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Kimberly Kiner

6 Steps to Creating SOPs for Quality and Compliance

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SOPs are crucial for ensuring compliance and conducting clinical trials. SOPs provide a standardized approach to clinical research processes, which is essential for maintaining consistency and quality across all study sites and participants. The lack of SOPs may result in several issues, such as inconsistent practices that result in disparities in data collection, analysis, and reporting, which may weaken the accuracy and dependability of the study outcomes.

Adhering to ethical and regulatory requirements in a research study can be challenging. Failure to follow standard operating procedures (SOPs) in clinical research can result in reduced efficiency and waste of time and resources in trying to determine the optimal way to perform tasks.

Why SOPs are Important for Clinical Research?

SOPs are important to clinical research as they provide:

  1. Detailed guidelines for the implementation of GCP principles which ensure that clinical trials are conducted in conformity with the ethical considerations and scientific quality standards.
  2. A standardized and streamlined approach to study procedures reducing variability of study tasks while also increasing inspection readiness strategies.
  3. Increased assurance of the safety and well-being of study participants as alignment of procedures and ethical practices and are in place.

Steps to Creating Effective SOPs

Creating effective SOPs can be challenging, but a well-designed and executed SOP can save time and resources, improve the quality of research, and reduce the risk of errors.

1.     Establish the SOP development team

The first step in creating effective SOPs for clinical research is to establish an SOP development team. The team should consist of individuals with relevant expertise and experience, including clinical research professionals, study coordinators, regulatory experts, and other stakeholders. The team should be responsible for overseeing the development and implementation of the SOPs.

2.     Identify the process

The next step is to identify the process for which the SOP is being developed. It is important to clearly define the process and the scope of the SOP. The process should be well understood by the team, and it should be clearly defined in the SOP to avoid any confusion or misinterpretation.

3.     Conduct a process mapping exercise

A process mapping exercise is a useful tool for developing SOPs for clinical research. It involves visually mapping out the process and identifying the key steps, inputs, and outputs. This exercise helps to identify areas where the process can be streamlined or improved, and it ensures that all steps are accounted for in the SOP.

4.     Develop the SOP

The next step is to develop the SOP. The SOP should be written in a clear and concise manner, using simple language. The SOP should include the purpose of the process, the step-by-step instructions for executing the process, the roles and responsibilities of team members, and any relevant references or supporting documents. The SOP should also include a section for deviations and corrective actions.

5.     Review and approve

Once the SOP has been developed, it should be reviewed and approved by the appropriate stakeholders. This includes the SOP development team, the study sponsor, the regulatory authority, and any other relevant parties. Feedback should be incorporated into the SOP, and revisions should be made as necessary.

6.     Train and implement

Training and implementation of the SOP should be conducted by the SOP development team. The team should ensure that all relevant personnel are trained on the SOP, and that the SOP is implemented consistently and effectively. The team should also monitor the implementation of the SOP and make any necessary updates or revisions.

Conclusion

In conclusion, creating effective SOPs for clinical research is critical for ensuring regulatory compliance, data integrity, and risk management. By following these six steps, the development team can create an effective and efficient SOP that will benefit the research team and the quality of the research.

 

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].

    How Changes in ICH E6 (R3) Guidelines are Changing the Future of Clinical Trials

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    ICH E6 (R3) Guidelines for Good Clinical Practices (GCP) have been a work in progress to put forward changes to the previous R2 version.  The overall purpose is to revise principles that account for ethical trial conduct, participant safety, and clinical trial outcomes that may be reliable. The ICH E6 R2 Guidelines for GCP consists of three key components:

    1. The overarching principle that will apply across the board
    2. Annex 1
    3. Annex 2

    Annex 1 currently reflects the principles in E6 (R2), with necessary updates and modifications. While Annex 2 contains additional information that should be considered in the case of non-traditional interventional clinical studies that are not included in Annex 1.

    Besides Annexes 1 and 2, the modifications in R3 consist of 12 major principles.  These 12 principles heavily focus on conducting clinical trials based on ethical principles, designing and conducting research that ensures patient rights, safety, and well-being.

    Moreover, the principles highlight the need to acquire informed consent where participants are aware of all the trials. Subjecting the clinical trial to an objective review is another critical principle, along with ensuring that all trials adhere to the requirements based on the latest scientific knowledge.

    Additionally, the principles highlight the importance of conducting the trial by an expert within the field and the necessity to include it in the scientific and operational design and execution of clinical trials. There is also an emphasis on designing the trial so that it’s comparative to patient risk and trial results while also ensuring that it’s clear and concise.

    R2 vs. R3 What is The Difference?

    R2

    R3

    Risk-based approach – The focus of E6 (R2) was on a balanced, risk-based approach to clinical trial design and execution.

    Risk-based approach -ICH E6 R3 is intended to promote this notion while also encouraging interested parties to incorporate this approach.

    Technology – E6 (R2) isn’t entirely equipped to deal with new technology.

    Technology – The rising usage of electronic data sources and risk management procedures is addressed in E6 (R3).

    Principle/Annex – R2 consisted of the overarching principle and annex 1.

    Principle/Annex – R3 has revised the overarching principle and annex 1. Moreover, there is an addition of annex 2.

    Is Clinical Research Industry Going to Face New Challenges?

    Any change can bring about challenges; however, the gravity of the challenges depends on the quality design of the trial(s) currently in place. There is an evident need to ensure the reliability of clinical trial results. Without this, all the resources used to accomplish the findings would result in a loss of millions of dollars. This is precisely why the ICH E6 R3 has emphasized using Risk-Based Quality Management (RBQM) and Risk-Based Monitoring (RBM).

    Many of the methods and technologies that researchers are already using in clinical trials will be simplified by the new ICH advice, especially when it comes to risk-based monitoring (RBM). The industry may anticipate guidelines on remote evaluation and observation, as well as a technical design that is flexible enough to accommodate both existing platforms and future developments, assuring trial integrity while removing the effort of confirming non-critical evidence.

    Conclusion

    Although many clinical researchers have yet to get accustomed to the ICH E6 R3 or implement it, the clinical importance of applying these guidelines will streamline research and produce more accurate and reliable results. Moreover, ICH E6 R3 will ensure inspection readiness ensuring no hindrance to clinical trials, which is why immediate implementation of ICH E6R3 guidelines are truly beneficial.

    The process of building quality into the design of a trial can be arduous without the sound quality management system (QMS) in place.  Don’t have the time to ensure your system has the quality that exceeds compliance to the ICH E6 R3 standards?  Contact us and let us help you implement compliance strategies and a streamlined process for your QMS prior to the rollout! 

     

    References

    CITI Program. 2021. ICH Releases Draft Principles for GCP | CITI Program. [online] Available at: <https://about.citiprogram.org/blog/ich-releases-draft-principles-for-gcp/> [Accessed 15 March 2022].

    ICH, 2019. Final Business Plan ICH E6(R3): Guideline for Good Clinical Practice. [online] Available at: <https://database.ich.org/sites/default/files/E6-R3_FinalBusinessPlan_2019_1117.pdf> [Accessed 15 March 2022].

    ICH, 2021. ICH-E6 Good Clinical Practice (GCP). [online] Available at: <https://database.ich.org/sites/default/files/ICH_E6-R3_GCP-Principles_Draft_2021_0419.pdf> [Accessed 15 March 2022].

    Mauri, K., 2021. Rewriting the Rules: How to Prepare for ICH E6 (R3). Pharmaceutical Outsourcing, [online] Available at: <https://www.pharmoutsourcing.com/Featured-Articles/579132-Rewriting-the-Rules-How-to-Prepare-for-ICH-E6-R3/> [Accessed 15 March 2022].

    MY EXPERIENCE AS AN FDA INVESTIGATOR

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    I have been asked so many questions about my FDA career and what it was like working with the FDA.  I thought it would be best to write about my experience in an interview-based article according to the most frequently asked questions.

     How were you introduced to the FDA?

    I was introduced to the FDA in my last year of college at Rutgers University.  As I was prepared for graduation and entering the workforce, I also attended as many job fairs as possible. I thought that submitting my resume to as many companies possible would increase my chances of getting hired after graduation.  Of all the numerous job fairs I attended, FDA was only present at one of them.   I met the FDA representative, who was also the District Director, had a great conversation with her and handed her my resume which was added to the stack of resumes from hundreds of other candidates.

    How did you get hired to work for the FDA?

    Getting hired to work for the FDA was not easy.  After graduation, I was determined to have a career relative to biology or similar scientific field and the FDA was one of top companies I wanted to work for.  I was very persistent in having my name and resume stand out from the others.  For months, I called the District Director every other day to check in and see if she reviewed my resume.   My persistence paid off.  A couple of months later, I finally received a call from the district office to come in for a face-to-face interview.

    What was the hiring process like?

    The hiring process was pretty rigorous.  The interview was a few hours long.  It included an overview of FDA and discussion about me and my experience (although very limited as a college grad). It also included a long list of case-based scenarios along with questions on how I would handle each case.  The purpose of these questions was to test my moral character, sound judgement and ability to protect confidential information. 

    After being considered a potential candidate, I moved on to the next phase where there was the typical drug test, credit check and a detailed background check.  The background check not only included a criminal history check but a thorough investigation on me as person.  Not only were my past and current employers contacted and visited, but all of my neighbors from my current and past addresses as well!  

    What was a typical day in the life of an FDA Investigator?

    A day in the life of an FDA Investigator primarily involves preparing for and conducting inspections according to your specialty (Pharmaceuticals, Devices, Foods, Biologics).

    Inspections can be as short as a few hours or as long as a few weeks depending on the size of the firm and complexity of the inspection.  Other tasks include handling and investigating customer complaints and recalls in addition to attending meetings and continuous training sessions. Overall, the job entails a lot of travel, but the majority of it is local. 

    What’s the difference between FDA investigator and Inspector?

    FDA Investigators (or Consumer Safety Officer -CSOs) differs from FDA Inspectors (or Consumer Safety Inspectors- CSI) in that Investigator positions requires a Bachelor of Science (BS) degree (usually in science or engineering) whereas the CSI position does not.

    In addition, the role and responsibilities of an Investigator and Inspector are different.  Investigators are responsible for conducting domestic & international inspections and investigations in the areas of food/imports, pharmaceutical, biologic, BIMO and medical device; whereas Inspectors are responsible for performing import work which includes physically inspecting imported products in the aforementioned areas.   GCP/BIMO inspections, will always be conducted by an FDA Investigator.

    Why did you leave the FDA?

    Leaving the FDA and my colleagues was bittersweet.  I enjoyed working at the FDA but compensation was low (GS-5 which is $25K a year) as is expected for a government position.  At the time, there were so many opportunities in the industry looking for someone with my experience paying 2-3x as much, I could not say no.  I was curious to see what the industry had to offer.

    Any regrets leaving the FDA?

    Initially, I had regrets and wanted to kick myself for leaving, but as I started working in the industry and gaining more experience with CROs, pharmaceutical and medical device companies, my regrets started to dissipate.  I realized how valuable it was to work on “the other side” as it only diversified and enhanced my knowledge and experience.  If anything, continuing to work with the FDA would have limited me from seeing and understanding both perspectives.  Having the experience of seeing both sides (industry vs FDA) is truly priceless.

    Have more questions? Feel free to contact me at info@2kclinicalconsulting.com

    FDA’s CAPA Checklist for Medical Devices

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    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

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    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!

    Important Aspects of Vendor Management Oversight

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    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)

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    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.

     

    How to Increase Visibility for an Inspection-Ready TMF

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    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 scrutinized objects 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 easy–to–access, clear, and transparent for all parties involved is the goal for your TMF. While 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 locations. To 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!  

    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.