Webinar: Remote and Virtual GMP Audits

Find out about our four-step approach to remote and virtual GMP auditing which helps you to unlock supply chains and meet cGMP needs in clinical trial supply or routine commercial operations. Watch part two.

Here is an edited transcript of the video, outlining the four-step process for remote audits.

What can we do to keep our pharmaceutical supply chains in operation? This question is equally valid for existing products as well as for materials to support forthcoming clinical trials (e.g., investigational medicinal products, or IMPs). How can we do this while keeping the balance of regulatory compliance and patient safety at the forefront of our minds? We have developed a four-step process for remote audits.

1. Risk-based assessment
2. Remote PQS assessment
3. Remote audit
4. On-site audit

This section poses a series of questions. The questions seek specific information that will enable us to make informed decisions. The information gained will allow us to decide if we are happy to proceed or if it is best not to continue.

In this risk-based assessment phase, we are drawing upon information that is available to us. Typical questions that might be asked at this stage include:

• What is the regulatory oversight of the facility in question?
• Do they have appropriate licenses and registrations that are up to date?
• Do they cover the scope of the material or the product that we are interested in?
• What is the inspection history of the facility?
• When were the last inspections, and what were the outcomes?
• Do we know about any recalls or any restrictions that were placed on the site?

It is important to consider the site and where it sits within the company’s structure. In this instance, consider the following:

• Is it part of a larger organization?
• Does it operate to a common PQS?
• Is there corporate oversight of the facility?

And importantly, what activities is the site performing for us?

• Is it providing an excipient or an active pharmaceutical ingredient/product?
• Is it providing partial manufacture or total manufacture?
• What are the QC elements associated with that?
• What are the cross-contamination risks that we are concerned about?

Here it is important to know about the products. What other products are manufactured at the site, and how concerned are we about them in terms of carrying out this risk-based assessment? When carrying out an effective risk-based assessment, it is important to know the nature of the materials and the products the site will produce for us.

At this stage, you must ask:

• Is it an excipient or an active pharmaceutical ingredient?
• Is it a dose form?

If it is a dose form, is it aseptically prepared, or is it a sterile product? Is it an ATMP or a biologic?

There are different risks associated with each of these materials that must be considered, but also the stage of development: Is the product in the R&D phase, early-phase clinical, late-stage clinical or a commercial product? The risk-based approach that we are championing here is to collate the information and then carefully evaluate the risk to see whether you feel it’s appropriate.

The remote PQS assessment is a “desktop-style” review in which we can request information from the site relating to key policies and procedures. We can review this information in a very similar way to how we would check it during an audit at the facility. Several high-level documents will provide a good understanding of how the site is managed. These include the site master file, which offers us a good overview of the facility, and the management review, which might tell us a little bit more about the culture of the organization. We might also look at training, data integrity and internal audits.

Then we need to consider a series of critical PQS elements that we might wish to review, such as investigations, CAPA management, change control, validation, calibration, and PPM and supplier management.

Then there are some other elements related to the individual materials or products that might be of interest, such as PQR, contamination control, formulation, process and specifications, etc. Do not forget that this stage involves a remote review of master documentation.

While it is important to take time to look through master documentation, what we need to do is to look at the evidence of implementation and, in particular, control. Ideally, we want to talk with the subject matter experts for each of those key areas.

Talking to the subject matter experts can be an interesting challenge. Typically, in an in-person audit setting, you would have the chance to meet with and sit with the subject matter expert. Plan your meeting with a subject matter expert similarly for a remote audit. We suggest that you arrange individual sessions with those subject matter experts; look at specific example information for complaints and deviations, which you can review remotely; and then question the subject matter expert and talk in detail with them.

• Minutes of management review meetings
• PQRs
• Investigation reports
• Adherence to schedules
• Individual training records
• Executed batch records

One of the critical factors to keep in mind here is to be efficient in ensuring that remote audits do not carry on for longer than they should.

If you feel that the facility is suitable, then we could go for interim approval. However, there may be some mitigation that we want to introduce. Not having visited the facility, we might want to increase scrutiny or oversight on materials we are receiving, maybe via additional sampling or testing. We might also wish to apply additional QA oversight to the facility, or we may want to review entire batch documents or key parts. We may even want to see deviation reports, investigation reports or information from crucial quality attributes of the process itself. Therefore, there might be extra mitigation we want to put in place, being mindful of the fact that we haven’t had the opportunity to visit the site itself.

If we have successfully carried out a remote audit, later we could follow up with an on-site audit of a reduced duration. The on-site audit could then focus on the elements of the facility that we might not have had the opportunity to see while reviewing remotely.

Issues to consider in this instance include product material, specific information, contamination control and possibly looking at the utilities. We are very interested in seeing the facility itself, walking through areas and talking to individuals performing operations. Doing so would allow us to look at site culture and how the site is managed and operated.

The on-site elements now give us that opportunity to pick up issues such as CAPA follow-up or some of those items from the original remote assessment that we couldn’t look at in detail.

That’s an overview of the process we have developed, and we’ve created a toolkit around it. If you are interested in finding more information, then please do contact us by email at pharmamail@nsf.org or complete the form below entitled “Ready to Begin the Process.”