by Steven Drzick
Quality Assurance Professional
Prior to the 1970s, FDA assumed that throughout the industry, all data and reports that were submitted for NDAs, marketing permits, etc., were true and accurate. Several events occurred in the mid-1970s that proved the assumption to be false. Based on the investigations of Searle, Industrial Bio-Tech, Biometric Testing, and several other companies throughout the 1970s and early 1980s, several executives from two of those companies were criminally prosecuted and sentenced to prison. It was discovered that there was a crippling undercurrent of shady science, inept reporting and data collection standards, less-than-ideal living conditions for animals, and improper and sometimes non-existent oversight of contracted facilities. Unfortunately, the rampant problem was not limited to those above mentioned companies.
Along with the animal negligence, data- and report-related falsification and fraud issues, Sponsors and companies did not exercise any oversight of facilities/scientists that were contracted to conduct the studies. This received far less attention, but was still of great importance. Many of the specific citations and referenced findings alluded to the lack of or no oversight of Pathologists. Serious questions were asked on the integrity of work the pathologists conducted, but offered no follow-up or questions of said Pathologists.
From this, the FDA Good Laboratory Practices were created. Although each provision in 21 CFR Part 58 can be attributed to specific investigational findings, there was still no concrete regulation requiring inspection/qualification/oversight of contracted (or subcontracted) laboratories. One can infer by looking at 58.10, requiring that the Sponsor “…notify the consulting laboratory, contractor, or grantee that the service is part of a nonclinical laboratory study that must be conducted in compliance with the provision of this part,” and then tying that to 58.33 “The study director has overall responsibility for the technical conduct of the study…” and that “All applicable good laboratory practice regulations are followed.” Still, there is no specific reference in 21 CFR Part 58 where you can point and say “I have to qualify this test site for use on GLP Studies!” The only document that mentions a regulation closely related to the above statement is in the OECD Multi-Site Consensus Document No. 13.
Yet, we still conduct inspections, audits, and qualifications of testing facilities and subcontractors. Why is that? Mainly because the client/testing facility wants to be assured that the companies they choose to work with are of good quality and science, and assemble a good product/report that will stand firm under the intense scrutiny of a regulatory review/inspection.
Most inspections are formatted the same, to include audits of facility records, SOPs, training files, general practices, and if available, data and reports. These inspections may be an initial qualification, questionnaire, site visit, or a follow-up inspection. No matter if it is specialized or general, they all serve the same purpose: to determine the level of GxP Compliance in the facility.
The need for inspecting a facility also requires the need for personnel to host the inspection. Ordinarily this is conducted by a member of the Quality Assurance Unit (QAU), Study Director, or another appropriate senior-level member. This person should have the knowledge and ability to sit in a room with a client and answer a multitude of questions. They should also be able to enlist the assistance of other “subject matter experts.” Basic communication skills are imperative, as well as the ability to interact with many different and possibly difficult personality types.
There are many moving parts to a client audit, most of which occur behind-the-scenes, and most before the client even steps foot on campus!
- Sending requested documents (SOP Index, Regulatory History, Organizational Charts, Master Schedule, etc.)
- Planning possible travel arrangements
- Organizing meals
- Retrieving audit materials
- Securing audit room accommodations
- Scheduling study activities
- Retrieving data and report from Archives
- Compiling training files
- Retrieving facility records
- Organizing or training the audit hosting team
- Setting up a facility tour
- Organizing certain personnel to meet with the client
- Developing an audit agenda
- Ensuring all involved understand their roles
Once the audit begins, it is a continual effort to accommodate the changing needs of the client, get the appropriate documents, and make sure that all meetings/interviews/tours stay on schedule. It can sometimes turn into a very daunting task.
But that doesn’t mean it will not be a rewarding experience. Most client audits will allow you to get a new perspective on processes and procedures, and may also reaffirm or reinforce the policies already in place.
In order to effectively host client audits, you need to exhibit several skills: good communication, honesty, integrity, patience, respect, knowledge, and professionalism, and you must have the ability to deal with many different personality types. Good communication helps to minimize any confusion or misunderstanding of a request; honesty, integrity, patience, and respect will allow for a better rapport and transparency; knowledge and professionalism will allow you to answer questions effectively and appropriately: and the ability to deal with different personalities will help with the characteristics listed above. The better you are with these skills, the more effective (and efficient) the audit may be.
Most client audits are organized into sections:
- Introduction/General Facility Overview
- Facility Tour
- Records/Data Review
- Continued Records/Date Review
- Audit De-brief Meeting
More experienced (or specialized) client auditors may request certain equipment records, validation summaries or packages, or ask to focus on specific areas/departments. Client auditors will also pay particular attention to SOPs and documentation. It is very important, almost critical to the audit, that the host is able to provide these documents and records as quickly as possible; remember, the clients are only on site for a matter of hours.
During the audit, the clients may enter into a dialogue with the host on the items that they see or encounter during their inspection. This dialogue is good, as they are able to give a voice to any perceived issues, and the host has the opportunity to address these issues rapidly. Of course, there are those who remain quiet during the entire audit, and hit the host with a laundry list of findings during the Audit De-brief Meeting. If the latter occurs, it is important for the host to know how to deal with the situation. It may be a best practice, if a quick resolution to the item(s) cannot be achieved, to write down the concerns of the auditor and address them more formally. It is recommended not to not argue with the auditor; in these cases, your time is better served in finding out how many of these items will need to be addressed.
The Audit De-brief Meeting usually consists of the host(s) and client(s), and could potentially have a member of Testing Facility Management, specific Study Director(s), specific Operations staff, or any requested personnel. Issues encountered by the client are raised during this meeting, positives are shared, and comments and recommendations are given. As the host, it is your job to clarify what the expectations are for the next steps:
- Will they require a formal response?
- Will they issue a formal report?
- When will the formal report be issued?
- When is it expected to be returned?
- What specific characteristics are they looking for in the responses (CAPA, Investigations, etc.)?
- Do they want supporting documentation for the responses, etc.?
Make sure you adhere to any timelines requested, within reasonable parameters, and communicate to the responsible personnel what occurred during the audit.
Hosting clients can be an enjoyable, thought-provoking, and interesting endeavor. Many good ideas can come from the collaboration of multiple QA and scientific personalities. The clients may offer suggestion(s) on process improvement, or they may even take some ideas back to their facilities and implement. As a client host, you can be instrumental in helping to secure a Sponsor through integrity, honesty, patience, efficiency, interaction, and giving the client the attention they need to do their job effectively. You are the face of the company when hosting clients. You are the person they think of when the question is asked, “What do you think of this company?” Make sure the answer they give is the right one.