Ron Wolff, president of RK Wolff Safety Consulting Inc. and former Vice President of Regulatory Affairs & Toxicology at Pulmokine, is a long-time collaborator of KreaMedica. He has been working with KreaMedica since its inception and has come to know Karl-Rudolf Erlemann (Rudi), President & CEO of KreaMedica, and his team as trusted partners in supporting his client’s programs. Before starting his own consulting business, Ron had worked as a former Executive Director of preclinical safety assessment for Novartis, as well as at Nektar Therapeutics, Eli Lilly, and the Lovelace Inhalation Toxicology Research Institute.
As a seasoned expert in preclinical safety assessment and toxicology, with a particular focus on inhalation toxicology and pharmaceutical aerosols, Ron has contributed his knowledge to many joint projects with KreaMedica over the years. This long-standing partnership has supported successful outcomes for many clients.
“KreaMedica has been instrumental in navigating several challenges that have occurred with the different projects,” said Ron.
In an interview, he described the extensive interactions he has had with the KreaMedica team, highlighting how their deep expertise and coordinated problem solving helped resolve complex toxicology challenges and advance several compounds towards commercialization.
Challenge 1: Designing a complex toxicology study with multiple active ingredients
Ron and KreaMedica worked together to help an early-stage biotechnology company in the respiratory disease space get a successful IND application for one of their lead candidates. But like most IND submissions, this one was not without challenges.
The test agent in this project contained a combination of three active ingredients, requiring a toxicology study that could easily become unwieldy in scope and cost. Based on the initial assessment, the study design could require over ten different study groups—an extremely time-consuming and costly undertaking.
“The study design was one of the most complicated I have done,” said Ron.
In the end, the joint effort and expertise allowed to reduce the number of study groups down to eight. Ron expressed that KreaMedica was instrumental in developing and executing the successful study along with a Canadian CRO partner, ITR Laboratories Canada, located in Montreal, Quebec. The streamlined study design resulted in significant cost and time savings for the client without compromising data quality.
Challenge 2: Streamlining bioanalytical assays for multi-compound analysis
In addition to solving logistical challenges related to the study design, KreaMedica was also involved in helping facilitate bioanalytical work. The presence of three distinct compounds in the test formulation introduced complexity to bioanalytical methods. To avoid the need for separate analytical runs for each compound, the team designed an ingenious solution to dramatically reduce the number of runs.
“Rudi’s bioanalytical expertise helped immensely in developing a streamlined assay which allowed analysis of two of the compounds in one run,” said Ron.
This approach, executed with the help of a Quebec-based company Royalmount Laboratories, not only helped reduce the time and cost of the analytical work, but also decreased the variability between assays. The successful completion of these studies led to an IND submission, and the drug combination is now in clinical trials.
Challenge 3: Diagnosing and resolving unexpected toxicities in chronic inhalation studies
KreaMedica and Ron also collaborated on a different small molecule project for a clinical-stage biopharmaceutical company. After successful one-month toxicology studies, the 6- and 9-month chronic studies revealed unexpected toxicities, threatening the program’s continuation. KreaMedica’s team led an in-depth investigation and uncovered a key issue: a modification to the aerosol generation system had been introduced after the one-month studies.
“KreaMedica provided a much more extensive monitoring of the studies carried out by the CRO than is usually possible for a sponsor,” said Ron. This deep level of engagement and oversight was what helped identify the problem with the aerosol generation system. “KreaMedica’s team members are intimately familiar with the labs. They provide thorough and frequent project management and study monitoring, along with excellent insights.”
By identifying and correcting the system change, the team was able to restart the studies, salvaging a program that would otherwise have been abandoned. The studies are now supporting Phase 2 trials and potentially a New Drug Application (NDA) submission.
Facilitating collaboration and reducing development costs
The projects that Ron described involved many stakeholders with unique needs and constraints. In each case, KreaMedica played a crucial role as a cross-functional integrator, providing scientific oversight, project management, and troubleshooting across multiple engagements. This continuity and strategic input ensured smooth execution of projects and enabled all parties—consultants, CROs, bioanalytical labs, and sponsors—to work cohesively under a unified development plan.
“These services are invaluable,” expressed Ron. “KreaMedica helps with study designs, sending out RFPs to CROs to get the best possible prices for studies. The pricing for sponsors is considerably reduced when the studies are conducted in Canada under KreaMedica’s close oversight, adding up to substantial cost savings.”
By working with Canadian CROs, KreaMedica provides tangible financial benefits for its clients: a sponsor gets a reduced price for the study in addition to enhanced monitoring, thanks to KreaMedica’s proximity to the CROs. This eliminates the need for frequent trips to a remote site for the client and allows them to focus their efforts on other projects. KreaMedica also provides crucial supervision of the studies, reports, and project management services to keep things on track.
“The fact that KreaMedica is in close proximity to several key toxicology labs means that they can provide much more extensive monitoring than is usually possible for a sponsor,” said Ron. “They are highly knowledgeable and easy to work with.”
About Ron Wolff
Ron Wolff, Ph.D. was appointed vice president of regulatory affairs and toxicology in 2015 following several years as Pulmokine’s consultant on regulatory affairs. He assisted Pulmokine with regulatory matters and preparation of the company’s successful Investigation New Drug (IND) application for an inhaled PDGFR inhibitor for pulmonary arterial hypertension.
Dr. Wolff is president of RK Wolff Safety Consulting Inc. He is a former executive director of preclinical safety assessment for Novartis; senior fellow in toxicology at Nektar Therapeutics in San Carlos, California; group leader of inhalation toxicology at Eli Lilly; and senior scientist at Lovelace Inhalation Toxicology Research Institute. He has experience in toxicology in a wide range of areas, including respiratory, oncology, endocrine, infectious disease, and biologics with special expertise in inhalation toxicology with applications to pharmaceuticals and environmental and occupational health.
He has also served as chair of the Occupational Exposure Level (OEL) Committee of Eli Lilly, and is a co-author on the Product Quality Research Institute (PQRI) publication on safety qualification thresholds for leachables and extractables. He has published more than 150 articles on topics including inhalation toxicology, pharmaceutical aerosols, leachables and extractables, and oncology. He is a Diplomate of the American Board of Toxicology (DABT), a former member of the Board of Directors of the International Society of Aerosols in Medicine, and is a past-president of the American Association for Aerosol Research.
About KreaMedica
KreaMedica was founded in 2009 with a vision to revolutionize drug development through functional outsourcing. The Montreal-based company has planned, managed and executed over 150 development programs from lead candidate selection through non-clinical safety assessments and early clinical trials by outsourcing to their world-class CRO/CMO network. With a commitment to research, development and quality, KreaMedica has become a trusted “one-stop-shop” drug development partner, offering reliable solutions and cost-saving strategies for their international biotech and pharma clients.