Skip to Content

Should You Bring Your Trial Master File In-House? 

A Trial Master File (TMF) is an ecosystem of documents used by monitors, auditors, assessors, and sponsors to demonstrate that a clinical trial has been conducted in compliance with Good Clinical Practice (GCP) and the approved protocol. 

The TMF is an essential quality process, enabling documentation of all activity that has been performed during the study, and ultimately, should be inspection ready at any moment. Clinical trial sponsors are often challenged with the TMF process when bringing such responsibilities in-house, often finding it difficult to keep up with staffing needs, regulations, processes, and validation required. Outsourcing also brings in its own suite of challenges. 

This article discusses the advantages, disadvantages, and challenges of bringing your TMF in-house versus contracting with a Clinical Research Organization (CRO) or other third party so you can right-size your decision for your needs. 

Bringing Your Trial Master File In-House 




Contracting with a CRO to Manage Your Trial Master File 




As you navigate your TMF approach (or transition) and consider who will fill those critical resource gaps, make sure you take the time to review the advantages and disadvantages of each potential decision, and then decide based on least amount of risk to your study and organization. 

Whether you decide to bring your TMF in-house or outsource, you will need to consider the impact on your personnel and your internal infrastructure. Successful TMF management requires careful and constant attention to every process, procedure, and guideline, all to ensure the TMF is always inspection ready. 

To learn more about Halloran’s TMF strategy and implementation approach to support inspection readiness measures, contact us. 

Critical Steps Towards a Collaborative Partnership and Governance Model

When crucial clinical trial activities are delegated by a sponsor to their vendor, the sponsor must take measures to ensure the vendor or subcontractor is delivering the agreed-upon services. This is effective vendor management in clinical trials, requiring careful selection and review of the vendor’s qualifications. Of importance is the sponsor’s continuous oversight of the vendor’s performance because the sponsor is still responsible for their clinical trial outcomes and outsourced activities. Utilizing strategies to build and develop successful sponsor-vendor partnerships was a key topic at the recent SCOPE summit. During one session, a panel of industry experts provided an overview concerning creating the foundation of a governance model and establishing partnerships to drive clinical performance. 

But what does it mean to form a partnership? A partnership is an established relationship involving close cooperation between parties that have specified joint rights and responsibilities. There are steps the sponsor can take to build a successful relationship and establish a strategic partnership with the vendor from the onset. It starts with setting intentions to establish a long-term relationship.  

Step 1: Determine Your Strategic Pathway – The Scope 

The panel presented various perspectives regarding how to build a partnership, including insights from procurement, the sponsor, and the vendor. To follow are highlights from the panel’s discussion. 

The speakers included Gary Ellsworth, VP & Head IQVIA; Stacey Limauro, Executive Director, Clinical Operations, Deciphera Pharmaceuticals; Rene Stephens, Managing Director & CBO, Danforth Advisors; and Jodi Coughlin, Director, Vendor Relationship Management, Deciphera Pharmaceuticals. 

As a sponsor, it is essential to establish the goal of collaborating with a vendor and the desired outcome. To arrive at that goal, take a close look at your business needs and the outcomes desired. Each goal will vary by company based on the sponsor’s planned study activities and the risk associated with each outsourced activity.  

Step 2: Evolution of the Partnership – Choosing the Right Partner 

The sponsor must carefully evaluate the potential partner before a partnership is established, ensuring there are no significant differences among each company that could lead to conflict. The following criteria and questions were presented during the panel discussion to consider when choosing the right vendor partner. 

Define your Business Needs and Goals  

Evaluate the Culture of the Vendor 

Identify Key Stakeholders  

Step 3: Management and Governance 

There are many benefits for establishing a strategic partnership, but an investment of time and resources from both the sponsor and the vendor are necessary to maximize the outcome. Here are five suggestions to maximize the partnership from the beginning. 

Both Sides Need to Commit to a Model and Partnership 

Interview Key Executives from Both Organizations 

Schedule a Partnership Kick-Off Meeting 

Prioritize Teambuilding  

Maintain Enthusiasm 

Step 4: Remember, Performance Matters 

Vendor management in clinical trials is critical to ensuring a sponsor’s business requirements are being met while reducing costs and minimizing risks. Forming minimum standards for selection and management of vendors and implementing best practices is key to establishing a thorough approach to vendor management and leading to a successful vendor relationship journey. 

Halloran has helped many clients with selecting, qualifying, and developing oversight plans for vendors. Halloran utilizes their team’s extensive industry knowledge and experience to ensure an objective evaluation considering any mitigating risks you may encounter to land at an optimal project outcome. 

To learn more about vendor management in clinical trials, contact us. 

Navigating the Maze: The Vital Role of Collaboration and Leadership in Phase 2 Clinical Trials

In the intricate world of pharmaceutical development, the journey from a promising compound to a market-ready drug is certainly not linear. Amongst the many small wins come obstacles and challenges. How those challenges are managed in pivotal moments often defines success versus failure. One pivotal juncture in this voyage is the phase 2 clinical trial—a critical stage where the safety and efficacy of a potential drug are rigorously assessed. However, the success of phase 2 clinical trials does not solely hinge on scientific prowess; it requires a harmonious blend of clinical toxicology, quality assurance, regulatory expertise, and adept project management. It is akin to being an offensive coordinator who runs game plays in a key football match up, where each position plays a vital role, and a skilled leader is indispensable to anticipate the efforts. 

At the heart of this collaboration lies the need for a ‘quarterback’—a leader who not only understands the nuances of each discipline but also possesses the finesse to bring them together seamlessly. This quarterback is responsible for coordinating the game plays, ensuring that every aspect of the trial aligns with regulatory requirements, scientific standards, and operational excellence. They are key to creating a streamlined process set forth by the U.S. Food and Drug Administration (FDA). 

The FDA, with its stringent submission guidelines and specific format requirements, stands as the ultimate arbiter of a drug’s fate. Thus, having someone who speaks the language of the FDA, such as Halloran, becomes indispensable. We can navigate the regulatory landscape with finesse, speaking truth to power while mitigating risks and ensuring compliance. In this complex dance with regulatory authorities, transparency and accountability are paramount. With Halloran, the burden of regulatory scrutiny is shared accountability, alleviating the weight on the shoulders of the team and organization. 

Phase 2 trials demand intense scheduling, meticulous planning, and comprehensive summarization of data. Every move must be strategic, and every decision must be well-considered. It is not just about conducting experiments; it is about presenting a compelling case—one that convinces regulators of the drug’s potential while mitigating any concerns. With Halloran’s expertise, companies can navigate this maze with confidence, knowing they have industry experts by their side to ensure that years of development effort do not go down the drain. 

Moving from phase 2 to phase 3 is the culmination of years of planning, hard work, and strong execution—a transition that demands meticulous preparation. Success in phase 3 hinges on several factors: robust data from phase 2 trials, a well-defined regulatory strategy, efficient project management, strong clinical leaders, and the ability to address any skill gaps or expertise vacuums that may arise. It is about capitalizing on the momentum gained in phase 2 and leveraging it to propel the drug toward commercialization. 

Navigating phase 2 clinical trials requires more than just scientific acumen—it demands a multidisciplinary approach, effective leadership, and strategic foresight. With the right team, led by seasoned Halloran experts, drug developers can navigate the complexities of regulatory approval with confidence, ensuring that their journey from phase 2 to phase 3 is not just successful but transformative. 

Leveraging Outsourcing and Mixed Model Staffing Amid Layoffs: A Strategic Approach 

In the dynamic landscape of business, layoffs or losing momentum in a program with faulty data can often feel like a shotgun blast, leaving organizations scrambling to realign resources and maintain productivity. However, amidst the chaos, there lies an opportunity to adopt a more strategic approach to workforce management. As a leader facing either the decision or the fallout, outsourcing or mixed model staffing can not only mitigate the immediate impact of layoffs but also provide long-term cost savings and operational efficiency. 

1. Cost Savings and Reduced Overhead 

When faced with the necessity of shifting resources, companies often overlook the hidden costs associated with maintaining a full-time workforce. These costs include salaries, benefits, training, and infrastructure. By opting for outsourcing or a mixed model, organizations can significantly reduce these overhead expenses. Outsourced resources offer flexibility, allowing companies to scale their workforce up or down according to project demands, thereby eliminating the need for permanent hires and associated costs.  

2. Defined Start and End Dates 

One of the key advantages of outsourcing resources is the ability to establish clear start and end dates for projects. This ensures that organizations can align resources with specific objectives without the burden of long-term commitments. By delineating project timelines, companies can effectively manage budgets and allocate resources more efficiently.  

3. Addressing Gaps with A La Carte Solutions 

Layoffs often result in skill gaps within organizations, impeding productivity and progress. Outsourcing provides a solution by offering specialized expertise on a project-by-project basis. Companies can tailor their outsourcing arrangements to address specific skill gaps, thereby ensuring that critical tasks are completed without delay or compromise. 

4. Strategic Focus on Pain Points 

Rather than viewing layoffs as a signal to scale back operations, organizations can leverage outsourcing to strategically address pain points and optimize efficiency. Outsourced resources can provide valuable expertise into areas of improvement, helping companies streamline processes and reallocate resources more effectively. 

5. Tailored Solutions for Program Closure or Asset Maintenance 

Whether layoffs are prompted by unexpected clinical data or organizational restructuring, outsourcing offers tailored solutions to help companies navigate transitions smoothly. Outsourced professionals can assist with program closure, asset maintenance, or data management, ensuring that critical tasks are completed with diligence and accuracy. 

6. Enhancing Due Diligence and Regulatory Compliance 

In industries where regulatory compliance is paramount, outsourcing can provide a valuable resource for due diligence and compliance monitoring. Outsourced professionals can conduct thorough audits, perform regular outreach, and address data problems, thereby minimizing the risk of regulatory violations and associated penalties. 

In conclusion, organizational restructuring need not signify a retreat from productivity and progress. By embracing outsourcing as a strategic resource, organizations can navigate transitions with agility and resilience. Outsourcing offers a cost-effective solution to address skill gaps, optimize resource allocation, and maintain operational efficiency. Rather than viewing layoffs as a setback, organizations can seize the opportunity to realign resources, streamline processes, and position themselves for future success. 

Our Solution 

As a provider of clinical science lifecycle support services, our team of clinical operations experts takes on the roles to propel the success of your trial(s). We execute best practices, ensuring adherence to the highest industry standards. Our experts can evaluate the upcoming project deliverables, assess team dynamics, and identify risks and mitigations, all with a consistent focus on stakeholder needs. Whether you are experiencing staff turnover, your trial is experiencing significant issues, or you need solutions, we provide experienced resources to fill these gaps and help overcome study challenges.  

Implementing role-based engagements requires careful planning and communication, but the benefits can significantly contribute to the success of projects, teams, and organizations. We’re here to help.

Navigating the Path to FDA Approval: The Importance of a PDUFA Date

As a biopharmaceutical company advancing through the phases of clinical development, each step brings excitement and challenges. The decision to request a review date from the FDA, known as a PDUFA date, marks a significant milestone in the journey toward drug approval. However, this milestone comes with its own set of responsibilities and pressures. 

Understanding the Purpose of PDUFA 

The Prescription Drug User Fee Act (PDUFA) was introduced to address the growing concern over the FDA’s ability to review and approve new drugs promptly. Initially met with skepticism from the biopharmaceutical industry, PDUFA has since become a critical tool for both the FDA and drug makers. By collecting fees from drug companies, PDUFA ensures that the FDA has the resources necessary to review regulatory filings efficiently. Moreover, it establishes a clear timeline for the agency to make approval decisions, providing certainty for drug developers. 

The Importance of Rigor and Discipline 

With a PDUFA date in hand, the pressure is on to meet regulatory requirements and ensure a smooth path to approval. This requires a rigorous and disciplined approach to every aspect of the drug development process. From convening patient panels to inspecting sites for readiness, every detail must be meticulously managed to minimize risks and retain the certainty of the approval date. 

Navigating Treacherous Waters with Expert Guidance 

At this critical juncture, companies can benefit greatly from the expertise of organizations like Halloran. Acting as the harbor master, we possess an intimate knowledge of the regulatory landscape and can help navigate the treacherous waters of the approval process. From identifying hidden risks to providing guidance on inspection readiness, our team of experts is dedicated to ensuring a smooth path to FDA approval. 

Preparing for Success Beyond Approval 

While achieving FDA approval is undoubtedly a significant achievement, the journey does not end there. Companies must also prepare for the next steps, including commercialization and market entry. Failure to adequately prepare for these post-approval activities can result in delays and additional hurdles that may impact the success of the drug and the impact on patients. 

Halloran: Your Partner in Success 

At Halloran, we understand the challenges and complexities of the drug development process. With a proven track record of supporting companies through every stage of development, we have the expertise and resources to help you navigate the path to FDA approval with confidence. Whether you need guidance on inspection readiness or assistance with post-approval activities, we are here to support you every step of the way. 


Reaching the PDUFA date milestone is a testament to the hard work and dedication of your team. As you prepare to take the final steps toward FDA approval, remember that you are not alone. With the proper guidance and support, you can navigate the challenges ahead and bring your life-changing treatments to market sooner. Contact our Halloran team. We move forward to help you achieve success in the next phase of your journey. 

Moving Towards Sustainability in Clinical Research – a Call to Action  

The life sciences industry is becoming more focused on sustainability practices – a movement evident during the recent SCOPE summit. During my time at the event, I jumped at the opportunity to attend any session regarding advancing sustainability practices in clinical research. This is a subject of interest to me – not just from a personal perspective – but also from the lens of making a positive difference in my approach. 

SCOPE hosted several speaking sessions on reducing environmental impact in clinical trials, providing information about best sustainable practices. In one of the sessions, Jason Lanier, Environmental Sustainability Focus Area, Director, at Janssen Clinical Innovation, and David Lumby, Executive Director, EHS, at Thermo Fisher Scientific, shared their path towards sustainable clinical trials by identifying reduction strategies describing various hotspots of carbon emissions. They emphasized this is a collaborative effort to reduce the carbon footprint within clinical research. Jason Lanier later presented information regarding a clinical trial carbon calculator – a tool established to forecast the environmental impacts of trials. This tool will continue to be refined over time to improve usability and will become an open-access tool.  

On the last day of SCOPE, Michael Cohen, Senior Director of Environmental Sustainability, Strategy and Innovation, at Thermo Fisher Scientific, presented an overview of a pilot project that used self-driving, electric vehicles for patient clinical trial participants as a strategy to decarbonize patient travel and to also improve the patient experience.  

It was emphasized that there are additional strategic actions that can be taken to assist in moving the environmental impact closer to zero including site selection, recruitment, and the transport of patients. The goal is to continue to decrease the environmental impact and evaluate reductions in the short-term to have a long-term, positive impact.  

Following the summit, here are my reflections on new approaches to consider in your clinical trial design and operations to be part of the solution. 

Environmental Sustainability in Clinical Research: Approaches and Considerations 

As presented during one of the sessions at SCOPE, COVID-19 helped to propel and adapt processes that are more sustainable focused, but there is still more that can be achieved by the life sciences industry. Without sacrificing data quality or the patient experience, there are many aspects of clinical trials that have already become more environmentally friendly.  

Think about what you can do to be more efficient and to decrease the environmental impact of clinical trials. Here are a few approaches to bringing sustainability into clinical research.  

Meet the Patient Where They Are 

Transportation is one of the major contributors to global warming pollution. The average travel time for a patient to a clinical trial site is >2 hours.1 

Purchase Only What You Need 

Water is a Precious Resource That We Cannot Live Without 

Consider the Environmental Impact of Your Study Procedures 

It Has Been Reported That 20-30% of Established Research Sites Never Recruit a Patient1 

Stakeholders Can Serve as a Powerful Force for Change 

Raise Awareness 

In summary, global warming is directly impacted by increased greenhouse gas emissions. It produces devastating effects on our planet by accelerating climate change. 

Health Care Without Harm’s Health Care’s Climate Footprint green paper indicates the healthcare sector is a major contributor to the climate crisis –  “the greatest health threat of the 21st century – and therefore has an important role to play in resolving it.”2 The climate footprint from global healthcare is compared to the annual greenhouse gas emissions from 514 coal-fired power plants.”2 Imagine this, as quoted from the green paper, “If the health sector were a country, it would be the fifth-largest emitter on the planet.”2 

The life sciences industry can contribute to fighting the environmental crisis by making sustainable choices in the work we do. Start by focusing on the key drivers of emissions within clinical research because we all need to work together to converge on this topic as a shared purpose. Small changes can make a big difference. 

To discuss your clinical development and operations, contact Halloran. We’re ready when you are. 


  1. Pharmaphorum. “How are clinical trials becoming more environmentally friendly?” June 21, 2023. 
  1. Health Care Without Harm Climate-smart health care series Green Paper Number One. “Health Care’s Climate Footprint: How the Health Sector Contributes to the Global Climate Crisis and Opportunities for Action.” September 2019. 

Elevating Your Clinical Trial Audits with Artificial Intelligence and Centralized Monitoring 

Clinical trial audits serve as a tool to assess if a given auditee has the required qualifications and capabilities to conduct a set of tasks. Auditing assesses standards and regulations that have or will be met. Clinical trial activities may be delegated to vendors or suppliers, including Contract Research Organizations (CROs), sample processing laboratories, Contract Development and Manufacturing Organizations (CDMOs), imaging laboratories, Central Institutional Review Boards (IRBs), etc. 

In addition, audits can be used to verify the processes are followed, serving as a robust demonstration to health authority representatives that auditees are compliant and that processes impacting data integrity and patient safety have been thoroughly evaluated and vetted. Systematic audits instill confidence and assure regulatory bodies that the clinical trial sponsor maintains a vigilant oversight over every aspect of their clinical development program. 

While clinical trial audit programs can be tailored to support a sponsor’s requirements and goals, it is especially important to have a focused approach when conducting routine (data) audits (i.e., investigator site audits, Trial Master File audits, data management (vendor) audits, etc.) There are additional tools and tactics to identify data outliers that may pose a risk to their development program more efficiently. 

While attending the 2024 SCOPE summit, we listened to many sessions under the quality and monitoring and data tracks that resonate with our approach and client interactions. For example, assessing effective approaches for sponsors to review their data, identify outliers, and then remediate and act accordingly, are frequent conversations we have with industry.  

Coming out of the summit, we are even more encouraged to recommend ways to elevate clinical trial auditing practices to a more proactive approach. For example, by leveraging artificial intelligence (AI) and central monitoring (CM) generated data, sponsors (and auditors) may get a head start by reviewing AI or CM-generated information and proactively focus their data reviews in advance of their audit. We believe that if auditors are more equipped with the issues and risks in advance of the audit, they can conduct a more targeted data review and proactively identify potential non-compliances or observations. Here are our observations and recommendations. 

Leveraging Artificial Intelligence and Central Monitoring Outputs for Audit Preparation 

At SCOPE, there were numerous sessions on AI use cases across the life sciences industry, many of which focused on how to maximize the value of a company’s data. 

A common use case presented across these sessions was how to interact with the data using a more natural language where data analysis no longer needs to be done by data managers or statistical programmers. In a Chat GPT fashion, data reviewers could tell AI what data they wanted to see and how they wanted to see it. The data reviewer could then review the returned data set and drill down further without being required to write complex queries in a programmatic language.  

Leveraging AI to automate repetitive tasks was another prevalent theme during these sessions. Tasks, such as data analysis, can be accelerated with the identification of patterns and trends with machine learning, deriving actionable insights. Leveraging AI for data analysis also increases accuracy in finding outliers that were missed during human review to identify potentially missing data. 

This capability resonated with another repetitive task that is often overlooked or an afterthought until it is time for an audit – audit trail reviews. Audit trail reviews are key for a data integrity program to ensure the data is fully controlled, accurate, and complete; and until a problem has been identified, this activity does not always happen since it is generally a large data set that looks as expected. But this is a perfect use case for AI where a large data set can be analyzed by AI and outliers can be identified such as a user deleting a record with no reason documented or a user modifying a record that should not have access to that record. 

With the U.S. Food and Drug Administration’s (FDA) March 2023 draft guidance on Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations stating that sponsors, clinical investigators, and other regulated entities may be requested to provide all records and data needed to reconstruct a clinical investigation, including metadata and audit trails, it is clear this is a must-have.  

Utilizing CM data outputs to inform your clinical trial audits can make the selection of investigator site to audit straightforward. When preparing for an investigator site audit (ISA), the auditor may leverage CM metadata to select outliers to explore (i.e., investigator sites with high Serious Adverse Events (SAEs), protocol deviations, open action items, and data discrepancies) and zoom in on areas of risk efficiently.  

So, why not leverage AI to inform audit preparation and CM metadata to have more focused audit conduct by zooming in on the key outlier data to proactively identify and resolve areas of risk that may affect your clinical trial? The time is now. 

About Halloran’s Audit and Oversight Services 

At Halloran, we understand navigating the complexities of clinical trial audits requires precision, expertise, and a commitment to meeting the unique needs of our clients. Partnering with us will elevate your audit experience:  

Customized Audit Program Management and Execution: 
We pride ourselves on tailoring audit programs to your organization’s specific goals, objectives, and timelines   

Comprehensive Audit Support Throughout the Lifecycle:  
From inception to closure, we are your dedicated partner throughout the entire audit lifecycle. Our team doesn’t just develop programs; we stand by your side, offering unwavering support at every stage  

Client-Centric Approach:  
Your success is our priority. We craft programs aligned to your unique challenges and objectives to add the most value  

To discuss your audit strategy and approach, contact us today.

Quality Governance and Evolution of Quality Management Review 

Quality governance can be defined as an overarching framework that provides assurance of compliance with regulatory requirements, industry standards, and continuous quality improvement while enabling the risk and issue escalation process. Quality governance structures and processes provide transparency to an organization’s leadership on how well the Quality Management System (QMS) is functioning. It is through the evolution of Quality Management Review (QMR) that we can ensure continuing suitability and effectiveness by assessing an organization’s performance quality.

Today, with the rapidly changing regulatory environment and the upcoming adoption of ICH E6(R3)1, the concept of quality governance is being challenged across all organizations. It is no longer adequate to assume quality governance is a process owned by quality, but rather, it must be a responsibility retained by the entire organization. 

To take active steps in establishing effective quality governance, it is important to establish a clear pathway for issue escalation and information flow, paired with the distribution of adequate resources and support while driving the idea of continuous improvement.  

While acknowledging this can be overwhelming, here are essential considerations as you begin to build out your quality governance processes.  

Focus on Establishing a Quality Management Review (QMR) 

International Conference on Harmonisation (ICH) Q10: Guideline for Pharmaceutical Quality System states that it is essential for leadership to establish a company-wide commitment to quality.2 It is through the evolution of Quality Management Reviews that we can ensure continuing suitability and effectiveness by assessing the organization’s performance quality.  

It is a great forum to be able to evaluate the health of the QMS, review key quality metrics, discuss emerging trends, drive continuous improvements, assess resourcing, and share best practices. It is also an effective way to promote quality from top to bottom across an organization.  

The goal is to implement a culture of quality not only at an executive level, but throughout the entire organization. Proactively establishing a quality culture, where it’s recognized quality is everyone’s responsibility, will help the business to achieve and sustain compliance. A key foundation of establishing a culture of quality is by evolving a QMR, which allows organizations to take a more strategic and meaningful approach to quality and oversight by keeping everyone engaged. 

To evolve the Quality Management Review process, it is necessary to establish an organizational-wide QMR framework. A common pitfall when establishing a QMR framework is that it is only performed at higher levels of management. But when companies only have QMR at higher levels, there is no functional level transparency, and teams may have no interest because it is not apparent that quality is something for which everyone is responsible.  

A Quality Management Review needs to be a cascading framework that includes involvement up and down the organization to guarantee that quality governance fits into the organizational culture. 

QMR Can Be a Series of Reviews at Various Management Levels  

Holding a series of reviews at various management levels is an approach that allows timely and effective communication across the organization, creating an escalation process to raise appropriate quality issues to executive levels of management for review. However, if your organization is small, holding one QMR may be suitable.  

An example of the QMR hierarchy could be defined as executive level QMR, moving down to a departmental level QMR (i.e., research and development) and then to functional level QMRs (i.e., clinical, manufacturing, and regulatory). The inputs and outputs of each QMR are hierarchal with key information from the functional levels being reported up to a particular departmental level, and then again to executive levels. Quality initiatives and objectives are then disseminated from executive levels back down through the functional levels. In creating this framework, a culture of quality is promoted at all levels of the organization and incorporates all key stakeholders.

Once the QMR framework is established, the development of a quality plan is crucial to drive the process. Developing a quality plan at the executive management level allows for prioritization of key critical quality objectives for the organization. The quality objectives establish clear goals for the organization to achieve over a defined period, typically on an annual basis.  

At the executive level, the quality plan should be more strategic, focusing on overall organizational quality objectives, standardized quality metrics, identified risks, and continuous improvement initiatives. Once a quality plan is developed at the executive level, that strategic plan can then cascade down through departmental levels and then to functional levels. It is here that you will be able to take the strategic plan and adapt it to be more focused and tactical so that it is meaningful for each level of the organization. 

 Consider Differences in Priorities Across Business Areas  

For example, if a department area is Research and Development (R&D), the R&D quality plan will have different quality focuses and areas of identified risk than the next level quality plan for the functional area of Manufacturing. The department level plan will cascade down to the functional areas of the operation, with the flexibility for functional areas to further focus and establish their individual quality plans to be representative of the current objectives of that functional area.  

Functional area quality plans will differ based on their operations and risk evaluation. For example, clinical may focus on inspection readiness, risk-based auditing of sites, and protocol deviations, while regulatory may be more focused on Standard Operating Procedure (SOP) revisions for new regulatory requirements. 

Once your QMR framework and quality plans are established, you can also create standardized quality metrics for review during QMR. These actions are performed in tandem, but the quality plan should ideally highlight focus and risk areas for the year, while the standardized metrics are going to help monitor progress.  

To only incorporate performance metrics as part of a QMR without having a strategic quality plan may leave an organization in more of a reactive mode. 

Instead, strive to establish a quality plan that will drive the organization to reach a state of continuous improvement and standardized performance metrics, allowing for a measurement of that success or failure. Standardized quality metrics can include a variety of topics such as the number of regulatory inspections, audits findings, corrective and preventative actions (CAPAs), protocol deviations, serious safety issues, and training compliance. 

It is a good idea to define standardized metrics within a level specific QMR charter because that will ensure the organization states its purpose as a QMR and continues to observe and measure the same standardized metrics.  

At the functional levels, metrics will be more specific, and as outputs are rolled up throughout the QMR hierarchy, metrics begin to look broader and provide a better snapshot of the entire organization. 

So, You Have Established a QMR Framework, Quality Plans, and Standardized Metrics, Now What?

As the QMR framework matures and the organization becomes more sophisticated in using metrics, begin to establish Key Quality Indicators (KQIs) – a way to measure the overall success of an organization in meeting quality-based objectives. 

KQIs can also promote the development of Quality Tolerance Limits (QTLs) which is a level, point, or value associated with a parameter that, when deviation is detected, should trigger an evaluation to determine if there is a possible systemic issue.3 By utilizing both KQIs and QTLs, companies are able to respond proactively to potential issues at all levels in the organization and utilize the QMR hierarchy to elevate potential threats clearly and efficiently, ensuring appropriate risk-based action by the appropriate level of management. 

By building a quality governance framework, organizations are enabled to continue monitoring their QMS and focus on critical processes, championing continuous improvement. QMR allows organizations to reach their quality goals, concurrently enabling them to align with regulatory expectations. By building this QMR framework, and simultaneously promoting a culture of quality, they will begin to shift the view of the organization from being solely focused on compliance to that of more focused, quality goal setting, adopting a proactive posture and driving for continuous improvements.  

Need assistance with your Quality and Compliance program? Halloran teams provide QMS assessments, and design right-sized QMS’ to document processes, procedures, and responsibilities for achieving quality policies and objectives based on the size and operating model of their clients.  

Contact Halloran today. 


  1. International Council for Harmonisation Harmonised Guideline: Good Clinical Practice (GCP) E6(R3). May 19, 2023.  
  2. International Conference on Harmonisation Harmonised Tripartite Guideline: Pharmaceutical Quality System: Q10. June 4, 2008.  
  3. International Conference on Harmonisation Guideline Q9 (R1) on Quality Risk Management. February 3, 2023.  
  4. TransCelerate Biopharma, Inc. Risk-based quality management: quality tolerance limits and risk reporting. 2017.

Preparing Now for FDA’s START Program for Rare Disease Drug Developers 

On September 29, 2023, the U.S. Food and Drug Administration (FDA) took action to help further accelerate the development of novel drug and biological products for rare diseases. The action, an announcement of an opportunity for a limited number of sponsors to participate in a pilot program (Support for Clinical Trials Advancing Rare Disease Therapeutics (START)), allows for more frequent communication with the agency to address clinical development issues as they arise. 

As intended, insight gleaned from the START pilot program seeks to illuminate how best to propel more efficient development of potentially life-saving therapies with rare disease indications, as well as to guide sponsors towards generating robust high-quality and compelling data to support their future marketing applications. 

In recognition of Rare Disease Day, here is an overview of the START pilot program, expectations to consider if you are applying into the program, and early preparation considerations. 

START Program: Mission, Benefits, and Criteria 

The Orphan Drug Designation represents an important milestone for sponsors developing products for rare diseases. The designation carries significant benefits to the sponsor including tax credits, user fee exemptions, and market exclusivity. While the benefit of an early engagement with the FDA, such as a pre-Investigational New Drug (IND) meeting or an end of Phase 1 meeting, can certainly aid in the progression from an IND to approval, challenges remain for rare disease drug sponsors. 

All product activities (clinical, nonclinical, and chemistry, manufacturing, and controls (CMC)) in these development programs are challenged by multiple factors associated with expedited rare disease development programs. For example, clinical development must balance what is typically considered appropriately designed clinical trials against the ability to recruit patients (i.e. size and location of patient population), challenges in the use of placebo, and the small but robust clinical dataset intended to show substantial evidence of safety and efficacy. Encouragingly, these challenges have been recently highlighted by top FDA officials, including FDA commissioner Robert Califf, where he notes, “We’re about to see a tsunami of therapies for rare and ultra rare disease, and I don’t think any of us think the current pathways are optimal.”  

In hopes of addressing these challenges, the FDA has launched the START program, which will be open to up to three sponsors in both the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). The pilot program’s focus is to provide opportunities through the currently available meeting types for increased communication to aid in moving towards submission of a Biologics License Application (BLA) or a New Drug Application (NDA).  

For the initial pilot, the FDA has established program criteria: 

The third criterion differs for applicants of CBER and CDER: 

START applications for this initial pilot program are due to the sponsor’s IND no later than March 1, 2024, and require inclusion of the program development plan and status for CMC, nonclinical, and clinical. The sponsor should highlight the specific issues they are seeking enhanced communication with the FDA to address, and the timeline for the studies intended to provide the primary evidence to either support approval or future pre-BLA/NDA meetings. 

Selection will be based on the application criteria and factors such as potential clinical benefit, perceived benefit of enhanced communication to the proposed complications, breakthrough designation status, and the FDA has noted that for the initial pilot, significantly complicated combination products may be less likely to be selected.  

As this is the first year of applications, there is a vagueness to the selection criteria for the program, which will undoubtedly be further defined as the program develops. For instance, the program does not specifically require sponsors to have clinical data (just potential for clinical benefit); however, applications with clinical data may be able to better demonstrate their pathway to marketing application. As the START program further develops, this will be an aspect for early-stage IND programs to watch.  

As the START program is in its pilot stage, the exact implementation of ‘enhanced communication’ is still not clear. However, previous agency programs (i.e., the Emerging Technology Program) may give some insight into how this may occur. It is unclear at this stage if a specific group within the agency will be created and be responsible for these programs (i.e., the Emerging Technology Team), but the additional agency resources along with opportunities for additional and enhanced communication could address the potential pitfalls of program development.   

Early Preparation Considerations 

While much will be learned from the initial pilot program to aid potential applications for 2025, if the agency opens additional spots, sponsors should start to prepare now. The document will require significant cross-functional team input and sponsors should view the work at the level of a FDA meeting package. Addressing all aspects of development in meaningful detail will require the sponsor to plan, discuss, and agree upon reasonable development timelines prior to drafting. Sponsors should ensure their program management or regulatory teams have insight into all development plans across clinical, CMC, and nonclinical in preparation for preparing the application to ensure all challenges and discussion points are covered.  

Halloran can assist clients through these significant program management barriers to develop a successful START application, and partner on their continued rare disease program development journey through our clinical, regulatory, and program management expertise.  

Throughout the year, the START pilot program will be closely watched for aiding the selected sponsors in progressing the development programs for these rare diseases. The program will not fix all issues plaguing the development of products for rare diseases; however, the program offers the potential to alleviate many of the pitfalls sponsors encounter. The success of the pilot program will hopefully lead to increased opportunity in the 2025 application process in terms of the number of accepted applicants or expanding the eligibility criteria, and subsequently, the speed and ease at which these necessary products can be brought to market. 

The effect of the START pilot program will be closely watched for its potential success in developing programs through approval and for the trends in accepted programs.  

As you move through the early phases of clinical development, now is the time to consider and plan for the START program application as part of your regulatory strategy. Contact our team today to further the conversation. 

Small Biotech and Pharma Dilemma – Three Steps to Remain Competitive on a Budget 

While attending the annual SCOPE summit this year, listening to sessions and walking the exhibitor hall, a strong question, for me, resonated throughout the entire experience. That is, how can small biotech and pharmaceutical companies stay competitive within their realm by leveraging opportunities to advance clinical research while still navigating resource constraints?  

Let’s break this down. 

Large organizations are often backed by vast resources and deep-rooted market presence, often making it easier for them to leverage tools and technology to discover efficiencies and enhance their clinical research outcomes. Efficiency often means faster, and faster in clinical research, means money saved and potential speed-to-market. 

Over the past few years, there has been a surge in technology and services, all offering a speedy outcome. For example, Artificial Intelligence (AI) tools can support clinical research site optimization to reduce site startup timelines, clinical trial training vendors offer protocol compliance for patients and sites to reduce risk and enhance retention, and full-service decentralized clinical trial vendors offer full data management visibility, just to name a few tactics. 

But how can smaller organizations with limited resources take advantage of tools and technology (and make the right selection) with limited employees, funding, and perhaps, expertise? This question seeks to address and solve this dilemma: how to not get left behind in an environment where opportunities may not be as easily accessible for smaller organizations. 

In this article, I explore considerations for the smaller players to think like big players to remain competitive and discover efficiencies without breaking the bank and ‘keeping up with the joneses.’  

Step 1: Assess Roadblocks to Your Organizational Structure and Pipeline 

First, take a holistic view of your company’s organizational structure and pipeline, and seek to answer the following questions around what may be preventing you from getting to market more quickly. 

Step 2: Evaluate Tools and Technology Rightsized for Your Organization 

Approximately 1,000 vendors attended the SCOPE summit; the exhibitor hall was full of taglines promising faster data, improved speed to market, and patient data collection tools allowing for an easier and more efficient clinical trial experience for the entire clinical research ecosystem. Hypothetically, new CEOs of small biotech or pharmaceutical companies may believe their teams could complete a clinical trial in an unreasonably fast timeline if they utilized such tools. 

But what are the best practices when sorting through these options, particularly on a budget? First, ask the vendors the hard questions, including: 

Then, consider the resources needed to oversee the vendor, service, or product, and assess the lift on the employee(s). Fit the technology into the company based on your strategy and priorities, but do not overhaul your company for new technology just because it’s popular. Rather, prioritize the technology based on your company’s top priorities so that you right-size your selection(s). Ultimately, this is an approach for small biotech and pharmaceutical companies to stay competitive.  

Taking this critical and evaluating lens into vendor selection is essential. For example, there are more options than just the largest, more expansive Clinical Research Organization (CRO) available, and there are many vendors stating they offer similar clinical research outcomes. Since vendor selection is not a one-size-fits-all approach, if you are aligned with your strategy and priorities, that framework will successfully guide you in your evaluations and selections. 

Step 3: Decide and Execute, But Not Before Developing Your Oversight Plan 

So, you’ve decided to move forward with a tool or technology for your company. Before you purchase, the next important steps are developing an oversight plan and then executing on your decision.  

When evaluating and selecting a new technology, assessing oversight infrastructure and processes is a must. In addition to processes, you will need to establish accountability and responsibility for oversight tasks and how those processes and tasks will be documented. In addition, you will need to determine the appropriate level of oversight required. If the oversight plan hasn’t been fully developed, this is the time to do it before implementing your new technology.  

The oversight plan will outline the “who, what, and when” of bringing in a new vendor to your organization. While this plan may seem like another document, it details the communication structure between the sponsor and vendor and includes escalation pathways to follow if (and when) issues arise. The plan should outline the roles and responsibilities of individuals at both organizations, making it easier to understand peer-to-peer communication pathways. Clear timelines on deliverables should be documented, as well as the individuals held accountable.  

This plan should also include a governance structure to guide and manage the sponsor-vendor relationship, as well as processes to mitigate risks and actions in real time to prevent issues from escalating, as there will be documented mechanisms to identify risks. Upon completion of the oversight plan, teams across the organizations should feel confident in their processes, enabling a roadmap to success. 

A common clinical trial inspection finding by the U.S. Food and Drug Administration (FDA) is inadequate monitoring of clinical trials, so developing this plan is a critical foundational activity for the success of any trial.  

In summary, when faced with many opportunities and options to enhance your clinical research processes, timelines, and outcomes, if you prioritize your employees and their journey throughout your organization, you’ll often find the best roadmap to success and stay competitive within your realm. 

Passionate employees with the right skillset and mindset who believe in your company’s mission will often make as strong of an impact as the latest tool on the market. Tools, technology, and innovation are important in the clinical research space, but the key lies in the balance for small biotech and pharmaceutical companies to stay competitive and successful, especially on a budget. 

To discuss your Clinical Operations and Development approach and strategy, contact Halloran.