Formulation Development of Biotherapeutics & Vaccines

Formulation Development


HTD Biosystems offers formulation development services for biologics, including proteins, peptides, vaccines, and liposomes. We have extensive experience with various forms of modalities such as monoclonal antibodies, bispecific and multi-specific antibodies, fusion proteins, nanobodies, fab, enzymes, antibody-drug conjugates and pegylated proteins. 

Protein & Peptide Formulation Using iFormulate™ Platform

HTD has also developed a platform for formulation development using design of experiments (DOE) called iFormulate™. We identify a stable formulation during rational design using highly advanced tools including DMD, ML, and AI.

Formulation Development of Liquid, Frozen or Lyophilized products

We have helped our customers with development of liquid formulations for parenteral  delivery of proteins, antibodies, liposomes and vaccines that is Phase appropriate and fits the Product Target Profile. 

Co-formulation Development of Biologics  

Following an increased interest in coformulation development, we have developed a number of co-formulations and also published a cover article on co-formulation development of biologics in combination products in the American Association of Pharmaceutical Scientists (AAPS) Magazine on  Aug 2019. You can contact us to receive a reprint.
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High Concentration Protein Formulations

We have worked with development of several high concentration protein formulations for our clients. We have used various methods to increase protein concentration from 1 mg/mL to 200 mg/mL. We also scale up the process, using different methodologies including Ultrafiltration and diafiltration (UFDF).

Vaccine Formulation Development

Alum-based vaccines
We have extensive experience of formulation and lyophilization development of vaccines. You can learn more about our work with alum-based vaccines by reviewing one of the papers that we have published on Stability of a Trivalent Recombinant Protein Vaccine Formulation Against Botulinum Neurotoxin during Storage in Aqueous Solution here.
Liposomal vaccines
We have also developed several liposomal vaccine candidates for our clients and collaborators and helped tech transfer these formulations to GMP manufacturing sites.
Learn more about our vaccine development capabilities here.

Learn more about our formulation capabilities here.

Protein Formulation Development for Pulmonary Delivery

HTD has collaborated with several universities on formulation development. For example we worked with Professor Kathleen Stringer on development of a pulmonary formulation of tissue plasminogen activator. The results were published in a series of papers including:
Accelerated dosing frequency of a pulmonary formulation of tissue plasminogen activator is well-tolerated in mice, click here to read more.

Formulation Development of Liposomes, Lipid Nano Particles (LNP) & Gene Therapy Products

We offer services in liposome and LNP design, formulation and manufacturing process development. We have successfully developed several liposomal formulations for targeted delivery for cancer therapy. We can formulate and manufacture liposomes in several sizes and with different properties for interaction with specific immune cells and targets.
Find out more about our liposomal formulation and manufacturing capabilities Learn more.

Analytical Testing

HTD offers a range of analyses and studies to support biophysical characterization of proteins and other molecular entities to ensure that the formulation is supporting the quality attributes required for a stable formulation. Important quality attributes for proteins are identity, purity, content and activity. At HTD, we start the formulation development work by analyzing the biophysical activity of the molecule  under various formulation variables such as pH, and excipients.  

You can learn more on how we use DOE and high throughput analytics in formulation development by reading our published article in American Pharmaceutical review on 
Automated and Rapid Methods to Assess Quality & Stability of Biologics: Recent Developments and Practical Ways to Implement Them in Formulation Development

Protein Aggregation

We use a hollistic approach to understand the aggregation behavior of the molecule as a function of temperature, pH and in the presence of various additives. We offer different methods including:
    • Dynamic light scattering (DLS) 
    • Sub-visible particles by FlowCam Microscopy 
    • Protein Chip Bioanalyzer.

    Protein Conformation

    HTD offers a variety of high throughput methods to analyze protein conformation the impact of formulation and process variables on this important quality attribute. These include:

    Differential Scanning Fluorimetry (nDSF)​​​​: nDSF is a method that we use to determine thermal stability of proteins in different formulations and across different temperatures. Using this method, we can determine the protein denaturation temperature and unfolding. We will then investigate which excipients and formulations increase or decrease the denaturation temperature. Download our joint white paper with nanotemper here.

    Differential Scanning Calorimetry (DSC): An additional method that we use to determine thermal stability of molecules such as proteins in Aq. solutions is DSC. We also use this method for understanding the thermal behavior of a formulation, for example its freezing point, primary glass temperature and melting temperature of its components.

    Second Derivative UV Spectroscopy (2dUV): We have extensive experience with this method which is an additional method for characterization of protein conformational stability.  We can quantify the microenvironments around Phe, Tyr, Trp and detect conformational changes in the tertiary structure in formulation development.

    Viscosity

    At HTD we have different viscosimeters to determine viscosity of formulations. This is especially important for high protein concentration formulations that might have a high viscosity.

    Osmolality

    We offer osmolality measurements for determination of osmolality of the liquid formulations and reconstituted lyophilized formulations using an osmometer.

    Stability Studies

    Accelerated stability studies are a type of stability testing that is used to evaluate the stability of proteins in liquid and solid dosage forms under conditions that are more severe than those that the product will typically experience during storage and use. The goal of accelerated stability testing is to determine the shelf life of the product and to identify any potential degradation mechanisms.
    There are several factors that can affect the stability of proteins in liquid and solid dosage forms, including temperature, humidity, light exposure, pH, and the presence of other chemicals or contaminants. During accelerated stability studies, these factors are controlled and the protein is exposed to conditions that are more severe than those that it would normally encounter, such as higher temperatures or higher humidity levels.

    To conduct accelerated stability studies of proteins in liquid and solid dosage forms, a sample of the product is prepared and stored under accelerated conditions for a specified period of time. The protein is then analyzed at regular intervals to determine its stability, including its concentration, purity, and functional activity. Any changes in the protein's properties are monitored and used to determine the shelf life of the product and to identify any potential degradation mechanisms.

    Accelerated stability studies are an important part of the development and quality control of proteins in liquid and solid dosage forms, and they are essential for ensuring the safety and effectiveness of these products. HTD has expertise in accelerated stability studies and can provide high-quality services to our clients to support the development of safe and effective products.