In clinical trials, time is both an ally and an adversary. Efficient site initiation can make or break the success of a trial. Centralized processes are essential in expediting these timelines, bringing together standardized workflows, advanced technology, and meticulous quality assurance.

There are many benefits of a centralized CTMS business operations team, which acts as a hub for resources, updates, and information related to clinical trial management. An intuitive intake form, data accuracy, custom reporting, and streamlined decision-making processes can collectively help reduce bottlenecks and enhance overall efficiency in clinical trial initiation.

Intuitive Intake Form: Developing Clinical Trial Submissions

The foundation of successful centralization lies in the implementation of an intuitive study intake form. This form empowers stakeholders to easily submit their clinical trials, optimizing the utilization of their CTMS. Here’s how this streamlined process enhances efficiency and collaboration:

  1. Simplicity at its best: The intuitive intake form is designed to be user-friendly. There should be clear instructions and a straightforward layout to encourage active participation and guide stakeholders seamlessly through the submission process.
  2. Unified data repository: The intake form consolidates all essential trial details, eliminating fragmented communication and preventing information gaps.
  3. Catalyzing collaboration: Standardized data collection fosters seamless collaboration. With consistent and accessible information, stakeholders communicate more effectively. This can support better synergy in decision-making processes and insight into their clinical trial portfolio.
  4. Accelerated review and approval: An optimized intake form expedites the review and approval process, contributing to quicker site initiation and trial commencement.

Harnessing the Power of Centralized Processes

Centralization lies at the core of an efficient process. This enables streamlined operations, enhances collaboration, and enables stakeholders to access vital information from a single source.

By developing standardized workflows, establishing clear working instructions, and leveraging advanced technology, clinical trial management can achieve new levels of efficiency.

A Complete Approach: The Clinical Trials Management Hub

A centralized CTMS business operations team that unites all aspects of clinical trial management is important. The clinical trials management hub creates a CTMS business operations website, providing stakeholders with a comprehensive repository of resources, updates, and essential process and timeline information.

This hub approach not only fosters cohesion but also simplifies the management of multiple trials, reducing complexity and promoting effective collaboration.

Precision and Quality Assurance in Data Management

A crucial benefit of centralization is maintaining data accuracy. To ensure information housed in the CTMS is accurate, sites should develop and implement quality assurance processes.

This meticulous approach guarantees that decisions are based on reliable data, enhancing the overall integrity of the trials. An important piece of good data is persistent documentation. This includes helping with documentation and developing training both on the new processes and the application.

Empowering Decision-making through Custom Reporting

Centralization not only simplifies data access but also allows for insightful analysis. Developing custom reports during the intake process delivers significant ongoing benefits, allowing stakeholders to extract specific data insights.

When reliable data comes out of a CTMS, institutions, leadership, and study teams have better insight into their clinical trials, their timelines, and the areas they need to improve upon. This data-driven approach empowers stakeholders to make informed choices that expedite trial initiation.

When executed as a consolidated business operations unit, centralization can identify and remove bottlenecks. By streamlining processes, this approach can significantly reduce delays, leading to an overall improvement in the efficiency of initiating clinical trials.

Sponsor study team members and research sites each play a critical role in clinical trial executions. Especially as trials continue to increase in complexity, sites and sponsors can adopt strategies to avoid quality concerns and minimize cause for Food and Drug Administration (FDA) warning letters and inspections requiring additional time and resources.

What are Site Inspection Findings?

Sites working with an investigational new drug (IND) are often subject to an FDA site inspection. Through the inspection, any potential violations of the FDA’s requirements are documented in a Form FDA 483 as observations, also called findings or citations.

What are Site Deviations, Findings, and Failures?

Deviations, findings, and failures represent different instances when study conduct and processes don’t go to plan. Some deviations are less consequential, and both site staff and study team members can identify and document necessary action to intervene. For example, a common deviation occurs when a patient has to reschedule a procedure outside of a visit window, or a routine training has not been completed on time by a site staff member due to an extended leave.

Findings are more significant deviations the FDA has identified and reported. While a study may continue after a citation is issued, resources must be allocated to develop a corrective and preventative action (CAPA) plan to address the issue.

A site inspection failure can occur when there are broader concerns leading to an overall assessment. An example of this would be the inspected site did not meet regulatory standards. Both inspection findings and inspection failures could reduce the quality of the trial data, with inspection failures being most disruptive. These may result in reputational harm, elimination of subject data from evaluation, and ultimately could jeopardize regulatory approval. Despite the consequences, the FDA has reported a failure rate of 36% in clinical trial site inspections over the past five years. Advarra analysis of the FDA Inspection Observation Datasets from 2018 – 2022 shows the following causes make up 44% of all findings:

Failure to Follow Investigational Plan (21 CFR 312.60)

Citations for failure to follow the investigational plan contribute to over half of the failures recorded since 2018. Errors such as protocol non-adherence, missing protocol amendments, or lack of institutional review board (IRB) required review all fall within this code.

Inadequate and Inaccurate Records (21 CFR 312.62(b))

Categorized within the investigational plan regulations, there is a specific emphasis on accurate and complete documentation of all trial activities. Failures such as an incomplete subject record, missing investigator CV, failure to provide delegation of authority log, and more fall within this code.

So, how can sponsor, contract research organization (CRO), and site teams better collaborate to improve quality and efficiency in their studies?

Provide Visit Guidance and Calculators to Sites

A Tufts Center for the Study of Drug Development (CSDD) study found the mean number of deviations and substantial protocol amendments has increased across all trial phases. As a result, sites find themselves forced to navigate constantly evolving directions for conducting study visits and procedures on top of the increasing protocol complexity mentioned above.

To limit the risk of mistakes, sponsors and CRO teams should invest in support tools for sites offering additional guidance on upcoming visits and procedures like:

  • Adequate visit guidance, including step-by-step overviews of upcoming procedures
  • Video refreshers on the specific drug mechanism of action
  • Protocol text search so the site can rapidly find answers to questions

Visit calculators providing a date range for subsequent clinical visits also help ensure visits are conducted on time and with the required windows.

Over 80% of site respondents in our recent survey said additional study tools and guidance like the ones mentioned above are very or extremely helpful.

Provide Access to Ongoing Trial Training

Site staff turnover continues to disrupt trials and put strain on the remaining site team and new staff getting up to speed. In addition, many research trials are conducted over the course of many years. Recognizing the combination of challenges sites face, study teams should provide easy access to study-specific training beyond initial activation and investigator meetings. This enables higher levels of training compliance over the course of study conduct, as well as the necessary understanding of trial activities to perform the right task at the right time. In addition, providing CROs and sponsors visibility to site training compliance allows them to provide additional support and mitigate risk if necessary.

One top pharmaceutical company leveraged Advarra’s Longboat intuitive workflow technology to execute these strategies and reduced protocol deviations across their sites by 20%.

Read the Case Study

Centralize Access to Critical Resources and Documents

In addition to study guidance, it’s essential for each stakeholder to be aware of and have access to the timeliest information and documentation for a trial. But in today’s day and age, we’re all overloaded with notifications and alerts. Since we all rely on email or other communication channels, it’s easy to understand how a document could be overlooked or misplaced.

Tools designed to centralize access and monitor document versions are essential to reducing inspection findings. Documents should be well named and always up to date on the current version. Centralizing resources and documentation reduces the risk of errors, contributing to improved compliance and quality.

The clinical research industry, like many others, has continued to be challenged by staff turnover in recent years. Clinical research organizations everywhere are seeing an influx of employees leaving their positions to go elsewhere.

Staff turnover can greatly impact the quality and progress of an organization’s clinical trials and research projects. Understanding this issue is essential to a healthy research organization. This blog uncovers key aspects to consider as your organization addresses this issue.

High Turnover Rates

Staff turnover rates in the clinical research industry can be relatively high compared to other sectors. This is due to various factors, including the demanding nature of the work, regulatory pressures, and competition for talent.

Reasons for Turnover

There are several common reasons for staff turnover in clinical research, including:

  • Burnout and workload: Clinical research professionals often work long hours and face high-pressure situations
  • Career growth opportunities: Employees may leave if they perceive limited opportunities for career advancement within their current organization
  • Compensation and benefits: Competitive compensation and benefits packages are crucial for retaining talented individuals
  • Work-life balance: Maintaining a healthy work-life balance is challenging in clinical research, and dissatisfaction in this area can lead to turnover

Impact on Clinical Trials

High turnover can disrupt clinical trials and research projects. It can lead to delays, increased costs, and a loss of institutional knowledge, potentially compromising the quality and integrity of research outcomes.

Challenges for Recruitment

Frequent staff turnover also poses recruitment challenges, as organizations need to continually find and train new personnel. This can lead to further delays and costs.

Solutions and Strategies

To address staff turnover in clinical research, organizations should consider implementing the following strategies:

  • Enhancing workplace culture: Creating a supportive and inclusive work environment can improve employee satisfaction and retention
  • Providing professional development: Offering training, mentorship, and clear career paths can motivate employees to stay and grow within the organization
  • Offering competitive compensation: Regularly reviewing and adjusting salaries and benefits to remain competitive in the job market is crucial
  • Creating succession planning: Developing and nurturing talent within the organization through succession planning can mitigate the impact of turnover
  • Initiating communication and feedback: Regular feedback sessions and open channels of communication can help address employee concerns and foster a sense of belonging

Technology and Remote Work

Adopting technology and remote work options can also impact staff turnover. Telecommuting and using digital tools can provide flexibility, further improving work-life balance for clinical research professionals.

Future Trends

As the clinical research landscape evolves, industry stakeholders should stay informed about emerging trends and innovations potentially affecting staff turnover. This includes advancements in technology, changes in regulatory requirements, and shifts in patient-centric research approaches.

In conclusion, addressing staff turnover in clinical research is vital for maintaining the quality and efficiency of research projects. Organizations must prioritize strategies designed to enhance the work environment, support career growth, and ensure competitive compensation to retain and attract top talent in this critical field.

More than two decades ago, we created the OnCore clinical trial management system (CTMS) to serve as a comprehensive solution for a large academic medical center (AMC) to manage their research operations. Over the next decade, dozens of academic medical centers across the country adopted the CTMS. OnCore has since expanded to serve cancer centers as well, including many National Cancer Institutes (NCI)-designated centers.

As our customer community grew, so did the capabilities of the platform itself. Throughout the past two decades, OnCore has extended to track not just the protocol calendar, but aspects such as individual subject visits and details around financials. The ability to generate and create financial records, invoicing, and any number of tools allowing customers the ability to use the system to track almost every piece of the clinical research lifecycle – everything pertaining to a trial.

These changes have all been in collaboration with our users with the customer in mind. When OnCore was first developed, many, if not all research centers had their own processes in place with no sense of centralization. There was very little industry-wide standardization directing research site operations. Driven by input from our ever-expanding customer community, OnCore has sought to deliver standardized workflows for critical aspects of clinical trial management, including protocol and participant management, financial management and billing compliance, internal site communication and collaboration, and much more.

This customer-informed innovation, driven by our amazing community of more than 5,000 research professionals, has established OnCore as an invaluable tool for AMCs and cancer centers over the past 20 years. But how can we ensure the system continues to serve research professionals for the next 20?

Where we are Heading

As research has advanced, there’s a higher priority put on capturing data – not just through clinical research, but through all aspects of the medical industry. In order to accommodate to this, moving forward, we are focusing on how we can continue to help aggregate clinical research data in a meaningful way – not just from a reporting perspective. On top of this, we want to ensure we have the performance and data storage necessary for the amount of data captured, and the ability to make inferences about clinical research from that data.

The data collection process for a clinical trial has numerous steps. However, this is an opportunity to collaborate and understand how the research community can make the best use of modern technology to remove some of these manual steps. This not only saves time, but reduces duplicate data entry and processes within an individual trial and a research organization as a whole.

Cloud Storage

As we look to the future of our CTMS, we want to make sure it’s built in such a way it can support workflows for decades to come. Our goal is to build our system on the most modern framework that exists for hosting an application of this type. Our solution for this is utilizing Cloud storage.

Hosting OnCore on Advarra’s Cloud architecture is advantageous in more ways than one. It lets us utilize more modern tooling, enables the application’s performance and accessibility to be constantly available, and allows space and interconnectivity for hosting all Advarra solutions.

Analytics and Business Intelligence

Analytics and business intelligence have significantly evolved over the past two decades. Whereas these capabilities were a “nice to have” toolset in the early days of CTMS platforms, they are now vital to successfully managing a research portfolio.

OnCore already provides a wealth of comprehensive reporting capabilities. Moving forward, our vision is to evolve these businesses intelligence capabilities, while leveraging a much broader set of data sources for reports and dashboards. Imagine site staff having access to dashboards sourcing data not just from OnCore, but also from eReg, eIRB, eSource/EDC, and other platforms. This cross-platform reporting approach has the potential to significantly improve the way high-volume sites manage their operations.

Additionally, we aim to make this tool as user friendly as possible. Staff turnover and training continue to be pain points for the research community, and easy to use analytics, reporting and data aggregation is one of the ways we hope to ease the burden on research staff.

Single Sign-on (SSO)

Single sign-on (SSO) is a well-established authentication mechanism allowing users to leverage a single set of credentials across multiple applications. It’s already widely used by tens of thousands of organizations across the world, including research sites. Reducing site burden is a key focus area across the industry. As noted in Advarra’s 2023 Study Activation Report, sites continue to struggle with the wide array of they technology they are required to use to manage industry trials.  By unifying the sign-on process across site technology, we can take a significant step towards reducing that burden.

Further, our vision is to expand on the unified user experience by creating a dynamic “home page” for site staff. This will allow users access to all relevant Advarra platforms (e.g. OnCore, Clinical Conductor, Advarra eReg, Longboat, and more) while also providing information most relevant to the user. Whether it’s quick links to assigned protocols, analytics driven by those protocols, the user role, or centralized task lists—just to name a few—this approach has the potential to significantly improve the way we enable sites to do groundbreaking research.

With all of our systems in Advarra Cloud and connected through Advarra SSO, it makes it easier to exchange data between systems. It also enables us to better pivot in the future. Whether we are working to expand to new partners, or adjust for industry needs, we will be ready.

The study startup process involves a multitude of tasks and activities multiple teams coordinate to ensure the successful study initiation. Efficient and compliant study startup activities set the foundation for the entire research process. A key component in streamlining these activities is an effective quality management system (QMS). This blog explores the pivotal role QMS plays in study startup activities as well as how a right-sized QMS contributes to the overall success of clinical trials.

Understanding Study Startup Activities

Study startup is the phase of a clinical trial occurring after the protocol development and regulatory approval stages. It includes all activities required to prepare a study site for participant recruitment and enrollment. These activities may include:

  • Site selection and qualification: Identifying and evaluating potential study sites, assessing their capabilities, and ensuring they meet regulatory and ethical requirements
  • Regulatory submissions: Preparing and submitting applications for regulatory approvals, such as investigational new drug (IND) or investigational device exemption (IDE) applications
  • Protocol development: Creating a clear and comprehensive study protocol outlining the objectives, methodology, and ethical considerations of the clinical trial
  • Contract and budget negotiations: Negotiating agreements with study sites and vendors, including budget negotiations, to establish the financial and legal framework for the study
  • Investigator recruitment: Identifying and engaging qualified investigators and study personnel
  • Investigational product management: Ensuring the proper handling, storage, and distribution of investigational products to study sites
  • Ethics committee approvals: Obtaining approvals from institutional review boards (IRBs) to conduct the research
  • Training and site initiation: Training study site personnel on the study protocol, procedures, and documentation, and initiating the study at each site

The Role of QMS in Study Startup Activities

A QMS adhering to good clinical practice (GCP) and regulatory guidelines ensures the critical study startup activities outlined above are audit-ready. Implementing a QMS as a part of your study startup activities sets the foundation for a compliant framework.  This is crucial for inspections by regulatory authorities, which can occur at any phase of a clinical trial. A robust, right-sized QMS achieves:

Standardized Processes and Workflows

A well-implemented QMS establishes standardized processes and workflows for study startup activities. This helps each site follow consistent procedures, which reduces the risk of errors, omissions, or delays in meeting study milestones due to regulatory non-compliance.

Document Management

Effective document management is a core component of QMS. A successful QMS ensures study-related documents, such as the protocol, informed consent forms, and investigator brochures, are created in a controlled and standardized manner. This guarantees consistency and compliance. All necessary documents, including regulatory submissions, contracts, and training records, are organized, version-controlled, and should be readily accessible to relevant stakeholders during study startup.

Corrective and Preventive Actions (CAPA)

In the event of deviations or non-compliance, QMS facilitates the initiation of CAPA activities to address issues promptly and prevent their recurrence.

Risk Assessment and Management

Adopting a proactive approach to QMS means implementing risk management processes designed to help identify, assess, and mitigate potential risks associated with study startup. By systematically addressing risks and maintaining compliance, QMS helps reduce the likelihood of findings during audits or regulatory inspections. This proactive approach can prevent delays, compliance issues, and costly setbacks.

Training and Competency Management

QMS facilitates the management of training and competency assessments for study site personnel. Ensuring all team members are adequately trained and qualified is essential for the successful study initiation.

Continuous Improvement

Implementing a QMS encourages a culture of continuous improvement. Data collected during study startup can be analyzed to identify bottlenecks, inefficiencies, or areas for enhancement – leading to more efficient processes in future trials. A QMS can also track training records to ensure all personnel involved in study startup activities are adequately trained and qualified.

A robust QMS is an indispensable tool for sponsors, contract research organizations (CROs), and other stakeholders involved in clinical research. Its role in study startup activities cannot be overstated. Through a QMS, study protocols are developed, documented, and executed in a compliant, standardized, and efficient manner. By providing a structured framework for document control, risk management, training, and audit readiness, sponsors, and sites are taking the necessary steps to assure regulatory authorities of the ethical and compliant conduct of their clinical trials.

A phased approach to quality management systems (QMS) ensures quality is embedded at every stage, from discovery to post study. A common misconception in the manufacturing and research development landscape is quality systems can be bought off the shelf and there are no significant differences among the proliferation of quality systems.

Clinical research is grounded in scientific integrity, participant safety, and data reliability. A robust QMS is an integral component of clinical research. A ReadyQMS approach to implementing QMS within the clinical research lifecycle ensures a structured and comprehensive methodology to maintain quality throughout the research process.

Discovery

Establishing a quality mindset at this phase sets the stage for effective enterprise quality planning. A key first step in a phased approach is risk assessment: Before conducting any clinical research, assess any potential risks to patient safety, data integrity, and regulatory compliance. This involves identifying all critical processes in the trial and any potential hazards or deviations potentially arising.

Pre-clinical

Building a quality framework at the pre-clinical stage is critical for setting the stage for timely and compliant study startup. An effective QMS must include standard operating procedure (SOP) development. These SOPs serve as the foundation for consistent execution and accountability for staff throughout the study. Procedures for every process in the trial, from patient recruitment to data management, are documented in SOPs.

Design Protocol and Planning

The trial design itself is meticulously planned to ensure the trial’s scientific rigor and relevant. This often includes:

  • Formulation of objectives
  • Endpoints
  • Patient populations
  • Statistical analyses

Identifying adequate resources, including qualified personnel, appropriate facilities, and necessary equipment, are characterized and allocated. The quality of these resources plays a pivotal role in the trial itself. At this stage, many sponsors are working with their strategic partners to supplement internal expertise to provide the most beneficial outcomes.

Training and Competency Assessment

In addition to identifying resources, training and competency assessments are built into a quality framework. Every member of the clinical trial team undergoes rigorous training on the trial protocol, SOPs, regulatory requirements, and other pertinent topics. Competency assessments are essential to ensure the team is qualified and prepared.

Study Startup

Study startup activity checklists are both extensive and exhaustive. A phased approach QMS means processes are finalized under an established quality framework. It also means everyone is following the same procedures to ensure both ethical and unbiased participant recruitment.

Study Conduct

Monitoring quality and compliance is the bedrock of a ready QMS during study conduct. Regular monitoring of trial sites ensures everyone is following the correct SOPs and protocols. Audits, which are independent evaluations, are periodically performed to verify compliance with regulatory standards and the trial protocol. Data collection and management and quality checks are set in place to ensure data accuracy, consistency, and integrity. Data management processes involve timely data entry, validation, and review.

Study Close

Once the trial is complete, data is statistically analyzed and findings are reported. This phase requires a stringent QMS to ensure the integrity of the results. All trial documents, including raw data, consent forms, communications, and reports, are archived as per regulatory requirements. This ensures any future queries or inspections can be adequately addressed. Post-trial, a comprehensive review is undertaken to evaluate the successes and areas of improvement. Lessons learned are used to enhance the QMS for future research.

The clinical research lifecycle’s phased approach to QMS ensures quality is embedded at every stage, from initiation to closure. By incorporating QMS at the discovery stage, regulatory agencies are assured that clinical trials are compliant and protect participants’ safety as well as ultimately leading to reliable results benefitting patients and advancing medical science.

Ensuring the safe and secure transport of investigational products (IP) is a core part of biosafety. This critical task requires meticulous planning and rigorous procedures to avoid any hazards potentially arising during the journey of an IP from the controlled environment of a pharmacy or preparation room to its destination.

Think about the familiar paths we traverse every day of our lives. I’m a runner, and there are sections of my neighborhood I’ve crossed numerous times. But a distracting thought (or a speeding squirrel) can change that familiar territory without warning, causing me to trip and fall.

It’s the same with the transport of an IP. Even if the environment is familiar, with or without hazards, the unknown or unlikely is a biosafety consideration.

Controlled Environment and IP Containment

The potential for a release, and the risk associated with a genetically engineered IP, are part of the IBC’s assessment purview under National Institutes of Health (NIH) Guidelines.

When the IP leaves the controlled environment of a pharmacy or preparation room, IP’s containment effectively becomes the controlled environment in itself. The containment must then prevent spills or leaks if the IP is dropped. This is a matter of protecting not just the IP’s integrity, but also the safety of employees, the community, and the environment from any adverse effects (AEs) potentially resulting from an accidental release.

Therefore, using the appropriate transport container is essential to prevent spills or releases. Even if you’re just traveling a familiar path across the hall, the unknown can still trip things up.

Requirements for Transport of Investigational Products

Accidents can happen. So, how do we ensure the transport container for an IP is up to this crucial task? Here are some fundamental guidelines:

  • The transport container should be sealed and leak-proof. Glass can easily shatter – plastic containers are the preferred choice. They’re sturdy, less likely to break, and can be easily decontaminated and cleaned after use.
  • A sealed container prevents leaks of any liquids or aerosols, so look for an O-ring or a sealing component in the lid. A secure latch is crucial to create a tight seal; it ensures the lid stays put and the contents remain safely inside, even if the container takes a tumble.
  • Size matters. Choose a container appropriately sized for its contents. And don’t forget to affix a biohazard sticker to the exterior for quick and clear identification.
  • Some institutions require additional specific paperwork, so be sure to review internal policies prior to transport of the investigational products.
  • If your IP is headed to a satellite location in a vehicle, you’ll need to follow the Department of Transportation (DOT) Hazardous Materials Regulation 49 CFR Parts 171-180, which allows for “in commerce” transport of materials or under the Materials of Trade (49 CFR 173.6)

Transport in a vehicle requires additional considerations such as:

  • Preventing the transport container from shifting enroute by securing an external container within the vehicle.
  • Maintaining the correct temperature for the IP, which may include using dry ice, wet ice, or heating packs.
  • Preparing for unforeseeable release with a small spill kit.
  • Maintaining the appropriate paperwork and labeling to identify the material’s hazards.

In conclusion, whether you’ve been conducting clinical trials involving recombinant nucleic acids for years or are just beginning to navigate the NIH Guidelines, your site should always assess transport procedures.

Using an appropriately sized, sealed, leak-proof container is best practice for transport from across the hall, within a building, or across a short distance to a satellite clinic. This is also the minimum requirement for transport under NIH Guidelines.

Safely and securely transporting an IP is a shared responsibility, requiring constant vigilance and a commitment to ongoing learning and adaptation.

Moving IP from a controlled environment means taking it to an area with increased risk of release and exposure. Remember, we’re not merely moving materials from point A to point B—we’re playing an essential role in the advancement of human health. Let’s ensure we do so safely and responsibly.

Clinical trials receive a lot of oversight from regulatory agencies, as well as independent committees reviewing different aspects of the trial. Depending on the nature of the trial, the independent committees involved may include:

  • Institutional review boards (IRBs)
  • Institutional biosafety committees (IBCs)
  • Scientific review committees (SCRs)
  • Endpoint adjudication committees (EACs)
  • Data monitoring committees (DMCs)

In particular, IRBs are likely the most well-known of the independent oversight committee functions. While IRBs are also known as research ethics boards (REBs), ethics committees (ECs), or independent ethics committees (IECs), we will refer to this committee as an IRB in this blog.

Each committee plays an important role in providing trial oversight. They aim to keep participants and research staff safe, and help the IRB determine if a trial has an adequate safety monitoring plan as required by Food and Drug Administration (FDA) regulation 21 CFR 56.111(a)(6).

In this blog we look at the specific role DMCs play in overseeing research, and how IRBs rely on the independent DMC’s oversight of interim trial data to ensure an adequate safety monitoring plan is in place.

What Is an Independent DMC?

A DMC is an independent group of experts who conduct a periodic review of accumulated interim data during a clinical trial. DMCs are strenuously recommended for certain clinical trials by both U.S. FDA and EU European Medicines Agency (EMA) guidelines.

Particularly in trials with a blind or placebo control, the DMC’s purpose is to review unblinded trial data as it is collected to detect and report safety concerns, early evidence of benefit or harm, and futility of the treatment, using criteria outlined in the clinical trial protocol.

DMCs are typically comprised of five to six members, including biostatisticians and clinicians. All must be independent of the trial sponsor.

Sponsors are responsible for creating the DMC for a trial, or engaging an independent firm to create and administer the DMC on the sponsor’s behalf.

Many sponsors use independent administrators to support DMC separation and independence as an independent oversight committee.

The DMC typically operates under a detailed charter outlining what data the committee will review, how members are selected and vetted for conflicts, and other operational considerations governing how the committee runs. This includes the format for reporting and providing recommendations back to the sponsor.

What’s the Difference Between a DMC and a Data Safety Monitoring Board?

In short, both FDA and EMA use “data monitoring committee” to describe the group, independent of the sponsor, who is charged with looking at the data to determine when trial endpoints and other milestones are met.

In North America, these groups are also referred to as data safety monitoring boards (DSMBs). In other parts of the world, they are also known as data and safety monitoring committees (DSMCs), independent data monitoring committees (IDMCs), and other similar titles.

Regardless of the name, the concept and purpose of these committees are the same: providing independent oversight of certain aspects of the study. In blinded research, DMCs evaluate unblinded study results to determine if endpoints and other milestones have been met.

When is a DMC Needed?

FDA guidelines outline when the agency expects a data monitoring committee to be created. However, sponsors may engage independent DMCs for other types of studies, and on occasion, the IRB may determine there is a need for a DMC as part of the clinical protocol’s overall data safety monitoring plan.

In brief, the FDA recommends sponsors consider using a DMC when:

  • The trial is blinded or has endpoints, such that an independent group must evaluate unblinded data to determine if the study has met pre-determined endpoints, futility, or other stopping rules and should be terminated early
  • There are other reasons for a safety concern (e.g., a particularly invasive procedure)
  • There is prior information suggesting the possibility of serious toxicity where interim analysis of adverse event data is necessary to determine if toxicity endpoints are met
  • The trial is large, or of long duration, and multicenter, where a single group in needed to evaluate and analyze the consolidated interim study data

Most commonly, DMCs are created for later phase, randomized, drug and device studies. In these studies, there is a need for an independent committee to evaluate interim study data for emerging participant safety issues and to determine if stopping rules have been met.

The DMC is advisory to the sponsor and provides an opinion, based on interim analysis, as to whether the trial should continue as it has been, receive changes to the trial design, or be stopped early. Most DMC charters give the committee the power to make recommendations only. Unlike the IRB, which under the FDA regulations has authority to disapprove or terminate approval for research (21 CFR 56.113), the DMC only plays an advisory role to the sponsor.

Where Does a DMC Fit With IRB Review?

U.S. FDA regulations stipulate IRBs must determine that “where appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.” (21 CFR 56.111(a)(6))

The IRB must determine if an appropriate plan is in place to adequately monitor data to ensure participant safety. This is typically referred to in the clinical protocol document as the data safety monitoring plan (DSMP).

One of the primary ways a sponsor satisfies this regulatory requirement is to utilize an independent DMC as part of the plan. The IRB will typically view a monitoring plan, which incorporates an independent DMC as “adequate provision” to ensure data is monitored for safety.

During the trial, as part of the required continuing review process, the IRB typically requests copies of the DMC’s recommendations to the sponsor. In this way, the IRB can leverage the work of an independent DMC and its recommendations in a few different ways. They can determine if there is any new information which may impact the IRB’s decision to approve the research to continue, require alterations to the research, inform participants of potential new risk information, or not approve the research to continue (21 CFR 56.109(f)).

DMC and IRB Relationship

IRBs do not see unblinded study data and are not in a position to know unilaterally if trials have met stopping rules. They must rely on independent DMC review, and other oversight committees, to work collaboratively to protect clinical trial participants.

As an example, at Advarra, our IRB diligently reviews each trial’s data safety monitoring plan to ensure it is adequate to satisfy the FDA regulatory criteria. Many times, the safety monitoring “plan” will include an independent DMC. In these circumstances, the IRB routinely verifies if the DMC recommends stopping the trial early or making any changes to reduce participant risk.

The DMC and IRB are two committees, with different roles and focuses, both working together to independently oversee a clinical trial and the safety of the participants.

Note: This article was originally published on July 1, 2021, and has been updated to include new and clarifying information.

In the clinical research space, GxP is a set of quality regulations and guidelines designed to establish the safety, efficacy, and integrity of pharmaceuticals, medical devices, and clinical trials. This blog explores key concepts, regulations, and the importance of GxP in delivering successful clinical trials.

GxP: An Introduction

The term GxP represents a general abbreviation for “good practice” guidelines and regulations, with the “x” acting as a placeholder relevant to a particular field. Traditionally, based on the clinical research lifecycle, this includes:

  • Good clinical practice (GCP)
  • Good laboratory practice (GLP)
  • Good manufacturing practice (GMP)
  • Good pharmacovigilance practice (GPvP)
  • Good distribution practice (GDP)

Meeting good practice standards is paramount to the success of potentially lifechanging clinical research; strict adherence to GxP guidelines ensures patient safety and product quality while assisting research teams in meeting critical regulatory requirements for advancing study milestones.

GxP in Clinical Trials

To yield the best possible outcomes for clinical trials, GxP guidelines and compliance regulations assures regulatory agencies the safest and most productive research efforts are being delivered to the market.

Rigorously maintaining GxP compliance standards throughout each phase of the clinical trial process is essential to:

  • Protecting the safety and wellbeing of trial participants
  • Ensuring the quality and integrity of trial data
  • Facilitating the production of beneficial medicines and treatments

Failure to adhere to GxP guidelines and regulations can result in severe and even tragic consequences. Research teams can receive warnings from regulators, on the basis of which they may be required to enact corrective plans and/or to obtain FDA confirmation before resuming development. In more serious instances, sponsors might see their products recalled entirely.

GxP in Medical Devices

It’s no surprise: Developing and manufacturing medical devices is so highly regulated, and this regulatory approach extends to the recent proliferation of medical devices created using artificial intelligence and machine learning (AI/ML). Working together, the U.S. Food and Drug Administration (FDA), Health Canada, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) established a set of 10 principles to guide regulation of such AI/ML-developed devices. These principles serve as a foundation for the advancement of good machine learning practice (GMLP). They also aim to ensure medical devices created through the use of AI/ML are secure, efficient, and maintain a high level of quality.

Device manufacturers must adhere to GMP and GDP, both of which help to ensure:

  • Devices are consistently manufactured and stored
  • Distributed devices are consistent and of high quality
  • Minimized risks to end-user safety and well-being

Violating these GxPs requirements for device manufacturing could result in audit observations, product recalls, loss of revenue, government fines, and legal liability.

Compliance and Regulatory Bodies

Meeting critical study milestones is often dependent on compliance with relevant GxP requirements. Absent GxP guidelines and regulations compliance, clinical research stakeholders’ risk everything from product failure or recall to endangering the lives of trial participants. In the event of GxP noncompliance, stakeholders must absorb the consequences of ceasing operations until GxP violations are remedied.

GxP Challenges and Best Practices

Achieving and maintaining GxP compliance is not easy—it’s a multi-factorial responsibility requiring constant vigilance and assessment. A common challenge for many clinical trial stakeholders involves maintaining adequate GxP documentation – without this, it can result in fines and sanctions. FDA Observation Form 483 pertains to an absence of written procedures and may be used where corrective and preventive actions (CAPA) processes are not adequately defined or followed.

Clinical trial stakeholders should be able to demonstrate their compliance controls have been observed and conformed to, along with identifying and correcting potential non-conformance in end-products. In order to do so, this requires thorough implementation of several GxP best practices: documentation, communication, traceability, and accountability.

GDP is Key to Maintaining Compliance

Want to instill confidence in your GxP? Keep your data and documentation up to date and have controls in place to avoid tampering. GDP also informs regulators that, not only have required activities been undertaken, they’ve also been recorded at the right time.

Follow Record-keeping and Documentation Requirements

Doing so keeps processes trackable and makes it possible to hold companies fully accountable for their data integrity and quality of their end products.

Document Every Critical Action Across Development, Manufacture, and Delivery

For GxP compliance, it is essential to document every critical action made by every employee in the product’s development, manufacture, and delivery. Make sure this documentation is auditable and is comparable to the risk posed by non-conformance.

Quality Management Systems Support GxP Compliance

For several GxP categories, a key best practice for maintaining compliance is implementing a quality management system (QMS).

  • GLP ensures the quality and integrity of non-clinical laboratory studies that support research for products regulated by government agencies. A QMS ensures laboratory-run studies are planned, performed, monitored, recorded, archived, and reported under the right conditions and in a consistent and repeatable manner.
  • For GMP, the rules for regulation differ depending on the country. However, GMP requires products are consistently of high quality, are appropriate for intended use, and meet requirements for clinical trial authorization.
  • GPvP ensures companies continue to monitor the safety of the medicines they have developed after they have been launched in the market. GPvP best practices include maintaining a QMS capable of storing huge quantities of safety data used to monitor and report on the safety of potentially marketable drugs.
  • Finally, GDP governs the wholesale distribution of medicines, keeping products safe and in usable condition for consumers. GDP provides distributors with auditable systems to ensure safe storage and transport, contamination prevention, and recall management, while helping make certain only authorized products enter the distribution network. Using a QMS encourages greater accountability, traceability, and cooperation throughout the supply chain.

Future Trends and Innovations

The processes for achieving and maintaining compliance with GxP guidelines and regulations are increasingly subject to modernization. In clinical trials, for example, documentation processes can become streamlined through the use of eSolutions such as an electronic trial master file (eTMF). This allows all regulatory documents, whether originating with a sponsor or at a site, to be managed, signed, and securely exchanged to relevant stakeholders for long-term storage in an eTMF, while providing shared access amongst its users.

Similarly, clinical trial management systems (CTMS) have revolutionized the way researchers can conduct and manage clinical studies effectively. Because trials are becoming more complex, a CTMS is integral to maintaining a thorough and transparent process and facilitating GxP compliance efforts. Many CTMS platforms can optimize finances, assist with regulatory compliance, and streamline overall clinical research operations for all types of research sites, site networks, hospitals, and health systems.

Overall, the most impactful solutions will be those enhancing how researchers can maintain thorough organization of documentation, achieve quality data management, and keep robust oversight capabilities through each phase of clinical study. This all helps keep study teams on track towards producing impactful beneficial medical treatments and medical devices.

Making Clinical Research Safer, Smarter, and Faster

GxP programs can be complex and difficult to manage. GxP guidelines and regulations are in place to ensure the highest quality and most reliable end products are delivered to patients without compromising their wellbeing.

For life science organizations, prioritizing GxP regulations compliance can accelerate therapies to market, all while making your clinical research safer, smarter, and faster in the process.

For decades, many research sites have primarily relied on institutional review board (IRB) oversight provided by committees that are administered by the local institution conducting the research. IRBs administered by independent organizations have long been an option for research sites who do not administer their own local IRB. They’re also an option for all other types of sites to reduce internal burden and potentially help decrease study startup timelines.

Recently, federal requirements have shifted to require most multisite clinical trials to rely on a single IRB (sIRB) for oversight at all participating sites, specifically for any multisite research receiving support from the U.S. government. This eliminates the patchwork of multiple local IRBs reviewing a single trial, instead channeling every site to an sIRB reviewing for participant protections for the entire study.

In addition, the FDA has issued a draft rule indicating their goal of requiring sIRB review for all studies falling under the FDA purview (including any clinical trials involving experimental products – drugs, devices, etc.). While there is no current timeline for implementation of this new rule, many institutions are actively working to determine how to manage these studies moving forward.

What is an sIRB?

Single IRB review (also sometimes known as central IRB review) means a single IRB of record reviews for all clinical trial sites participating in a multisite study.

While central IRB review has been an option in the U.S. for decades, in recent years, the practice has become required for many organizations who fund or support clinical research.

The sIRB movement seeks to streamline a critical research process and reduce administrative burdens while maintaining appropriate participant protections.

Why Does my Study Need an sIRB?

When the human subject protection regulations were originally established, clinical trials primarily took place at institutions and academic medical centers, with few (if any) trials conducted at independent research sites. Due to the regulations governing human subjects research, these institutions established IRBs locally to review the research conducted at their own institution.

In recent years, research conduct has evolved to also include commercial or unaffiliated sites, which might or might not have a local IRB to rely on. Commercial sites in particular are set up to conduct only research activities, compared to sites adding research activities to existing clinical responsibilities.

All research is moving toward more streamlined conduct because of factors such as costs and competition. Because of this, sites can choose to rely upon any IRB their sponsor or contract research organization (CRO) designates.

A CRO’s Role in sIRB Review

A CRO is tasked with facilitating the operational aspects of the research on behalf of the trial’s sponsor, assuming the sponsor’s regulatory compliance obligations (21 CFR 312.52). Sponsors expect CROs to utilize their expertise so the trial is conducted as responsibly and efficiently as possible.

In recent years, CROs and study sponsors are having all sites (or as many as possible) rely on the same sIRB. By doing so, they reduce the administrative burden of managing disparate reporting requirements and submission systems/processes for multiple IRBs.

For example, any time there’s an amendment, the sIRB can handle it for all sites, rather than submitting the amendment to several IRBs through their individual processes, portals, review timelines, etc. This ensures efficient startup, and ensures amendments are efficiently and consistently introduced across all sites and participants.

The Rise of Central IRBs

In the later years of the 20th century, CROs proliferated and competed to improve study timelines for their sponsor clients. Sponsors also began to push for greater research efficiencies internally and with their partners. More commercial and unaffiliated sites then entered the research field, and central IRBs began playing a larger role.

Within the last two decades, institutions began to establish relationships with external IRBs for a few reasons, including to:

  • Make their programs more competitive for sponsored research
  • Augment internal resources
  • Expand bandwidth
  • Replace dismantled local IRBs

In 2006, the FDA published guidance making it clear the agency supports the use of centralized IRB review, paving the way for future regulatory actions. The guidance emphasizes sIRB’s value in increasing efficiency and reducing administrative burden.

Subsequent sIRB Initiatives

In 2016, the National Institutes of Health (NIH) announced its Single IRB Policy, requiring domestic awardees and domestic sites conducting NIH-funded multisite research to move to an sIRB of record. The revised Common Rule mandated sIRB oversight for cooperative research, effective January 2020.

Signed into law in 2016, the 21st Century Cures Act suggested centralized IRB review as a way for the U.S. government to reduce “duplication of effort” in human subject protections. It also removes “local” from “IRB” in the device regulations, another step to enable sIRB review. FDA’s 2022 NPRM may be considered a response to the Act’s requirement to harmonize FDA regulations with the Common Rule.

Single IRB (sIRB) vs Central IRB (cIRB) – What’s the Difference?

Read the blog

How to Rely on an sIRB

When relying on an sIRB, there are certain policies and processes organizations should consider establishing to support a collaborative and compliant working relationship.

Reliance Agreement

As soon as you determine you will rely on an sIRB, each site and the sIRB should work to establish a reliance agreement, if one isn’t already in place. This helps define responsibilities between the sIRB and the institution conducting research.

Establishing a reliance agreement lets them understand each other’s priorities and obligations, brings stakeholders together to discuss, and allows institutions to understand what’s worked for other institutions and how they can maximize their relationship with their sIRB.

A reliance agreement is required for Federalwide Assurance (FWA)-holding institutions to rely on another (or external) IRB. While this is not required for all relationships, it’s best practice to have an agreement in place.

Communicate Effectively

Almost as important as the reliance agreement is your communication plan with the sIRB. This benefits both parties since everyone is working toward doing things correctly and efficiently while maintaining compliance.

Effective communication goes beyond establishing a plan. Institutions need to be comfortable going to their sIRB for any questions they have, whether that’s clarification about a decision or to request meeting minutes. It’s important to remember this relationship should be collaborative and transparent for all stakeholders.

Communicate Internally

After the sIRB working relationship is established, the rest of the institution’s research team should be trained on sIRB policies and processes. Making sure everyone understands the local requirements and submission processes and procedures will help keep the right people informed throughout the process and move research forward.

Benefits to sIRB Review

Partnering with an sIRB provides significant benefits to sites and sponsors:

  • For sponsors, they are assured the research will be reviewed and conducted under a single IRB review framework, and ongoing reviews and amendments will be processed with speed and precision.
  • For sites, there can be a tangible decrease in staff workload, as well as reduced risk to the institution in knowing an organization with the appropriate policies, procedures, and expertise is conducting IRB reviews.

Note: This article was originally published on July 21, 2022, and has been updated to include new and clarifying information. 

Rapid growth in gene therapy is expected to receive additional support as the Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER) prepares to launch Operation Warp Speed for Rare Diseases.

Gene therapy has achieved notable successes, particularly in treating resistant or refractory B cell leukemias (achieving overall response rates around 90% or greater) and the speed with which COVID-19 vaccines were developed under the original Operation Warp Speed.

Now, FDA’s CBER is setting its sights on making ambitious strides toward tackling rare diseases.

Why Warp Speed for Rare Diseases?

The 1983 Orphan Drug Act defines a rare disease as a disease or condition affecting less than 200,000 people in the United States. There are over 7,000 rare diseases affecting more than 30 million people in the U.S., many of which are life-threatening. Most rare diseases do not have treatments. The Orphan Drug Act creates incentives for developing orphan drugs to treat such diseases.

Given the relatively small populations affected by any one rare disease or condition, a pharmaceutical company developing an orphan drug may reasonably expect the final approved drug to generate relatively small sales (when compared with the drug development costs) and consequently incur a financial loss.

However, recent advancements in the clinical use of recombinant DNA (rDNA) technology creates opportunities for changing this calculation and addressing a great, unmet medical need.

“I am very excited for the field because I feel like we’re beginning to get to a critical mass, where a single method or product can be deemed safe and then adapted for many uses,” said Dr. Peter Marks, head of FDA’s CBER – the organization responsible for regulating gene therapies.

Many rare diseases, like cystic fibrosis and sickle cell anemia, are monogenic in nature, caused by mutations to single genes. From a technical standpoint, such diseases should be easier to treat with current gene therapy technology. (More common diseases caused by multiple genes, like cardiovascular disease or diabetes, are less ideal targets, as they pose greater challenges with current capabilities.)

FDA CBER began issuing approvals for gene therapies in 2015 and issued the first approval for a rare disease gene therapy in 2017, with the second rare disease approval issued in 2019. The pace has since increased: 2022 and 2023 each saw three approvals issued. Operation Warp Speed for Rare Diseases looks to accelerate both drug development and approval.

According to Dr. Marks, “…[I]t would be a shame if all we manage to do, every year in the next few years, is approve another two or three gene therapies—that’s a failure,” he said. “Success would be…, if not exponential, at least some logarithmic progression here toward more and more gene therapies being approved.”

What is the FDA Proposing to do?

The FDA plans to launch Operation Warp Speed for Rare Diseases in 2023 with a focus on increased communication between the agency and drug and biotech companies. This will aid clinical development and preparation for investigational new drug (IND) and biologics license application (BLA) submissions.

The project should also help clinical research sponsors take advantage of various FDA pathways for accelerated review and approval. The enhanced guidance could involve a discussion regarding the use of surrogate endpoints thought to predict clinical benefit. To simplify the regulatory submission process, regulators could rely on what’s known about one gene therapy to inform the regulatory review of another investigational product utilizing similar gene delivery mechanisms.

The FDA has already taken steps to increase efficiency and bandwidth for the review of gene therapies. The agency’s Office of Tissues and Advanced Therapies (OTAT), which reviews gene therapies, has been elevated and is reorganized as the Office of Therapeutic Products.

This project seeks “to improve functional alignment, increase review capabilities, and enhance expertise on new cell and gene therapies… to further accelerate the pace of development of therapeutics for very small populations with very high medical need.”

How Can Research Professionals Mitigate Risks with Engineered Genetic Materials?

Gene therapy products may pose unknown risks, and Dr. Marks said there is much to learn about the field.

“We still have much to learn about how gene therapy products work, how to administer them safely, and whether they will continue to work properly in the body without causing adverse side effects over long periods of time,” Dr. Marks said. “[W]e may need to accept some level of uncertainty around these questions at the time of approval.”

The risks associated with the research of engineered genetic materials are why the National Institutes of Health Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) provide the standard for oversight of research involving genetic engineering and gene therapy.

NIH Guidelines are promulgated by the NIH Office of Science Policy (OSP), and call for local oversight at the research site by an institutional biosafety committee (IBC) reporting to the NIH OSP.

IBCs are charged with protecting study personnel, the community, and the environment from exposure to engineered genetic material. An IBC may also advise the IRB to aid in assessing risks to the study participants.

The IBC review requirement applies to gene therapy research at sites that receive funding from the NIH or that have ever participated in NIH-funded research. Sponsors or sites that have received any NIH funding are obligated to comply with IBC review regardless of whether the funding is associated with the gene therapy study.

In cases where the agency did not provide monetary support, IBC review may still be necessary if the NIH collaborated in the research of the study agent or provided materials for its development (NIH Guidelines Section I-C-1-a-(2)).

Even if there are truly zero NIH funds or collaboration involved, IBC review is considered a best practice.

What Should Sites do to Prepare for Operation Warp Speed for Rare Diseases?

The best way a site can prepare to participate in gene therapy studies is to register an IBC with the NIH and become familiar with the basic requirements for IBC review.

Each site’s IBC must first register with the NIH OSP before convening a meeting or issuing an approval. The NIH OSP will review the proposed committee members’ qualifications to confirm the IBC meets the NIH Guidelines’ requirements.

The NIH OSP review of a site’s IBC registration may take four to six weeks. Sites can compress timelines by registering their IBCs well before having a new study for IBC review. This way sites are ready to start the IBC review process immediately, staying one step ahead of their less proactive colleagues.

Furthermore, sites with registered IBCs already in place may choose to position themselves as “gene therapy ready” to be more attractive to sponsors and contract research organizations (CROs) during the site selection process.

Keep in mind, there is no cost to register an IBC with the NIH. Research sites without access to an IBC may consider relying on a commercial IBC. Additionally, pharmaceutical companies and CROs conducting multisite clinical trials may benefit from efficiencies provided by centrally administered IBC reviews, utilizing a model similar to central IRB reviews.

Gene therapy research is booming in the clinical setting. In this blog, we summarize the growth, risks, and regulatory requirements for gene therapy research. We also discuss how a centralized biosafety review process can benefit this type of research.

Defining the Boom in Gene Therapy Research

The gene therapy field is experiencing explosive growth in today’s competitive research environment. Gene therapy involves the transfer of engineered genetic materials to human research subjects.

These studies were previously considered to be highly experimental and limited to early phase trials at a handful of highly specialized academic medical centers. However, well-established safety profiles, promising research results, and the FDA issuing the first gene therapy approvals in recent years have led to dramatic growth.

Searching clinicaltrials.gov for gene therapy studies results in 5,720 hits, with 1,304 studies currently recruiting or enrolling research subjects. As of June 2023, 416 Phase III studies are listed, representing a growing pipeline of gene therapy products preparing to undergo consideration for FDA approval.

Risks and Regulatory Requirements

Most clinical researchers are familiar with the regulatory requirements pertaining to the FDA phases of review as well as with IRB review. However, gene therapy studies require additional review to assess the risks associated with the engineered genetic material, especially as the technology frequently utilizes genetically engineered viruses to deliver genetic information into target cells.

Viral infection involves the transfer of the virus’ genetic material to host cells, making viruses ideal tools for gene transfer—once the genes responsible for viral replication and disease are removed. While genetically modified viruses have a greater safety profile than the naturally occurring unmodified variety, they remain infectious and capable of causing harm.

NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) provide the standard for oversight of research involving genetic engineering and gene therapy. The NIH Office of Science Policy (OSP) promulgates the NIH Guidelines and calls for local oversight at the research site by institutional biosafety committees (IBCs) reporting to the NIH OSP.

IBCs are charged with protecting study personnel, the community, and the environment from exposure to engineered genetic material. An IBC may also advise the IRB to aid in assessing risks to the study subjects.

IBCs are comprised of at least five members, including at least two unaffiliated community members. Together, they collectively possess the expertise to assess the risks associated with the proposed research which may include preclinical, clinical, or non-clinical research.

IBC membership is required to include additional expertise for research involving animal models, human subjects, high-containment infectious disease laboratories, industrial scale greater than 10 liters, and plants or plant pathogens.

IBC review involves assessing the risks associated with the genetically modified investigational product, as well as the adequacy of a facility’s safety practices and training intended for use of the investigational product at the site.

  • The IBC ensures the site has adequate incident reporting and response plans in place to address potential occupational exposures, spills, or environmental releases of the investigational product.
  • The IBC may review informed consent forms (ICFs) and other research subject materials to mitigate possible risks to casual or close contacts in the community.
  • Reviewing the site’s plans for disposal of the investigational product and associated biomedical waste allows the IBC to ensure environmental protection.

Find out how a major CRO leveraged central IBC review and activated sites to “ready to enroll” 78% faster. Read the Case Study

Efficiencies from a Centralized IBC Review

While NIH Guidelines call for IBCs to provide local oversight at the site level, the process can be externally administered by a central body to provide similar benefits as centralized IRB review (also known as single IRB or sIRB review).

Organizations providing centralized review can provide greater speed and efficiencies. Many offer a web-based submission portal, which allows sponsors and CROs to create a single submission for multiple sites.

Additionally, centralized IBC organizations can administer IBCs for sites lacking their own committees. They can also serve as a second committee specifically for clinical trials when the existing IBC lacks the expertise for such reviews (many local IBCs focus only on preclinical or non-clinical research).

The greatest benefit of centralized IBC review is faster turnaround times from submission to approval. Academic medical centers are typically limited to monthly IBC meetings and routinely take two to three months to issue an approval for a gene therapy study. Centralized IBC organizations have more frequent committee meetings: For example, Advarra’s IBC can provide turnaround times of 10 days or less for registered sites.

Similar to sIRB review benefits, as a result of these centralized IBC efficiencies, sponsors can experience faster study startups, achieve experimental endpoints earlier, and cut costs. Sites working with a centralized IBC are more competitive for being selected for studies and are more likely to meet recruitment goals.

Most importantly, a centralized review process lets patients experience accelerated access to the latest biomedical science has to offer.

Note: This article was originally published September 18, 2019, and has been updated to include new and clarifying information.

Login
Scroll to Top