Service Offering: Circular Dichroism of solid particles


A tool to measure bio-stability and vaccine potency for DS & DP.


Find out more about this technique and see what our clients say about our service and how it has helped them.

XstalBio have proprietary technology available for licensing that can solve a wide range of bioformulation and delivery problems. These include manufacture and delivery of high concentration protein solutions, sustained release of biologics, thermally stable vaccines containing antigens and PRR ligands and dry biologic powders for delivery by inhalation.

Technology

XstalBio tackles challenging biologic formulation issues such as:

  • Required dosing too frequent
  • Controlled release of API required (alter the PK profile)
  • Unacceptable loss of high potency API at low concentrations
  • Competitors hold blocking formulation patents
  • Alternative delivery method favoured
  • Better adjuvant needed for target antigen(s)
  • Cellular immune response required or duration of immunogenicity too short
  • Elimination of cold-chain is desired
  • CoG of product too high
  • API  can be too viscous at high concentration

 

Key Product Enabling Technologies

High dosage delivery of proteins:

Stable solid-state formulations for reconstitution to very high aqueous concentrations



Key Characteristics for high dosage delivery:  

  • > 200 mg/ml for therapeutic mAbs
  • Rapid reconstitution at point of use  
  • FDA approved parenteral excipients
  • Osmolality applicable for subcutaneous administration
  • Viscosity allows delivery through 27 gauge needle
  • Extended shelf-life


Sustained-release of biologics:

Controlling API release over periods of days to weeks

  • Applicable to peptides, proteins, nucleic acids, polysaccharides etc
  • Straightforward, high yield manufacturing process
  • Administer using 27 gauge needle in WFI
  • No polymers - release controlled by dissolution of calcium phosphate
  • FDA approved parenteral excipients
  • API unmodified and stabilised within particles
  • Manufacturing is straightforward to apply and integrates into XstalBio's exisiting manufacturing process 

 

Vaccines employing innovative adjuvants:

Co-delivery of antigen(s) and immunostimulant(s) to antigen presenting cells (APC)

  • Applicable to acellular antigens, killed viruses, bacterial lysates, toxoids, plasmids
  • Immobilisation on particles of size  and shape similar to bacterial pathogens
  • Adaptive immune response  tailored by choice of TLR agonist
  • Administer parenterally (27 G) or via alternate delivery routes
  • Exclusively approved excipients with excellent tolerability
  • Multivalent vaccines manufactured rapidly with straightforward QC
  • Exceptional high and low temperature storage stability
  • No cold-chain requirement

 

Cold-chain free biologic formulations:

Solid-state products stable on exposure to elevated temperature and humidity

 

 

  • Excellent retention of bioactivity with wide range of biomolecules
  • > 40 client API successfully formulated
  • Excellent resistance to stress with negligible protein aggregation or fragmentation
  • mAb formulations stable for 1 year at 40 ºC
  • Free flowing dry powders of cytokines, hormones, plasmids, mAbs and mAb-derivatives
  • Starting point for wide range of alternate delivery routes


Pulmonary delivery of biologics - systemic and topical

XstalBio has developed it’s proprietary protein-coated microcrystal (PCMC®) technology to produce a respirable, stable pulmonary product with excellent powder handling characteristics and a broad applicability for a range of potency requirements.

 

We can straightforwardly control the API payload of PCMC® for both high and low potency requirements.

Uniquely Placed: Particle engineering for advanced delivery

The XstalBio-PCMC® particles are uniquely placed to deliver two or more biological actives that are simultaneously immobilised in a chosen pre-set ratio on the surface of the particles, e.g. vaccine and adjuvant, e.g. CpG.  XstalBio’s particle engineering allows excellent delivery of multiple actives in a defined and predictable ratio. Importantly, control over particle size and shape is achieved by choosing the most appropriate processing conditions. 


Platform manufacturing process:

Straightforward (semi-) continuous precipitation approach applicable to wide range of biologic products

  • Uses off-the-shelf components and low-footprint facilities
  • GMP compatible process developed in collaboration with Boehringer Ingelheim Pharma using QbD approach
  • Potential for very high throughput and lean manufacture
  • Process highly differentiated  providing enhanced freedom to operate
  • Can be integrated with existing fill-finish processes

 

Manufacture: Straightforward and robust

PCMC® for pulmonary delivery is straightforward to manufacture and has been scaled for production of clinical batches of product in collaboration with Boehringer Ingelheim Pharma KG.  XstalBio’s manufacturing process via third party diligence has been shown to be robust, straightforward, cost-effective and high yielding.

PCMC® for pulmonary delivery is available for licensing from XstalBio.

 

Client Programs - Milestones delivered

For third party clients, we have produced a range of pulmonary powders of proprietary small proteins, mAbs and mAb fragments.

A 6 month program with a XstalBio client achieved all of the following milestones:  

FORMULATION CHARACTERISTIC DESIRED

ACHIEVED?

Particle sizes:  x 90 < 10 µm, x 50, 0.5µm – 3µm

 YES

Moisture Adsorption:   < 1 % over 0 - 75 % R.H. T 25 ºC 

YES

No deliquescence below 90 % R.H. at 25 ºC

YES

Protein Stability: accelerated 3 month program, 40 ºC, 75 % R.H.

YES

Sol aggregates: < 5 %, no visible aggregates                

YES

Solid-state form: high crystallinity, no tendency to form amorphous material

YES

Emitted Dose: > 80 % at 60 L/min

YES

Fine Particle Fraction (FPF): > 50 %                           

YES

Particle stability: no change, following storage for a minimum 3 months

YES

Device performance with PCMC®

We recently collaborated with Aptar coupling their  Prohaler device with XstalBio PCMC to assess pulmonary performance.  Delivering high payloads of API, FPFs of preliminary non-optimised test formulations delivered > 40 % FPF and emitted doses of > 96 % at low, 0.5 L inhalation volumes.

To find out more information on our Pulmonary Technology Offering, please contact us

 

CentuRecon

 

 

CaP delivery for BMP & orthobiologics