• Synthetic route selection, technical transfers, optimization, route scouting and proof-of-concept studies.

• Phase-appropriate process development (“fit for purpose”).

• Identification of the most stable crystal polymorph or salt form.

• Partner closely with analytical and formulation development, nonclinical and clinical development, quality assurance, and CMC-regulatory.

• Identification of appropriate analytical methods for material release and in-process control.

• Raw material evaluation and selection, specification setting for all starting materials, reagents, intermediates, and products.

• CDMO/CRO vendor identification, evaluation and selection. Technical transfer from process development vendor if needed.

• Technical oversight of drug substance manufacturing for the following:

  • Non-GMP demonstration batches of drug substance (API) suitable for analytical development, stable polymorph determination, salt selection, or drug product preformulation/formulation studies.

  • GLP drug substance suitable for preclinical toxicology studies, formulation, analytical method validation.

  • GMP drug substance for use in drug product manufacture and clinical trials.

• Technical review, editing and sign-off of manufacturing batch records and release of drug substance.

• Evaluation of requests for quote (RFQs/RFPs) and generation of technical strategy, time estimates, and analytical aspects of proposals for clients.

• Cost estimates for current processes and recommendations for improvement.

• Generation of alternate, novel synthetic routes to valuable materials.

• Review of technical capabilities and recommendations for valuable process chemistry, analytical and manufacturing upgrades or expansion.

• Technical oversight of process development and GLP or GMP manufacturing.

• Impurity identification through a combination of analysis and knowledge of reaction mechanism.

• Full impurity characterization (NMR, MS, IR, ROI, ICPMS, XRD, DSC, TGA, IC).

• Cost of good estimates (COGs) and raw material vendor price negotiations.

Review and determination of drug substance material needs for preclinical and clinical pharmaceutical development. Tracking of drug substance supply.

Generation of requests for quotes (RFQs), vendor evaluation and selection, project oversight. Inspection of CROs/CDMOs/Manufacturing.

Management of process research and development, demonstration batches, preclinical (GLP) batches and GMP manufacturing.

Cost of good estimates (COGs) and raw material vendor price negotiations.

Tracking of timelines and cost. Item description

Establishment of appropriate regulatory starting materials (RSMs).

Impurity assessment. Identification and characterization of starting material, process, and degradation impurities.

Potential mutagenic impurities (PGI) hazard assessment and impurities classification.

Nitrosamine risk assessments.

Impurity control strategies.

Expert direction and management of appropriate isolation and purification techniques.

CMC author drug substance portion (3.2.S) of investigational new drug application (IND).