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Integrating Inspection Readiness into Daily Operations at Clinical Sites

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Ensuring GCP compliance and inspection readiness should not be a frantic scramble in the days before an FDA visit. Instead, clinical research sites can integrate these critical elements into their daily operational workflows. By embedding GCP compliance and inspection readiness into everyday practices, sites can maintain a constant state of readiness, improving both efficiency and compliance. Here’s how your site can achieve this.

Establishing a Culture of Compliance

Create a culture where GCP compliance is a fundamental part of every action and decision. This involves training all team members—not just once a year but as a continuous learning process. Utilize regular staff meetings to discuss compliance updates, share insights, and reinforce the importance of maintaining high standards in every task.

Systematizing Compliance Checks

Incorporate routine compliance checks into daily operations. For example, end each day or week with a quick review of documentation practices or data entry accuracy. Implementing electronic systems that automatically flag errors or inconsistencies can help maintain compliance without significant manual oversight.

Simplifying Documentation Processes

Streamline documentation processes by using tools and systems that integrate compliance into their design. Electronic data capture (EDC) systems, for example, can ensure that all data is recorded accurately and is audit-ready at any moment. These systems can reduce the burden on staff and prevent common documentation errors.

Proactive Risk Management

Incorporate risk management into your daily operations by identifying potential areas of non-compliance and addressing them proactively. Regularly update risk management plans based on new insights and past inspection outcomes. This proactive approach not only prepares sites for unexpected inspections but also helps in continually improving the quality of the research conducted.

Regular Audits and Feedback Loops

Implement a schedule of regular internal audits to assess compliance. Use the findings from these audits to adjust processes and training as needed. Additionally, establishing a feedback loop where staff can report potential compliance issues or suggest improvements can enhance overall compliance and readiness.

By making GCP compliance and inspection readiness a part of the daily routine, clinical research sites can alleviate the stress of FDA inspections and focus more on conducting high-quality research. This integration leads to a more organized, efficient, and compliant operation.

For clinical sites looking to enhance their operational workflows to include continuous compliance and readiness, professional development and training are key. The course “Preparing for FDA GCP Inspections – Best Practices for Clinical Sites” offers in-depth strategies and insights into making compliance a seamless part of daily operations.

Are you ready to transform your site’s approach to FDA inspections? Enroll in “Preparing for FDA GCP Inspections – Best Practices for Clinical Sites” and ensure your team is always inspection-ready. Enroll in the course for expert guidance and practical strategies tailored to your needs.

Clinical Trial Trends in 2024: Innovations and Evolutions in Inspection-Readiness

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As we navigate through the new year of 2024, the clinical trial landscape is experiencing transformative changes, particularly in the aspect of inspection-readiness. This abbreviated article provides a focused look into how these changes are influencing trial preparedness for regulatory inspections.

  1. Advancements in Inspection-Readiness The integration of new technologies and methodologies has brought about a significant shift in how clinical trials prepare for inspections. Innovations such as digital documentation systems and AI-driven compliance tools are streamlining the process, ensuring trials are always inspection-ready.
  2. Real-Time Data Monitoring The adoption of real-time data monitoring systems is a game-changer. These systems provide continuous oversight of trial data, flagging inconsistencies and areas of concern well before an inspection, thus reducing the risk of non-compliance.
  3. Decentralized Trials and Inspection Challenges Decentralized clinical trials (DCTs), while offering numerous benefits, also present unique challenges in maintaining inspection-readiness. Our article discusses strategies to overcome these challenges, ensuring DCTs adhere to regulatory standards effectively.

Conclusion The full article, accessible to our subscribers, delves deeper into how these trends are reshaping inspection-readiness in clinical trials and explores the evolving regulatory expectations and how companies are adapting to meet these new standards.  🔗 Subscribe now for full access to in-depth insights.

Your Insight Counts How do you think technology will further impact inspection-readiness in clinical trials beyond 2024?  Let us know in the comments section.  We look forward to hearing from you!

Tips on Establishing an Inspection Readiness Training Program

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The task of documenting and maintaining records can prove to be a daunting one in the world of clinical research.  Effective resource allocation constitutes a delicate equilibrium. Striking the right balance between dedicating resources to training and compliance initiatives while judiciously managing costs becomes an intricate endeavor for organizations. It is critical to be attentive to resource needs in addition to ensuring that employees receive comprehensive inspection-readiness training in preparation for health authority inspections.  The do’s and don’ts of inspection readiness training that contributes to readiness success includes the following:

Do:

  1. Consistent Training Plan – Establish a regular schedule for training sessions, ensuring that all team members acquire a comprehensive understanding of health authority regulations and adherence to documented standard operation procedures.
  2. Exemplary documentation standards – Stress the importance of meticulous and comprehensive documentation. Implement and practice the most effective methods for maintaining impeccable records.
  3. Comprehensive cross-training – Promote cross-functional training initiatives aimed at nurturing a corporate culture deeply ingrained in compliance across various departments within your organization’s structure.
  4. Realistic scenario simulations – Create mock inspection scenarios that closely resemble real-world situations. This valuable exercise will help identify weaknesses and areas in need of improvement.
  5. Proactive regulatory awareness – Continuously monitor and stay informed about regulatory updates, adjusting your training programs to align with these evolving regulations.

Don’t:

  1. Discount the gravity of compliance – Never underestimate the gravity of aligning with regulations. Forgoing due diligence or shortcutting compliance requirements can result in grievous regulatory issues.
  2. Neglect training documentation – Never depreciate the importance of documenting training, both in terms of accuracy and completeness. Neglecting to properly oversee and document training can furnish a breeding ground for critical compliance and data discrepancies.
  3. Neglect post-training reinforcement – The failure to revisit training and scrutinize employee compliance can vitiate the efficacy of the training initiative. Assure that senior leadership exudes unwavering commitment to the training program.
  4. Defer compliance or cultivate a culture of blame – Do not defer the serious consideration of compliance until impending regulatory inspections materialize. Shun the cultivation of a culture that lays blame upon employees who are may not be main contributors to the errors or data discrepancies.
  5. Underestimate resource allocation – Do not underestimate the resource allocation requirements for the efficacious execution of training and compliance endeavors. Insufficient resource allotment can enervate the quality of training and impede compliance endeavors.

In conclusion, maintaining inspection readiness is a continuous process that demands diligence, commitment, and a robust training program. The challenges posed by evolving regulations and complex documentation can be overcome by following the dos and don’ts outlined above. By investing in comprehensive inspection readiness training program, organizations can safeguard their reputation, product quality, and, most importantly, patient safety in an ever-evolving regulatory landscape.

If you need to develop an inspection-readiness training program and need assistance, Contact us for a free consultation! We would love to hear from you to discuss strategies!

5Cs to Inspection Readiness Success (for Clinical Sites)

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By the 2K Blog /team

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) Plans – Part 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 to create, improve, revise 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? Become a subscriber to download our free Inspection Readiness Checklist!

 

 

Preparing For Pharmacovigilance FDA Inspections

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The concept of pharmacovigilance—derived from the Greek and Latin ‘Pharmakon’ (medicinal substance) and Vigilia (to keep watch)—emerged in earnest among physicians and other health experts almost 200 years ago. Initially, the practice amounted primarily to letters and reports written by physicians on the safety and effectiveness of various drugs given to their patients.

Pharmacovigilance inspections (Good Pharmacovigilance Practices, GVP) are designed to assess compliance with the legally prescribed mandatory reporting of adverse drug reactions in clinical trials as well as spontaneous reports. 

The three (3) most common findings noted from FDA’s Post-marketing Adverse Drug Experience (PADE) inspections according to the Bioresearch Monitoring (BIMO) Fiscal Year 2021 Metrics  are:

  • Failure to develop written procedures for the surveillance, receipt, evaluation, and reporting of post-marketing adverse drug experiences
  • Late submission of 15-day Alert reports
  • Late submission of the annual safety report

This article will list ten (10) key areas or documentation to have ready for FDA in an upcoming GVP inspection.

What To Have Ready for an Inspection

  1. Written Procedures
    You must develop, maintain, and follow written procedures for the surveillance, receipt, evaluation, and reporting of post-marketing safety information. This includes procedures for managing safety information with contractors and business partners, as applicable.
  2. Individual Case Safety Reports (ICSRs)
    ICSRs describe one or more adverse experiences related to an individual patient or subject. A valid ICSR contains a suspect drug, an adverse experience, an identifiable patient, and an identifiable reporter.
  3. Scientific Literature Reports
    Regarding scientific literature reports, ensure that there is documented evidence of:
     Scientific literature reviews and the frequency of each review.
     Submission of expedited ICSRs for adverse experiences obtained from the published scientific and medical literature that are both serious and unexpected
    • Foreign Post-marketing Adverse Experience Reporting
      For participating affiliates, subsidiaries, contractors, and business partners outside the United States, ensure the following:
       There are written procedures that address the surveillance, receipt, evaluation, and reporting of adverse experiences.
       There is documented submission of serious and unlabeled (i.e., unexpected) adverse experiences to the FDA within 15 calendar days.
    • Solicited Safety Data
      Solicited safety data arises from organized data collection systems, which may include patient assistance programs, patient support programs, physician engagement programs, or any active solicitation of information from patients or providers, when contact between the sponsor company and the patient or provider is predictable in the context of a specific program.
    • Aggregate Safety Reports
      For each approved application or biologics license, FDA requires the submission of Periodic Reports, which describe safety information obtained during the reporting interval. The reporting interval is quarterly for the first three years following the approval of the application or license, and annually thereafter, unless FDA instructs the sponsor otherwise.
    • Contractor Oversight
      Oversight of outsourced services may include a broad range of activities to ensure that all outsourced services and activities associated with post-marketing safety are performed according to applicable FDA regulations.
    • Electronic Submissions
      Determine if safety report submissions are in an electronic format that FDA can process, review, and archive, as required.
    • Waivers
      Any post-marketing safety waivers from the regulatory requirements must follow applicable procedures and terms of the waiver.
    • Recordkeeping
      For approved drugs or biologics, ensure that all records containing information relating post-marketing safety reports (whether submitted to FDA) have been maintained for a period of 10 years, or for combination products, the longest retention period applicable.

    Conclusion

    Post-marketing safety data collection and adverse event reporting is a critical element of the Food and Drug Administration’s post-marketing safety surveillance program for FDA-regulated drug and therapeutic biologic products.  Incorporating the FDA requirements and guidance into your inspection readiness program contributes to the success of your GVP inspection.

    5 Reasons Why QA Is Essential in Clinical Trials

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    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].

    FDA vs EMA in Terms of GCP Inspections

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    The national and global regulations for conducting clinical trials involving human participants are known as Good Clinical Practice (ICH-GCP). They include not only quality criteria, but also regulatory guidelines to ensure that all newly created pharmaceuticals and medical devices have been clinically shown to benefit the health of the public.  The FDA and the EMA are two of the most important regulatory authorities involved in ensuring patient safety and data integrity, and here is some information about both.

    FDA vs EMA

    The United States Food and Drug Administration (USFDA) is a division of the United States Department of Health and Human Services. All investigative product and approved products  (drugs and devices) sold in the United States are reviewed, approved, and regulated by the FDA both domestically and internationally. The European Medicines Agency (EMA), on the other hand, controls the drug development process for all European Union member countries.

    How do the FDA and EMA work differently?

    Inspection Focus:

    FDA Investigators will spend some time looking at generic processes, but their main focus will be on research activities. The overall approach will be to follow the Bioresearch Monitoring Program guidelines and check conformity on each study. While the EMA will analyze study details in their trial master file (TMF) review, their Subject Matter Expert (SME) interview will focus mostly on general processes.

    Trial Master Files (TMF):

    There is no particular FDA mandate for organizations to develop a trial master file in the United States, but if the regulatory body wants ICH GCP to be followed, then a trial master file must be created and maintained.

    Inspectors from the EMA, on the other hand, will conduct a thorough and comprehensive assessment of the TMF and, with rare exceptions, will prepare to browse without assistance. TMF review will normally take up major time during the inspection. Moreover, these organizations anticipate that the majority of study documents will be accessible directly within the TMF and will be recorded in a timely manner. If a TMF is ready for an EMA inspection, it is probably ready for any other significant agency as well.

    Document Review:

    According to the EMA’s inaugural documents, the agency’s main goal was to recognize the importance of improving patient-reported health-related quality of life (HRQOL). The EMA’s patient-reported outcomes (PRO) advice focuses on numerous domains for generalized HRQOL assessment, whereas the FDA’s focus is on symptom-specific measurements. This distinction can be seen in the pazopanib approval documentation. While the EMA included HRQOL data from pazopanib phase III studies in its assessment, the FDA statement makes no mention of this objective.

    Conclusion

    The two most influential regulatory agencies, USFDA and EMA, assure us that we can trust the industry as their respective accomplishments become more transparent in improving current processes and safeguarding patients and the clinical industry’s future.

     

    References

    CTA. (2019, January 11). Observations from GCP sponsor inspections. Clinical trials arena. Retrieved October 11, 2021, from https://www.clinicaltrialsarena.com/comment/how-to-prepare-for-gcp-sponsor-inspections.

    EMA. (2021, August 10). European Medicines Agency. Retrieved October 11, 2021, from https://www.ema.europa.eu/en.

    NCBI. (n.d.). FDA in PMC. National Center for Biotechnology Information. Retrieved October 11, 2021, from https://www.ncbi.nlm.nih.gov/pmc/funder/fda/#:~:text=FDA%20is%20responsible%20for%20protecting,manufacturing%2C%20marketing%2C%20and%20distribution%20of.

    NIRH. (n.d.). Trial Master File. Trial master file. Retrieved October 11, 2021, from https://www.ct-toolkit.ac.uk/routemap/trial-master-file/.

    Shalby, M. (2018, August 3). Good clinical practice: FDA vs. Ema. LinkedIn. Retrieved October 11, 2021, from https://www.linkedin.com/pulse/good-clinical-practice-fda-vs-ema-michaela-shalby/.

    Getting to the Core of the CAPA System – The Root Cause Analysis

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    You have just undergone an audit and discovered a gap in your process.  What’s the next step?  The key to inspection readiness is having an effective CAPA system that not only correct the issues but also prevent them from happening again. Only by identifying the root cause of the problem will you be able to prevent it from happening again.

    When it comes to diagnosing the source of an issue in a fast-paced industry, speed is important. As a result, many departments rely on the tried-and-tested procedures of Root Cause Analysis (RCA) and Corrective Action Planning (CAPA) to identify and prevent problems. Here’s a closer look at Root Cause Analysis.

    What Is a Root Cause Analysis?

    Root Cause Analysis (RCA) is a technique for determining what, how, and why an event occurred so that preventative measures can be adopted. Data collection, root cause identification and execution are all part of it. To put it another way, RCA is a set of procedures that allows you to delve behind the surface of a problem to uncover causal pathways that lead to the problem’s underlying root causes.

    What Are the Root Causes?

    To comprehend fundamental causes, we must first comprehend what the issue is in the first place. A problem could be a divergence from customer specifications or another type of non – compliance at its most basic level.  The root causes of these issues are the precise, root factors that can be properly identified, are within the company’s authority to address, and result in effective solutions to prevent relapses.

    How Are RCA and CAPA Connected?

    The CAPA as discussed before,  is the action phrase, whereas if RCA is the subject. The root cause is what is causing the problem, and the CAPA is what will be done to fix it and keep it from occurring again.

    The 5 Why’s in RCA

    The 5 Whys is a simple yet powerful cause-and-effect method for determining the fundamental cause of a problem. You’ll begin by identifying the problem (RCA input), then query why each issue is happening until you find the root cause. Keep in mind that you don’t have to stop at five; in some circumstances, six or seven repeats may be necessary.

    The Action Plan

    The team must build suitable countermeasures or remedial activities after determining the root cause.  The team should also devise a strategy for putting the solutions into effect. The counter-measures can be divided into two categories:

    • Short-term Action Plan: Countermeasures that can be implemented quickly, usually in less than a week
    • Long-term Action Plan: Long-term or lasting solutions are usually more difficult to implement and may necessitate additional resources. All “long-term” action plans should be completed in less than one month. If not, they should be sent to the Continuous Improvement (CI) team for review.

    Conclusion

    By discovering the underlying cause and taking action to prevent it from reoccurring, the establishment of a comprehensive, well-planned Root Cause Analysis (RCA) methodology can be extremely beneficial to a department in terms of inspection readiness. Many of the lessons learned during a successful RCA can be applied to similar designs or processes.

    Need to strengthen the Root Cause Analysis of your CAPA System? Contact us! We’d love to hear from you to discuss strategies!

     

    References

    • Buchholz, V. (2019). What Went Wrong and How To Fix It.
    • Quality-One. (2021). Root cause Analysis (RCA). Quality. Retrieved September 10, 2021, from https://quality-one.com/rca/.
    • Wikimedia Foundation. (2021, July 13). Five whys. Wikipedia. Retrieved September 10, 2021, from https://en.wikipedia.org/wiki/Five_whys.

     

    3 Surefire Ways your TMF can extend your Inspection

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    The Trial Master File (TMF) is the backbone of the clinical trial. It consists of essential documents which not only enable the conduct of a clinical trial, but also enable the evaluation of the quality of data produced.

    One of the questions asked at the beginning of an inspection is: “Where and how are your documents stored?”.  It is expected that all responsible parties know the location(s) of all paper/hybrid, and electronic documents that comprise the TMF.  Most importantly, it is expected that the TMF is readily accessible and audit-ready.

    The reality is…this is not always the case.  In most cases, the TMF is often forgotten and becomes a disorganized “pile of files”.  As a result, inspections can be extended for this reason.

    In fact, MHRA stated that that 35% of inspections were extended and required extra days particularly due to critical findings of TMFs.

    Three (3) critical findings and surefire ways a TMF can extend your inspection are:

    1. Lack of Access – The majority of time, the full TMF is not readily available or accessible to inspectors causing a delay in document review.

    2. Poor Indexing – Oftentimes, the person designated to the TMF has issues locating documents during inspections due to poor indexing.

    3. Incomplete/Missing Files – This is self-explanatory. Files that are inaccurate, incomplete or missing/misfiled can certainly cause a delay. Furthermore, uploading last minute documents to the eTMF (electronic Trial Master File) is a red flag as inspectors can see the download date and time of each document.

    Sounds familiar?

    Well, this can all be prevented with 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

    Inspection Preparation Concepts for Clinical Research Sites

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    The first thought that typically comes to mind when you hear about an upcoming FDA inspection at your site is the logistics– where to meet, document review, and your facility’s condition.  There are however, other factors to keep in mind for both on-site and remote inspections.

    This article will briefly cover the basic principles of a GCP inspections and what clinical site staff should expect and keep in mind for future inspections.

    FDA Investigators (commonly known as Inspectors) regularly visit clinical research sites to conduct inspections and ensure GCP requirements are being followed.  In fact, according to FDA’s inspection metrics, almost 800 BIMO or Bioresearch Monitoring  inspections are conducted  at clinical research sites every year (with the exception of the pandemic in year 2020).

    What to expect

    Whether an FDA Investigator conducts an on-site or remote inspection, he/she will need to show his/her credentials and show an FDA-482 prior  to discussing the inspection’s purpose, scope and  number of days according to the size and complexity of the trial(s) being inspected.

    In general, the first day of inspection will also require the review of pre-inspection records, site files and subject files.  Interviews will also be conducted with the study personnel, such as the study coordinator(s) and the Principal Investigator to determine compliance to the regulations, protocol/investigational plan and other study-related procedures.

    At the end of each day, the inspectors will do a summary of findings, as well as a general verification of their checklist to confirm if inspection criteria were fully covered and all requested documentation received.

    The most important aspects that FDA Investigators  focus on are patient safety and data integrity. They will look at patient consents, adverse event/experience reporting, and anything that could potentially jeopardize the patient’s safety. They also ensure data integrity by confirming the absence of data transcription errors  and compliance to  the regulations, protocol and other study requirements according to CPGM (Compliance Program Guidance Manual) for Clinical Sites.

    What to keep in mind

    • Plan Accordingly – Keep a checklist available to ensure documents are inspection-ready. site staff are adequately prepared and technology is properly working for provided access and sharing documentation (especially for remote inspections).
    •  Practice Interview Skills –During the interviews, it is important to inform your staff about the Do’s and Don’ts of interviewing including how to answer the questions asked by the inspectors. For example, all site staff should be prepared to discuss topics such as:
      • Training – Safety-related, Protocol, Case Report Form
      • Delegation of study-related tasks/PI Oversight
      • Subject recruitment
      • Informed consent process
      • Source documentation
      • Data entry
      • Investigational product or device handling

    Interviewees only need to answer the question directly with no additional information. Moreover, if you don’t know the answer to a certain question, it is acceptable to say that you don’t have access to that information at the time and that you will get back to them with an answer later.

    • Don’t get defensive/ask questions – Be sure that none of your staff are getting defensive with the FDA inspector as this might come back to haunt you.
    • Ask for Clarification – If you need clarification or have questions about the findings reported by the FDA inspector, it is totally acceptable to point them out. However, defensive behavior is never a good idea.

    Key Takeaway

    Inspections are an important aspect of clinical research trials.  A proactive approach and consistent preparation from clinical site personnel at the start of a trial, results in a successful inspection at the end.

    Need an Inspection Preparation checklist for your site?  Feel free to download our free Inspection Preparation Checklist as a preparation tool.

     

     

     

    Our Mission and Purpose

    The mission of 2K Clinical Consulting, Inc. is to ease the burden of GxP compliance and to transform the effectiveness of professionals and compliance systems worldwide.

    Our History

    2K Clinical Consulting, Inc. is the vision of former FDA Investigator, Kimberly Kiner, who empathized with facilities and sites that struggled with understanding and complying with regulations. After years in the field, Kimberly transitioned into the private sector and acquired international experience in compliance, monitoring and study management while she worked for pharmaceutical and invitro/medical device companies as well as CROs. This work experience is what sparked her desire to work as a consultant for organizations such as the Association for Clinical Research Professionals and the Society of Clinical Research Associates. Kimberly later went on to train providers such as Compliance Online and Fx Conferences. This exposure became the gateway to connecting with other experts and teaching professionals resulting in an engaging experience for clients that closes the gap in best practices within the realm of compliance.