its auditing activities and expectations and the impact this has had, and to gauge emerging priorities for a time beyond the pandemic, in February 2022 Rephine conducted some research among both pharma clients and senior auditors internationally. Of the ~30 people we polled, just over half were in the Quality function of pharma companies (the balance comprising professional auditors), and around two-thirds of responses were from Europe, the remainder primarily from Asia – most notably India.

Although there is the potential for some of this to be covered within virtual sessions, in this scenario it is the auditees that are in control of what is shown. There is much less scope for auditors to spontaneously go off plan and explore behind closed doors if they have a hunch about something and want to look into it further.

As a consequence, auditors taking part in the survey cited the restricted scope for real-life face-to-face interaction, and the ability to apply their softer skills (eg that sixth sense, honed with experience, that something warrants further investigation) as the second major challenge with remote audits. Specifically, the reduced opportunity to identify non-compliance with required standards was of grave concern for professional auditors.

Clients, too, strongly agreed that this limitation presented a concern, though overall they worried more about technology-based issues such as a loss of connection, potentially preventing or interrupting remote inspections.

Further reflecting the lack of trust in remote auditing as a permanent solution, two-thirds of pharma clients said they wouldn’t accept a remote-only audit as a means of qualifying a new API supplier. (Auditors responded similarly.) Too much would be left to interpretation, without the option of a physical site visit and a chance to meet teams and assess facilities and processes in person.

Following the same logic, almost two-thirds of client company QA respondents said they would not be comfortable going more than two years before re-auditing, following a remote inspection: a fifth said they would want to redo the audit within a year. (For auditors taking part in the survey, two-thirds said they would look to re-audit within a year following a remote-only inspection.)

For services like packaging (particularly secondary packaging), remote audits felt more tolerable for pharma clients, but for suppliers of active ingredients or finished products indefinite reliance on virtual inspections was unthinkable. The vast majority agreed or strongly agreed that remote/virtual audits were a good temporary solution during the pandemic, but ultimately that an on-site audit carries more weight. A sizeable proportion of client QA respondents felt too that remote auditing could even require additional resources, compared with an in-person inspection (in other words, this isn’t a more time-efficient or cost-effective option).

Going forward, two-thirds of audit clients suggested they would be happy with a hybrid approach to supplier auditing, in which routine aspects such as sharing and completing documentation could be done remotely while on-site inspections took place physically. A third said they would favour a return to 100 per cent in-person audits. Only 1 client expressed a preference for persisting with remote audits across both the documentation element and physical inspections.

Open responses in the survey suggested that for remote auditing to have any long-term value this would be for occasional use and in the context of a long-term, trusted relationship, and where standard operating procedures had been shared ahead of time. For auditors, it was felt that any decisions about continued use of remote audits would need to be risk based, and would depend heavily on the willingness of auditees to cooperate, for instance in making the right documents and people available to maximise what was possible.

Almost all favoured the idea of working with an independent third-party auditor to generate a single, comprehensive report that could be shared with multiple customers, to reduce risks associated with allowing multiple auditors on site over 1-3 years.

It was through conducting this kind of activity, with strict observance of social distancing, testing and PPE use, that our own auditors were able to continue conducting on-site audits throughout the pandemic. Although numbers of physical audits halved during 2020 in favour of increased remote activity (and the sharpest reduction in activity was really only during that first global lockdown from March-May of 2020), by 2021 highly accredited auditors located on the ground in target markets were largely back on site – with 82 per cent inspections conducted in person and just 11 per cent done virtually (compared to a ratio of 72 per cent on-site/28 per cent remote audits in 2020).

One of the disciplines encouraged by regular inspections is that of being audit-ready (in other words, maintaining consistently high standards) at all times. Remote documentation sharing and virtual inspections played a useful part in the pandemic crisis. However, there is no substitute for onsite auditing and remote activity is best used to support that.

Maintaining high standards of supplier compliance depends on the optimum blend of audit approaches, with remote activities back up by on-site re-audits. Whatever the allowances that have been made by regulators during the unprecedented conditions of the last two years, the onus is now on all manufacturers and suppliers to carry out the most effective auditing activity, to maintain their reputation and to keep patients safe.