Drug development companies come in all sizes and compositions, and it is safe to assume that no matter the makeup – they are all feeling the effects of the global pandemic, both professionally and personally, in their communities. Smaller pharmaceutical and biotechnology companies likely feel these implications more acutely, especially for projects that begin with a few scientists and a molecular breakthrough and need to be taken to the next step to access this critical market. From securing funds, limited internal capacity and other challenges that come with being smaller, these companies also face added obstacles throughout the drug development process.
Getting a compound to Investigational New Drug (IND)-enabling studies and the completion of the overall drug development application represents a major milestone for any company and project team. However, the preclinical testing process can be challenging for those with lean team structures or narrow expertise, and it represents a paradigm shift from discovery research to regulatory toxicology. In this case, small drug development companies can use these specific strategies and tactics to help them plan effectively and efficiently.
Start with the End Goal in Mind
Successful drug development can often be attributed to teams that plan realistically and proactively for proper preclinical studies and the completion of the IND application. These teams start with the ideal filing date and work backward, asking themselves if the timing is practical and taking into account the realistic capabilities of their staff and other resources.
Smaller companies should keep the end goal top of mind and account for the various pieces of the puzzle. Fundamental aspects of successful teams include:
- Understanding of the current market conditions
- Assessed demand for new drugs and novel approaches
- Current intelligence and available therapies in the therapeutic area of interest
- Realistic budgeting
- Thorough research and development
- In vitro molecular characterizations
- Highly functional modes of communication with outsourcing providers
With a firm grasp on these elements and a focus on the end goal, making sufficient headway to meet key benchmarks for time, money and resource allocation becomes achieved more easily. Productive companies are continually asking themselves important questions such as, "Have we met financial milestones?" Or, "Have we assembled a dynamic, effective and productive working group?" Mindset is everything, and moving a compound forward from kickoff to market is an extensive and dynamic process.
Drug Development Paralysis
Every drug development company knows the value of communication, but an easily forgotten factor is a definition of roles and responsibilities in each development area. Remaining open and adaptable to whatever the process throws at them is an important quality for smaller drug development companies. Rather than always wondering if there is a piece to the puzzle that's missing, assign roles and clarify ownership to mitigate team stasis. Dropping the ball on working with outside partners, logistical needs and other major areas can be detrimental to a project, so having leaders across all sectors maintains clear and measurable goals, unambiguous responsibilities and relevant communications critical to success.
Embracing Adversity
When things go wrong, it's easy to panic. For example, if preclinical testing reveals adverse toxicology findings in a compound, it can be interpreted as a failure in a variety of ways, and in reality, it is not. An old saying in the industry is "toxicology happens." Safety assessments provide an ideal opportunity to characterize the direct and indirect effects (if any) of the drug. As such, unexpected toxicity or technical challenges can serve a useful purpose, providing the team with valuable insight as to unforeseen events and outcomes. The best thing to do in this situation is to start asking questions, both with the team and with your testing partners.
A drug development company can gain quite a bit of insight from these inquiries and reviews, which will ultimately shape both the characteristics of preclinical assessments and the First-in-Human (FIH) clinical trials. With the right partnership, working through this data can narrow the focus of safety testing when trying to understand complex molecules. Companies that ask an abundance of questions, even when feeling outside their realm of expertise, provide themselves the chance to have productive conversations and garner a stronger relationship with the safety assessment service providers.
Assessing Safety
Often due to constrained resources and occasionally by choice, most smaller drug development companies operate with a limited supporting team, which increases the risk for knowledge gaps to emerge – specifically when assessing the preclinical safety of a molecule. For example, if the makeup of a team's expertise is primarily in research and development, the focus of preclinical development skews toward investigating efficacy and proof of concept, resulting in the testing unintentionally overlooking some safety elements. If the team is well-versed in developmental biology and Good Laboratory Practice (GLP)-enabling in vivo study design but lacks relevant regulatory expertise, gaps in appropriate study designs and IND-enabling program content can occur. Investing in all of these critical areas is essential to minimize any delays of biology, safety or a regulatory agency's expectations.
Drug development companies need to prioritize and invest in an objective, well-defined plan to assess safety. The safety assessment plan should include a characterization of the molecule and a robust safety profile of its dosage level and regimen in the selected test systems. Drug developers need to account for testing surprises, which are inherent to comparative pathobiology and potential species-specific sensitivities. By initiating a safety assessment evaluation earlier and planning for surprises, the project stays on track for designated timelines in a proactive manner.
If assessing safety is out of a team's wheelhouse, finding an outsourced testing laboratory for one or more elements of the development plan provides a beneficial resource. These testing laboratories can act as objective partners to contribute an unbiased perspective and help develop a well-rounded study program. Testing laboratories willing and able to meet specific sponsor needs can deliver considerable value to small drug development companies.
The most effective testing laboratories free up drug developers' internal capacity to focus on what their experts specialize in and add expertise that isn't as strong internally. They can also customize their resource allocation to the individual needs of its customers and build credible associations with experts in the field of toxicology. In the eyes of regulators, this can engender trust that the data generated from the IND-enabling studies are true, accurate and compliant. Also, it is essential to use experienced testing laboratories when your drug is unique (structurally, pharmacologically and mechanistically) and when there may be specific regulatory and scientific considerations in the chosen path for drug registration (such as orphan diseases or first/only in class therapeutics for terminal diseases).
Evaluating Relationships
Outsourcing is an essential resource for drug development companies without access to a dedicated, internal laboratory. As the COVID-19 pandemic has disrupted production, supply chains and even international protocols and operations, finding a lab with the capacity, redundant systems management and access to the necessary resources can be challenging. Drug development companies should confirm that their current and future lab testing partners have plans and accommodations to mitigate or at least minimize these impacts through well-develop processes and procedures.
Approach the investment in outsourcing to a testing lab as establishing a true partnership, rather than enlisting a turnkey service provider. Drug development teams are most effective when they work closely with their partner organizations and function as a unit. Finding an outsourced testing lab that will approach the relationship in the same way can be a challenge, so it's best to do your homework when performing vendor assessments.
To identify an accountable, collaborative testing laboratory, start by understanding their core values and leadership. A testing lab's primary goal should be to help bring new drugs to market that will benefit the greater good. These laboratories should recognize that every project has a modest start, and small drug development companies make some of the most significant discoveries. These testing labs shouldn't allow larger contracts to take precedence due to the size of their expenditure. Laboratories that make even the smallest of drug development companies feel valued and supported throughout the process are worth the cost. Still, it's important to be transparent with your strengths and weaknesses so that all resources are brought to bear.
Selecting a Partner
Rapid, cost-efficient, and high-quality – these are the three common priorities in selecting a testing partner. As the selection process comes to a close, consider what the long-term impacts are when making any compromises in this triad. Don't forget what the financial implications could be if the testing lab does not treat the project with equal attention as they do larger clients.
Before signing on the dotted line, every potential client should ask the following questions:
1. Does this laboratory offer both scientific and operational resources?
An integrated partner can streamline the responsibility of the developer's primary point of contact by consolidating partners to one or two labs. Sharing data and results internally to a centralized organization typically becomes more efficient. Study timelines can also flex to respond to unforeseen needs since resources are ample. For instance, a lab can make up for adverse events that materialized during a study by adjusting schedules at another stage downstream. If a lab uses this study's results to select dose levels or final animal assessments in the pivotal, IND-enabling study, the testing lab can quickly adapt pre-study procedures to accommodate those changes. Finally, bundling testing programs to reduce costs, improve report timeliness and consistency of content, may better conserve budgetary resources, and potentially reduce the time spent auditing different testing labs.
Drug development companies who inquire about the cross-functional opportunities of an outsourced partner should vet the candidate labs for a range of capabilities inherent to the drug development program. From biomanufacturing, molecule characterization, production scale-up, analytical services, unique technical capabilities and more, the greater functionality and capabilities a testing partner's umbrella has, the more value they can deliver to a small team.
2. What is the lab's capacity and current access to scarce test systems?
The global pandemic's implications are far-reaching and unpredictable. Finding a lab with a proven response to protect their employees and deliver on timelines affords the security of keeping projects on track as much as possible. Some labs in North America are still enduring resource limitations and time constraints, so this may ultimately be the time for both small and large drug development companies to expand their consideration to international providers for preclinical safety studies.
On top of sufficient capacity, small companies need to find testing partners with adequate access to restricted tests and animal systems. Availability can be hindered based on international shipping barriers, and getting studies scheduled with hard-to-find test systems is no small feat. Even if a testing laboratory can accommodate testing programs that align with planned timelines, if they do not have access to models and finite resources, setbacks will occur. Delays in study conduct can ultimately lead a company (with somewhat limited flexibility) to missing filing deadlines, resulting in a cascade of unfortunate events.
3. Does the lab have positive relationships with Regulatory Authorities?
An outsourced partner’s regulatory compliance, in areas such as the U.S. Department of Agriculture, the U.S. Food & Drug Administration, animal welfare compliance and universally compliant GLP systems, is required. However, a testing laboratory's relationship with regulatory authorities is generally more complex and unique to each market. When it comes to these testing partners, evidence of a positive and constructive working relationship is seen not only in inspection reports, but also how responsive their quality systems are to the dynamic of oversight and change. As a whole, these relationships can impact a company's chance for successful submissions and approvals.
It is a common misconception that regulatory authorities are to be feared. Instead, drug development companies should view them as another critical partner in the process. Testing laboratories that work closely with both their clients and regulators can take steps to facilitate those relationships and improve your chance of success. This affiliation can assist a drug developer in getting ahead of evolving expectations and build credibility with salient regulatory bodies.
These relationships require a commitment of time, energy and resources both for the testing laboratory and the drug development company. Knowledge of regulatory expectations directly impacts the quality and integrity of the drug development program design and resulting data and reports. Gauging this needed competence will require some deliberate inquiries and time, so vetting for established connections can be a strategic advantage in creating a dialogue about the compound and testing program.
4. How does the audit process work?
In this exceedingly work-from-home world, many companies are not routinely traveling to perform the standard inspections of outsourced vendors. However, that doesn't make the need for assessing testing labs and service providers disappear.
Many companies have developed remote access systems for their clients, one of them being virtual facility audits. Even when different time zones are at play, vendors are going above and beyond to meet the needs of current and prospective customers. Whether that means creating a secure portal to review standard operating procedures (SOP) or staying after hours to meet the staff, vendors have developed new and creative solutions for the audit process in response to this need. The future obstacles presented by global events are unclear, and it's unrealistic to wait them out to find a lab testing partner. Testing labs and drug development companies are taking a new approach that can answer pressing questions from the safety of remote locations.
5. Is a scientific or regulatory consultant needed?
Many teams were stretched thin (whether it be capacity, personnel, expertise or experience) well before global emergencies. Now, conditions have amplified those challenges. Taking on too much responsibility can cost companies more in the long run than making the necessary investments upfront, whether that is committing the time for rigorous vendor assessment or securing adequate financial and scientific resources.
Be it a well-known testing lab that can manage complex programs or an independent consultant that can keep a team abreast of the latest industry and regulatory developments, small drug developers must recognize their gaps and find resources to fill them. Don't shy away from these opportunities. Many vendors either have the expertise internally or work with independent experts. When it comes to the latest guidance in areas such as biocompatibility standards for in vitro and in vivo testing, ignoring weaknesses can prompt regulatory setbacks if improper methods are applied; it's simply not worth the risk.
To successfully submit an IND application to the U.S. FDA (or to one or more global authorities), drug development teams need to proactively detail a clear plan with the end goal in mind: a successful, on-time submission to the agency and the ultimate approval for FIH studies. Carefully selecting the right contract provider can make all the difference in the ultimate success of the program. For many, these projects are a culmination of their life's work. In truth, everything starts small, and this is where the great discoveries have been made.
Moving beyond the preclinical safety assessment and development stage is a strenuous, costly process. In trying times, virtual, small and mid-size companies cannot be left behind. Their contribution to the progress and innovation of the pharmaceutical and biotechnology industry is invaluable, continually challenging the status quo, applying new and relevant technologies to improve the quality of our lives and communities. These companies should not feel neglected or alone in their efforts.