Process Analytics
MedScope has substantial experience developing process analytic technoloies for real time in process manufacture control. MedScope is a rapid development organization, and in most instances can initiate value-based discussions within 24 hours. Please contact us at 802-236-8650 or info@medscope.com. 

Process Analytics - Percent Dissolved Oxygen PAT To Optimize Recombinant Growth Factor 
Continuous monitoring system for a protein refolding reaction to provide consistency in product quality and process performance across batches. A small-scale bioreactor (3 L) is used to understand the impact of aeration for refolding recombinant human vascular endothelial growth factor (rhVEGF) in a reducing environment. A reverse-phase HPLC assay is used to assess product quality. The goal in understanding the oxygen needs of the reaction and its impact to quality, is to make a product that is efficiently refolded to its native and active form with minimum oxidative degradation from batch to batch. Because this refolding process is heavily dependent on oxygen, the % dissolved oxygen (DO) profile is explored as a PAT tool to regulate process performance at commercial manufacturing scale. A dynamic gassing out approach using constant mass transfer (k(L)a) is used for scale-up of the aeration parameters to manufacturing scale tanks (2,000 L, 15,000 L). The resulting DO profiles of the refolding reaction show similar trends across scales and these are analyzed using rpHPLC.

Process Analytics - Real Time Noninvasive Spectroscopy w Automated Sampling
Noninvasive spectroscopic methods such as Raman, near infrared, and dielectric spectroscopy provide real-time information on cell culture and fermentation processes, combined with periodic aseptic batch sampling, thereby allowing hands-off, contamination-free sampling; automated sample scheduling; automated at-line analysis of whole broth and cell-free samples; increased sampling frequencies; increased sampling reproducibility;  and increased data reliability.

​Process Analytics - Drug Substance: Process Step Description + Desired Outcome of Unit Operation
1. Cell Culture to generate cells grown in Bioreactor. Desired outcome is PAT measurement and control of critical mass of protein-producing cells. 

2. Fermentation to produce desired protein in Bioreactor. Desired outcome is PAT measurement and control of target protein concentration.

3. Homogenization (bacteria only) to rupture cells. Desired outcome is PAT measurement and control of amount energy necessary to break cell membranes to expose the protein.

4. Harvest to separate protein from cell matter . Desired outcome is PAT measurement and control of centrifuge to separate proteins from cell matter.

5. Purification to further separate protein from other impurities using chromatography columns, filters. PAT measurement and control to purify protein while sustaining within solution without physical disruption of the protein.

​Process Analytics - Drug Product: Process Step Description + Desired Outcome of Unit Operation
1. Formulation is adjusted to add compounds to stabilize and adjust potency. Desired outcome is PAT measurement and control to ensure formulation is potent and product is an effective stable biopharmaceutical.

2. Fill/Finish in order to segregate into separate doses (freeze ifnecessary). Desired outcome is PAT measurement and control of appropriate fill level and properly dosed and frozen vials.

3. Package/Seal in order to ensure appropriately sealed and boxed vials with appropriate labelling. Desired outcome is PAT measurement and control of capping and labeling.

4. Cold Chain from manufacturer to vendor by consistent control by maintain temperature during transport. Desired outcome is PAT measurement and control of  insulated packaging and refrigerated vehicles to ensure effective therapy is delivered to patient.

Major steps in the drug substance portion of biomanufacturing
- GLP/GMP compliance
- Assays validated to ICH and USP standards
- FDA registered facilities/comprehensive quality system
- Regulatory Assistance and Support/CMC Documentation









    MedScope - BioProcess Consultants
        QbD/CMC/cGMP Consultants in Gene Therapy, Immunotherapy, Small Molecule, LentiVector Development: Inception to Launch
          802-236-8650
   info@medscope.com

 Commercial Operations
 - LentiVector
 - Development/Mnftr
 - Cell Line Mnftr
 - Continuous Manufacturing
 - Process Analytics (PAT)
 - DOE, Multivariate Design
 - Scale-Up,-Out,-Down
 - Development Protocols
 - Equipment
 - Single Use
 - Strategic De-risk

Regulatory Science
 - CMC Development
 - Comparability Studies
 - Device Design Controls

Analytical Development
 - Bioanalytic Assays
 - Immuno/PK
 - Product/Impurity
 - Single Use
 - Extractables/Leachables

Medical
 - CMO/Med Affairs
 - Preclinical Development
 - Clinical Development
 - CMC/Commercial Develop
 - Rare Disease
 - Pediatric 
 - Breakthrough Therapies

Manufacturing and ComOps
 - Capital Equipment
 - BSL-2, ISO7
 - Closed Manufacturing
 - Suppliers
 - Tech Transfer

Facilities & Locations
 - 100,00 ft2 Mnftr/Lab Space
 - 50,000 ft2 Office Space 
 - Cambridge, MA
 - Burlington, VT

Quality
 - Documentation
  - WIFI Controls 
 - QBD, SOP, WI
 - BPR, Protocols, 
 - Audits, PAI, 

Sales & Marketing
 - Global Strategic Pricing
 - General Management,
 - Strategic Planning
 - Market Plans
 - Alliance Management

Advocacy - Gene Therapy
 - GeneTherapy Cost Models
 - FDA Realignement
 - Workforce Development
 - Regs Patient Bedside Mnftr

U.S. Defense
 - Biologics Rapid Detection
 - Biologics Rapid Response
 - DARPA, SBIR

Computation
 - Protein/DNA Modelling
 - Process Capability
 - Remote RT OPC/OLE



802-236-8650, info@medscope.com