An intelligence hub innovating and accelerating groundbreaking therapies to address unmet medicinal needs
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Small-molecules, cells, nucleic acids, antibodies, recombinant proteins, antigen heteropolymers, Antibody-drug conjugates (ADCs), vaccines, AAVs and combinations
Research, pre-clinical, clinical, market authorization in global markets and product lifecycle investigations.
We troubleshoot manufacturing process, GMP manufacturing, analytical (methods, QC testing, characterization, and strategies) specifications, shelf life or stability, product quality, and regulatory challenge and provide appropriate mitigation strategies.
We also troubleshoot organization structure and workflows and provide strategies for speed and efficiency.
Below are examples of some breakthroughs:
Challenge: For 30 years of research the gene of a kinase could not be expressed sufficiently, and the expressed protein was not soluble.
It was not known that a commercial CXCR ligand to be used for a high-throughput screening (HTS) was not functional.
Accomplishment: Achieved a 40-fold yield in purified functional protein, which achieved unprecedented mechanism of action discoveries about this cancer and viral infection target.
Identified conformational heterogeneity in the product and <2% was functional. The scheduled HTS was cancelled, and a new reagent was development initiated
Challenge: Solubility of samples from an IgG4 drug substance (DS) batch was found to be different in different labs.
It was necessary to optimize an AAV process for %full without ultracentrifugation.
Accomplishment: Identified process related causes that suggested a potential failure of the on-going phase III trial. A new process development was initiated.
Identified process opportunities that increased %full for >70% without ultracentrifugation. A new purification platform found.
Challenge: Due to a high variability of an ELISA, the quality of drug substance batches from a CDMO was not certain.
A variable bioassay did not show any significant trend for stability of an antibody drug conjugate (ADC).
Accomplishment:Improved the ELISA, which revealed that all the drug substance batches were below specification for clinical trials.
After optimization of the assay to <5% CV, a novel critical quality attribute (CQAs) was revealed that rendered the product less suitable for sustained clinical benefit. The platform was terminated.
Challenge: A drug product (DP) had to be placed in quarantine during transit to clinical sites because of a gap identified in the bioburden testing of the source DS.
Multiple batches of an AAV DS showed OOS for aggregation at multiple timepoints of a 15-month stability study. Five quality investigations had failed to identify a root cause. This triggered an MAA major objection.
Accomplishment:A scientific and technical driven impact assessment justified that the DP was suitable for the clinical trial, which were to start in one week.
A thorough assessment of all previous investigation reports using an innovative quality tool, followed by targeted investigational hypothesis experiment, identified root causes and appropriate mitigations to the satisfaction of the EMA.
Challenge: There was an urgent business need to accelerate a combination therapy to BLA.
An HMW OOS was identified in master stability drug product batch that was already dosed.
Accomplishment: Used risk assessment that reduced method validation timeline by 70%. Enabled 14 months acceleration to BLA.
The investigation identified a process-induced chemical reaction that impacted the quality of that batch only. The report was accepted by the health authority without impact to the clinical studies.
Challenge: A biologic that was in phase III clinical trial showed inconsistent solubility in two different analytical labs.
An unexpected event was observed with a drug in phase III clinical trial.
Accomplishment: Identified a process-related conformational heterogeneity as the cause of inconsistent solubility. With a potential impact on clinical outcomes, a new manufacturing process was initiated.
Using a cross-functional scientific and technical team, identified a novel MOA and clinical opportunity. This enabled major clinical decision and insight into a new drug target opportunity.
Challenge: CE-SDS was previously filed as a CQA but the purity levels measure by CE-SDS was later declining below specification with scaling up of the process.
There were >100 objections, including major and other concerns, to a submission for market authorization.
Accomplishment:The assessments and experimentations revealed the CE-SDS result was not a CQA. The health authority accepted removal of CE-SDS test from the control strategy.
A scientific and technical driven analysis and risk assessment eliminated all objections and market authorization was granted timely.
Challenge: An unusual dark coloration was observed in a soap product. All new batches were lost and there was no hope for future batches to be successful.
The result of a safety attribute on a new commercial batch was OOS, which implicated an inconsistent manufacturing process. Market authorization was at risk.
Accomplishment:A science and technology driven investigation with follow up experimentations revealed the cause from corroded manufacturing chamber that needed replacement.
A detailed investigation revealed the cause from inherent sensitivity of the assay that became evident with more testing experience. The proposed mitigation strategy was accepted by the health authority.
Challenge: An outsourcing model was believed to need more full-time equivalents (FTEs) because about 80% of the protein types produced externally were not functional.
Failures of various assays at multiple contract testing organizations (CTOs) resulted in a large number of CTOs, which impacted time and cost.
Accomplishment: From a thorough assessment of the company model, a cross-functional structure was established. This led to a reduction in FTEs from 16 to 2 and an increase in functional protein types to >90%.
An outsourcing strategy was established that enhanced relationships with external partners enabled a clear path to strategic consolidation to few CTOs and an enhanced consistency of results from a CTO.