Conference Posters - 2021

Subtitle for Academic Research Poster (48x36 inches)

Fostering GxP Quality Principles in Unregulated Areas of Life Sciences through Culture of Quality

Your names and the names of the people who contributed to this presentation

INTRODUCTION

GxP was originally developed with the purpose of ensuring enhanced quality standards of the complete stream of medicinal products’ lifecycle, from the early stages to the continuous monitoring of marketed drugs The main objective is promoting the safety and well-being of patients and consumers

However, these rigorous quality standards are not applied to the research environment where scientific knowledge grows and where candidate drugs are developed

Although this research might not have direct impact on patient safety, it stands at the origins of scientific discoveries Poor data integrity and low process standardisation due to the lack of binding regulations can potentially jeopardise the research results

However, the risks related to the absence of the binding regulations in research can be avoided by fostering strong Culture of Quality

The present poster aims at exploring and discussing which areas of Life Sciences currently are not covered by GxP guidelines and how they can potentially benefit from the application of agile GxP quality tools and processes

How the Unregulated Areas of Life Sciences Benefit from the GxP Quality Culture

GxP quality assurance practices can be particularly effective in the following areas of Life Sciences where they can improve the reliability and accuracy of experimental data:

STAFF TRAINING AND QUALIFICATION

Creation of a standardised training plan with a set of predefined trainings speeds up the process of newcomers' qualification and decreases the possibility of operational errors

EQUIPMENT CONTROLS

Standardisation of the periodic controls of the experiment equipment ensures that they are used in a fully operational state

RECORD MANAGEMENT

Good practices of documents and records management improve the archiving and integrity of experimental data over time

NON-CONFORMITY TRACKING

Introduction of the metrics for non-confromities has potential to increase the quality level and reduce the waste by avoiding recurring errors

AUDITING

Independent evaluation of the processes sheds the light on potential risks that are hard to detect for the team that conducts routine operations

PERFORMANCE MONITORING

Indicators help to recognise areas with high performance as well as those with low performance and organise activities accordingly

Creating Quality Framework in Life Sciences: Agile Tools

The following agile tools are just examples of how simple and straightforward quality processes can help in achieving high quality standards in an unregulated area in Life Sciences.

ESSENTIAL PROCESSES PROCEDURES

Identifying the essential and critical processes to be described appropriate procedures helps to create alignment between processes These procedures can also be subsequently training of the new employees

SELF-INSPECTION CHECKLISTS VS AUDITS

Audits can be expensive in terms of costs, expertise, resources time Moreover, audits should be conducted by trained experts extensive knowledge of methodology and legislation At the same time, audits represent an opportunity for continuous improvement In pursue of a similar result in terms of continuous improvement, research teams can develop self-inspection checklists in order to conduct internal assessments

Challenge and Potential Constraints

Lack

Lack

JUST-DO-IT APPROACH TO SOLVE NONCONFORMITIES

Adopting a sustainable and reasonably cheap "Just do it" approach by implementing immediate actions to solve nonconformities simplifies the CAPA (Corrective actions , preventing action) standard process, while achieving its main purposes An internal register can be used to track the immediate actions and evaluating the non-conformities alongside the actions efficacy in the long term

INDUCTION TRAINING PLANS WITH TRAINING CHECKLISTS

Using checklists based on training requirements, workloads and experience of the new employees optimises the training organisation Following the induction training, the knowledge of policies, processes and practices should be verified

First Examples of GxP Application in Non-regulated Areas of Life Sciences

A growing number of publications suggests how the implementation of GxP quality standards could be beneficial to the research areas where the development and maintenance of a QMS is not required

Case One: ISO 9001 and ISO 17025 Accreditation

Entity: Institute of Science and Technology for Ceramics, an Italian public research center (1)

Results of the GxP Application: Improvements in the following areas: increased staff motivation and commitment, enhanced traceability of data, improved training documentation

Case Two: Implementation of a GLP-based QMS

Entity: Brazilian basic research laboratory (2)

Results of the GxP Application: Reported improvements in the following areas: management of personnel, facilities, raw data control, equipment, material and reagents, document control and record keeping

Case Three: Implementation of a QMS

Entity: French horticulture and seed research laboratory(3) Results of the GxP Application: Reported improvements in the following areas: management of personnel, facilities, raw data control, equipment, material and reagents, document control and record keeping

fostered in research environment allows improvement and optimisation of processes, and motivation among employees errors and waste of resources

The application of agile tools allows standards through fostering Culture unregulated areas of Life Sciences in reducing the risks related to the low

Authors

Andrea Berardi - Senior GxP Consultant & Auditor / CSV Consultant, seQure

Giorgia

References

(Sao Paulo), Oct-Dec 2012 pag 491497.

3. Molinéro-Demilly V. et al. (2018) “An overview of Quality Management System implementation in a research laboratory”, International Journal of Metrology and Quality Engineering, 9, 2.

The challenges of remote audits or telework of nonclinical studies in Japan

Noriaki Katanozaka (Sekisui Medical Co.Ltd), Akira Yamazaki (Kyowa Kirin Co., Ltd.), Yoshiaki Hiraishi (Terumo Corporation), Terukazu Kitahara (Instem)

Introduction

The Covid-19 pandemic has also had a significant impact on institutional activities, GLP qualification inspections by monitoring authority and sponsored on-site investigations into CROs in Japan. The impact is that some work has been replaced with telework at the facility, and regulators and sponsors have switched part of audit from on-site to remote. This time, we conducted a questionnaire survey on remote inspections within JSQA. Based on the results, we will consider the implementation status and issues of remote audit in Japan. We also consider remote approval of records and documents in telework and ensuring the reliability of external computerized systems such as the cloud computing.

Questionnaire analysis

Remote auditing has been already widely accepted under the Covid-19 pandemic. However, the scope of remote auditing is limited to document investigations. PMDA also conducts remote audits not only in GLP but also in other fields.

Advantage/Disadvantage/Problem

Perspective from Sponsors advantage disadvantage

No need to consider travel time to inspection location 4

Sharing documents prior to the audit will lead to efficient reviews during the audit period. 2

Participation from multiple locations 1

Even with video, there is a limit to the scope of what can be seen compared to an on-site audit. 2

There is a limit to the number of documents that can be reviewed on the audit day. 2

If the document is not presented smoothly, it may have a negative effect on the sponsor's impression. 1

Perspective from CRO advantage disadvantage

Audit programs can be easily arranged according to requests. 4 It is difficult to respond flexibly on the day of the audit 2

It is the same description as the second advantage from the sponsor's point of view described in the previous table. 2 It takes too long to prepare for the request. 2

It is possible that the time of preparing for the customer visits. 1

Limited amount of document can be viewed on the day of the audit. 1

In common opinion with the contractor and the CRO, there were many opinions that it was easy to adjust the inspection schedule because there is no need for the auditor to move to the location where the audit will be conducted.

As the second most common opinion, since document can be shared in advance, the time that was used for document review during the on-site audit can be allocated for question and answer sessions and discussions.

At many GLP facilities in Japan, raw data is paper-based data. In other words, the digitization of measurement data and experimental records has not progressed. Therefore, it takes a lot of time to scan them and create a PDF.

From a Data Integrity perspective, it is necessary to electronic raw data and introduce electronic signatures used to approve electronic data, depending on the risk.

By taking such measures, it is expected that the reliability of telework and remote work will be built.

There are still many challenges in migrating from raw paper data to raw electronic data, but a risk-based approach needs to be addressed to ensure the reliability of the data.

Usage of cloud computing in Japan

In Japan, suppliers are considering the use of cloud computing systems for GLP studies, but we believe that there are still risks in using them for GLP studies. The risks we consider include the following, but are not limited to;

• Communication with users, service suppliers, and data centers

• GLP education and training for staff working in service suppliers and data centers

• Electronic data archiving process

Conclusion

Onsite audits and remote audits have their advantages and disadvantages, respectively. It is expected that a risk-based audit style that combines the strengths of each other will be established in Japan as well.

Thus, remote auditing encourages us to digitize data and records, and to ensure the reliability of electronic data and records, which is also necessary from the perspective of data integrity. The operation of the computerized system that makes this possible is our challenge.

Document - based Conformity Audit

Type of inspection (11companies) by PMDA

Remote audit

Audit by monitoring authorities

Experience of remote audit SLA

Pharmaceuticals and Medical Device companies

CRO

Supplier audit and monitoring for test facilities

A Reflection of GCP Auditing During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

Introduction

Since the start of 2020, the Coronavirus-19 (COVID-19) pandemic has had a significant impact on clinical research and created many challenges in maintaining quality oversight for us as Quality Assurance (QA) within a Contract Research Organisation (CRO). We discuss the associated risks and the strategies we implemented to manage these over the past 18 months. Within the poster we also address the lessons learnt, how we incorporated these into an agile, risk-based auditing strategy and how we can adapt the aforementioned strategies developed for the current clinical trial landscape to complement the evolution of auditing of clinical trials.

Quality Oversight During the Pandemic

It was important to determine the impact of the COVID-19 pandemic on our auditing strategy, and which new processes for trial conduct implemented in response to the pandemic carried the most risk. The most impacted audit type was the investigator site audit; with travel restrictions that prevented auditor access and the unavailability of investigator site personnel to accommodate on-site audits. This audit type became rapidly more difficult to perform. Audits that typically utilise electronic systems, for example, database and electronic Trial Master File (eTMF) audits were least impacted. New processes, such as the implementation of remote monitoring strategies and decentralised procedures relating to trial subject visits for ongoing studies, and the fast set-up of new COVID-19 studies also carried potential risks that required quality oversight.

Adapted Investigator Site Audits

The first step in our approach was to develop the scope for remote Good Clinical Practice (GCP) investigator site audit. It was based on our routine on-site investigator site audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 as well as data privacy guidelines according to the region of the audit. Due to different access restrictions related to Electronic Health Records (EHR), review of documentation containing trial subjects’ identifiable information was excluded from the scope of the audit when necessary, e.g. in Europe. Our audit scope focused on electronic systems such as eTMF, Electronic Data Capture (EDC) and Interactive Response Technology (IRT) used within clinical trials which allowed us to continue to identify sites issues, meet the needs of our clients for oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal Investigator (PI) and site monitor via telephone or videoconference. This approach to auditing investigator sites also proved to be time-effective for site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed and conducted internally with feedback collated from auditors and auditees before being offered to clients as an alternative option for auditing when travel restrictions prevented on-site audits. The majority of on-site audits performed since the start of the COVID-19 pandemic have been performed by auditors within their country of residence due to the continuing restrictions on international travel. For investigator site audits that could be performed on-site, the pandemic required us to be flexible with our routine audit scope. This included reducing or omitting the conduct of a facility tour and performing site staff interviews and meetings remotely. In addition, a review of updated Informed Consent Forms (ICFs) and management of Investigational Medicinal Product (IMP) shipments to subjects’ homes was included, if applicable to the study. A COVID-19 document checklist was generated for both remote and on-site investigator site audits as additional clinical trial documents required review e.g., updated risk assessments and clinical trial storyboards tracking actions taken during the COVID-19 pandemic. Due to frequent updates to regulatory guidance the checklists were reviewed and updated regularly.

COVID-19 System Audits

Although system audits are a well-known audit type, ongoing clinical trials were impacted by the pandemic, and the frequently changing regulatory guidance for management of these trials required us to be more agile than usual. Consequently, we quickly developed a new COVID-19 impact system audit scope to add to our existing system audits types. The purpose of these audits was to assess the impact of the COVID-19 pandemic on the management and continued compliance of ongoing clinical trials. This included the review and assessment of newly implemented or revised trial processes in accordance with regulatory guidance for the applicable region.

Another consequence of the pandemic was the commencement of COVID-19 related clinical trials which required short timelines for their set up and initiation creating potential risk. Therefore, a COVID-19 study set-up and initiation system audit scope was developed to allow quality oversight of these initial processes for such trials. This audit scope included the review of submissions to Ethics Committees (ECs) and Regulatory Authorities (RAs), and the specific plans in place for the conduct of the studies and overall evaluation of compliance with applicable regulations.

Distribution of Audit Type

of on-site investigator audits Percentage of remote investigator site audits

Key Takeaway

Analysis of Audits

By reviewing the percentage distribution of audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had on our auditing requirements. While the total numbers of audits performed remained relatively consistent, in the above bar chart we can clearly see the dramatic decrease in performance of on-site investigator site audits from 100% in Quarter 1 (Jan-Mar) of 2020 to 25% in Quarter 2 (Apr-Jun) of 2020 when the COVID-19 pandemic had impacted travel around the world. For the remote investigator site audits performed, 69% of which were conducted on behalf of clients, auditors identified critical, major and minor findings which demonstrated that this audit scope added value to our audit programs and allowed continuing quality oversight. After 18 months of the pandemic, we have performed an average of 50% remote investigator site audits and expect this trend will continue into 2022.

Remote Quality Oversight Remote Investigator Site Audits System

Time and Cost-effective

Time and Cost-effective

Assess Processes Adapt Ongoing Regulatory Compliance

• System Audits enable assessment of clinical trial processes and can be easily adapted to contribute to the ongoing regulatory compliance

Audits

Remote Quality Oversight Remote Investigator Site Audits System Audits

Assess Processes Adapt Ongoing Regulatory Compliance

The Future of Auditing

Using the audit strategies implemented during the height of the COVID-19 pandemic and from what we know of the much-anticipated ICH E6 Revision 3 updates we are preparing for the future of auditing by incorporating these newly developed strategies into our risk-based auditing strategy.

Inaccessibility to areas of the world has always presented challenges to auditors, particularly during the pandemic. Travel limitations will likely continue for a multitude of reasons such as political unrest and health and safety risks. Improved electronic system access for clinical trials facilitates the performance of remote investigator site audits, which presents the possibility to virtually access and increase quality oversight in countries that were seldom selected for audit but are seeing an increase in clinical trial activity, along with reducing our travel related environmental footprint. We also cannot deny that, in comparison to on-site audits, remote audits can lessen the burden on the auditee by reducing audit hosting responsibilities.

Our newly developed COVID-19 system audit scopes were amended as required to accommodate the dynamic regulatory environment. While we do not anticipate having to adopt such measures in the future with the development of ICH E6 Revision 3, we understand there will be a need to remain agile in our approach to auditing. The change in ICH GCP guidelines, which aims to facilitate clinical trial innovation and responding to the needs of trial subjects, will require increased quality oversight during the adoption process and beyond. New system audit scopes could play a key role in assessing trial management and regulatory compliance. We also anticipate an increase in the use of innovative technology, adapted for the requirements of trial design and subject needs, and a decrease in on-site subject visits, with the adoption decentralised clinical trials. Artificial intelligence may bring new solutions for auditing in the future to analyse more data in a shorter time and further facilitate audit planning. A risked based approach will still be key for clinical trials, but technology will enable Critical-to-Quality factors to be determined that could be assessed and reviewed remotely as part of the audit process.  As clinical trial technology evolves our remote audit scopes can be improved and adapted to ensure continuing quality oversight on behalf of both CRO and clients while maintaining Parexel’s patient-centric approach.

• Remote investigator site audits present a method for maintaining quality oversight that is both time and cost-effective

Kathleen De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth Parexel International

relating trial subject visits ongoing studies, and the fast set-up new COVID-19 studies also carried potential risks that required Adapted Investigator Site Audits investigator site audit. was based our routine on-site investigator audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 well data privacy guidelines according region the audit. Due different access restrictions related to Electronic Health Records (EHR), review documentation containing trial subjects’ identifiable audit scope focused on electronic systems such eTMF, Electronic Data Capture (EDC) Interactive Response Technology (IRT) used within clinical trials which allowed continue identify sites issues, meet the needs our clients oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal investigator sites also proved time-effective site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed conducted internally with feedback collated from auditors and auditees before being offered clients alternative option for auditing when travel restrictions prevented on-site audits. performed auditors within their country residence due the continuing restrictions international travel. investigator site audits that could be performed on-site, pandemic required be flexible with our routine audit scope. This included reducing omitting the conduct facility tour and performing site staff interviews and meetings remotely. addition, review updated Informed Consent Forms (ICFs) and management Investigational Medicinal Product (IMP) shipments subjects’ homes was included, applicable study. COVID-19 document checklist generated both remote and on-site investigator site audits additional clinical trial documents required review updated assessments and clinical trial storyboards tracking actions taken during reviewed and updated regularly.

COVID-19 System Audits Although system audits well-known

Kathleen De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth

During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

Analysis of Audits reviewing percentage distribution audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had our auditing requirements. While the total numbers audits performed remained relatively consistent, the above bar chart we can clearly see the dramatic decrease performance on-site investigator site audits from 100% Quarter (Jan-Mar) 2020 25% Quarter (Apr-Jun) 2020 when the COVID-19 pandemic impacted travel around the world. remote investigator site audits performed, 69% of which were conducted behalf clients, auditors identified critical, major and minor findings which demonstrated this audit scope added value our audit programs and allowed continuing quality oversight. After months Presented Research Quality Association (RQA) 2021 International Conference

Key Takeaway

Key Takeaway

Takeaway

Key Takeaway

• Remote investigator site audits present a method for maintaining quality oversight that is both time and cost-effective

Introduction Quality Oversight Analysis of Audits

Future of Auditing

type, ongoing clinical trials were impacted by regulatory guidance for management of these Consequently, we quickly developed a new our existing system audits types. The purpose COVID-19 pandemic on the management trials. This included the review and assessment in accordance with regulatory guidance for the commencement of COVID-19 related clinical set up and initiation creating potential risk. initiation system audit scope was developed to for such trials. This audit scope included the (ECs) and Regulatory Authorities (RAs), and the studies and overall evaluation of compliance with of Audit Type

Percentage of remote investigator site audits

Kathleen De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth

Parexel International

Presented at Research Quality Association (RQA) 2021 International QA Conference

Remote Quality Oversight Remote Investigator Site Audits

Time and Cost-effective

• System Audits enable assessment of clinical trial processes and can be easily adapted to contribute to the ongoing regulatory compliance

System Audits

Time and Cost-effective Remote Quality Oversight Remote Investigator Site Audits System Audits

Assess Processes Adapt Ongoing Regulatory Compliance

Assess Processes Adapt Ongoing Regulatory Compliance

The Future of Auditing

Using the audit strategies implemented during the height of the COVID-19 pandemic and from what we know of the much-anticipated ICH E6 Revision 3 updates we are preparing for the future of auditing by incorporating these newly developed strategies into our risk-based auditing strategy.

Inaccessibility to areas of the world has always presented challenges to auditors, particularly during the pandemic.

Parexel International

relating trial subject visits ongoing studies, and the fast set-up new COVID-19 studies also carried potential risks that required Adapted Investigator Site Audits investigator site audit. was based our routine on-site investigator audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 well data privacy guidelines according region the audit. Due different access restrictions related to Electronic Health Records (EHR), review documentation containing trial subjects’ identifiable audit scope focused on electronic systems such eTMF, Electronic Data Capture (EDC) Interactive Response Technology (IRT) used within clinical trials which allowed continue identify sites issues, meet the needs our clients oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal investigator sites also proved time-effective site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed conducted internally with feedback collated from auditors and auditees before being offered clients alternative option for auditing when travel restrictions prevented on-site audits. performed auditors within their country residence due the continuing restrictions international travel. investigator site audits that could be performed on-site, pandemic required be flexible with our routine audit scope. This included reducing omitting the conduct facility tour and performing site staff interviews and meetings remotely. addition, review updated Informed Consent Forms (ICFs) and management Investigational Medicinal Product (IMP) shipments subjects’ homes was included, applicable study. COVID-19 document checklist generated both remote and on-site investigator site audits additional clinical trial documents required review updated assessments and clinical trial storyboards tracking actions taken during reviewed and updated regularly.

COVID-19 System Audits Although system audits well-known

Analysis of Audits reviewing percentage distribution audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had our auditing requirements. While the total numbers audits performed remained relatively consistent, the above bar chart we can clearly see the dramatic decrease performance on-site investigator site audits from 100% Quarter (Jan-Mar) 2020 25% Quarter (Apr-Jun) 2020 when the COVID-19 pandemic impacted travel around the world. remote investigator site audits performed, 69% of which were conducted behalf clients, auditors identified critical, major and minor findings which demonstrated this audit scope added value our audit programs and allowed continuing quality oversight. After months Presented Research Quality Association (RQA) 2021 International Conference

A Reflection of GCP Auditing During the Coronavirus-19 and the Impact on Future Audit Strategies

Auditing During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

A Reflection of

Introduction

Introduction

COVID-19 System Audits

Key Takeaway Future of Auditing

Introduction

Introduction Quality Oversight Analysis of Audits

Since the start of 2020, the Coronavirus-19 (COVID-19) pandemic has had a significant impact on clinical research and created many challenges in maintaining quality oversight for us as Quality Assurance (QA) within a Contract Research Organisation (CRO). We discuss the associated risks and the strategies we implemented to manage these over the past 18 months. Within the poster we also address the lessons learnt, how we incorporated these into an agile, risk-based auditing strategy and how we can adapt the aforementioned strategies developed for the current clinical trial landscape to complement the evolution of auditing of clinical trials.

Quality Oversight During the Pandemic

It was important to determine the impact of the COVID-19 pandemic on our auditing strategy, and which new processes for trial conduct implemented in response to the pandemic carried the most risk. The most impacted audit type was the investigator site audit; with travel restrictions that prevented auditor access and the unavailability of investigator site personnel to accommodate on-site audits. This audit type became rapidly more difficult to perform. Audits that typically utilise electronic systems, for example, database and electronic Trial Master File (eTMF) audits were least impacted. New processes, such as the implementation of remote monitoring strategies and decentralised procedures relating to trial subject visits for ongoing studies, and the fast set-up of new COVID-19 studies also carried potential risks that required quality oversight.

Kathleen

Parexel International

Presented at Research Quality Association (RQA) 2021 International QA Conference

Adapted Investigator Site Audits

The first step in our approach was to develop the scope for remote Good Clinical Practice (GCP) investigator site audit. It was based on our routine on-site investigator site audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 as well as data privacy guidelines according to the region of the audit. Due to different access restrictions related to Electronic Health Records (EHR), review of documentation containing trial subjects’ identifiable information was excluded from the scope of the audit when necessary, e.g. in Europe. Our audit scope focused on electronic systems such as eTMF, Electronic Data Capture (EDC) and Interactive Response Technology (IRT) used within clinical trials which allowed us to continue to identify sites issues, meet the needs of our clients for oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal

Although system audits are a well-known audit type, ongoing the pandemic, and the frequently changing regulatory trials required us to be more agile than usual. Consequently, COVID-19 impact system audit scope to add to our existing of these audits was to assess the impact of the COVID-19 and continued compliance of ongoing clinical trials. This of newly implemented or revised trial processes in accordance applicable region.

Another consequence of the pandemic was the commencement trials which required short timelines for their set up and Therefore, a COVID-19 study set-up and initiation system allow quality oversight of these initial processes for such review of submissions to Ethics Committees (ECs) and specific plans in place for the conduct of the studies and applicable regulations.

Distribution of Audit

Percentage of Distribution

Percentage of on-site investigator audits 100% 100% 75%

De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth

relating trial subject visits ongoing studies, and the fast set-up new COVID-19 studies also carried potential risks that required Adapted Investigator Site Audits investigator site audit. was based our routine on-site investigator audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 well data privacy guidelines according region the audit. Due different access restrictions related to Electronic Health Records (EHR), review documentation containing trial subjects’ identifiable audit scope focused on electronic systems such eTMF, Electronic Data Capture (EDC) Interactive Response Technology (IRT) used within clinical trials which allowed continue identify sites issues, meet the needs our clients oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal investigator sites also proved time-effective site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed conducted internally with feedback collated from auditors and auditees before being offered clients alternative option for auditing when travel restrictions prevented on-site audits. performed auditors within their country residence due the continuing restrictions international travel. investigator site audits that could be performed on-site, pandemic required be flexible with our routine audit scope. This included reducing omitting the conduct facility tour and performing site staff interviews and meetings remotely. addition, review updated Informed Consent Forms (ICFs) and management Investigational Medicinal Product (IMP) shipments subjects’ homes was included, applicable study. COVID-19 document checklist generated both remote and on-site investigator site audits additional clinical trial documents required review updated assessments and clinical trial storyboards tracking actions taken during reviewed and updated regularly.

Analysis of Audits reviewing percentage distribution audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had our auditing requirements. While the total numbers audits performed remained relatively consistent, the above bar chart we can clearly see the dramatic decrease performance on-site investigator site audits from 100% Quarter (Jan-Mar) 2020 25% Quarter (Apr-Jun) 2020 when the COVID-19 pandemic impacted travel around the world. remote investigator site audits performed, 69% of which were conducted behalf clients, auditors identified critical, major and minor findings which demonstrated this audit scope added value our audit programs and allowed continuing quality oversight. After months Presented Research Quality Association (RQA) 2021 International Conference

Key Takeaway

Since the start of 2020, the Coronavirus-19 (COVID-19) pandemic has had a significant impact on clinical research and created many challenges in maintaining quality oversight for us as Quality Assurance (QA) within a Contract Research Organisation (CRO). We discuss the associated risks and the strategies we implemented to manage these over the past 18 months.

During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

A Reflection of

Within the poster we also address the lessons learnt, how we incorporated these into an agile, risk-based auditing strategy and how we can adapt the aforementioned strategies developed for the current clinical trial landscape to complement the evolution of auditing of clinical trials.

Quality Oversight During the Pandemic

the pandemic, and the frequently changing regulatory trials required us to be more agile than usual. Consequently, COVID-19 impact system audit scope to add to our of these audits was to assess the impact of the COVID-19 and continued compliance of ongoing clinical trials. of newly implemented or revised trial processes in applicable region.

1/4

Quality Oversight During the Pandemic

Introduction Quality Oversight Analysis of Audits

Quality Oversight

It was important to determine the impact of the COVID-19 pandemic on our auditing strategy, and which new processes for trial conduct implemented in response to the pandemic carried the most risk. The most impacted audit type was the investigator site audit; with travel restrictions that prevented auditor access and the unavailability of investigator site personnel to accommodate on-site audits. This audit type became rapidly more difficult to perform. Audits that typically utilise electronic systems, for example, database and electronic Trial Master File (eTMF) audits were least impacted. New processes, such as the implementation of remote monitoring strategies and decentralised procedures relating to trial subject visits for ongoing studies, and the fast set-up of new COVID-19 studies also carried potential risks that required quality oversight.

Future of Auditing

Kathleen

Parexel International

Presented at Research Quality Association (RQA) 2021 International QA Conference

Adapted Investigator Site Audits

The first step in our approach was to develop the scope for remote Good Clinical Practice (GCP) investigator site audit. It was based on our routine on-site investigator site audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 as well as data privacy guidelines according to the region of the audit. Due to different access restrictions related to Electronic Health Records (EHR), review of documentation containing trial subjects’ identifiable information was excluded from the scope of the audit when necessary, e.g. in Europe. Our audit scope focused on electronic systems such as eTMF, Electronic Data Capture (EDC) and Interactive Response Technology (IRT) used within clinical trials which allowed us to continue to identify sites issues, meet the needs of our clients for oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal Investigator (PI) and site monitor via telephone or videoconference. This approach to auditing investigator sites also proved to be time-effective for site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed and conducted internally with feedback collated from auditors and auditees before being offered to clients as an alternative option for auditing when travel restrictions prevented on-site audits.

The majority of on-site audits performed since the start of the COVID-19 pandemic have been performed by auditors within their country of residence due to the continuing restrictions on international travel. For investigator site audits that could be performed on-site, the pandemic required us to be flexible with our routine audit scope. This included reducing

Another consequence of the pandemic was the commencement trials which required short timelines for their set Therefore, a COVID-19 study set-up and initiation allow quality oversight of these initial processes for review of submissions to Ethics Committees (ECs) specific plans in place for the conduct of the studies applicable regulations.

Distribution of

Percentage of on-site investigator audits 100% 100%

Analysis of Audits

By reviewing the percentage distribution of audits investigator site audits we can assess the impact requirements. While the total numbers of audits

De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth

relating trial subject visits ongoing studies, and the fast set-up new COVID-19 studies also carried potential risks that required Adapted Investigator Site Audits investigator site audit. was based our routine on-site investigator audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 well data privacy guidelines according region the audit. Due different access restrictions related to Electronic Health Records (EHR), review documentation containing trial subjects’ identifiable audit scope focused on electronic systems such eTMF, Electronic Data Capture (EDC) Interactive Response Technology (IRT) used within clinical trials which allowed continue identify sites issues, meet the needs our clients oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal investigator sites also proved time-effective site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed conducted internally with feedback collated from auditors and auditees before being offered clients alternative option for auditing when travel restrictions prevented on-site audits. performed auditors within their country residence due the continuing restrictions international travel. investigator site audits that could be performed on-site, pandemic required be flexible with our routine audit scope. This included reducing omitting the conduct facility tour and performing site staff interviews and meetings remotely. addition, review updated Informed Consent Forms (ICFs) and management Investigational Medicinal Product (IMP) shipments subjects’ homes was included, applicable study. COVID-19 document checklist generated both remote and on-site investigator site audits additional clinical trial documents required review updated assessments and clinical trial storyboards tracking actions taken during reviewed and updated regularly.

Analysis of Audits reviewing percentage distribution audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had our auditing requirements. While the total numbers audits performed remained relatively consistent, the above bar chart we can clearly see the dramatic decrease performance on-site investigator site audits from 100% Quarter (Jan-Mar) 2020 25% Quarter (Apr-Jun) 2020 when the COVID-19 pandemic impacted travel around the world. remote investigator site audits performed, 69% of which were conducted behalf clients, auditors identified critical, major and minor findings which demonstrated this audit scope added value our audit programs and allowed continuing quality oversight. After months Presented Research Quality Association (RQA) 2021 International Conference

Key Takeaway

Introduction Quality Oversight Analysis of Audits

Quality Oversight

Future of Auditing

Kathleen De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth Parexel International

Presented at Research Quality Association (RQA) 2021 International QA Conference

A Reflection

review of submissions to Ethics Committees (ECs) specific plans in place for the conduct of the studies applicable regulations.

During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

Distribution of

Quality Oversight During the Pandemic 2/4

It was important to determine the impact of the COVID-19 pandemic on our auditing strategy, and which new processes for trial conduct implemented in response to the pandemic carried the most risk. The most impacted audit type was the investigator site audit; with travel restrictions that prevented auditor access and the unavailability of investigator site personnel to accommodate on-site audits. This audit type became rapidly more difficult to perform. Audits that typically utilise electronic systems, for example, database and electronic Trial Master File (eTMF) audits were least impacted. New processes, such as the implementation of remote monitoring strategies and decentralised procedures relating to trial subject visits for ongoing studies, and the fast set-up of new COVID-19 studies also carried potential risks that required quality oversight.

Adapted Investigator Site Audits

The first step in our approach was to develop the scope for remote Good Clinical Practice (GCP) investigator site audit. It was based on our routine on-site investigator site audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 as well as data privacy guidelines according to the region of the audit. Due to different access restrictions related to Electronic Health Records (EHR), review of documentation containing trial subjects’ identifiable information was excluded from the scope of the audit when necessary, e.g. in Europe. Our audit scope focused on electronic systems such as eTMF, Electronic Data Capture (EDC) and Interactive Response Technology (IRT) used within clinical trials which allowed us to continue to identify sites issues, meet the needs of our clients for oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal Investigator (PI) and site monitor via telephone or videoconference. This approach to auditing investigator sites also proved to be time-effective for site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed and conducted internally with feedback collated from auditors and auditees before being offered to clients as an alternative option for auditing when travel restrictions prevented on-site audits.

The majority of on-site audits performed since the start of the COVID-19 pandemic have been performed by auditors within their country of residence due to the continuing restrictions on international travel. For investigator site audits that could be performed on-site, the pandemic required us to be flexible with our routine audit scope. This included reducing or omitting the conduct of a facility tour and performing site staff interviews and meetings remotely. In addition, a review of updated Informed Consent Forms (ICFs) and management of Investigational Medicinal Product (IMP) shipments to subjects’ homes was included, if applicable to the study. A COVID-19 document checklist was generated for both remote and on-site investigator site audits as additional clinical trial documents required review e.g., updated risk assessments and clinical trial storyboards tracking actions taken during the COVID-19 pandemic. Due to frequent updates to regulatory guidance the checklists were reviewed and updated regularly.

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Percentage of on-site investigator audits

Percentage of Distribution

Analysis of Audits

By reviewing the percentage distribution of audits investigator site audits we can assess the impact requirements. While the total numbers of audits in the above bar chart we can clearly see the dramatic investigator site audits from 100% in Quarter 1 (Jan-Mar) of 2020 when the COVID-19 pandemic had impacted investigator site audits performed, 69% of which identified critical, major and minor findings which value to our audit programs and allowed continuing pandemic, we have performed an average of 50% this trend will continue into 2022.

of GCP Auditing During the Coronavirus-19 Pandemic

relating trial subject visits ongoing studies, and the fast set-up new COVID-19 studies also carried potential risks that required Adapted Investigator Site Audits investigator site audit. was based our routine on-site investigator audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 well data privacy guidelines according region the audit. Due different access restrictions related to Electronic Health Records (EHR), review documentation containing trial subjects’ identifiable audit scope focused on electronic systems such eTMF, Electronic Data Capture (EDC) Interactive Response Technology (IRT) used within clinical trials which allowed continue identify sites issues, meet the needs our clients oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal investigator sites also proved time-effective site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed conducted internally with feedback collated from auditors and auditees before being offered clients alternative option for auditing when travel restrictions prevented on-site audits. performed auditors within their country residence due the continuing restrictions international travel. investigator site audits that could be performed on-site, pandemic required be flexible with our routine audit scope. This included reducing omitting the conduct facility tour and performing site staff interviews and meetings remotely. addition, review updated Informed Consent Forms (ICFs) and management Investigational Medicinal Product (IMP) shipments subjects’ homes was included, applicable study. COVID-19 document checklist generated both remote and on-site investigator site audits additional clinical trial documents required review updated assessments and clinical trial storyboards tracking actions taken during reviewed and updated regularly.

A Reflection of

Impact on Future Audit Strategies

Analysis of Audits reviewing percentage distribution audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had our auditing requirements. While the total numbers audits performed remained relatively consistent, the above bar chart we can clearly see the dramatic decrease performance on-site investigator site audits from 100% Quarter (Jan-Mar) 2020 25% Quarter (Apr-Jun) 2020 when the COVID-19 pandemic impacted travel around the world. remote investigator site audits performed, 69% of which were conducted behalf clients, auditors identified critical, major and minor findings which demonstrated this audit scope added value our audit programs and allowed continuing quality oversight. After months Presented Research Quality Association (RQA) 2021 International Conference

Key Takeaway

During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

Quality Oversight During the Pandemic 3/4

COVID-19 System Audits

Key Takeaway

• Remote investigator site audits oversight that is both time and (COVID-19) pandemic has had a significant challenges in maintaining quality oversight for Contract Research Organisation (CRO). We discuss the implemented to manage these over the past 18 months. learnt, how we incorporated these into an agile, adapt the aforementioned strategies developed for complement the evolution of auditing of clinical trials.

Introduction Quality Oversight Analysis of Audits

Quality Oversight

Although system audits are a well-known audit type, ongoing clinical trials were impacted by the pandemic, and the frequently changing regulatory guidance for management of these trials required us to be more agile than usual. Consequently, we quickly developed a new COVID-19 impact system audit scope to add to our existing system audits types. The purpose of these audits was to assess the impact of the COVID-19 pandemic on the management and continued compliance of ongoing clinical trials. This included the review and assessment of newly implemented or revised trial processes in accordance with regulatory guidance for the applicable region.

Oversight During the Pandemic

Future of Auditing

the COVID-19 pandemic on our auditing conduct implemented in response to the pandemic type was the investigator site audit; with travel the unavailability of investigator site personnel to became rapidly more difficult to perform. Audits example, database and electronic Trial Master File processes, such as the implementation of remote procedures relating to trial subject visits for ongoing studies also carried potential risks that required Audits

Another consequence of the pandemic was the commencement of COVID-19 related clinical trials which required short timelines for their set up and initiation creating potential risk. Therefore, a COVID-19 study set-up and initiation system audit scope was developed to allow quality oversight of these initial processes for such trials. This audit scope included the review of submissions to Ethics Committees (ECs) and Regulatory Authorities (RAs), and the specific plans in place for the conduct of the studies and overall evaluation of compliance with applicable regulations.

Distribution of Audit Type

Kathleen De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth

Parexel International

Remote Remote Investigator Site Audits

Percentage of on-site investigator audits

Presented at Research Quality Association (RQA) 2021 International QA Conference

the scope for remote Good Clinical Practice (GCP) routine on-site investigator site audit scope, relevant audits during COVID-19 as well as data privacy audit. Due to different access restrictions related to documentation containing trial subjects’ identifiable the audit when necessary, e.g. in Europe. Our such as eTMF, Electronic Data Capture (EDC) and

Percentage of Distribution

Percentage of remote investigator site audits 100% 100% 75% 67% 35% 56%

22% 65% 44%

78%

• System Audits enable assessment easily adapted to contribute

System Audits

Assess

Assess

Remote Remote Investigator Site Audits System Audits

The Future of Auditing

Using the audit strategies implemented during the the much-anticipated ICH E6 Revision 3 updates newly developed strategies into our risk-based auditing

for evolution of auditing of clinical trials.

During the Pandemic

relating trial subject visits ongoing studies, and the fast set-up new COVID-19 studies also carried potential risks that required Adapted Investigator Site Audits investigator site audit. was based our routine on-site investigator audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 well data privacy guidelines according region the audit. Due different access restrictions related to Electronic Health Records (EHR), review documentation containing trial subjects’ identifiable audit scope focused on electronic systems such eTMF, Electronic Data Capture (EDC) Interactive Response Technology (IRT) used within clinical trials which allowed continue identify sites issues, meet the needs our clients oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal investigator sites also proved time-effective site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed conducted internally with feedback collated from auditors and auditees before being offered clients alternative option for auditing when travel restrictions prevented on-site audits. performed auditors within their country residence due the continuing restrictions international travel. investigator site audits that could be performed on-site, pandemic required be flexible with our routine audit scope. This included reducing omitting the conduct facility tour and performing site staff interviews and meetings remotely. addition, review updated Informed Consent Forms (ICFs) and management Investigational Medicinal Product (IMP) shipments subjects’ homes was included, applicable study. COVID-19 document checklist generated both remote and on-site investigator site audits additional clinical trial documents required review updated assessments and clinical trial storyboards tracking actions taken during reviewed and updated regularly.

of newly implemented or revised trial processes in accordance with regulatory guidance for the applicable region.

During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

Analysis of Audits reviewing percentage distribution audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had our auditing requirements. While the total

Key Takeaway

COVID-19 pandemic on our auditing implemented in response to the pandemic was the investigator site audit; with travel unavailability of investigator site personnel to rapidly more difficult to perform. Audits database and electronic Trial Master File such as the implementation of remote relating to trial subject visits for ongoing also carried potential risks that required

Introduction Quality Oversight Analysis of Audits

Quality Oversight

Another consequence of the pandemic was the commencement of COVID-19 related clinical trials which required short timelines for their set up and initiation creating potential risk. Therefore, a COVID-19 study set-up and initiation system audit scope was developed to allow quality oversight of these initial processes for such trials. This audit scope included the review of submissions to Ethics Committees (ECs) and Regulatory Authorities (RAs), and the specific plans in place for the conduct of the studies and overall evaluation of compliance with applicable regulations.

Site Audits

Quality Oversight During the Pandemic 4/4

Distribution of Audit Type

Future of Auditing

Kathleen De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth

scope for remote Good Clinical Practice (GCP) on-site investigator site audit scope, relevant during COVID-19 as well as data privacy different access restrictions related to documentation containing trial subjects’ identifiable when necessary, e.g. in Europe. Our eTMF, Electronic Data Capture (EDC) and clinical trials which allowed us to continue to oversight, accommodate investigator site Interviews were conducted with the Principal videoconference. This approach to auditing site staff and cost-effective for both the This audit scope was developed and auditors and auditees before being offered to restrictions prevented on-site audits.

Presented at Research Quality Association (RQA) 2021 International QA Conference

start of the COVID-19 pandemic have been residence due to the continuing restrictions that could be performed on-site, the audit scope. This included reducing performing site staff interviews and meetings

Analysis of Audits

By reviewing the percentage distribution of audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had on our auditing requirements. While the total numbers of audits performed remained relatively consistent, in the above bar chart we can clearly see the dramatic decrease in performance of on-site

• System Audits enable easily adapted to contribute

System Audits

Remote Investigator Site Audits System Audits

Assess

Assess The Future

Using the audit strategies implemented the much-anticipated ICH E6 Revision newly developed strategies into our Inaccessibility to areas of the world Travel limitations will likely continue Improved electronic system access which presents the possibility to virtually for audit but are seeing an increase We also cannot deny that, in comparison to reducing audit hosting responsibilities.

Our newly developed COVID-19 system regulatory environment. While we of ICH E6 Revision 3, we understand in ICH GCP guidelines, which aims will require increased quality oversight play a key role in assessing trial management

Parexel International

Percentage 25% 33%

relating trial subject visits ongoing studies, and the fast set-up new COVID-19 studies also carried potential risks that required Adapted Investigator Site Audits investigator site audit. was based our routine on-site investigator audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 well data privacy guidelines according region the audit. Due different access restrictions related to Electronic Health Records (EHR), review documentation containing trial subjects’ identifiable audit scope focused on electronic systems such eTMF, Electronic Data Capture (EDC) Interactive Response Technology (IRT) used within clinical trials which allowed continue identify sites issues, meet the needs our clients oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal investigator sites also proved time-effective site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed conducted internally with feedback collated from auditors and auditees before being offered clients alternative option for auditing when travel restrictions prevented on-site audits. performed auditors within their country residence due the continuing restrictions international travel. investigator site audits that could be performed on-site, pandemic required be flexible with our routine audit scope. This included reducing omitting the conduct facility tour and performing site staff interviews and meetings remotely. addition, review updated Informed Consent Forms (ICFs) and management Investigational Medicinal Product (IMP) shipments subjects’ homes was included, applicable study. COVID-19 document checklist generated both remote and on-site investigator site audits additional clinical trial documents required review updated assessments and clinical trial storyboards tracking actions taken during reviewed and updated regularly.

44%

newly developed strategies into our risk-based auditing

Analysis of Audits reviewing percentage distribution audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had our auditing requirements. While the total numbers audits performed remained relatively consistent, the above bar chart we can clearly see the dramatic decrease performance on-site investigator site audits from 100% Quarter (Jan-Mar) 2020 25% Quarter (Apr-Jun) 2020 when the COVID-19 pandemic impacted travel around the world. remote investigator site audits performed, 69% of which were conducted behalf clients, auditors identified critical, major and minor findings which demonstrated this audit scope added value our audit programs and allowed continuing quality oversight. After months Presented Research Quality Association (RQA) 2021 International Conference

Key Takeaway

such as eTMF, Electronic Data Capture (EDC) and within clinical trials which allowed us to continue to clients for oversight, accommodate investigator site safety. Interviews were conducted with the Principal telephone or videoconference. This approach to auditing time-effective for site staff and cost-effective for both the oversight. This audit scope was developed and from auditors and auditees before being offered to when travel restrictions prevented on-site audits. the start of the COVID-19 pandemic have been residence due to the continuing restrictions audits that could be performed on-site, the routine audit scope. This included reducing performing site staff interviews and meetings Informed Consent Forms (ICFs) and management shipments to subjects’ homes was included, if document checklist was generated for both remote additional clinical trial documents required review storyboards tracking actions taken during the updates to regulatory guidance the checklists were

Analysis of Audits

Introduction Quality Oversight Analysis of Audits

Future of Auditing

Kathleen De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth

Parexel International

Presented at Research Quality Association (RQA) 2021 International QA Conference

A Reflection of

During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

Q4 2019 Q1 Q2 Q3 2020 Q4 Q1 Q2 2021

Analysis of Audits

Analysis of Audits

By reviewing the percentage distribution of audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had on our auditing requirements. While the total numbers of audits performed remained relatively consistent, in the above bar chart we can clearly see the dramatic decrease in performance of on-site investigator site audits from 100% in Quarter 1 (Jan-Mar) of 2020 to 25% in Quarter 2 (Apr-Jun) of 2020 when the COVID-19 pandemic had impacted travel around the world. For the remote investigator site audits performed, 69% of which were conducted on behalf of clients, auditors identified critical, major and minor findings which demonstrated that this audit scope added value to our audit programs and allowed continuing quality oversight. After 18 months of the pandemic, we have performed an average of 50% remote investigator site audits and expect this trend will continue into 2022.

Inaccessibility to areas of the world has always presented Travel limitations will likely continue for a multitude Improved electronic system access for clinical trials which presents the possibility to virtually access and for audit but are seeing an increase in clinical trial We also cannot deny that, in comparison to on-site reducing audit hosting responsibilities.

Our newly developed COVID-19 system audit scopes regulatory environment. While we do not anticipate of ICH E6 Revision 3, we understand there will be in ICH GCP guidelines, which aims to facilitate clinical will require increased quality oversight during the play a key role in assessing trial management and of innovative technology, adapted for the requirements on-site subject visits, with the adoption decentralised for auditing in the future to analyse more data in based approach will still be key for clinical trials, but that could be assessed and reviewed remotely as remote audit scopes can be improved and adapted clients while maintaining Parexel’s patient-centric

Presented at Research Quality Association (RQA) 2021 International QA Conference

Audit Type

COVID-19 System Audits Although system audits well-known

Audits System

A Reflection

Assess Processes Adapt Regulatory Compliance

relating trial subject visits ongoing studies, and the fast set-up new COVID-19 studies also carried potential risks that required Adapted Investigator Site Audits investigator site audit. was based our routine on-site investigator audit scope, relevant regulatory guidance for conducting trials and audits during COVID-19 well data privacy guidelines according region the audit. Due different access restrictions related to Electronic Health Records (EHR), review documentation containing trial subjects’ identifiable audit scope focused on electronic systems such eTMF, Electronic Data Capture (EDC) Interactive Response Technology (IRT) used within clinical trials which allowed continue identify sites issues, meet the needs our clients oversight, accommodate investigator site staff availability, and maintain trial subject safety. Interviews were conducted with the Principal investigator sites also proved time-effective site staff and cost-effective for both the CRO and clients while still providing quality oversight. This audit scope was developed conducted internally with feedback collated from auditors and auditees before being offered clients alternative option for auditing when travel restrictions prevented on-site audits. performed auditors within their country residence due the continuing restrictions international travel. investigator site audits that could be performed on-site, pandemic required be flexible with our routine audit scope. This included reducing omitting the conduct facility tour and performing site staff interviews and meetings remotely. addition, review updated Informed Consent Forms (ICFs) and management Investigational Medicinal Product (IMP) shipments subjects’ homes was included, applicable study. COVID-19 document checklist generated both remote and on-site investigator site audits additional clinical trial documents required review updated assessments and clinical trial storyboards tracking actions taken during reviewed and updated regularly.

During the Coronavirus-19 Pandemic and the Impact on Future Audit Strategies

Analysis of Audits reviewing percentage distribution audits types performed across on-site and remote investigator site audits we can assess the impact the COVID-19 pandemic had our auditing requirements. While the total numbers audits performed remained relatively consistent, the above bar chart we can clearly see the dramatic decrease performance on-site investigator site audits from 100% Quarter (Jan-Mar) 2020 25% Quarter (Apr-Jun) 2020 when the COVID-19 pandemic impacted travel around the world. remote investigator site audits performed, 69% of which were conducted behalf clients, auditors identified critical, major and minor findings which demonstrated this audit scope added value our audit programs and allowed continuing quality oversight. After months Presented Research Quality Association (RQA) 2021 International Conference

Key Takeaway

Audits

22% 33% 65% 44%

The Future of Auditing

78%

Using the audit strategies implemented during the height of the COVID-19 pandemic and from what we know of the much-anticipated ICH E6 Revision 3 updates we are preparing for the future of auditing by incorporating these newly developed strategies into our risk-based auditing strategy.

Introduction Quality Oversight Analysis of Audits

Q3 2020 Q4 Q1 Q2 2021

Inaccessibility to areas of the world has always presented challenges to auditors, particularly during the pandemic. Travel limitations will likely continue for a multitude of reasons such as political unrest and health and safety risks. Improved electronic system access for clinical trials facilitates the performance of remote investigator site audits, which presents the possibility to virtually access and increase quality oversight in countries that were seldom selected for audit but are seeing an increase in clinical trial activity, along with reducing our travel related environmental footprint. We also cannot deny that, in comparison to on-site audits, remote audits can lessen the burden on the auditee by reducing audit hosting responsibilities.

Future of Auditing

Future Auditing

Kathleen De-Lacy Adams, Debbie Gardner, Karolina Grzesik-Goedhart, Marta Michas, Lisa Murchie, Mapaseka Oliphant and Sara Dodsworth

Parexel International

Presented at Research Quality Association (RQA) 2021 International QA Conference

Our newly developed COVID-19 system audit scopes were amended as required to accommodate the dynamic regulatory environment. While we do not anticipate having to adopt such measures in the future with the development of ICH E6 Revision 3, we understand there will be a need to remain agile in our approach to auditing. The change in ICH GCP guidelines, which aims to facilitate clinical trial innovation and responding to the needs of trial subjects, will require increased quality oversight during the adoption process and beyond. New system audit scopes could play a key role in assessing trial management and regulatory compliance. We also anticipate an increase in the use of innovative technology, adapted for the requirements of trial design and subject needs, and a decrease in on-site subject visits, with the adoption decentralised clinical trials. Artificial intelligence may bring new solutions for auditing in the future to analyse more data in a shorter time and further facilitate audit planning. A risked based approach will still be key for clinical trials, but technology will enable Critical-to-Quality factors to be determined that could be assessed and reviewed remotely as part of the audit process.  As clinical trial technology evolves our remote audit scopes can be improved and adapted to ensure continuing quality oversight on behalf of both CRO and clients while maintaining Parexel’s patient-centric approach.