Over the last decade, there have been significant changes in the legislation governing the development of pharmaceutical and biologic products—many of these aimed at improving patient safety. A number of these changes have focused on developing, more quickly, a better understanding of the benefits versus the risks of prescribing medicine to individual patients, post-approval. This has elevated the importance of an effective pharmacovigilance system as a factor in considering whether or not to grant regulatory approval of both new chemical entities and new indications for existing drugs.
However, there is often a poor understanding of just how much can be known about the relative benefits and risks of a new medicine prior to marketing approval. Due in part to recent high profile cases of approved drugs being withdrawn from the marketplace, there is a common perception among patients and healthcare providers that post-approval safety surveillance is ineffective.
It is common practice to allow up to 5 days for the conduct of a routine pharmacovigilance system audit, including a nominal 2 days for travel to and from the site. When compared to this standard, it was determined that a routine audit of either a corporate affiliate or a vendor could be completed in 3 days using the remote auditing process without any reduction in either audit scope, or the quality of the oversight. Without the need to travel, there was an estimated saving of 28 days over the course of 14 audits. Additional benefits included a significant reduction in travel-related costs and the ability to audit sites that were not readily available due to factors such as political unrest or health risks. The time allowed for audits associated with licensing, merger, and acquisition activities was more variable, but the same cost savings were realized.
Conducting pharmacovigilance system audits remotely has proved to be a cost-effective way of maintaining oversight of on-site pharmacovigilance activities irrespective of whether these were being conducted by a company affiliate, a vendor responsible for patient-oriented programs, or were being evaluated as part of a licensing opportunity due diligence. The remote auditing process also lends itself to other relevant pharmacovigilance system activities including regulatory inspection preparedness or auditor training, and we are in the process of exploring these additional opportunities. Without the need to travel, there was a saving of 2 days per remote audit over the course of this program. Additional benefits included a significant reduction in travel-related costs (flights, meals, and accommodation), the ability to reschedule audits more easily since travel arrangements were not a factor, and the ability to audit sites that were not readily available due to factors such as political unrest, inaccessibility or local health risks such as Ebola outbreaks.
However, there are significant limitations to conducting audits remotely, and cost savings should not overshadow these. Perhaps the single most important limitation is the reliance on communications technology, especially teleconferencing. Even with the very best telecommunication facilities, it is not possible for an auditor to read the body language of interviewees, and this is sometimes the first indication to an experienced auditor that a site may have issues. In addition, where English is not the first language of the participants, long-distance communication can prove challenging, and this needs to be considered during audit preparations. For some of our audits, a local company representative with pharmacovigilance experience was present at the site and able to provide support under the direction of the auditor. Sitting in the same room as an interviewee also makes it easier for them to illustrate their answer to the auditor’s questions using aids that they have brought with them. In our experience, computer desktop sharing technologies go some way towards facilitating explanations, but only if the interviewee is proficient in using them. Video-conferencing facilities would remove many of the limitations inherent to teleconferencing, and although this technology is commonly available within larger companies, it is currently cost-prohibitive for many smaller companies.
Another potential challenge is the sharing of documents. While centralized electronic document management is widespread in larger pharma and biotech companies, smaller companies, affiliates, and vendors may still operate a paper-based system. This can make sharing documents during the pre-audit and audit phases problematic, since exchanging documents using facsimile machines, while secure, is not a workable solution. In addition, emailing scanned documents outside of a secure company network does not preserve confidentiality and cannot be considered a viable way of distributing audit documentation. Digital photographs of the audit site also have limitations. For example, a photograph of an archive from the outside may show a closed access-controlled door, when in reality the door is frequently propped open to allow staff easy access through the door because their arms are often full of folders. Another example that may not be readily visible in digital photographs is where source data files are left on desks overnight instead of being locked away. We have not yet requested a live video tour of a facility during a remote audit, but the technology is readily available and may offer advantages over digital photographs.
It should be remembered that many auditors use their travel time to review audit documentation or draft reports, so while cost savings are real, travel time savings may be less than they initially appear. Additionally, although auditors do not have to cope with travel-induced jet lag during a remote audit, conducting an audit according to local business hours can be challenging, particularly from a home office.
In conclusion, remote auditing at this point in time is particularly well suited to lower risk sites such as local affiliate offices, and when used as a follow-up to a face-to-face audit or to monitor progress on a CAPA. Although feedback from those participating in the remote audits was positive, this process does not replace the need for on-site audits; it does, however, allow a more sustained degree of oversight when integrated into a carefully planned, risk-based pharmacovigilance system audit program.