2k Clinical Consulting, Inc.

5 Reasons Why QA Is Essential in Clinical Trials

The coordinated and impartial review of all clinical trial-related activities and records is known as quality assurance. In the case of a clinical study, the quality assurance department has a wide range of responsibilities. Quality Assurance (QA) departments frequently aid in inspection readiness by establishing investigator site selection guidelines and identifying service providers to be audited, such as laboratories, packaging and supply chain vendors.

The Ongoing Challenge

The continuous monitoring of data collection processes and data management policies at every level of the study is an ongoing challenge in managing the quality of clinical data and maintaining compliance. This includes the following:

  • verifying that the data collected during the trial is consistent with the procedure (case report form [CRF] vs. protocol)
  • ensuring the validity of the data in the CRF and data acquired in source documents (CRF vs. source documents)
  • guaranteeing that the analyzed data correspond to the CRF data (database vs. CRF)

This confirms the need for QA involvement in clinical trials specifically in terms of inspection readiness.

Reasons Why Quality Assurance (QA) is essential

  1. Time Saver

While continuous monitoring during a clinical trial is a taxing task, it can save you from wasting hundreds of hours rectifying shortcomings within the trials at a later stage. Errors recognized in their initial stages are easier to modify to achieve desired outcomes. Whereas, delays can worsen the problem in clinical trials and inevitably push back the desired result, which can hinder the inspection readiness process.

  1. Money Saver

While many believe that investing in quality assurance from the get-go is not only time-consuming and costly, it is quite the opposite. Errors during the trial stage lead to millions of dollars lost during the production stage and major delays in inspection readiness, which can further add to the cost. Sometimes dropping the trial before entering the production stage due to a lack of quality assurance become inevitable.

  1. Boosts Client Confidence

Businesses that are known to ensure quality assurance are more likely to retain trust and confidence from clients and customers alike. During clinical trials, clients are more likely to follow the lead and trust the process when their standards of expectations align with the trials working. When boosting clients’ confidence, it is essential to highlight both the “whats” and “hows” of the trial, and quality assurance helps deliver the “hows” of the trial to keep your clients’ mind at ease.

  1. The Backbone of Consistency

When it comes to clinical trials, it is of utmost importance that each drug produced be of the same quality to prevent ill-desired outcomes. In clinical research, the quality assurance process ensures internal consistency by scheduling regular operational checks at each level of the trial process and data collection processing to validate trial procedure compliance and data validity.

  1. Leads to Accountability

When quality assurance is the working foundation of a clinical trial, each individual involved plays a vital role in ensuring that they deliver top-notch results in making the trial a success. Hence, the need for excellence permeates every aspect of a company in which quality assurance is at play.

Conclusion

Maintaining integrity and precision during a clinical trial is an ongoing, dynamic process that is the key to inspection readiness. This continuing process necessitates modifying processes and effectively conveying these adjustments to all investigators and support staff. This is why quality assurance involvement is essential and a key component to the clinical Quality Management System (cQMS) overall.

Need to strengthen or supplement your QA component? Contact us for a free consultation! We would love to hear from you to discuss strategies!

 

References

  • BROWN, C., 2019. Price Check: How to Cut Costs in Clinical Trials. [online] Anjusoftware.com. Available at: <https://www.anjusoftware.com/about/all-news/insights/cut-costs-clinical-trials> [Accessed 8 April 2022].
  • JLI Blog | Global Training & Education Provider. 2018. Quality Control and Quality Assurance in Clinical Trial | James Lind Blog. [online] Available at: <https://www.jliedu.com/blog/clinical-trial-quality-control-assurance/#:~:text=In%20clinical%20research%2C%20quality%20control,and%20reliability%20of%20the%20data.> [Accessed 8 April 2022].
  • Manghani, K., 2011. Quality assurance: Importance of systems and standard operating procedures. Perspectives in Clinical Research, 2(1), p.34.
  • Parashar, P., 1995. Patient Satisfaction – A valid tool of quality assurance (C. Q. I). J Family Community Med, 2(2), pp.7-8.
  • The Important Site. 2022. 10 Reasons Why Quality Assurance Is Important – The Important Site. [online] Available at: <https://theimportantsite.com/10-reasons-why-quality-assurance-is-important/#:~:text=Quality%20assurance%20is%20a%20process%20all%20organizations%20should,who%20could%20be%20with%20the%20company%20or%20independent.> [Accessed 8 April 2022].
  • Valania, M., 2006. Quality Control and Assurance in Clinical Research. [online] Applied Clinical Trials Online. Available at: <https://www.appliedclinicaltrialsonline.com/view/quality-control-and-assurance-clinical-research> [Accessed 8 April 2022].
  • WCG Avoca. n.d. Inspection Readiness: What is it and how do we get there?. [online] Available at: <https://www.theavocagroup.com/inspection-readiness-what-is-it-and-how-do-we-get-there/> [Accessed 8 April 2022].

Key Aspects of an Inspection Ready TMF

Having a complete Trial Master File (TMF) is the highest priority for sponsors in terms of providing an accurate picture of the affiliated clinical trial.   This article speaks about key aspects and techniques to implement in order to have an inspection-ready TMF.

Key Aspects of an inspection ready Trial Master File

   Important aspects of having an inspection-ready TMF is to:

      ✓ Include documentation which is able to ‘tell the story’ of the trial.

      ✓ Contain a detailed time period, coexistent in time of facts and observation.

      ✓ Have an electronic source which documents are clearly stated.

     ✓ Update regularly and  implement proper Quality Check (QC) techniques.

QC techniques

Five QC techniques to implement to ensure an inspection-ready TMF are to:

  1. Look through the auditors eyes – Reviews are made from the source of information provided. Research requirements and expectations of health authorities in order to properly look at the data from an auditor’s perspective.
  2. Collect Information-All documentation from Core and Country levels such as the Protocols, Investigational Plans, Informed Consents, etc. should be thoroughly reviewed as the foundation QC’ing data from local site documentation.
  3. Site Sampling – Site Sampling is being able to look into all records based on a sample taken from a number of high enrollers, noncompliant and terminated sites.
  4. Review and Cross Check – Reviews are taken on bother paper and electronic Trial Master File. Each has different mode by which it is reviewed:

            For Paper files, review and cross check:

  •      Original hardcopies– all original documents must be properly checked if they are correct and signed accurately.
  •      Filing & Organization – ensure that there are no missing or misfiled files that can cause delays during an audit or inspection.

          For an electronic TMF, review and cross check:

  •       eTMF Study Access – review current project team list to verify correct access to study files
  •       eTMF Filing & Organization – Check for duplicates and errors in Indexing (or naming) and uploads
  1. Follow up to Resolution –  It is imperative to follow up all issues to resolution which means having an effective the root cause and all other corrective and preventive actions in place, including steps on how any investigation should be taken, and who should be involved and the process.

Overall, it is critical to be knowledgeable about key aspects of industry standards and regulations.  An inspection ready TMF takes proper planning, as noted in our article Planning for TMF Success, and effective QC measures as discussed in the following Trial Master File training sessions:

The “Audit-Ready” TMF: Concepts & Strategies (basic)
The “Audit-Ready” TMF: Tools &Techniques to effective QC Reviews (intermediate)- COMING SOON
The TMF Challenge: Part of the IRS (Inspection Readiness Survival) Series (advanced)-COMING SOON

 

 

 

 

 

 

 

 

How to Increase Visibility for an Inspection-Ready TMF

The Trial Master File (TMF) stores all essential documents pertaining to the conduct of a clinical trial in compliance with Good Clinical Practice (GCP) guidelines.  It is the “backbone” that tells the story of a clinical trial at every phase from start-up to closeout and is one of the most scrutinizeobjects during an inspection.  

Ensuring that the Trial Master File is inspection-ready and visible to all participating parties is no easy task and requires consistent effort. In this article, we will detail Trial Master File setup and how you can increase its visibility.  

Setting up the Trial Master File 

Having a system that is easytoaccess, clear, and transparent for all parties involved is the goal for your TMFWhile TMFs have traditionally been in paper format, it is now the norm to use an electronic trial master file or eTMF.  

Digital systems can provide a centralized storage system, security, project management, audit trails, and numerous tools to track a study’s progress efficiently.  Every TMF system needs to contain all essential documents as outlined in section 8 of the ICH E6(R2) GCP guideline. However, the work doesn’t stop there.  

Don’t forget that TMF-maintenance is an ongoing process that should accurately reflect the clinical trial at any particular stage. Another factor to consider as you set up the TMF is training. Having procedures and a Trial Master Plan in place ensures that your team is routinely maintaining the TMF and appropriately communicating with the CRO, sponsor study teams, and investigational sites for up-to-date records.  

Increasing visibility of the Trial Master File 

Your TMF should be inspection-ready regardless of what phase you are at in the clinical study. The nature of the eTMF system lends itself to increased visibility, but its perpetual state of change can also dampen this effect if not properly maintained. Consider the following tips for enhancing the visibility of an eTMF: 

  1.  Prepare documents ahead of time – while eTMFs are great for storage, the essential documents can easily get lost and misfiled if the filing system is unorganized and maintained by staff at different locationsTo avoid having inaccessible documents during an inspection, train staff on maintenance, proper filing, and procedures emphasizing the importance of compliance in the system.  
  2. Integrate eTMF systems to facilitate collaboration  – one of the benefits of an eTMF is its ease of access from anywhere at any time. However, sometimes software conflicts limit visibility and prevent Sponsors or CROs from filing documents properly. When implementing an eTMF, look out for systems that can easily integrate with other platforms to facilitate collaboration and exchange of documents between study stakeholders. 
  3. Update performance metrics – on top of storage capabilities, eTMF systems can also track key performance metrics: Timeliness, Quality, and Completeness. Like the documents, these numbers also need to be updated to be useful for improved future performance. These metrics can provide all parties involved insights into how current processes are running and how they can be improved.  
  4. Make the inspection as easy as possible for the Inspector – part of facilitating an inspection is to make the inspector’s job as easy as possible, so every detail counts. Make sure that they can easily access documents, view documents in their original size and perhaps on multiple screens, as well as annotate in the system if possible.   

Conclusion   

Increasing visibility of your TMF can seem like a daunting task, but it doesn’t have to be. With the introduction of eTMFs, it has never been easier to conduct clinical trials. With the above tips in mind in setting up and enhancing visibility in the eTMF, you are on your way to having an inspection-ready TMF!  

Location Matters…

What’s wrong with this picture?

On a typical workday, you may see nothing wrong with this picture…but place an FDA Investigator or other regulatory Inspector in this room, and you may it see differently. I’ve had the opportunity to work as an FDA Investigator working in the GxP (primarily GMP) world.  I left that career and transitioned over to the industry (AKA ” the other side”) in GCP starting out as a Clinical Research Associate (CRA).  

As an FDA Investigator inspecting all types of manufacturers, I was accustomed to reviewing documents in immaculate, spacious conference rooms.  When I became a CRA monitoring clinical sites, however, I had a rude awakening and was quickly humbled by my designated monitoring space. There were no spacious conference rooms…sometimes no room at all.  With some sites, I was placed in a small cubicle.  With other sites, I sometimes shared the busy desk of either the Principal Investigator, Sub Investigator or Study Coordinator. 

But the most memorable experience was when I was placed in the break room /copy/printer room where I shared a table with documents and binders from other trials and was entertained by interesting (and sometimes incriminating) conversations from site staff. 

At that point, I couldn’t help but reminisce on my prior career as an FDA Investigator thinking “Boy, would I have a field day if I were an FDA Investigator placed in this room!”

 But I’m no longer an FDA Investigator…I’m on the “other side” now, training others on audit/inspection readiness and providing tips on how they should prepare and set up appropriately for an inspection. 

Important tips to know when it comes to set up is to adequately prepare your staff and facility including inspection and support rooms.

FACILITY AND STAFF PREPARATION

When preparing the facility, for an on-site audit or inspection, select a private area, or conference room that has a phone and, a copy machine for document requests.  It is important that other areas such as work areas and printing rooms are clean and free of loose documents. 

Finally, support areas or affiliated departments such as the pharmacy and or laboratory should be assessed to ensure all documents and staff are inspection-ready.

Also post designated signs throughout nearby areas notifying others of the inspection to ensure all nearby conversations are minimized during the inspection.

INSPECTION ROOM VS SUPPORT/WAR ROOM

The Inspection Room should be a quiet, private and paper-free located near the Support/War Room.  This room should also be set-up with computers and screens for the FDA Investigator to review records and electronic systems used in the trial.

The Support/War Room which is a combination of clinical site and sponsor support, should be equipped with working electronics (such as email, printer, Instant Messaging) and dedicated to providing all needed documentation for the inspection.

KEY TAKEAWAY

In order to fully prepare for an audit or inspection, you must consider the rooms in your facility as part of readiness planning and preparation.  After all, LOCATION MATTERS!

 

How To Implement Lessons Learned From Regulatory Inspections

This article will highlight some of the steps you can take to implement lessons learned and optimize your company’s policies and procedures in terms of compliance and alignment with the regulations. 

Different regulatory agencies perform frequent inspections to ensure compliance with pertinent study-related processes and their respective regulationsLearning lessons from these regulatory inspections and implementing them as part of your processes or Quality Management System will tremendously help you in the future. 

Implementing the lessons learned from regulatory inspections 

Immediately after an inspection, there should be a process in place for implementing lessons learned. Here are the steps to implement lessons learned from regulatory inspections: 

1.Identify Lessons Learned 

Identifying comments and recommendations made during recent regulatory inspections is valuable for future inspectionsYou also need to prepare for and conduct a Lessons Learned session. 

  1. Prepare for lessons learned session – the preparation should be done in advancewhere you organize areas that prevent discrepancies and missing information. You should have standard criteria for each clinical study you are conducting. 
  2. Lessons Learned Session – this step focuses on identifying the successes and failures of your processes as it relates to your trials, which also includes some recommendations on how to improve performance for future regulatory inspections. 

Ask the following questions: 

  • What went right during the inspection? 
  • What went wrong during the inspection? 
  • How can we improve for future inspections?

2. Document Lessons Learned 

After capturing lessons learned, you should document everything into a comprehensive report that summarizes the inspection and what everyone can do to improve in the future. You can also conduct interviews with your team members to discuss what went right and what went wrong.  Finally, you can share the report with your team members and executive team emphasizing how this will help you improve performance and readiness for future inspections 

3.  Analyze Lessons Learned 

Analyzing and organizing the lessons learned from regulatory inspections is also a key step to improve your preparedness in the future. You can continue to conduct meetings to assess when training will be implemented based on new or updated processes. 

4.  Archive Lessons Learned 

Once you have finished the steps listed above, you need to organize and file the lessons learned documentation along with other reports from prior audits and /or regulatory inspections.  While everyone should have access to the documents in your facility, you need to place some focus on keyword research since it will help you get access to the wanted lesson.  

5.  Retrieve lessons learned 

The final step of the Lessons Learned process, especially as new trials arise, is to retrieve the documentation and reflect on successes and failures Focus on how your team can maximize successes and minimize and failures in preparation for the next trial.    Having a collection of lessons learned documents is a great asset that serves as powerful inspection readiness tools and allows you and your team to prepare for upcoming clinical trials in addition to future inspections in the most effective way possible. 

Takeaway message  

Preparing yourself and your team before an inspection is vital to ensure that everything goes smoothly. Learning from previous lessons and implementing your new knowledge is indispensable to achieve the goal of continuous improvement and successful inspections. 

If you have any questions or concerns, please do not hesitate to share your thoughts in the comment section below. 

5Cs to Inspection Readiness Success (for Clinical Sites)

By Kimberly Kiner

Q: When is the best time to start preparing for an inspection?   

    1. After database lock 
    2. After the inspection announcement 
    3. After IND/IDE Submission 

‎A: If you answered C, you are correct. ‎‎ ‎‎ ‎‎Inspection Readiness is an ongoing process that starts at the beginning of the trial. ‎

We all know that inspections can be quite stressful; however, a stressful environment can be minimized with proper preparation and inspection readiness techniques.  This article will discuss the 5C IRS (Inspection Readiness Success) Model as one of the strategies that can be utilized as an inspection readiness technique for clinical research sites.

The 5Cs are: 

  1. Collect Information – In collecting information, it’s important to consider researching from both internal sources (e.g. prior audits, inspections and monitor visit reports) to determine existing gaps in your processes in addition to external sources (e.g. websites of regulatory authorities such as USFDA, EMA, Health Canada, etc.) to review guidance materials, requirements and expectations.

  2. Collaborate with the sponsor – Be proactive in utilizing inspection readiness tools and collaborating with the monitor & sponsor’s inspection team for additional support in preparing for inspections and implementing effective inspection readiness strategies.

  3. ‎Communicate with stakeholders‎‎ – ‎‎Communicate with internal stakeholders (colleagues, PI, monitor) to address gaps in study-related documentation to ensure that they‎‎ ‎‎are present, ‎‎complete‎‎ and accurate.‎‎ ‎‎ ‎‎ I‎‎t’s equally important to ensure that staff are properly prepared to communicate with external stakeholders (e.g. regulatory authorities) and able to interact ‎‎effectively ‎‎with the Inspector/FDA Investigator prior to, during and after the inspection.‎‎ ‎‎ ‎‎ ‎

  4. Correct via CAPA (Corrective and Preventive Action) PlansPart of having an effective Corrective and Preventive Action plan for each finding is to include all of the elements such as:

    • Root Cause – Why did this happen? Was it a systemic or isolated event? 
    • Correction – What correction was done to immediately resolve this finding?
    • Corrective Action – What will be your corrective action and how will you implement to ensure this finding does not recur?  For example, you may need need to createimproverevise SOPs and checklists/templates and retrain staff on the revised processes.
    • Preventive Action –  What are you checks and balances?  Incorporate preventive measures within a timeframe (e.g. 3- 6 months) to ensure similar finding(s) never happens again.  

  5. Conduct Compliance Checks –  Compliance checks involve the evaluation of the implemented processes from your CAPA.   Utilize checklists at frequent intervals to reveal gaps and determine what’s working vs. what’s not.  In addition, review findings from monitoring visits as gauge for compliance checks especially if time and resources are limited at your clinical research site.

Remember, inspection readiness is an ongoing process.  Incorporating an Inspection Readiness strategy, such as the 5C IRS (Inspection Readiness Success) Model, in your daily operations not only creates a culture of compliance, but also allows your site to proactively prepares for and contributes to the success of future inspections.  

Need a checklist for your site? 

Download our free Inspection Readiness Checklist today!