2k Clinical Consulting, Inc.

Source Documentation: “May the SOURCE Be with You…”

Lack of consistent, clear, and adequate source documentation is one of the most typical inspection results in investigator site inspections. This is also the most discovered flaw during sponsor audits. To guarantee that the study results are established on the foundation of trustworthy and legitimate data, investigator sites must be reminded of the need for good documentation practices. 

The origins of excellent documentation standards can be found in the (International Conference of Harmonizaton – Good Clinical Practice) ICH-GCP, which defines source data and source documents. 

 ICH E6 1.51 source data 

This includes all original documents and authenticated copies of original records of clinical results, observations, or other activities in a clinical trial that are required for the trial’s restoration and assessment. The documents containing source data are referred to as sources. 

ICH E6 1.52 source documents 

This includes original documents, data, and records such as hospital records, clinical and office charts.  The ALCOA-C acronym (attributable, legible, contemporaneous, original, accurate and complete) was coined by the US Food and Drug Administration to describe key characteristics of acceptable documentation. The World Health Organization has also adopted these. These requirements have changed over time. More ‘letters’ have been added by the EMA to indicate features of good source documentation, particularly for computerized systems. 

 Common Findings Associated with Source Documentation 

Following are the common findings associated with source documentation: 

  1.  It was not possible to validate the eligibility criteria. 
  2. Because there were multiple entries for the same data point, it was impossible to tell which one was the correct source record. 
  3. Inconsistencies in records were used to corroborate the study’s primary effectiveness outcome. 
  4. Abnormal lab values were not indicated on lab reports nor any contradicting material gathered in source documentation have been shown clinical importance. 
  5. Missing pieces of information from subject interview scales, a slew of unexplained revisions months after the initial entries, and contradictory data; erroneous subject identification, inaccurate date were identified. 
  6. Factually inaccurate paperwork regarding drug disposition—dates, amount, and subject use were found.  

How Can Documentation Be Improved? 

Documentation can be improved by the following ways:

  • Give PI the responsibility to assign tasks to the trained staff. 
  • Commitment and continuous presence must be acknowledged by the Principal Investigator (PI) throughout the study. 
  • Sites conducting the study must prepare SOPs which ought to be shared with the Contract Research Organization (CRO) or study sponsor. 
  • All technical aspects must be clear of confusions and errors prior to starting work on any study.
  • The sponsor and/or the CRO ensure PI’s commitment to the study.  

 Conclusion 

The ALCOA-C and other properties indicated by regulatory agencies and GCP should be demonstrated in source documents. During regular audits, the most frequently stated findings are those linked to source documentation. The PI’s dedication to the trial and participation in it makes a tremendous difference. Efforts to educate sites, understand their practices from the pre-study visit onwards, and to monitor and train them on a regular basis will all aid in increasing and sustaining the quality of site source documentation procedures. 

 

References 

“ALCOA”: Elements of good documentation. (n.d.). Retrieved October 24, 2021, from https://blink.ucsd.edu/research/policies-compliance-ethics/compliance/ALCOA-Standards-210304.pdf. 

Bargaje, C. (2011, April). Good documentation practice in clinical research. Perspectives in clinical research. Retrieved October 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121265/. 

Commissioner, O. of the. (n.d.). List – ich guidance documents. U.S. Food and Drug Administration. Retrieved October 24, 2021, from https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/ich-guidance-documents. 

GLP documentation. (2007). Good Laboratory Practice Regulations, 241–258. https://doi.org/10.3109/9780849375842-11  

 

 

FDA vs EMA in Terms of GCP Inspections

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

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.

 

FDA’s CAPA Checklist for Medical Devices

Since the year 2010, the most prevalent FDA audited observations in the medical device business have been “insufficient corrective and preventative action procedures.”  Its recurrence as the most common issue year after year indicates that many device firms have problems with their CAPA (Corrective and Preventive Action) systems, both known and unknown.  While the instant conformity risks are clear, those that leave firms open to major quality system flaws that can fester and spread beneath the radar of their quality management system (QMS) put patients and organizations at risk.

FDA publishes its own monitoring guide. It lays out the precise objectives for inspectors when reviewing a medical device CAPA system and supporting paperwork. Additionally, it also assists manufacturers in meeting the broad standards for effective CAPA.

What is the FDA CAPA Checklist for Medical Devices?

  1. Check if the CAPA system procedure(s) that satisfy the QMS regulation’s requirements have been identified and assessed.
  2. Check to see if the right sources of product and quality concerns have been uncovered. Ascertain that data from these sources is examined in order to ascertain current products and the quality issues that may necessitate remediation.
  3. Check to see if any product sources and quality data have been identified that may reveal unfavorable trends. Ascertain that the statistics from these sources are analyzed to identify possible product and quality issues that may necessitate intervention.
  4. Put the information management system to the test. Examine the data received by the CAPA system to ensure that it is complete, accurate, and reliable.
  5. Check that proper statistical approaches are used to detect recurring quality issues (if necessary). Check to see if analysis results are compared and contrasted across different data sources in order to discover and develop the scope of the product and manage any quality issues.
  6. Check to see if the procedures for failure investigation are being followed and determine whether the level of investigation is appropriate to the significance and risk of the nonconformity. Check to see if failure investigations are carried out to find the root cause (where possible) and if there is a system in place to prohibit the distribution of defective investigational devices.
  7. Determine whether or not suitable steps have been taken in response to serious product and quality issues uncovered through data sources.
  8. Determine whether corrective and preventive measures were effective and whether they had been checked or validated before being implemented. Confirm that corrective and preventive interventions have no negative impact on the final product.
  9. Check to see if remedial and preventive actions for quality issues were taken and recorded.
  10. Assess whether information on quality issues, as well as corrective and preventive measures, was adequately communicated, including for management review.

Conclusion

After evaluation of the CAPA process for devices, it is important that device firms narrow the gap between regulatory expectations and existing processes. This ensures that the devices are aligned with an FDA-compliant CAPA system. 

Need to strengthen your CAPA System? Contact us! We’d love to hear from you to discuss strategies!

 

References
The FDA Group. (2018). What The FDA Expects From Your CAPA Process. The FDA Group. https://www.thefdagroup.com/blog/what-fda-expects-from-your-capa-process.
Rodriguez, J. (2016). In CAPA In The Pharmaceutical And Biotech Industries: How To Implement An Effective Nine Step Program. Essay, Woodhead Publishing.

 

Understanding the CAPA Process

A corrective and preventive action (CAPA) plan is a set of steps done to address a compliance problem and, more significantly, to keep it from happening again. The immediate noncompliance and the broader nature of the problem will be the subject of a CAPA plan. It entails investigating the root cause and comprehending the problem, finding a solution, and ultimately avoiding recurrence. CAPA systems are important in clinical trials as it can be used to

  1. Address audit or inspection findings,
  2. Improve compliance and
  3. Reduce risk.

Importance of CAPA System in Clinical Trial Settings

During the clinical trial process, compliance to the GCP quality standard ensures that the information and drawn conclusions are credible and correct, as well as that the trial subjects’ rights, integrity, and confidentiality are safeguarded. The CAPA system ensures that the aforementioned conditions are met.

But how can we ensure that we are following the right steps? Read ahead about the phases of the CAPA system.

Phases in Implementation of the CAPA System

Before you start a clinical trial, keep in mind the following phases to implement a successful CAPA system.

  1. CAPA Initiation and Problem Identification: To begin the CAPA process, the problem identification and commencement phase needs recording the issue. The description should include who, what, when, where, why, and how many people were involved. A detailed report is favorable.
  2. Risk Analysis: A risk analysis should be conducted based on the risk to the patient, user, business, and compliance. CAPA deadlines should be determined by the outcomes of the risk analysis. Low-risk problems, obviously, will not have the same sense of urgency as high-risk problems.
  3. Correction: To prevent additional deviations or discrepancies, correction  should be undertaken as early as possible. To identify if there are any systemic difficulties, the organization should examine linked processes and products.
  4. Root Cause Analysis & Investigation: The following are some of the most commonly used tools/methods for conducting investigations to find the underlying cause of a problem;
    1. Flowcharting
    2. Brainstorming
    3. Affinity diagrams
    4. Fishbone diagrams
  5. Corrective or Preventive Actions: Corrective and preventative activities are long-term strategies for resolving or eliminating the cause of a nonconformity or a possible nonconformity.
  6. Implementation: Corrective and preventative actions are initiated and implemented during the implementation phase to address the root cause or causes of a nonconformity. Procedural upgrades, training, and process improvements are just a few examples.
  7. Verification of Implementation or VOI: VOIs are used to ensure that promised and planned corrections, containment, corrective actions, and preventive actions were carried out.
  8. Verification of Effectiveness Plan (VOEP): The effectiveness plan phase establishes and defines preset criteria for determining whether corrective and/or preventive activities were successful.
  9. Verification of Effectiveness (VOE): The verification of effectiveness phase entails analysing and recording the VOE plan’s stated criteria. A successful effectiveness verification should show that the genuine root cause of the problem was correctly identified and that the remedial and/or preventive actions were helpful.
  10. Closure: This is the final step in the CAPA procedure. Only once the verification of efficacy has been satisfactorily performed should a CAPA be closed. If a CAPA is discovered to be unsuccessful, it is recommended starting a new one while referencing the old one.

Conclusion

CAPAs are required by regulations, standards, and guidelines by health authorities across the globe.  Having a CAPA system in place assists a clinical trial by strengthening its market advantage, reducing unnecessary costs and improving processes if completed appropriately. To ensure that the process phases are clearly defined, each phase of a CAPA should be its own part on a form as an electronic workflow.

Struggling with creating effective CAPAs for your site or department?  Contact us! We’d love to hear from you to discuss strategies!

All About Protocol Deviations

The protocol for a clinical trial describes the entire study in detail, including the operational details of how it should be carried out. The purpose of the study protocol is to protect the health and safety of study participants while also proving efficacy of the product; however, when tasks are done outside the protocol, deviations are required.

What is a Protocol Deviation?

A protocol deviation happens when the activities of a researcher deviate from the Institutional Review Board-approved protocol without having severe implications, such as missing a visit window because the participant is travelling. It’s not as bad as a protocol violation which is a deviation from protocol that materially:

  • Decreases the quality or integrity of the information,
  • Causes the Informed Consent Form to be erroneous, or
  • Has an impact on the safety, rights, or wellbeing of a participant.

How Protocol Deviations Fit in a QMS

Some examples of protocol deviations occurring are:

  • Enrolling ineligible subjects
  • Lack of re-consenting subjects after amended protocols
  • The consent is missing signatures from subjects.

When deviations occur, the handling and resolution is intertwined in the QMS to ensure inspection readiness.  The organization could have a brainstorming session to discuss the deviation’s potential causes and effects in addition to what steps will be taken to prevent or mitigate the risk. These mitigations can then be monitored and reviewed on a regular basis, with specified thresholds for when a problem with trial registration becomes a substantial problem.

Important vs Non-Important Deviations

Once a procedure deviation has been found, it can be classified as either important or not important. Important protocol deviations can be defined using risk-based methodologies from ICH E6 R2.

Important protocol deviations are defined as subsets of protocol deviations that have the potential to have a major influence on the completeness, correctness, or reliability of essential study data, as well as a subject’s rights, safety, or well-being. Important protocol deviations, for example, could include enrolling individuals who do not meet critical eligibility criteria or neglecting to collect data needed to interpret primary endpoints, both of which could jeopardize the trial’s academic validity.

The International Conference on Harmonization (ICH) does not have a clear definition of a non-important protocol variation. As a result, if a procedure deviation does not match the requirements for being vital, it is considered non-important. Important and minor protocol deviations are both gathered, processed, and reported, albeit the processes may differ.

Conclusion

The cornerstone of a well-executed clinical trial is a well-thought-out and thorough protocol. Attend all sponsor-related meetings linked with the clinical study as the lead investigator. If you have any questions about the protocol or any study-related documentation, you should ask them right away to avoid any problems later. Finally, review the study, visit schedule and make plans ahead of time to prevent deviations.  

Struggling with minimizing protocol deviations for your site or department?  We’d love to hear from you to discuss strategies!

 

 

 

 

 

Important Aspects of Vendor Management Oversight

An FDA inspection can be triggered by a variety of factors with submission of an application for product approval as one of the most popular factors.   With the increasing need to outsource to clinical research vendors, inspections of sponsor companies tend to focus on vendor management and oversight as one of areas of the clinical QMS (Quality Management System).  

The Importance of Vendor Management

Vendor Management is important because it can help you mitigate risks by reducing specific risks concerning operations and hidden costs from the vendor. Secondly, maintaining quality vendor management allows you to keep track of the vendors’ performance against the contract. Lastly, it’s not easy to come across good vendors for clinical settings. You must maintain your relationship with them to ensure the process remains efficient.

Vendor Management Oversight that You Should Keep In Mind:

To ensure business continuity with your key vendors, you’ll need a good vendor management process in place, as well as a documented plan for dealing with any concerns that develop.

A well-designed vendor managing process framework has seven key points:

  1. Determine which vendors need to be kept an eye on: These should always include your key and high-risk vendors, but they can also include other significant (but lower-risk) partnerships.
  2. Define the metrics you want to track: Assessments should comprise both quantitative and qualitative indicators.
  3. Make a list of your data sources and organize them: Questionnaire survey, procedures and policies manuals, SOC and audit reports, and third-party data intelligence technologies, to mention a few, can all be used to collect managing data. Make sure you have the data sources needed to input the types of indications you’ll be tracking. 
  4. Make a list of your SMEs (Subject Matter Experts):  When it comes to SMEs, they are the people who have the particular knowledge you’ll need to assist with certain elements of managing. Experts in project management, CRO and laboratory partnerships are particularly common.  
  5. Assign roles and duties clearly: While the person who controls the vendor relationship should be in charge of managing their vendors, there are many additional SMEs (Subject Matter Experts) involved in the process. Make sure to spell out who is responsible for what and when. 
  6. Establish mechanisms for escalation: It’s crucial to know which issues need to be escalated and what alternatives you have for addressing them when difficulties arise throughout the vendor managing process (which they always do).  Extending your due diligence, upgrading contingency measures, or even changing (or terminating) the contract are all options. The types of issues that require escalation and the methods you can use should be defined in your framework. 
  7. Taking advantage of technology: Finally, using technology to monitor vendors makes the process a lot easier. This includes your vendor management system as well as active managing tools that allow you to access external data sources.

 Conclusion

Regardless of the number of vendors you work with, efficient vendor management is a critical aspect of inspection readiness. To build an efficient strategy that will guide a collaborative relationship with vendors, you must first grasp the benefits and challenges of vendor management. To guarantee that your vendors give maximum value to your organization, supplement your process with vendor management best practices.

 

 

The Importance of a Clinical Quality Management System (CQMS)

There has never been a better time to be in clinical research. From constant scientific innovation to being a part of a community of academic experts, there are seemingly endless opportunities to grow. While it all might seem exciting from the outside, organizations still face some internal challenges.

One such obstacle is the current clinical quality management systems (CQMS) in place at many start-ups or small firms. Their QMS are often not in line with global regulatory authority regulations or are deficient in the level of documentation needed to reconstruct and defend every aspect of clinical trials.

This can be fixed by having the basic quality systems embraced at every level of the organization in order to set the foundation for internal compliance and vendor oversight. In this article, we’ll discuss in detail about what the CQMS is, its key elements, and why it is important to implement in your organization.

What is a Clinical QMS vs QMS?

Every organization has a blueprint by which it operates under called the “quality system”, also known as the “quality management system” (QMS). It is a dynamic mechanism that overlooks and aims to improve core processes at maximum efficiency. The goal of the QMS is to provide a high-quality product at the lowest cost. In action, the QMS implements specific concepts, standards, methodologies, and tools to achieve quality-related goals.

On the other hand, the CQMS is a quality system more specific for clinical research and study management. It helps manage documents, processes, quality events, audits, and many more activities that occur throughout a clinical trial. More specifically, this system facilitates activities across the Clinical Quality and Clinical Operations sectors to improve efficiency, promote risk mitigation and risk management practices, and expedite drug development and delivery.

Key Elements of a Clinical QMS: Quality Management System Solutions

When setting up and implementing a CQMS, these are the key elements that should be highlighted:

  • Any processes should be well-defined prior to documentation. The organization should then determine the level and detail of procedural documentation that is needed to describe these processes. Procedural documents should detail policies, standard operating procedures, working instructions, etc.
  • Resources, Roles and Responsibilities. Both material resources and staff should be described in this part of the CQMS. Staff members should have clear roles and responsibilities that will directly affect operations and quality of outcomes. Leadership should be proactively managing resources on a consistent basis.
  • This includes collaborations, such as joint product development or outsourced activities. An organization has to understand the needs, expectations, limitations, and risks that will be carried out in such partnerships.
  • Risk Management. While you cannot predict every scenario that will happen, a risk management process will allow an organization to better predict such situations and prioritize resources to address the most significant risks that do arise.
  • Issue Management. This type of framework gives an organization the ability to quickly identify, investigate, assess, elevate, and communicate significant issues. Ideally, it should work in a way that issues will not recur and continue to improve the quality of clinical studies.
  • Knowledge Management. Knowledge is critical to the success of an organization’s performance. A knowledge management framework allows information to be applied by employees faster.
  • Documentation Supporting Achievement of Quality. There should be an appropriate level of documentation to back up the risks and significance of a clinical trial activity that will satisfy quality objectives and stakeholder requirements.

Important Benefits of QMS

An effective QMS system will result in better outcomes across all areas of your organization. Some of the most important benefits of a QMS include:

  • Identifying and improving processes
  • Improving patient safety in clinical trials
  • Providing a consistent framework for regulatory authorities
  • Streamlining clinical trial processes
  • Assuring data integrity
  • Reducing delayed studies
  • Resolving repetitive quality issues
  • Lowering costs

Conclusion

One of the reasons why some organizations struggle to achieve quality results is because of the lack of a framework that could help them better guide their processes and performance. A CQMS empowers organizations to define, learn, and improve upon every aspect of their process not only to improve performance and outcomes, but to also meet different stakeholders’ expectations. Implementing a CQMS will enhance an organization’s performance and inspection readiness and will ultimately facilitate the approval of investigational products.

 

Steps on Implementing a Clinical QMS

By Afifa F. – 2K Clinical Consulting, Inc. 

 There is a popular saying in quality management that if you do not have the process written down, then it probably didn’t happen. Just like any other business, Clinical trials must have a management system as well. This needs to be well-conceived  as well as systemized.  

 What is a QMS in Clinical Setup? 

QMS are standardized procedures with guidelines. These particular guidelines are the backbone for all procedures to be carried out. A clinical quality management system (CQMS) is meant to keep track of all the records, activities, tasks, processes, important events, interactions, inspections, and training that must be administered and controlled during the study’s lifespan.. 

 What are the Benefits of QMS in a Clinical Trial? 

The Clinical Quality Management System program provides improved patient safety by enhancing quality, ensuring data security, reducing clinical trial bottlenecks, and bringing products to the market faster. 

 QMS Implementation Steps 

The following steps must be covered to effectively implement Clinical QMS: 

  1.  Mapping and Defining Your Process  – The production of process maps will compel the associated clinical trial members to visualize and define its processes. They will determine the connection pattern of those operations to be carried out during the process. Process maps are essential for determining who is responsible. Lastly, they help to clarify the flow of the clinical trials execution. 
  2.  Defining the Clinical Trials Quality Policy – Objectives are required in all quality management systems. Each employee must recognize the impact they have on quality. Your quality policy influences your quality objectives. It’s quantifiable and implemented across all the project team members involved in the clinical trials process.    The goal could be in the form of key success criteria. This aids an organization in stressing the path to its mission’s fulfilment. These performance-based indicators provide a metric for determining whether or not the organization is meeting its goals. 
  3. Developing Scale to Track Critical Success Factor – Scales and measurements keep track of progress once important success criteria are defined. This can be accomplished using a data reporting technique that collects specified information. Leaders should be informed of the information that has been processed. The purpose of the method is to improve the customer satisfaction index score. There must be a goal and a metric for determining whether or not that objective has been met. 
  4. Defining Defects for Each ProcessNon-conformances occur as a result of a flaw in the product or a flaw in the process. It is necessary to measure and repair any problem that occurs. This can be done by determining what has to be done to fix the problem.
  5. Documenting and Keeping RecordsQMS includes keeping record of information in the form of documents. The golden tip is to start from a less hefty documentation and move onto the more important ones. 
  6. Defining the Process QualityInternal audits, management reviews, corrective and preventive action processes, and communication channels are all part of your quality assurance approach. 
  7. Understanding the Trainings to be IncludedEveryone must demonstrate competence in the job. Training is simply the beginning and can take place on the job, in a classroom, or virtually. Internal auditor competency and CAPA training are two significant training areas. 
  8. Using the QMSUsing the QMS ensures that the highest quality product is produced. The procedure entails gathering non-conformances and their records, auditing data in accordance with the corrective and prevention plan and reviewing data in accordance with the Failure Mode Effective Analysis (FMEA) to be prepared for any concerns.
  9. Measuring, Monitoring and Implementation of Plans to Improve Output – Using a quality management system entails gathering data and analyzing it to see if it is fit for purpose and can produce the desired results. You will have to keep track of objectives and define new metrics for performance. You must have a keen eye for details by recognizing trends, patterns, and correlation. After identifying trends, you and your team must prepare for arranging new objectives, plan prospects that will help you reach these new goals and must keep the mindset of “maintaining the quality”.  

 Key Takeaway 

In order to provide quality data and a clinical trial that is inspection-ready, a clinical QMS must be implemented. By doing so, you will be able to obtain and retain accreditation, which will be necessary both locally and internationally. 

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