Xyzagen’s consultants are experts in drug discovery, development and FDA regulations and guidelines. We support clients in their regulatory interactions through written documents, oral communication, and face-to-face meetings. Our consultants can then manage the scientific oversight of the agreed upon and required nonclinical in vitro/ in vivo ADME, bioanalytical, clinical pharmacology components to your development program
How do you know you’re fully and timely meeting your Nonclinical ADME/Metabolite ID/Clinical Pharmacology scientific and regulatory requirements? The key is a sound regulatory strategy, but it’s not always possible to identify all of the challenges a priori. Sometimes a strategy just isn’t good enough since your molecule may not exhibit the proper balance of pharmacology, pharmacokinetics and safety. You may have advanced the wrong molecule forward to IND candidate stage in order to meet a corporate goal. Xyzagen will integrate scientific, nonclinical, clinical, chemical, intellectual property, anticipated corporate constraints and overall drug development expertise to support its clients regulatory strategy. Each strategy is product and indication unique but a strategy, both regulatory and scientific strategies are based in understanding the therapeutic target landscape and the issues of the products in the market. A regulatory strategy only focus that only addresses the regulations is not a strategy for success.
• Regulatory Due Diligence
• Critical Review And Gap Analysis Of Regulations Relative To Scientific Datasets
• 505(B)(2) Strategies
• FDA Correspondence Interpretation And Regulatory Guidance
• FDA Meeting And Teleconference Participation (E.G., Pre-IND, End Of Phase 1 [EoP1], End Of Phase 2 [EoP2], Pre-NDA, Pre-BLA, And Type C Meetings)
Advisory Committee Preparation And Participation
Xyzagen’s regulatory and scientific writers have extensive experience in scientific due diligence and writing regulatory documents. We strive to understand and integrate the broader clinical strategy while being attuned to the details we’re best at; nonclinical pharmacology, ADME and Clinical Pharmacology/PK. You know your molecule best so the message that is conveyed to the reviewer (journal, regulatory agency or due diligence corporate partnership) must be impactful, clear, concise and speak with one voice. We will work with you to meet your specifications and timelines using your templates and style guide, or our own, to create submission-ready eCTD documents 2.4, 2.6.2 through 2.6.7 and 2.7.1 and 2.7.2
• Investigator Brochures (IBs)
• Conversion of Legacy to eCTD or de novo eCTD formats
• 505(b)1 and 505(b)2 INDs, CTDs and NDAs
• Technical and scientific review and QC checks of regulatory applications
• Primary research manuscripts and white papers for nonclinical, and clinical publications
• Subject-specific literature searches, reviews and summaries
• Nonclinical and Clinical Study Reports
• FDA/EMA meeting packages, pediatric plans and orphan applications
Pharmacokinetics and Toxicokinetics are only as good as the bioanalytical method underpinning the kinetic analysis. If the bioanalytical method has high variability then it can impact an understanding of the pharmacokinetics. For instance, if your unvalidated method had high variability (100% CV) at the low end of the concentration range then you may improperly calculate the half-life your molecule your developing, which could impact your modeling and simulation.
However, not every method must be validated. It depends on the stage of drug discovery and development for your program. You also do not need each newly discovered metabolite to be validated into your GLP method.
Our bioanalytical consultants can ensure that the method you’re having developed at your contract lab is fit for purpose to the stage of development.
Xyzagen offers complete in vitro/in vivo pharmacology, ADME (absorption, distribution, metabolism, excretion), and pharmacokinetic (PK) strategy consulting, implementation and oversight services. Our consultants can help move your molecule from a PreIND asset to clinical development as efficiently as possible. Xyzagen’s consultants have contacts with additional 3rd Party CROs that can support your drug’s development.
• Preclinical in vitro/ in vivo ADME/PK plan development and implementation
• Strategy for development of small and large molecules
• Strategy, study planning and evaluation, and regulatory submissions
• Data analysis, interpretation, and presentation
• Regulatory ADME, pharmacology, and toxicokinetics (TK)
• Critical review and gap analysis of submissions
• Due diligence and ADME/Clin Pharma Gap Analysis
Xyzagen can design any Phase 1 study and request competitive bids. But a single phase 1 study (unless it is a biopharmaceuticals/bioequivalence study) is not a clinical strategy and as such the study should be part of a larger integrated program between the nonclinical studies and the clinical PK studies; be they in healthy volunteers or patients. As part of the study design phase, our senior consultants will conduct a review of your clinical pharmacology strategy to establish an understanding of existing data and how to maximize the impact of the next study on the overall plan. We will also evaluate the in vitro data to determine in a Phase 1 study is necessary (e.g. DDI studies).
• First-Time-in-Human (FTIH)
• Single Ascending Dose (SAD)
• Multiple Ascending Dose (MAD)
• Food Effect
• Drug-Drug Interaction (DDI)
• Hepatic Impaired
• Renal Impaired
• Bioavailability (absolute and relative)
• Formulation assessment (IR to XR formulation conversion as part of a 505(b)2 strategy)
• Intrinsic / Extrinsic Studies
• Special Populations
• Alcohol Interaction
• Site of Absorption
• Radio-labeled Mass Balance
Incorporating appropriate patient based sample collection and pharmacokinetics into your phase 2 and 3 studies is the basis of the eventual population pharmacokinetic modeling and simulation.
Talk to our scientists about the best strategy of incorporating PK assessments into your patient clinical studies.
Our consultants have published on Population PK and PK/PD Modeling and Simulation. If your company does not have a pharmacometrician on staff then talk to us about how we can help review your CROs modeling and simulation work to determine if its accurate and meets the program’s scientific and regulatory needs.
