Page 7 | Advarra

A well-trained, effective, and efficient team is key to a successful clinical trial. Especially in the post-COVID world of changing work modalities, implementing a training program can seem more confusing than ever.

The forced exodus to all-virtual environments opened the door to more flexibility in developing and delivering training. With the changed landscape, training now has the potential for greater effectiveness and efficiency. Finding the best solutions starts with evaluating your training needs. Let’s review the breakdown of types, goals, principles, and strategies for ensuring you have a trained and effective team.

The Three Models of Site Training

With so much material to cover, it can be difficult to know where to start. Also, there are different ways to convey the same information. When thinking of the best training avenue for your audience, think of three common training models:

Live training: Always synchronous (scheduled/real-time interactions), delivered in person or virtually
eLearning: Delivered live, self-paced (asynchronous), or scheduled
Blended: Delivered in person and self-paced, live virtual and self-paced, or in an asynchronous cohort

Each model has its benefits and its drawbacks. Live training can be conducted in person or virtually. This type of training means immediate feedback, and gives the option for live coaching and community building. But live training is both tricky to scale up and more expensive, given the costs of travel, time, staff, and space. Additionally, the information is delivered outside of the work environment, meaning it’s decontextualized and possibly less sticky.

eLearning, which became ubiquitous during the pandemic, offers a unique set of benefits, including:

Improved knowledge retention
Consistency
Cost efficiency
Easy to scale and schedule

Keep in mind, however, eLearning programs require a big upfront effort and expense to develop, not to mention technologic proficiency.

A blended approach combining live and eLearning models is often the best of both worlds, facilitating knowledge retention, efficiency without losing contextualization, lower cost to productivity, scalable, easy to schedule, consistent, and can include live coaching. Again, scheduling and developing resources remain the key challenges for the blended model.

Training Principles, Motivations, Tools, and Success Metrics

Advarra looks at training through the lens of awareness and automation, in which the type of retention required drives the degree of automation used in the training. For example, if an employee needs to simply remember things, high automation – such as eLearning – may be perfectly sufficient. If an employee needs to understand and execute complicated steps, live training may be most appropriate.

Understanding the “why” behind training is crucial for adult learners. While the significance of communicating the training’s relevance is always important, it’s even more pressing in the context of eLearning. Here are four principles to follow when developing your training program:

Make sure your staff knows the “why” behind the material
Be clear on when and how they will use the skills they are learning
Use examples of past successes and highlight problems training solves
Offer ways the employee can continue training on their own via self-guided materials and other resources

Creating, Delivering, and Tracking Your Training

Fortunately, many of the tools necessary to create and deliver content are probably already in house. Content production tools include the Microsoft Office suite, Adobe suite, Articulate Suite, Google Suite, and smartphones. For content delivery, consider Zoom or other teleconference products, email platforms, messaging tools, QR codes, wikis, and SharePoint. To deploy, track, and measure results, consider Office Suite and/or Google Suite: O365 Power Automate, Google forms, wikis, the company’s intranet, and even a simple spreadsheet.

Metrics of Success

Finally, how do you assess a successful training? Has the information stuck for everyone? There are several metrics, from anecdotal to measurable success. Live trainings rely on staff feedback, user surveys, and the instructor’s impressions, as well as quizzes and/or projects, which is also useful for eLearning. A longer-term metric is simply on-the-job feedback from supervisors and job performance reviews. As your training program grows, keep track of the results and adjust your approach accordingly.

How Advarra Creates Scalable, Effective, and Efficient Training

No matter where you are in your company’s training program, Advarra Training can make it more effective with our three tiers of training, divided by effort through the lens of production and delivery.

Tier One: Easy-to-scale, high-production effort wherein the employee does the training virtually and asynchronously, with self-service access to existing content provided and delivered by Advarra.

Easily scaled, low effort
Client uses existing Advarra resources
Low effort by client involvement

Tier Two: Training involves low production effort and medium delivery effort, meaning we work together to adapt training materials to your needs. Materials can be streamlined but are not automated.

Scalable, but with more effort
Client pays for Advarra’s time
Train the Trainer and Trainer Bootcamp options

Tier Three: High production and delivery effort wherein Advarra creates training for your staff, finding novel solutions to novel problems and providing templated, non-automatic solutions where efficient.

Lowest scalability, has concentrated impact
Client pays for Advarra’s time, expertise, and access to unique resources
Includes contextualized training, paid product training, and certifications

As a partner, Advarra brings certain advantages, insights, and products, including learning management system (LMS) capabilities with a robust eLearning library, reducing the upfront burden of creating your own eLearning program. Learn more about our custom LMS portals, good clinical practices (GCPs) training, HIPAA learning program, and more.

Institutional biosafety committees (IBCs) frequently receive questions about the proper methodology for preparing a syringe for transport from a drug room or pharmacy to the clinic where the injection will be administered. This article explores tools and techniques to safely mitigate occupational exposure risks when preparing a syringe for transport to the clinic. (buy zolpidem overseas)

Sharps Precautions

A sharp is an instrument capable of puncturing, cutting, or scraping the skin, typically in the form of syringes, needles, or scalpel blades. Care must be taken to avoid sharps-related injuries and exposures. Injuries from sharps in a research or clinical setting are a serious problem for employees, as the CDC estimates almost 400,000 needlesticks and other sharps-related injuries occur to healthcare personnel each year. These injuries are often associated with occupational exposure to human bloodborne pathogens such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV).

Healthcare workers are frequently taught never to recap syringes after use. However, when preparing an investigational product (IP) in a drug room or pharmacy, you need to recap the syringe and transport it to the clinic for injection. There are two things to bear in mind when doing so:

Do not simply recap a syringe or transport an uncapped syringe from one room to another
A loaded syringe can be safely capped using either:
- A safety engineered syringe
- The one-handed scoop technique
- A recapping tool
- Tools or special sharp containers to remove the needle and replace with a fresh and already capped needle

Personnel must be familiar with the design and use of safety sharps in order to use them properly. The images below include examples of safety sharps and tools for safely recapping syringes.

If safety sharps are not available, use the one-handed scoop technique to slide a needle into a cap laying on a horizontal work surface. The main idea is to not hold the cap with your hand to avoid accidental needle sticks. Once the needle is in the cap, it can be safely secured with the free hand.

Another approach involves a recapping tool to hold the cap while recapping, rather than relying on one’s hand. Tools can also be utilized to remove the needle prior to replacing it with a fresh and already-capped needle.

All potentially infectious sharps must be disposed of in a biohazard sharps container immediately after use without recapping. Needles must not be bent or sheared.

Safety-engineered Syringes

Recapping tools

Needle Uncapper, Recapper & Syringe Holder

Transport to the Clinic

Once loaded and capped, the syringe must be transported to the clinic in a sealed, leak-proof, and biohazard-labeled container. The container can be a rigid plastic container (e.g., Tupperware) or a designated IP transport container. The secondary container is intended to prevent IP spills if the syringe is either dropped or damaged and leaks.

The IBC’s Focus on Occupational Safety and Environmental Protection

The IBC’s role under National Institutes of Health (NIH) Guidelines is to assess and mitigate risks in research involving engineered genetic materials. The IBC reviews the risks associated with the IP as well as the containment and safety practices for use of the IP at the research site in order to protect the research staff’s safety. The IBC also looks to protect the public health of the community around the site and the environment. Components of the IBC’s review include safety practices for use of the IP as well as incident response plans for handling spills, occupational exposures, or environmental releases.

If you’d like to discuss safety practices for performing research with engineered genetic materials at your site, contact us at IBC@advarra.com.

In the last few years, the clinical research industry has seen a bigger push for electronic informed consent (eConsent) than ever before. Although it’s becoming more widespread, there are currently no definitions for eConsent in the Human Subjects Protection– it’s a concept only described in guidance. eConsent typically refers to the use of electronic systems and processes to:

Convey information related to the study, and/or
Obtain and document informed consent

These parameters are broad and vague. eConsent can include something as small as research staff collecting an eSignature via PDF, or as large as using a comprehensive eConsent platform. Essentially, if any component of your informed consent process involves an electronic aspect, you’re conducting eConsent.

A Note on 21 CFR Part 11

21 CFR Part 11 only applies to studies subject to FDA oversight. However, even if your study is not subject to FDA oversight, it’s a useful framework as you navigate how to use your eConsent system. Even if it may not necessarily apply, the FDA has documentation on electronic consent and record keeping to consider as you develop an eConsent process.

Consent Requirements Through an eConsent Lens

In the world of eConsent, general informed consent requirements still apply. No matter what type of study is conducted, research staff must convey information about the research in a way so the prospective participant has sufficient opportunity to discuss and consider whether or not participation is right for them. Consent language must be understandable, presented in lay terms, and without exculpatory language. Additionally, the eConsent process must minimize the possibility of coercion or undue influence.

For studies subject to the Revised Common Rule, there are additional requirements. Participants must receive information a reasonable person would want to have, and the process must begin with a concise and focused presentation of key information. Staff must also organize the consent process to facilitate potential participants’ understanding.

Additional Legal Considerations in eConsent

If your study includes an eConsent component, there are additional legal considerations. For example, eSignatures must be valid, and your team must be able to confirm the identity of the participant signing the form. The person signing the form must also be legally able to consent. Thinking about ways to confirm this, as well as accounting for when a legally authorized representative (LAR) may provide consent on behalf of a subject, is critical before even rolling out an eConsent.

An eConsent must also be easy to understand for the participant – which, in most cases, is easier to do via an electronic platform than through paper consent forms. eConsent provides a unique opportunity to ensure the participant truly understands the consent form. Both text and information delivery can become more dynamic, giving staff the opportunity to ensure participant comprehension. This may ultimately lead to fewer dropouts as the study moves along.

Although eConsent provides a greater opportunity for understanding the study, you still need to develop a way for participants to openly discuss what they are reading about, giving them room to ask questions. Additionally, there should not be skip logic in the consent such that a prospective participant can skip crucial research information – all consent content must be presented to the participant so they can review the information and consider it before proceeding.

Institutional Review Board (IRB) Review of Consent

Before using any part of eConsent in research, it must be reviewed and approved by an IRB. While this process is specific to Advarra, your IRB may operate similarly. It’s best to confirm with them before moving forward. When seeking IRB approval at Advarra, the sponsor and site will attest that their eConsent system/process, along with the protocol plan to obtain electronic signatures, conforms to regulatory guidance and IRB ethical expectations for obtaining documented research consent.

Sponsors and sites can provide attestation through responding to a series of statements within the IRB submission. The IRB evaluates responses to the series of attestation statements, and then issues approval to use eConsent. If the IRB has any questions or concerns, they will address them prior to approval.

After the IRB initially approves eConsent usage, they will likely place expectations on the site or sponsor. Prior to using eConsent, submit any subject-facing materials, such as web-linked materials, graphics, glossary, etc. If the eConsent system or protocol plan to obtain documented eSignatures changes, the site or sponsor should submit a modification.

A rare, or orphan, disease by definition affects a small percentage of the population — fewer than 200,000 people in the U.S. But the numbers add up, and taken together, rare diseases impact an estimated 30 million Americans. Orphan drugs have historically faced a number of barriers, such as limited research and development (R&D) investment due to an expected lack of profitability as well as challenges in clinical trial design and recruitment. Before 1983, only 38 orphan drugs had received U.S. Food and Drug Administration (FDA) approval. Since then, the FDA has significantly changed its approach to rare and orphan diseases.

The FDA Since 1983

The Orphan Drug Act of 1983 was instrumental in changing the number of orphan drugs approved in the U.S. The law established the Office of Orphan Products Development, providing financial incentives for pharmaceutical companies to develop orphan drugs and making it more viable to invest in orphan drug research and development. The impact was clear: Between 1983 and 2020, FDA approved 599 orphan drugs.

Since 1983, the FDA has continued to expand its attention to rare diseases and the drugs treating them. In 2016, the FDA granted 333 (57%) of the 582 orphan drug designation requests it received – nearly 10 times the number of designations the agency awarded in 1986.

The agency’s 2019 guidance, Rare Diseases: Common Issues in Drug Development, called attention to the need for natural history studies for rare diseases. The guidance provided the agency’s thinking on the design and implementation of such studies. It also broadened eligibility for orphan drug clinical trials conducted to demonstrate safety and effectiveness of orphan drugs. Today, nearly a third of all pipeline drugs are indicated for rare diseases, and the FDA continues to provide public support for awareness programs, such as 2022 Rare Disease Day.

FDA Expedited Programs

While the Office of Orphan Products Development is responsible for reviewing applications and assigning orphan designations, it is not involved in a drug’s approval. That is part of the responsibility of the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER). These centers, in conjunction with the FDA and U.S. Department for Health and Human Services (DHHS), prepared guidance on expedited programs for sponsors of orphan drug trials.

Because most rare diseases are indeed “serious or life-threatening disorders with unmet medical needs,” orphan drugs may be able to take advantage of at least one of the FDA’s four expedited programs:

Fast-track designation: Helps get drugs treating serious and life-threatening conditions to market as quickly as possible
Breakthrough therapy designation: Gives priority review to therapies offering substantial advantages (based on early clinical trials) over existing options for patients with severe or life-threatening diseases
Priority review designation: Indicates the FDA’s goal of taking action on the application within six months
Accelerated approval: Allows drugs for serious conditions filling an unmet medical need to be approved based on “a surrogate endpoint”

Other FDA Orphan Disease Focus Areas

The FDA and the life sciences industry recognized the impact of the Orphan Drug Act and the advances in medicine over the past few decades. In order to support the continued need for rare disease drug development, the FDA took action to ensure they could continue to drive progress in this area. In 2017, the agency launched its Orphan Drug Modernization Plan, designed to help enable a “more efficient, scientifically advanced, predictable and modern approach to the approval of safe and effective treatments for rare diseases.”

In addition, the FDA funded the Rare Disease Cures Accelerator, which set out to facilitate cooperation and standardization to enhance the clinical trial process for rare diseases. This initiative includes a data analytics platform, RDCA-DAP. The platform aims to use standardized data to “inform rare disease characterization, clinical trial design and other critical questions in rare disease drug development.” By pulling together existing data and making that data available, RDCA-PAP seeks “to accelerate the regulatory approval of new therapies.”

A Lasting Impact

Through its various initiatives and programs, the FDA shows a demonstrated, increased effort in supporting the development of rare and orphan drugs. This is especially important as we consider roughly 90% of rare diseases have no approved treatment and orphan drug development takes 18% longer than the average time required for new drugs, according to the Tufts Center for the Study of Drug Development.

However, it remains important to plan and seek expert advice as early in the development process as possible. Partnering with experts with FDA and orphan drug experience is key to successfully navigating the regulatory environment for rare and orphan diseases.

Perhaps one of the most important aspects of a clinical trial is the informed consent process. Stemming from the ethical principle of Respects for Persons in 1976, the Belmont Report established informed consent parameters, a process designed to provide information to allow potential participants to make the best decision for themselves. This must occur prior to participating in the research.

Since then, there have been U.S. federal regulations established for informed consent, primarily through OHRP, and codified in 45 CFR 46.116 and 46.117. FDA-regulated products are codified in 21 CFR 50.25 and 50.27.

Currently, there are no federal regulations specifically covering electronic consent. This blog defines eConsent, offers considerations for conducting eConsent, and navigates communicating with your institutional review board (IRB) as you figure out how to include this process at your organization.

What is eConsent?

Simply put, eConsent is the documentation of informed consent that is done electronically. It can facilitate informed consent over long distances via methods such as video conference, telephone, or eConsent platform.

Using various media can enhance the potential participant’s understanding of the clinical trial while being more interactive. eConsent can include hyperlinks, images or videos, and other interactive elements. The idea is to give potential participants a better understanding of things such as definitions, procedures they will have, or perhaps what it will look like to them the day they come into the clinic, all in an understandable and easy-to-read format.

eConsent is not an all or nothing process, and it does not mean you will conduct all of your informed consents virtually, remotely, or without study team interaction. Depending on your study type and needs, eConsent can be used:

A fully in-person consenting workflow
A fully virtual or remote consenting workflow
A hybrid in-person and virtual consenting workflow

Moving to an eConsent method should positively impact your staff and study timelines, too. Ultimately, you should want to see staff time going toward meaningful and valuable things. From a data perspective, on average, 5-8% of data entered is wrong – think one in every 20 fields has an error. If your organization can reduce errors through having correct dates in the right places and documents where they need to be, it will benefit researchers analyzing data, the monitors, and the rest of the staff.

eConsent Considerations

There are many elements to consider when designing a research study to include eConsent, including programmatic, study, and regulatory factors.

Programmatic

You should understand if your research site can access proper technology to adequately execute an eConsent process. Technology should enhance the process, not become burdensome. Is it easy to use for your coordinators? Ask yourself this question before implementing a process on coordinators that could potentially add more work on top of what they’re already doing.

It helps to create template plans and standard operating procedures (SOPs) outlining how to conduct a consenting process over video conference, phone, or without any direct contact. As staff talk to potential participants, they will need to have account access to record information and track consenting. These SOPs should help everyone understand how to make the process more sustainable. It also helps to work with your IRB to create consistencies across studies to avoid study deviations.

Study

Using eConsent still needs to make sense to both staff and participants. As previously mentioned, using eConsent doesn’t mean all informed consents are conducted without an in-person component. Keeping this in mind, study staff will need to decide who needs to be in the room while having these conversations.

Additionally, there must also be a component defining how staff will assess participant understanding. There are many factors to consider as you ensure your participants will still understand the consent process, including:

Do they have technology available and know how to use it?
Is the informed consent form (ICF) in their primary language?
Are you gaining their trust before inviting them to participate?
Do they know how to get any study questions addressed?

Regulatory

Staff teams must also make sure regulatory compliance is upheld during the electronic consenting process. If you’re conducting Food and Drug Administration (FDA)-regulated research, electronic signatures will fall under 21 CFR Part 11 compliance. In order to meet this standard, you must make sure both your platform and processes are validated before moving forward.

For non-FDA-regulated research, participant confidentiality is still of utmost importance. Data, including participant signature, name, and identification in the research, must also be protected. Enforcing processes will make sure everything is protected.

Communicating With Your IRB

As your organization begins to move towards an electronic consenting process, you must communicate with your IRB. Keep in mind, the IRB only grants permission, not forgiveness. Your IRB must issue approval on your processes prior to using eConsent.

Your IRB will have many of the same considerations for an eConsent process as a traditional consent process. They’ll look for components such as if the consent form is in a participant’s primary language and uses understandable terms. Participating in a clinical trial often takes up a considerable amount of time for a participant. The IRB will want to know if they are given opportunities to ask questions during the consenting process, receive clarifications, and have time to decide if this opportunity is right for them.

Lastly, technology is a huge component of eConsent. With this in mind, IRBs will want to know how equitable selection of participants occur. Will technology usage inhibit people with impaired access from being able to participate? Having these questions at the ready as you approach your IRB will help keep the process smooth and show the IRB you’re keeping the participants in mind.

Institutional biosafety committees (IBCs) frequently receive questions about the proper type of hood for use with biological materials and the difference between biosafety cabinets versus clean benches. While both pieces of equipment are hoods with directional airflow, they function differently and are intended for different purposes. This article explores how these tools work and why biosafety cabinets are preferred in research involving cell and gene therapies.

What is a Biosafety Cabinet?

Biosafety cabinets (BSCs) protect the product as well as the user and the environment. They operate under negative air pressure (i.e., suck inward), protecting the user from exposure to aerosolized infectious agents. The air sucked into the hood is sterilized by high efficiency particulate air (HEPA) filtration before being exhausted out, thereby protecting the environment.

How is a Biosafety Cabinet Different from a Clean Bench?

Clean benches or laminar flow hoods work under positive air pressure (i.e., blow outward) and are only intended for work with non-hazardous materials. Use of hazardous materials in a clean bench can increase the risk of occupational exposure and contamination of the room in which the work is being done.

We’ve also created the following quick reference guide to illustrate the difference between these tools and their airflows.

Biosafety Cabinet (BSC)

BSCs operate under negative air pressure (i.e., sucks inward), protecting the user from exposure to aerosolized infectious agents. Any infectious aerosols are sucked in through the grills positioned at the front and back of the work surface and removed by HEPA filtration. The hood also blows sterile (HEPA filtered air) from the top down towards the work surface to protect the product from contamination with non-sterile ambient room air.

Clean Bench or Laminar Flow Hood

Clean benches are only intended for work with non-hazardous materials. A clean bench operates under positive pressure and blow sterile (HEPA filtered) air towards the worker, preventing the product from being contaminated with non-sterile ambient room air. If a clean bench is utilized with infectious agents or other hazardous materials, it will blow those materials towards the worker and increase their risk of exposure. It will also spread contamination throughout the room.

Why Does the IBC Prefer Researchers use a Biosafety Cabinet vs a Clean Bench?

BSCs provide a greater measure of safety than working on a countertop. They provide sterile air to prevent environmental contamination of the investigational product and sterilize the exhaust air to prevent occupational exposure and environmental release of the drug. In the case of IBC review, we’re preventing exposure to biologics such as engineered genetic materials and/or infectious agents.

Disinfecting Work Surfaces in Clean Benches and Biosafety Cabinets

Work surfaces, such as the horizontal surface inside the BSCs, must be disinfected following work or spills involving biohazardous materials. Disinfectants registered with the Environmental Protection Agency (EPA) should be utilized. Also, be mindful of whether the disinfectant is compatible for use with the hood’s metal surface. Some research sites utilize 10% bleach solutions for disinfection. Bleach is corrosive and can cause metal surfaces to rust if left on the surface for extended periods. If you utilize bleach to disinfect metal surfaces, remember to remove the bleach after sufficient contact time has elapsed for disinfection (i.e., 5-10 minutes), and then remove the bleach with either water, 70% ethanol, or other disinfectant wipes to protect the metal surfaces.

Not all hoods are created equal. While a BSC provides greater protection of the investigational product, the research staff, and the environment, a clean bench can actually increase the risk of occupational exposure, contaminating the pharmacy area, and environmental release with the investigational product.

Cannabis use has become widespread. As such, we are seeing an uptick in research examining the therapeutic effects of cannabis and its constituents.

Currently, cannabis use is legal across many states in the U.S., with 37 states approving medicinal use and 18 approving recreationally. However, it’s not legal federally and is considered a Schedule I drug by the U.S. Drug Enforcement Administration (DEA), meaning it has no accepted medical use and a high potential for abuse.

While there isn’t a significant amount of research on cannabidiol (CBD), it’s easily accessible in the U.S. Even though CBD and cannabis usage has grown, and marketing claims have proliferated regarding potential therapeutic applications, there is still little research on their effects on the human body. This can make research challenging, but not insurmountable. How can researchers further the investigation of cannabis and CBD in research?

The 2018 Farm Bill

In order to understand the current status on cannabis and CBD research studies, it’s important to understand where each product stands. The 2018 Farm Bill removed hemp from the Controlled Substance Act. Cannabis plants and derivatives containing no more than 0.3% THC are no longer controlled substances under federal law. So, cannabis derivatives in the form of CBD then became legal in all 50 states.

Importantly, the 2018 Farm Bill preserved FDA authority to regulate products with cannabis or cannabis-derived compounds under the Federal Food, Drug, and Cosmetic (FD&C) Act and Section 351 of the Public Health Service Act. Cannabis and cannabis-derived compounds are treated the same as other FDA-regulated products and subject to the same authorities and requirements.

With the exception of one highly purified form of CBD (Epidiolex), no other CBD products are currently FDA approved. In order to treat diseases or be used therapeutically, drugs must either receive premarket approval through the FDA’s new drug application (NDA) process, or conform to a “monograph” for a specific drug category, which fits under FDA’s over-the-counter (OTC) drug review.

Even though the 2018 Farm Bill makes it legal for U.S. citizens to purchase and use CBD, it’s not lawfully marketed under the FDA and doesn’t meet investigational new drug (IND) exemption criteria of a lawfully marketed product.

Funding Research on Cannabis

Even though CBD doesn’t meet criteria for IND exemption or the FDA’s OTC drug review, it still can be studied in humans. Some may wonder, is the FDA open to approving and funding research on cannabis? The short answer is yes.

With this in mind, when researchers submit a new study involving CBD for IRB review, they must consider whether they need an IND for CBD as a drug. Examples of this might include investigating CBD to treat neuromuscular pain, nausea, or a project exploring whether CBD is a potential treatment for smoking cessation. The FDA is granting INDs for such CBD research.

Scientific and Ethical Challenges

With the limited background information currently available in cannabis research comes scientific and ethical challenges researchers and IRB reviewers need to be aware of.

One such challenge is the lack of standard formulation of CBD. Each type varies in strength based on the grow of the plant and extraction methods, and it also may vary in administration roots. As such, there are implications in standardizing doses and for reproduction of research results. One key element in IRB review is consistent dosing. IRB reviewers want assurance each participant receives the same level of product throughout the entire study and, ideally, potency levels remain consistent from one study to another.

Finally, while CBD is generally well tolerated, it is not without risks, especially when used with other drugs and all protocols should have considerations and monitoring for subject safety.

Advarra experts Sharon Ayd and Leslie Paul answer questions from their webinar, The IND Journey Phase I – Navigating Success.

Q: If an emergency use authorization (EUA) is granted, once there is an approved treatment, does that mean that the EUA is no longer valid?

A: Yes, the EUA is just temporary. If the sponsor wants their drug approved, they need to complete all clinical studies and submit an application.

Q: Please discuss the transfer of investigational new drug (IND) sponsorship from one sponsor to another and that process.

A: This does not usually happen. The sponsor is the pharmaceutical company conducting the trial. I can think of no reason they would transfer this to another sponsor. If you mean using a different contract research organization (CRO) for the different phases of clinical trials – that’s different. There is no problem doing this.

Q: What are the minimum requirements necessary to build a robust quality management system (QMS)?

A: For good manufacturing practice (GMP), you will want to refer to the FDA (Food and Drug Administration) Guidance for Industry CGMP for Phase I Investigational Drugs and address all elements: Personnel, QC Function, Facility and Equipment, Control of Components, and Containers and Closures, Manufacturing Records, Laboratory Controls, Packaging, Labeling and Distribution, and Recordkeeping. For good clinical practice (GCP), refer to ICH E6 (R2) Section 5 and address all quality elements. Of note, you should pay attention to the following elements: Quality Management, Quality Assurance, and Quality Control. Also consider CRO oversight, trial management, data handling and record keeping, as well as allocation of responsibilities.

Your approach to building your QMS will depend on your organization and on what you are doing directly versus what you are outsourcing. An important aspect of your QMS is establishing a robust process for vendor management.

For more information on key components of a fit-for-purpose, phase-by-phase QMS guidance download Advarra’s whitepaper Steps to Implementing a Quality Management System.

Q: What must be done to prove oversight?

A: For all vendors, having documented qualifications prior to use is important. Contracts may include provisions related to oversight, such as the right of the sponsor to audit the vendor. Also consider quality agreements for key vendors, such as contract development and manufacturing organizations (CDMO) and CROs. Quality agreements provide more details regarding how the sponsor and vendor work together. They may include key performance indicators (KPI) and key risk indicators (KRIs) to monitor vendor performance.

Keep any records showing how the sponsor oversees vendor activities. This includes audit records, meeting agenda and minutes, KPIs, KRIs, and records related to quality issues. For GMP vendors, documented reviews of records such as analytical testing and batch records, is also important.

Q: How specifically would a sponsor perform a periodic audit of a vendor?

A: Audits are typically scheduled for one or two days depending on the scope and may be conducted onsite or remotely. Prior to the scheduled audit, the sponsor should send a confirmation letter and agenda. The auditor prepares by reviewing relevant information, such as contracts, as well as select QMS documents and records. During the audit, the auditor conducts interviews and reviews documents and records to assess the vendors’ facilities and equipment, organization and personnel, QMS, and operations. The standard for the audit used depends on the type of vendor and would include the applicable regulations and ICH guidelines.

Q: What is your advice for approaching the regulatory strategy? Do you search for similar products, and use existing IND criteria requirements against the latest manufacturing guidance docs? How does one learn the most appropriate etiquette and terminology when serving as a novice regulatory affairs person without a manager?

A: Working in a pharmaceutical company is the best way to learn this. Each company will have its own processes, but they will all have the same result. While there are courses and even degrees in regulatory affairs, hands-on experience will teach you general topics.

Q: Is the sponsor allowed to record the pre-IND meeting, as opposed to providing copious notes

A: No, this is not allowed.

Q: Can you ship a drug from another country to the U.S. while the IND is in review?

A: No, nothing can happen until the IND is cleared.

Q: Just to confirm, is an IND required if the drug in question is not intended to be shipped across state lines?

A: No, however, then you would be dealing with seeking an IND exemption from the FDA.

Q: Can you explain what are the items included in the briefing document?

A: This is a complex topic and is best outlined in the FDA’s guidance document.

Q: What is the typical time period between the submission of the briefing package and the pre-IND meeting?

A: The FDA’s guidance document indicates the briefing package is submitted four weeks before the meeting

Q: What and when is the best way to communicate with FDA, after the pre-IND meeting, if the clinical study design needs to be modified?

A: The FDA provides guidance for this topic.

Q: What is the major IND filing difference between investigator-initiated trials (IIT) and IND trials?

A: In IITs, an investigator is usually a physician or an academic institution, and the interest is usually in studying a drug in an area of research in which they practice. The sponsor-initiated IND is conducted by a pharma company seeking commercial approval.

Q: When you want to do a study of an FDA-approved drug under an investigational indication, is an IND still required or can you seek an exemption?

A: It depends, but the answer is usually yes. There are only a few very specific exemptions from an IND. Here is the guidance document that will give you more detail.

Guidance for Clinical Investigators, Sponsors, and IRBs, Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Food Safety and Applied Nutrition (CFSAN), September 2013, Clinical/Medical.

NOTE: A stay is in effect for parts of subsection VI.D of this guidance. Additional information about this stay can be found in the Notice of Stay published in the Federal Register, October 30, 2015 (80 FR 66907)

Q: What is the definition of a drug? At what point does the drug substance become a drug product?

A: The definition of a drug from the Federal Food, Drug, and Cosmetic Act is found in 21 USC 321 Definitions; generally, section (g) (1) The term “drug” means (A) articles recognized in the official United States Pharmacopoeia,[1] official Homoeopathic Pharmacopoeia of the United States, or official National Formulary, or any supplement to any of them; and (B) articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and (C) articles (other than food) intended to affect the structure or any function of the body of man or other animals; and (D) articles intended for use as a component of any article specified in clause (A), (B), or (C). A food or dietary supplement for which a claim, subject to sections 343(r)(1)(B) and 343(r)(3) of this title or sections 343(r)(1)(B) and 343(r)(5)(D) of this title, is made in accordance with the requirements of section 343(r) of this title is not a drug solely because the label or the labeling contains such a claim. A food, dietary ingredient, or dietary supplement for which a truthful and not misleading statement is made in accordance with section 343(r)(6) of this title is not a drug under clause (C) solely because the label or the labeling contains such a statement.

The term drug substance and drug product are found in the NDA regulations 21 CFR 314.3, and are defined as:

Drug product is a finished dosage form, e.g., tablet, capsule, or solution, that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients.

Drug substance is an active ingredient intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the human body but does not include intermediates used in the synthesis of such ingredient.

Q: If you would like to conduct an IND study using patients both inside and outside of the U.S., is this acceptable to the FDA? Would they prefer the initial Phase I subjects to be only in the U.S.?

A: Yes and it is common. Phase I (and every subsequent phase) can be in the U.S. or outside. You will need FDA input, so the U.S. population is included in the right places.

Q: Normally, how much “efficacy” versus “safety” data is required to allow a Phase I trial of a new molecular entity? Are there exceptions on a drug-by-drug submission basis?

A: The answer is derived from nonclinical pharm/tox studies in animals. There are numerous studies and determining which studies are the right ones requires an expert toxicologist. This is a discussion you have with the FDA but only after following published guidance. Yes, each drug has its own requirements.

Q: The speaker just stated that the Meeting Package is due 60 days before the meeting date. My understanding is that the meeting request is due 60 days prior, and the meeting package is due 30 days prior. Could you please confirm?

A: Current guidance can be found here.

Q: When is an IND exemption needed?

A: Here is guidance that should answer your question:

Guidance for Clinical Investigators, Sponsors, and IRBs, Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted without an IND, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Food Safety and Applied Nutrition (CFSAN), September 2013, Clinical/Medical.

NOTE: A stay is in effect for parts of subsection VI.D of this guidance. Additional information about this stay can be found in the Notice of Stay that published in the Federal Register, October 30, 2015 (80 FR 66907)

Q: Ex-U.S. studies – isn’t there a difference between if/how IRBs versus ethics committees (ECs) fulfill commitments noted on the Form FDA 1572?

A: For FDA 1572 is a Statement of Investigator under US Regulations/Laws. The principal investigator (PI) signs it when they are conducting a study under an IND. The form lists the IRB/EC but does not bind the IRB/EC in how it operates. IRBs are subject to 21 CFR 56 IRBs.

Ex-U.S. ECs must comply with 21 CFR 56 when overseeing a study that is being conducted under an IND, and must also comply with local regulations.

For more information on form FDA 1572 refer to Frequently Asked Questions – Statement of Investigator (Form FDA 1572).

Q: When you are expanding a label, does the IND automatically become a Phase II study?

A: No. To get an approved NDA or Biologics License Application (BLA) you must conduct all phases of clinical studies. Then you can submit an application for approval. If you get approval, then you can conduct clinical trials for other disease indications. If you successfully complete all phases of clinical testing, you can submit a supplemental application for a label expansion.

Q: What is the most advisable pre-IND meeting process?

A: You must follow FDA’s guidance for a pre-IND meeting process.

For research sites whose communities include large populations of non-English speakers, it may be standard operating procedure (SOP) to obtain a translated version(s) of the study’s informed consent document at the beginning of each study. That way, when a non-English speaking potential study participant shows interest in the trial, researchers can help the potential participant learn more about the research without missing a beat.

But what about situations where a non-English speaking potential participant shows up unexpectedly, and there isn’t enough time to obtain a translated study consent?

Enter the short form consent.

Regulatory Perspective on Short Form Consents

The regulations require presenting study information in a language understandable to research participants—this includes, of course, the informed consent document and process.

45 CFR 46.117(b)(2) and 21 CFR 50.27 allow researchers to provide non-English speaking potential participants with an oral presentation of the informed consent information in conjunction with a written short form consent document and a written summary of the oral presentation.

A witness must be at hand for the oral presentation, and the participant must receive copies of the short form and summary documents. The long form English consent may serve as the written summary.

FDA and Office of Human Research Protections (OHRP) guidance documents suggest the agencies clearly prefer a non-English speaking participant review a translated version of the complete study consent. But we know this may not always be possible.

How do You Use a Short Form Consent?

For those unexpected situations, some institutions and institutional review boards (IRBs) maintain an approved short form consent translated into multiple languages. This way, researchers don’t have to turn away a potential study participant just because the study consent is not available in the non-English speaker’s language.

Keep in mind: The short form consent isn’t the perfect solution—an interpreter must also be present to assist with the oral consent presentation. Documentation requirements still must be followed as well. This includes:

The short form consent should be signed by the study participant or the participant’s (LAR)
The written summary should be signed by the person obtaining consent
The witness (who may also be the interpreter) should sign both the short form and the summary
- While not required, OHRP guidance and best practice suggest the witness should be fluent in English as well as the participant’s language

The short form consent can be a useful tool for unexpected situations, but it should not be used when investigators already anticipate non-English speakers will enroll in the research. If you expect non-English speaking participants, be proactive and have the study consent translated into the language(s) commonly used in your community.

Remember, informed consent is an ongoing process. While the short form consent can help during the initial consent discussion, researchers still need to assemble the proper communication tools to ensure the non-English speaking participant understands matters things throughout the study.

Non-English speaking study participants require additional support throughout the course of a study, but with the right tools and a little regulatory know-how, researchers can help ensure these participants are able to provide meaningful research contributions and reap potential benefits.

Note: This article was originally published August 30, 2017, and has been updated to include new and clarifying information.

To protect human subjects in clinical research, the Food and Drug Administration (FDA) maintains and enforces specific regulations. Research stakeholders must track, document, and store the required information for trial oversight and monitoring to comply with regulations. This blog identifies applicable regulations and outlines regulated documents and data in clinical research and the systems used by sponsors, contract research organizations (CROs), monitors, and research sites to collect, exchange, and store them.

Introduction to Required Research Documents and Regulatory Compliance

There are three primary regulations impacting trial documentation:

ICH Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting for trials involving the participation of human subjects. In short, GCP dictates what data and documents need to be collected, stored, and audit-ready.
FDA 21 CFR Part 312 describes specific roles, responsibilities, and documentation requirements for investigational new drugs (INDs).
FDA 21 CFR Part 11 (commonly known as Part 11) “applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted.” Since many clinical research teams leverage electronic systems to manage clinical trials, ensuring compliance with 21 CFR Part 11 is essential.

Additional Resource: Regulatory Fine Points: What Sites Need to Do for Part 11 Compliance

What is an Electronic Master File (eTMF)?

An electronic trial master file (eTMF) is a technology solution designed to organize, collect, store, track, and archive required and essential study documents. The eTMF is an electronic version of the trial master file (TMF) that is now industry standard. Historically, the TMF was organized in paper form.

The TMF is the collection of required documents associated with a single clinical trial that demonstrate the trial’s compliant conduct and all associated activities for evaluation by regulators. If you think of the clinical trial process as a journey, with a start and a finish, each step along the way must be captured and updated in a central location: the TMF.

According to FDA and international GCP guidelines, TMFs are required for every study but are not required to be electronic. By regulation, sponsors are responsible for the maintenance, accessibility, and accuracy of the TMF. If a sponsor chooses to utilize an eTMF, they are responsible for ensuring the system is secure and 21 CFR Part 11 validated.

What Documents are Collected and Stored in an eTMF?

GCP guidelines dictate which documents need to be included and categorized in the eTMF. For example:

Essential study documents:
- Protocol, protocol amendments, investigator’s brochure, procedures and manuals, visit guidance, etc.
Training documentation and materials:
- Certificates, videos, supporting content, etc.
Funding documentation:
- Contracts, budgets, negotiations, etc.
Safety documentation:
- Safety letters, serious adverse event (SAE) reports, etc.
Ethics committee’s documents:
- Protocol amendments, approvals, communication, etc.
Audit or monitoring documents:
- Onsite visit records, audit findings, etc.
Participant information:
- Informed consent forms, visit guidance, brochures, recruitment materials, patient diaries, etc.
Site-specific documents:
- Site CVs, training documentation, site standard operating procedures (SOPs), etc.

What Systems Integrate with an eTMF?

Most of the documents required for collection and storage within an eTMF originate outside of sponsor systems. If a research site stores study documents in an electronic investigator site file (eISF), those documents would need to be routed to the corresponding eTMF.

Software and platforms such as an electronic IRB (eIRB) system, eRegulatory (eReg) management system, email programs, and clinical trial management systems (CTMS) can integrate with an eTMF. Integrating systems reduces the amount of work needed to manually move documents from one system to another, and it also reduces the risk of mistakes.

What is an Electronic Investigator Site File (eISF)?

An electronic investigator site file (eISF) is a technology solution designed to organize, collect, store, track, and archive required and essential study documents for an individual site involved in a particular research study. The eISF is an electronic version of the ISF, which was historically organized in paper form. The eISF at an individual research site works together with the sponsor’s eTMF, which collects and stores data associated with each research site involved in the clinical trial. A research site is also responsible for storing and archiving their ISF.

Additional Resource: 12 Items Auditors Look for When Reviewing an Investigator Site File

What Documents are in an eISF?

Like an eTMF, an eISF collects and stores clinical research regulatory documents, but only related to a particular research site. For example:

Essential study documents:
- protocol, protocol amendments, investigator’s brochure, procedures and manuals, visit guidance, etc.
Site-specific documents:
- site CVs, training documentation, site [SOPs], etc.
Site-specific participant recruitment and engagement information:
- informed consent forms, visit guidance, brochures, recruitment materials, patient diaries, etc.
Site-specific monitoring or audit records

What is the Difference Between an eTMF and eISF?

An eISF is a subset of documents required to be collected and stored in an eTMF. An eISF is compiled by an individual research site, while all eISF documents within the eTMF are collected and compiled by the research sponsor.

How Long Must Essential Clinical Research Documents be Archived for?

The records in both an eISF and eTMF for each clinical trial must be stored and accessible for 25 years after a study closes. Regulators, monitors, and other auditors may access the documents over time to review trial conduct and data.

What is Secure Document Exchange?

Secure document exchange describes the workflow for exchanging regulated research documents between research stakeholders. Secure document exchange can help reduce administrative burden, improve data accuracy and security, and automate document collection and updating.

Most document exchange activities happen during the study startup process of a clinical trial. To start a clinical trial, sponsors, CROs, and research sites need to work together to make sure everyone is ready to do the research and meets all the regulatory requirements. Historically, these processes have been burdensome to both sites and sponsors due to lack of communication between technology systems.

Advarra enables efficient and compliant document management for both sites and sponsors. Secure document exchange between Advarra’s eReg and Study Collaboration Platform provides end-to-end integration for automated, seamless exchange of research documents between sites, sponsors, and CROs. Longboat also allows sponsors to manage documents and provide a site eISF to global research sites without their own regulatory management system.

As a drug successfully makes it through the development process, sponsors will inevitably need to submit a new drug application (NDA) to the Food and Drug Administration (FDA). While it may seem like a straightforward process to some, there’s room for many elements to be missed as sponsors prepare for the application submission.

Failure to Have a Pre-Investigational New Drug (IND) Meeting

There are a myriad of regulations coming into play during the drug development process. Because of this, the FDA understands sponsors may need help making sense of regulations. The FDA issued guidance on when formal interactions should occur between them and a sponsor. One such meeting is the pre-IND meeting.

The pre-IND meeting is a sponsor’s opportunity to interact with the agency before initiating the clinical study. In this meeting, they’re able to receive insight and feedback regarding critical issues. There are benefits to holding a pre-IND meeting, such as:

Verifying the appropriate animal model is used to determine product safety
Determining if the toxicology data is sufficient to justify a first-in-man study
Discussing data concerns or potential roadblocks
Developing a relationship with the agency team reviewing the submission

Even though it’s only recommended for an organization to take a pre-IND meeting with the FDA, there could be consequences if sponsors fail to take the meeting. If a sponsor chooses not to take advantage of the FDA’s pre-IND meeting, it can potentially lead to FDA rejection of the IND or result in a clinical hold.

Too Much Data or Unnecessary Information

Including unnecessary information, disorganized data, or dense text are common missteps when sponsors submit IND applications. Committing these errors increases the amount of time it will take the FDA to review your IND. Additionally, it makes it easier for errors to slip through the cracks, risking outright application rejection.

Providing too much information in your application may reveal a lack of cohesive strategy within your company, and including large amounts of data without explaining it will slow down the review process. Conversely, failing to present the information concisely is a major flaw. Providing brief points to serve as a guiding point throughout the documents helps reviewers know what is relevant in the application.

Poorly Written or Unorganized IND Application

Oftentimes, IND writers will make the mistake of focusing solely on the science and will disregard everything else. If a submission is difficult to read, reviewers are more likely to place it on hold or reject it outright. As you write your application, think of the FDA reviewers evaluating the document. Not only should you include the appropriate amount of data, but what does your grammar and formatting look like? Having a poorly written IND application will frustrate and confuse the reviewers.

In order to avoid a study placed on hold or rejected, there are best practices to abide by:

Operate under the guise of your reviewers may know the basics of your therapeutic area but may not be as familiar with specific details.
Similar to adding the right amount of data to your application, don’t overload the IND with unnecessary information. As you write your IND, stay focused.
Use common words whenever possible, and if you need to use abbreviations or technical terms, accurately define them.
Break up large paragraphs of text with figures and tables to make it more visually appealing.

Before submitting the IND, have one person review the full document to ensure consistencies. This is especially important if there are multiple writers contributing to the IND; one reviewer helps ensure consistency among writing styles.

Leaving Out Pertinent Chemistry, Manufacturing, and Controls (CMC) Details

Using nonclinical data or manufacturing information that doesn’t adequately support the clinical protocol hurts the IND application. It’s critical to ensure all nonclinical data supports the clinical design and provides adequate justification of the desired labeling claims – including basic exposure data. In order to achieve this, teams must undergo detailed planning and have a strong knowledge base of IND regulations.

In your IND application, you must specify how your organization will assure patient safety. Including information such as a drug or biologic’s quality, purity, and strength will help with specification, as well as help reviewers assess production’s adequacy and consistency.

Leaving out data pertinent for evaluating testing procedures will make it difficult for reviewers to determine the proposed study’s quality. Ensure your study has evidence to support the robustness of the assay used in evaluating the clinical trial. Include representative output data such as chromatograms and procedural details in the form of standard operating procedures (SOPs).

Inadequate Support

One of the biggest reasons sponsors receive a clinical hold is the IND lacks organization and clarity. An IND application should provide reviewers with clear data and explanation for results. Make sure these results match your protocol and avoid irrelevant information, because that can reduce your impact.

Additionally, not clearly stating the drug’s or biologic’s potential risk in the submission may raise a red flag. Potential issues of concern need to be presented in a forthcoming and transparent manner during and following the regulatory review. Failure to do so will impact the sponsor’s credibility. It’s the sponsor’s responsibility to provide the FDA with the information in a manner to help them understand the safety issues raised, as well as how they will be mitigated.

The sponsor must also provide all the information related to the application. Common errors in IND preparation include:

Forgetting to provide relevant explanations or supporting data for the results
Failing to properly match results to the protocol

Sponsors must note: study data standards are required for commercial INDs as of December 17, 2017, for both nonclinical and clinical studies. This is a specific requirement to comply with the Clinical Data Interchange Standards Consortium (CDISC).

Lack of Experience

Many organizations lack experience in compiling an IND submission. It takes a highly skilled team and resource sharing to produce high-quality work, as well as hands-on experience successfully submitting IND applications. With experience comes a deep understanding of the IND submission process and up to date FDA guidance to the table. Previous experience meeting with FDA personnel can help with every step of the IND process.

It’s also important to pay attention to the details. Making inadvertent mistakes in the IND submission is the most common reason for technical rejection of the electronic common technical document (eCTD) filing. Double-check the application to make sure the correct eCTD format is followed, and all pre-clinical data and documents are included. It’s also worth it to look over the submission twice to ensure it is sent to the correct center.

It’s easy for someone to underestimate the time required to develop an IND application and complete the submission – especially if they don’t have much experience preparing an application. It may take 12-14 months to complete the IND package, not including the time commitment for the pre-IND. Keeping this in mind, it’s in your best interest not to wait until the last minute to begin preparations.

Establishing a compliant pharmacovigilance (PV) function from scratch is often an overwhelming exercise for emerging biotech organizations, typically competing with the priorities of bringing a new drug to market. However, asking the right questions before starting the journey can mitigate the risks of PV findings and ensure a successful PV function build for the organization. This blog outlines four common but critical questions to ask when supporting emerging biotech organizations as they establish a successful PV organization.

Q: When is the appropriate time to establish a PV organization?

A: Emerging biopharma organizations are like snowflakes: no two fit a standard mold. There are many interdependencies, differences in risk tolerances, talent, experiences, drug safety profiles, and chosen vendors, to name a few. There are many aspects to understanding the right time to build a PV organization. It can take tremendous business acumen from the Chief Medical Officer (CMO) and clinical leaders to understand the triggers for engaging help.

It is both a common and a best practice to begin initial conversations with a PV expert during Phase II but before Phase III clinical trials. Important triggers to start this discussion include:

Realization of being late to the game. There is no organized PV function within the Phase II to Phase III timeline or when the new drug application (NDA)/marketing application approval is 18 to 24 months out.
The numbers game: Safety reporting relative to the number of patients, trials, products, partners, contract research organizations (CROs), serious adverse event (SAE), and countries becomes too difficult to manage under the current model
The stage and complexity of developmental programs help define the appropriate time to investigate a PV resourcing model.
Clinical trial SAE/suspected unexpected serious adverse reaction (SUSAR) volume reaches an inflection point whereby the CRO’s ability to manage processing in a timely and accurate manner is compromised.
The organization determines that an unacceptable risk of not having PV expertise exists.

I have seen too many organizations delay, thinking they do not yet need a PV presence, and then they place the emergency call for help.

Q: What are the essential roles during the early stages of a PV organization, and why?

A: This answer to this question is multifaceted. The triggers for hiring PV and supporting staff, part-time contractors, or other staff augmentation are often convoluted business decisions. This is challenging for emerging biopharma organizations because PV resources are highly specialized, rare, and expensive.

We typically see a need to hire a safety scientist with generalist and operational skills early on. This role can work to onboard a safety services provider and assist with PV case processing and reporting activities.

At the functional build stage, an incalculably small number of organizations need a full-time Head of Pharmacovigilance. During a standard work week, there would not be enough hours to keep this role busy. The best practice for growing biopharma organizations would be to fulfill this role with an experienced, part-time Acting Head of Pharmacovigilance who is integral to the safety governance model and has availability a few hours each week to oversee the medical and business aspects of the growing PV function. The situation becomes murkier since vital, quantified PV resources are rare in the marketplace. Contracting with part-time expertise is an intelligent and efficient way to share top talent.

Dr. John Price authored a paper on this topic a few years ago for anyone considering a PV functional build: Pharmacovigilance in Crisis: Drug Safety at a Crossroads, Clinical Therapeutics, Vol 40, # 5, 2018, 790-797.

Roles within quality assurance, regulatory affairs, and project management also provide valuable partnerships as processes are codified into standard operating procedures (SOPs), regulatory pathways are formed, and a safety governance model is established.

Q: What role does a drug safety program play in a PV organization?

A: A PV organization needs a robust drug safety program, focusing on establishing the following supportive components for many of the reasons stated above:

Quality controlled documents
Signal detection and management
Safety governance model
Safety review team and safety surveillance plan
Inspection readiness
Safety services provider and safety database

Q: What would be the top strategic insights you would offer to an emerging biopharma to consider when establishing a PV organization?

A: I see these insights as three distinct pieces.

First, lacking a clear vision is problematic because teams need to understand what the organization is striving for. Many clinical and business leaders understand the need for PV but have difficulty visualizing the tactical components and the future state. It is so complex that they often do not know where or how to start.

Second, leaders don’t always know the differences between strategies and tactics. Understanding the differences makes life easier when planning complex projects. Strategies are road maps. They get you from where you are today, the “R state,” to where you need to be, the “2B state” or future state. Tactics are the vehicles to help you get there. An effortless way to remember the differences is that tactics cost money; strategies don’t.

Also, critically important to establishing a sound architecture for a PV organization is maintaining a strategy-based plan and not an issues-based plan. This would result in an optimized way of moving toward the 2B state. Even good leaders spend an inordinate amount of time planning for issues that may never come up. Since the vast majority of issues identified are relatively inconsequential, they would not be the focus of a strategy-based plan. If a problem is insurmountable, it will become a critical success factor in a strategy-based plan that would need to be addressed, or it would add a high probability of failure.