Exploring why timelines weigh so heavily on drug developers, how to evaluate preclinical testing deadlines and insight on the industry’s best practices can set drug developers up for success on their next program. Drug development companies that use timeline projections to their advantage and apply timesaving techniques can often reduce the amount of pressure felt throughout this process.
Pressure points for drug developers
It is no industry secret that testing and regulatory submission deadlines constitute a significant source of stress for drug development companies, and this strain can stem from a multitude of factors.
Smaller drug development companies may have comparatively limited resources that can make the research and development (R&D), along with the regulatory required testing processes, more demanding and arduous. Lean staffing can lead to specific knowledge gaps, despite any niche expertise represented on the team. For example, a drug development company may have an incredible R&D biologist but may not have a team member as well-versed in the intricacies of Investigational New Drug (IND) enabling toxicology testing. This company makeup can make planning for regulatory required testing and data compilation more difficult, and potentially threaten the success of the compound.
Additionally, smaller drug development companies have an increased obligation to fundraise and must keep constant tabs on the financial burn-rate. While necessary, it can lead to an imbalance in other sectors of the business and contribute to delays. Make sure enough time is constituted to fundraising efforts while still leaving space for traditional development work. It is easy to overlook the fundraising time commitment and how this will interfere with development timelines.
Larger drug development companies, on the other hand, often trace timeline pressure back to the regulatory filing deadline. Large drug development companies are working against a target date to complete preclinical studies, analyze data and compile an application. Many larger drug developers feel the clock ticking as soon as they receive the program, which acts as both a motivational force as well as a constant stressor to become the first to have an approved drug with a filed patent.
Acknowledging stressors and their origins helps drug developers plan for timeline restrictions and accuracies. Whether developers are small, large or in between, appropriate planning can make sure timelines are achievable, and no gaps are left unaddressed.
The art of planning
Comprehensive and steady planning protects progress and keeps programs on track. The most successful drug development companies are continually overseeing their testing to ensure it aligns with their planned timelines and adjusting schedules as necessary. To do this, drug developers need to acknowledge the key considerations—testing objectives, potential obstacles and regulatory obligations—when evaluating preclinical testing timelines.
Drug developers should start planning with the end goal of their program in mind when creating accurate and reasonable timelines, which in many cases is a successful IND filing. By working backward from this goal, timelines become more precise and detailed. Additionally, it is easier to find planning gaps where the deadline is unrealistic for the testing and the necessary amount of work at hand.
To set themselves up for the best chance at success, drug developers should create or review this timeline with an outside source, such as a consultant or laboratory testing partner, for accuracy. These sources can confirm the palpability of the schedule and point out any missed steps.
A pragmatic approach that drug developers should implement is clinical trial planning before preclinical work even begins. The in vivo and in vitro preclinical testing design needs to support the planned First in Human (FIH) trial. Therefore, the clinical trial plans need a certain level of foresight. One example is the intended dose route and frequencies; if the drug is to be administered via intravenous infusion once a week, it is essential to include proper infusion duration and frequencies for the appropriate preclinical test systems.
When it comes to the study design, there is not a one-size-fits-all approach and drug developers cannot lean on a list of standard studies for sufficient submissions. Instead, customizing testing to the specific drug and the intended population is necessary for approval from regulatory agencies. A small molecule anti-microbial drug, for instance, requires a different testing strategy than an immuno-oncology product because determining the safety and efficacy of the two compounds will require different regulatory plans. Planning these processes thoroughly and continuously monitoring will help narrow down more realistic timelines for testing and submission.
When done correctly, Gantt charts can act as a guide to reference for the next steps in the program’s evolution. Using them like this reduces the stress ordinarily associated with timelines and, instead, turns them into a tool.
With the preclinical goal of successfully filing regulatory submissions, drug developers can look upon regulatory requirements for options to alleviate timeline stress.
Drug developers should view regulatory agencies as a partner, rather than perceiving them as another hurdle to set them back. Regulators can offer insight into the strength of a drug development plan, what it may be missing and raise questions or concerns that a drug developer can address in studies and submission packages. Thus, before testing begins, drug developers have an opportunity to correct any design flaws that could have put the submission at risk. Ultimately, building relationships and having productive meetings with regulators can help with the structure, organization and pragmatism of a drug development timeline.
Drug developers can also use common regulatory practices for a timeline advantage. One often-overlooked timesaving technique is dual filing, meaning filing under two or more regulatory bodies to access various markets simultaneously. There are many scenarios where dual filing makes the most sense financially and from a timeline perspective. If a drug developer is planning to file with the U.S. Food and Drug Administration (FDA) now, and China’s National Medical Products Administration (NMPA) soon after, it may be best to file dually to avoid the need to duplicate studies. Drug developers should weigh their options and proceed with the most cost-effective approach. With the proper planning and foresight, this approach could significantly affect submission timing by advancing into markets earlier and utilizing fewer preclinical studies while avoiding duplications.
Advice on timesaving techniques
Understanding strategies that can mitigate the strain of disrupted timelines can significantly support the preclinical testing process and move projects forward more efficiently. Recognize these industry best practices as a helpful start:
1. Contact a testing partner early. Vetting testing laboratories is a time-consuming process. By anticipating testing needs and beginning the process early, drug developers can minimize the chances of delays. Many drug developers vet multiple testing laboratories to get a full snapshot of available options and price ranges. Moreover, with the restrictions from the COVID-19 pandemic, many testing laboratories are offering virtual audits for those vetting them. Even if a drug developer decides not to outsource testing to a particular testing laboratory immediately, it is important to create relationships with professionals in the testing space, which can pay dividends downstream.
2. Ensure vendor capacity and flexibility. When a drug developer has identified a testing laboratory, it is critical to confirm their capacity. If a testing laboratory doesn’t have the space, staff and resources or time to conduct the studies, it can send the drug developer back to the drawing board to find another laboratory testing partner. Currently, many testing laboratories have limited staff, laboratory space, or access to a specific animal model, making it essential to check in with them about lead time and capacity. Drug developers need to be cognizant of the current gap in the industry and acknowledge how it may affect their timelines. Work with the testing laboratories to ensure they are as committed to the compound as the drug developer is.
3. Send enough test article—and on time. If the testing laboratory receives an insufficient amount of test material, studies can’t begin as planned. Proper communication between the testing laboratory and the drug developer can help to avoid such delays. A testing laboratory can aid the drug developer in accurately predicting the necessary amount of test articles with required studies in mind. While the cost and availability of these articles can prompt drug developers to send them conservatively, the expense of resulting delays is usually much more significant. Additionally, drug developers need to account for international shipping and other obstacles to ensure that the testing laboratory receives the test article on time for testing to begin. It is common for laboratories to have advice and procedures on these timing requirements, so be sure to check in with them.
4. Streamline communication. Miscommunication is one of the largest contributors to timeline setbacks during preclinical testing. These setbacks can occur more frequently with a high number of testing laboratories who do not directly communicate with each other. Details can be lost or omitted when a single person is relaying communication between laboratories and other stakeholders, which can then affect the testing and submission timelines. For instance, if an unexpected metabolite is observed during metabolism testing or if a unique impurity is uncovered during the synthetic process, and the testing laboratory fails to obtain this information, studies could be delayed as the toxicologist works on the possible study design modifications. This miscommunication can prompt delays and sizeable cost inefficiencies. Consolidating testing to one or two testing laboratories can streamline communication and the preclinical processes, while also providing regulatory and clinical insight.
5. Anticipate the surprises. Although it is difficult to know how to prepare for unintended findings during preclinical testing, drug developers should do everything in their power to ready themselves and their partners for potential obstacles. Drug development companies can alleviate strain and dial down the severity of unexpected setbacks by building time into the overall testing timeline. When surprises do occur during development, ensure that the testing laboratory partner has the flexibility to reschedule studies and troubleshoot. This becomes essential when a drug developer needs to perform an additional investigative study as a consequence of an unanticipated surprise. If a laboratory testing partner can’t schedule the new study until later, the drug developer’s timeline is significantly elongated. To be prepared, drug development companies should fully understand the delay, cancellation and rescheduling policies and capabilities of all testing laboratory partners. Drug developers that are aware of these contractual policies can better prepare for when surprises occur and can develop and execute on the next steps.
Drug developers can alleviate stress when they start to use timelines as a tool for their program’s guidance, rather than a consistent barrier. Identifying strategies to consolidate inefficiencies or dissolve burdens will streamline the drug development process.
Be sure to review the industry’s best practices when it comes to creating and calculating a program’s timeline. Consulting a testing partner early on, sending a sufficient amount of test articles, avoiding miscommunication, securing capacity and forecasting surprises are all essential features to assess.
It’s true that unanticipated findings and testing surprises will always be a part of drug development, and learning how to handle and solve these issues can support preparedness and make the day-to-day work that much more rewarding.
Mingyi Trimble, ScD, DABT, is Senior Technical Director of Toxicology at WuXi AppTec Laboratory Testing Division. Dr. Trimble has over 15 years of preclinical development experience and is an expert in regulatory drug development for a wide range of therapeutic products and indications. After receiving her Doctor of Science degree in Toxicology and MS in Regulatory Toxicology and Risk Assessment from Tulane University in New Orleans, she began her career in the contract research organization (CRO) industry. In her current position as WuXi AppTec’s Senior Technical Director, Dr. Trimble provides technical and scientific support, enhancing WuXi AppTec’s ability to handle technical questions with a quicker response rate for our clients. Dr. Trimble is currently a Diplomate of the American Board of Toxicology since 2005 and she is an active member of the Society of Toxicology (SOT), American College of Toxicology (ACT), American Society of Gene and Cell Therapy (ASGCT), SOT Northern California Regional Chapter and SOT American Association of Chinese in Toxicology.