Issue link: https://www.e-digitaleditions.com/i/1300450
www.biopharminternational.com October 2020 BioPharm International eBook 43 ter is issued on a product/facility related to an acquisition, the like- lihood of a delay and loss of deal value is likely. The expectations for the exten- siveness of the information pro- vided will of course be dependent on t he stage of t he produc t(s) being evaluated. For early-stage produc ts, not all items w ill be available. The individual perform- ing the due diligence should lever- age FDA and European Medicines Agency guidance documents that list regulatory expectations at var- ious stages of development listed in Table II. For items that have not been completed at the time of the due diligence activity, it should be reasonable to ask what plans are in place to address these items. It is i mp or t a nt for t he va r i- ous disciplines carrying out the due d i l igence e xerc ise to com- mu n ic ate w it h e a c h o t he r a s C M C - r e l at e d it e m s a r e o f t e n not located in typical CMC data room files. For example, a tablet dissolution question may come from a pharmacokinetic reviewer. In this case, it is critical that the non-clinical, clinical, regulatory, a nd C MC representat ives work Regulatory Sourcebook Process Development Area Item Comments CMC regulatory Module 3 section of all filings Include amendments Correspondence relating to CMC issues May not be limited to the chemistry reviewer Drug product (formulation) Preformulation and physicochemical characterization reports Include salt, solvate/hydrate, and polymorph forms Items specific to the intended route of delivery Oral: Biopharmaceutical classification system classification, particle sizes of batches used, bioavailability in various species, Caco-2 permeability, food and alcohol effects, etc. Parenterals: Aseptic process validation, terminal sterilization feasibility, endotoxin control, filter validation, leachable and extractable studies, etc. DP development reports Including process validation Excipients assessment Compatibility, precedence, any novel excipients, drug master file available, transmissible spongiform encephalopathy information, etc. Device (Combination products) Design control information for any devices Human factors studies Drug substance (API) DS development reports Include structure elucidation and process validation Analytical Method development reports Include forced degradation studies, stress testing, validation, etc. DS and DP specifications and rationale Include intermediate specs DS and DP stability data Impurity and degradation product assessment Include levels seen to date, evaluation of potential mutagenic impurities, qualification levels, etc. Manufacture Details for DS, DP, and device manufacture Include all raw materials, their quality standard and source, in process specifications, details of any process analytical technologies, and possibly a typical batch record at an onsite visit Scalability assessment and plans for the DS, DP, and device processes Include any capital needs Capacity/availability at manufacturing sites Include future sites Inspection history over past five years for manufacturing sites Include future sites Cost of goods estimates for DS, DP, and packaging/device Overall Development timelines Development cost and cost of goods estimates Intellectual property related to the DS, DP and packaging/device Include composition of matter and process patents/applications and know how Ta b l e I. L is t of c r itic al ite ms to b e includ e d in t he c he mis t r y, manufacturing, and controls (CMC) due diligence assessment. DS is drug substance. DP is drug product. Accelerated biopharmaceuti- cal development has prompted clinical-stage therapeutic com- panies to establish partnerships with contract development and manufacturing organizations and heightened the importance of conducting chemistry, manu- facturing, and controls due dili- gence. Read more online in the article "CMC Due Diligence for Accelerated Biologic Drug Devel- opment and Manufacturing." —The editors of BioPharm International Additional Reading