PreClinical Safety (PCS) Consultants
Navigating The Evolving Terrain Of Preclinical Development

Navigating the intricate journey of a drug compound from bench to bedside necessitates manoeuvring a series of pivotal decision gates. One of the crucial gates is the preclinical phase—a determinant in advancing a drug candidate to Phase I clinical trials first and later to support subsequent clinical studies as drug development continues.

During this phase, approximately 75 percent of compounds are eliminated through a toxicology program designed to assess their safety. This stringent filtering process ensures only those compounds with the most promise and the least potential for adverse effects move forward in the development pipeline.

In this high-stakes landscape, PreClinical Safety (PCS) Consultants emerges as the key to unlocking the preclinical ‘decision gates’ in the drug development process.

PCS specialises in the entire spectrum of non-clinical development. From initial compound selection to securing regulatory approval, including pivotal early-stage transitions for clinical development, it offers a comprehensive suite of preclinical services.

This one-stop solution is rare in the industry, and is made possible by the cadre of PCS’ experts. Their expertise spans a range of disciplines, including clinical and non-clinical pharmacology, toxicology, toxicopathology, drug metabolism and pharmacokinetics, quality assurance, and regulatory services. In particular, the team specialises in developmental and reproductive toxicology (DART) and juvenile animal studies (JAS). Its evaluations and insights are instrumental in guiding key decisions, such as whether a drug should advance to clinical trials, requires modifications, or if the development should be halted.

Another interesting facet is how PCS strategically places its experts across Europe, the U.S., and Canada. This allows it to leverage the time zone differences to its advantage, facilitating uninterrupted service delivery for projects with stringent timelines.

“We are instrumental in guiding the research teams in solving many deep-rooted issues in project oversight, study planning and monitoring, or data interpretation for clinical trial readiness to yield the most meaningful and accurate results,” says Dr. Stephanie Plassmann, senior expert in non-clinical drug development, PCS, explaining how the company sets the stage for the safe and effective clinical trials.

Bridging the Knowledge Gap in Preclinical Research

PCS is at a crucial intersection in today’s shifting preclinical landscape. The retirement of baby boomers has accelerated a decline in specialised expertise, leaving a knowledge gap in the preclinical research and development domain.

At the same time, the dissolution of internal preclinical departments within many large pharmaceutical firms has propelled an increased dependence on contract research organisations (CRO) which specialise in preclinical operations, but don’t have the developmental expertise to bring a drug on the market. This disconnect between operations and strategy is challenging as both need to be closely intertwined for successful drug development. Therefore, not only proactive management of this process but also the knowledge to bridge this gap are of key importance.

Amid these sweeping changes, the role of the PCS team is even more indispensable. They stand as pillars of support for pharma and biotech companies, universities and investors navigating turbulent waters, lending their skills and experience to ensure continued quality and integrity in scientific studies and assessments, based on the specific requirements of their clients coming from a wide range of backgrounds.

These may include expert assessments of a specific set of data for further decision making or taking over the whole process of the non-clinical development of a new drug candidate on behalf of smaller companies which don’t have these resources in house, and anything in between.

One characteristic situation these days are symbiotic alliances of biotech companies with big pharma companies. These collaborations meld the financial support and clinical acumen of pharmaceutical giants with the innovative zest of biotech firms. On the other hand, to generate interest of potential partners, small and mid-size entities (SMEs) first need to develop their projects to a certain stage, such as clinical Proof of Concept in phase II which must be supported by preclinical studies. However, these ventures frequently encounter hurdles because of limited expertise in preclinical development, an area where PCS’ specialised skills can offer a robust advisory service to biotech entities in fortifying different phases leading up to the clinical trials.

A to Z of Preclinical Development

PCS places a high priority on ethical drug development, maintaining stringent standards for the safety and efficacy of drug candidates. The first step is strategic. PCS initiates the collaborative process with their clients by establishing an in-depth understanding of the clinical condition intended to treat, because non-clinical development is entirely driven by clinical development, reflected in the overall drug development strategy.

The pharmaceutical company developing a drug for a specific indication is the owner of this process. It is the clinical condition that determines adequate treatment requirements. These form the basis for planning the most appropriate non-clinical testing strategy, which is critical to succeed. When required, PCS plans the non-clinical testing strategy in close collaboration with their customers. Should these wish PCS to take over further responsibility for this part, the PCS team undertakes the efficient operational implementation on their behalf. One of the initial steps is the careful selection of optimal locations for conducting studies, with scientific integrity being pivotal.

Success is a continuous journey to ease the lives of those facing persistent, perhaps lifelong health challenges. We have to remain committed to our fight and do all we can to win

PCS works closely with study directors at the CROs to design non-clinical study protocols and supervises the studies for the Sponsor. A crucial element in scientific robustness is to determine appropriate dosage levels, the principal elements of which are laid down in the applicable ICH guidance documents. However, from a hands-on perspective, dosage selection is one of the most challenging aspects of this process and requires senior expertise to avoid the unnecessary repeat of studies, delays, and safety issues, which can have a major impact on timing, outcomes, and resources, and in the end delay if not impede market-entry.

Once the studies are completed or on an ad-hoc basis, PCS may undertake an integrated risk-benefit assessment to equip clients for a constructive dialogue with regulatory bodies. It is actively involved in preparing regulatory meetings, including documentation such as investigator’s brochures (IB), investigational new drug applications (IND), briefing books for scientific advice, and common technical documents (CTD) to guide its clients in regulatory discussions.

Recently, its service offerings were expanded to include ad hoc consultations in clinical pharmacology and early clinical pharmacological development. PCS aims to provide valuable guidance during the transition into clinical trials. This includes advice on the selection of starting dose levels, dose escalation schemes, and appropriate monitoring parameters in clinical trials and acting as a thought partner to discuss clinical considerations, ensuring a seamless translation from non-clinical findings to clinical applications.

Fostering the Next Generation of Scientific Leaders

Dr. Plassmann is acutely aware that nurturing young talent is instrumental in shaping the future of non-clinical drug development. Despite the sector’s demanding nature, she frequently provides training and mentorship to aspiring professionals, advocating rewarding experiences for those who fully commit themselves.

“In my view, this work is more than scientific inquiry—it is a personal mission. I consider it imperative to share my expertise with the younger generation, nurturing their scientific curiosity and encouraging them to contribute to meaningful advancements in healthcare,” says Dr. Plassmann.

One significant avenue through which Dr. Plassmann makes her impact is the Pharma Train-certified introductory course on human pharmacology. Conducted annually by the Association of Applied Human Pharmacology (see www.agah.eu), she holds a specialised session that delves into real-world preclinical development case studies. These case studies serve as learning experiences for participants to illuminate the intricacies of drug development.

She was also invited to contribute her expertise to a book by writing a chapter titled “Critical Aspects of Integrated Non-Clinical Drug Development: Concepts, Strategies and Potential Pitfalls.” The authorship is shared equally with one of her long-term senior team colleagues at PCS, Dr. Elisabeth (Lisa) O’Connor. This publication highlights possible challenges, errors, or risks that researchers might encounter in the preclinical phase, and provides certain crucial steps on how to anticipate, avoid or deal with them.

In collaboration with the European Federation for Exploratory Medicines Development (see www. eufemed.org), Dr. Plassmann also lectures regularly on safety pharmacology and its essential best practices at the Course: “Preclinical and Clinical Safety in Early Development Human Trials”.

Another area she is deeply immersed in is paediatric drug development. Her participation in annual stakeholder meetings has been pivotal in establishing reliable guidelines for characterising compounds tailored for paediatric populations.

Committed to Addressing Unmet Medical Needs

Dr. Plassmann often cites her early career experience at Roche in Basel, Switzerland, to illuminate the potential of non-clinical drug development for unexpected life-changing findings. During the height of the HIV epidemic in the 90s, she recounts a remarkable clinical trial of Saquinavir, a Roche-developed HIV drug. Saquinavir was tested in an early trial in young men critically ill with HIV. Astonishingly, all participants recovered, marking a pivotal moment that spotlighted the impact of successful drug development on human life. Although Saquinavir’s market approval took more years to come, the trial was an irrefutable testimony to the transformative power of pharmaceutical research.

Built on this formative experience, PCS is resolute to continue its trajectory in preclinical development. The aim is to drive medical progress, enhance patient health, and foster the growth of emerging healthcare professionals.

While the road to groundbreaking achievements may be fraught with challenges, Dr. Plassmann insists every incremental step is required to conquer greater distances to success.

“Success is a continuous journey to ease the lives of those facing persistent, perhaps lifelong health challenges. We have to remain committed to our fight and do all we can to win,” she says.

Her statement perfectly distils the unyielding resolve and commitment that drive PCS’ operations day in and day out.

Website: https://www.pcsconsultants.com/