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Fill Finish Services

Our fill/finish services are designed to deliver the lowest possible risk to patients while maintaining a high value proposition. Fill/finish includes formulation, vial filling, lyophilization, testing / stability testing and release of licensed products.

We assist all clients in the development of advanced specifications, as we move from adapting current components to ground-up design, taking maximal advantage of robotic and touchless equipment.

Fill finish capabilities

  • Closure by Design
  • Compatible for most Stringent case use requirements (i.e. ocular indications)
  • Interoperability between component vendors
  • Standardization
  • Revving software to minimize product loss Target <10mL for small volume fills
  • Early to late same site viral fill capabilities
  • State-of-the-art isolator technology to minimize risk to patient
  • Quality/Regulatory confidence in chosen isolator technology
  • Typical batch size from a hundred to 10k with capability of 25k or more (scale out)
  • Support for multiple container types: vials, syringes and cartridges (glass and plastic), 2R-20R with 50R (glass) coming
  • Add drug product capability to FDBT FBF Facility
  • Assess all small modular fillers
  • Utilize for high-value advanced therapy (viral vectors and gene therapy)

formulation development – balancing speed and science

Why is formulation development important?

Formulation development is the experimental design of a buffer and excipient combination that maintains the integrity of the purified protein during routine bioprocessing, storage, handling, and delivery to the patient.

Proteins are molecules with individual primary, secondary, tertiary, and quaternary structures that combine to form a unique three dimensional arrangement. These “higher order structures” give each protein its own “personality”. Molecular characteristics like these directly impact the formulation development process. The personality of your protein needs to be taken into consideration even before lab work begins.

Our formulation development services can help will develop a suitable liquid or lyophilized formulation for your drug substance or drug product to ensure stability of your molecule during preclinical, clinical or commercial use.

Our formulation development services

Formulation development at FUJIFILM Diosynth Biotechnologies includes biophysical characterization through bioanalytical assays, preformulation studies and formulation development, including mitigating stress-related molecular degradation and minimizing protein self-interactions to optimize solubility protein and stability.

Early molecular characterization using biophysical techniques provides increased success in the selection of formulation components and solution conditions that will lead to a stable parenteral drug candidate.

To help you fully characterize and understand your product and process, our laboratories are equipped with a broad range of modern analytical equipment, and a team with over 20 years of experience in formulation to assist you.

High-throughput bioanalytical assays and sample preparation

Formulation development efficiency is guaranteed by rapid, automated sample preparation and a toolbox of high-throughput bioanalytical assays including:

  • Understanding how to best utilize biophysical assays to understand a protein molecule’s unique characteristics (preformulation)
  • Optimizing formulation component selection early in the process by leveraging key biophysical analyses and stress response information
  • Performing protein formulation development with high throughput sample preparation and analysis by biophysical and physicochemical methods
Lab

Formulation Development

Preclinical/Phase I/II formulations can be frozen liquid, refrigerated liquid or lyophilized formulation dependent on intrinsic stability of each product. Frozen liquid formulations are typically the most rapid form used to support early clinical studies. Refrigerated liquid formulations are often preferred if product is stable but require additional buffer/excipient screening and real time stability at the actual storage temperature to demonstrate physicochemical stability. Lyophilized formulations can be used for proteins that may not be stable in liquid state.

Through developing an understanding of the thermal, physical, chemical, and conformational personality of the protein during preformulation, a rational design approach is used to develop a formulation for preclinical and early clinical studies.

Our design approach includes evaluating factors such as:

  • Effect of pH, buffer type, and ionic strength on conformational stability
  • Predictive solubility using Composition Gradient MALS (CG-MALS)
  • Effect of excipients ability to increase solubility and stability
  • Impact of stress through forced degradation studies
  • Accelerated stability

FUJIFILM Diosynth Biotechnologies performs protein formulation design with robotic high throughput sample preparation to ensure robust and reproducible development.

Based on the inherent knowledge of the protein, selection of pH/ionic strength/buffer/excipient screening may vary from selecting formulation components found in approved/commercial mAb biotherapeutics (e.g., for mAb formulation development) to de novo design incorporating preformulation knowledge to guide a statistical design-of-experimental (DOE) design to identify the effects and interactions of the formulation components as candidate formulations are selected. Regardless of the approach, FDB performs protein formulation design with robotic high throughput sample preparation to ensure robust and reproducible development.

The data driven formulation development studies will propose formulation candidates. Real time and accelerated stability studies then identify the recommended formulation. Arriving at a well understood and characterized formulation, our approaches help create an “insurance policy” for the successful clinical manufacturing campaign of your product.

As the clinical lifecycle progresses through Phase III and process validation, additional formulation development is typically performed. The following elements may need to be considered in developing the commercial presentation of the biotherapeutic product.

  • Buffer optimization and robustness studies
  • A change in the dosing schedule or dosage administration requiring a higher concentration formulation
  • Container closure/device compatibility study
  • Mock Shipping
  • A change in the route of delivery (intravenous, subcutaneous, intramuscular, etc.)
  • Introducing a delivery device (e.g., prefilled syringe)

Our formulation development services can help will develop a suitable liquid or lyophilized formulation for your drug substance or drug product to ensure stability of your molecule during preclinical, clinical or commercial use.

Formulation development services include:

  • Formulation development and optimization (liquid and lyophilized using SMART Freeze Dryer Technology) of Final Drug Product
  • High concentration Formulations
  • Standard approach to Monoclonal Antibody Formulation to reduce timelines and costs
  • Specialized Formulation Development for Product comparability (including biosimilar comparability)
  • Short and Long Term Storage Conditions (Freeze/Thaw Cycles)
  • Forced degradation programs (including identification of stability indicating assays and multi-lot comparison)
  • Design and execution of drug delivery studies including Device Compatibility and reconstitution

A comprehensive Biophysical Characterization ToolBox is used to understand your molecules personality, including:

  • Differential Scanning Calorimetry – MicroCal VP-Capillary DSC Units: Used in the evaluation of conformational/thermal stability
  • Circular Dichroism – Jasco J810: Used in the evaluation of secondary & tertiary structures
  • MALS – Wyatt DAWN ® HELEOS ™ II MALS/Calypso GC-MALS/Optilab ® T-rEX ™: Used to to determine molar mass, higher order structure
  • Fluorescence Spectroscopy – Perkin Elmer LS55: Used in the evaluation of tertiary structures
  • Dynamic Light Scattering & Zeta Potential – Malvern ZetaSizer Nano ZS: Used in determination of Zeta Potential, aggregates
  • Particulate Analysis (visible/subvisible) – HIAC 9703+, High Throughput Micro-Flow Imaging ™
  • Isothermal Chemical Denaturation (ICD) – AVIA Biosystems: Used to determine protein stability at room temperature or experimental temperature

Our extensive physicochemical methods include:

  • Chromatography: size-exclusion, ion-exchange, reversed-phase, hydrophobic interaction
  • Electrophoresis: iCE, CE-SDS, SDS-PAGE, microfluidic capillary electrophoresis
  • Mass Spectrometry: intact MS, primary sequence and modifications by LC/MSE
  • Potency: binding ELISA, enzymatic activity, cell-based assays
  • Glycan Characterization