How it Works





Drug Substance (API)

Clinical Development

 

“Changes of any kind in the API after clinical work has begun (Phase I) can

trigger additional preclinical and clinical studies, including clinical hold.”

CCMCO provides the following, comprehensive services for the Drug Substance (API):

 

  1. Design/SAR/Optimize the compound
    1. Bioavailability
    2. Solubility
    3. Physical state (polymorphs & particle size)
    4. Prodrugs
    5. Salt forms
    6. Stability
    7. Manufacturable (scalable all the way to commercial) and economical
    8. Formulatable into practical, patient friendly and cost effective dosage forms.
    9. Issue RFP to Proven, Qualified Vendors (competitive bid)
      1. Finalize Contract
      2. Direct, review, approve and document all outsourced activities:
        1. Manufacture & Characterization appropriate to clinical phase

                                                    i.     Design a feasible reaction scheme

  1. Scalable with predictable impurity profile

                                                  ii.     Process chemistry optimization

                                                 iii.     Demonstration batch (100’s of grams); preclinical ADME/PK; nonGMP

                                                 iv.     Clinical, toxicology, and safety pharmacology batch (1-10 kg’s); GMP

  1. All aspects of the API that influence bioavailability, safety, efficacy, stability, scalability, and cost are essentially locked in for the life of the API at this early point.  The future of the clinical program is riding on this initial CMC work.  Changes of any kind in the API after clinical work has begun (Phase I) can trigger additional preclinical and clinical studies, including clinical hold.
  2. Set specifications

                                                 i.     Meet regulatory expectations internationally

                                                 ii.     Pertinent and achievable through scale-up

                                                 iii.     Assure availability of API to initiate and advance the clinical program

  1. Develop & validate phase-appropriate, in-process and release analytical methods
  2. Design and execute an appropriate stability program
  3. Write the Drug Substance section (CTD) of all regulatory filings (IND, CTA, NDA, IMPD, IB, Protocols, etc.).

                                                  i.     Respond to all CMC regulatory inquiries and demands.

                                                  ii.     Represent the CMC function in all correspondence/meetings with agencies.







Drug Product (CTM)

Clinical Development

“Any change to the Drug Product after clinical work has begun (Phase I) can

trigger additional clinical studies (generally bioequivalency PK bridging studies) that delay the advancement of the pivotal clinical studies by several months.”

CCMCO provides the following, comprehensive services for the Drug Product (CTM):

 

  1. Design and optimize the dosage form(s)
    1. Preformulation

                                             i.     API characterization specific to the desired formulation(s)

                                             ii.     API/excipient compatibility

                                             iii.     Access to a low cost, private laboratory where preformulation and basic formulation work is completed in ca. 4 to 6 weeks.

  1. Formulations that are practical, patient friendly, and cost effective.

                                            i.     Oral solids

                                           ii.     Sterile parenterals

                                           iii.     Controlled release orals and parenterals

                                           iv.     Solutions

                                           v.     Topicals

  1. Manufacturable (scalable all the way to commercial) and economical
  2. Bioavailable

                                          i.     Solubilization

                                          ii.     Solid state manipulation

                                          iii.     Controlled release

  1. Stable
  2. Issue RFP to Proven, Qualified Vendors (competitive bid)
    1. Finalize Contract
    2. Direct, review, approve and document all outsourced activities:
      1. Manufacture & Characterization appropriate to clinical phase

                                                    i.     Design Phase-appropriate dosage form(s) per client’s objectives

  1. Quick, low cost entry into Phase I
    1. Powder-in-capsule or powder-in-bottle

                                    i.     Gets initial human PK and safety data

                                    ii.     Not acceptable for Phase II/III studies

                                    iii.     Requires formulation and bridging PK before Phase II

                                    iv.     Money and time saved initially is lost if program advances.  Requires formulation and bridging PK before Phase II.


  1. Formulation (can support all phases of clinical development)
    1. Design formulations based on dosing requirements, oral bioavailability, and issues with the API (solubility, stability, etc.)
    2. Prototyping and demonstration batch manufacture; nonGMP
    3. Clinical batch manufacture; GMP

                                          i.     Clinical supplies must be in commercial image and at commercial scale (at least 1/10commercial batch size)  once Phase III begins

  1. Design appropriate packaging/labeling for clinic, including international studies, that assures integrity of the dosage form(s).
  2. Distribution & Storage

                                                i.     Distribution network and warehousing, including cold chain

                                                ii.     Accountability and inventory control

                                                iii.     Set specifications

  1. Meet regulatory expectations internationally
  2. Pertinent and achievable through scale-up
  3. Assure availability of CTM to initiate and advance the clinical program

                                                 iii.     Develop & validate phase-appropriate, in-process and release analytical methods

                                                 iv.     Design and execute an appropriate stability program

  1. Shelf-life / expiry sufficient for reliable, economical clinical supply
  2. Write the Drug Product section (CTD) of all regulatory filings (IND, CTA, NDA, IMPD, IB, Protocols, etc.).

                                                  i.     Respond to all CMC regulatory inquiries and demands.

                                                  ii.     Represent the CMC function in all correspondence/meetings with agencies.

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