Formulation and lyophilization process development for live virus vaccines

ProJect Pharmaceutics expands its service portfolio to meet customer’s increasing need for the development of GMO S2 and BSL-2 biological products including live viruses.

ProJect Pharmaceutics is one of the leading European service providers offering tailored pharmaceutical formulations and lyophilisation processes for therapeutic proteins, peptides and other therapeutic compounds.

New safety facilities in dedicated labs and a deep understanding of the challenges when processing virus vaccines enable ProJect Pharmaceutics to provide specific solutions for this group of products of high complexity.

Smart formulations and manufacturing processes to safeguard the efficacy of the finished drug product are provided together with mandatory safety requirements up to GMO S2 and BSL-2 classification.

Maintaining the native quaternary structure of the virus capsid and avoiding virus aggregation is the key to maintain its full biological activity even under stress conditions like elevated temperature, freezing and freeze drying. Cutting-edge analytical high-throughput methods have been implemented in our biological safety lab in order to select the most effective combination of excipients for the final drug product. The GMO S2 and BSL-2 safety lab is equipped with a dedicated pilot freeze dryer to design tailored lyophilisation cycles both maximally robust and efficient. PJP’s long lasting experience and comprehensive know-how of lyophilisation enables our customers to follow new paths in process technology. Customers will benefit from safer products with an optimized stability profile and reduced manufacturing costs.

For more information please visit: www.project-pharmaceutics.com or contact:
ProJect Pharmaceutics GmbH
Fraunhoferstraße 22
D-82152 Martinsried
+49 (0) 89 452289700

High Protein Concentration Formulations

Munich, October 29, 2015 – ProJect Pharmaceutics introduces a science-based approach to develop best-in-class formulations for convenient use in pre-filled syringes

Transforming therapeutic proteins into high-concentrated, stable and easy to use medications for subcutaneous self-injection can add up to a major challenge along their clinical development. A formulation’s fundamental qualifications such as appropriate physico-chemical stability, container material compatibility and viscosity must be taken into account to support an acceptable in-syringe shelf-life as well as convenience in regard to syringe-ability. However, in order to take all of the requirements to a maximum and develop a pioneering new drug in a pre-filled syringe presentation, a great extent of knowledge, expertise and sophisticated analytics is needed that are sparingly found in this developing market to date.

ProJect Pharmaceutics, one of the experts in formulation and process development for parenteral drugs, has specialized in this emerging field with a key expertise in development of stable, effective and syringe-able formulations and their eligible processes. Be it conformation of de novo drug products towards a pre-filled syringe application or transfer of existing drug products into the like, ProJect Pharmaceutics features all the required key qualifications in that field.

By applying an elaborate science-based approach to meet well-discussed critical quality attributes such as e.g. maximum effectiveness, high concentration for low injection volume, low aggregate content and low viscosity, ProJect Pharmaceutics offers profound guidance and support on the development of pioneering parenteral biologics.

‘Predictive formulation analytics’ positions ProJect Pharmaceutics towards a rational design of high-concentrated but low viscous and easy injectable formulations:

flowchart

Minimizing viscosity and aggregation by actively maximizing repulsive protein-protein interaction in solution is one of the key techniques used. Additionally, shifting thermodynamic protein stability in solution to its maximum prove another key requisite promoting long-term stability of liquid formulations in pre-filled syringes.

Designed formulations’ syringe-ability is measured directly in-system mimicking the typical administration procedure of the patient instead of through viscosity only.

In case stability in aqueous solution is found to be limited by the biologic ́s inherent sensitivity freeze-drying clears the way forward. Innovative design of lyo-formulations and freeze-drying processes developed by ProJect Pharmaceutics reliably overcome the hurdles of reconstituting high-concentrated protein lyophilizates.

Supply of aseptic pre-clinical study material in pre-filled syringes at pilot scale complete ProJect Pharmaceutics’ excellence as your pharmaceutical service provider in this exigent field of highly concentrated protein formulation development.

Meet ProJect Pharmaceutics at Bio Korea 2015

Join Dr. Andreas Schütz for his presentation: “Formulation and lyophilization process development for biopharmaceutics” at Bio Korea 2015 from April 8–10, in Seoul, COEX international convention center. His talk is scheduled April 8th, 15:30 at Business/Technology Presentation Forum.

Please contact our office at if you need further details on the conference or wish to meet us at there.

ProJect Pharmaceutics and TUM-Spin-off ImevaX announce agreement on development of pharmaceutical formulation for IMX101

Munich/Martinsried, November, 2013

ProJect Pharmaceutics announces that it has signed a development agreement with ImevaX, a spin-off project from the research group of Prof. Dr. Markus Gerhard from the Technische Universität München, Institute for Medicinal Microbiology, Immunology and Hygiene, aimed at developing a formulation for a recombinant vaccine against Helicobacter pylori. IMX101 is a multicomponent vaccine, making the formulation development particularly challenging.

The contract covers activities in developing a rational formulation based on ProJect Pharmaceutics´ Predictive Formulation Analytics. This technology offers an innovative scientific approach for designing optimized protein formulations by determining the most favorable composition for the native structure of the protein with regard to its intra- and intermolecular physicochemical properties. By analyzing the response to certain excipients the most promising formulation candidates can be identified quickly and reliably reducing the need for extensive stability testing.

Promising formulation candidates have successfully been evaluated and are continuously optimized within the development program since its launch in mid 2013. Financial terms of the current agreement are not disclosed.

About project ImevaX

As part of the GO-Bio start up program of the German Ministry of Research and Education (BMBF), the TUM-based Spin-off project ImevaX from the research group of Prof. Dr. Markus Gerhard from the Technische Universität München, Institue for Medicinal Microbiology, Immunology and Hygiene, develops highly specific vaccines against pathogens that cause chronic infectious diseases. Its technology identifies immune modulatory bacterial factors that are then used to develop effective vaccines against infections of global relevance. ImevaX is planned to be founded as a biotech company in 2014.

For more information please visit: www.imevax.com or contact:
Medizinische Mikrobiologie, Immunologie und Hygiene
Trogerstraße 30
D-81675 München
+49 (0) 89 4140 2477
Prof. Dr. Markus Gerhard:

Introducing formulation and lyophilization process development for cytotoxic and other highly potent drugs

ProJect Pharmaceutics expands its service portfolio to meet customer’s increasing need for the development of cytotoxic and other highly potent drugs such as immunotoxins.

ProJect Pharmaceutics is one of the leading European service providers offering tailored pharmaceutical formulations and lyophilisation processes for therapeutic proteins and peptides.
New safety facilities in dedicated labs and a deep understanding of the challenges when processing highly potent drugs enable ProJect Pharmaceutics to provide specific solutions for cytostatic agents and immunotoxins.

Many pharmaceutical ingredients of this class show limited solubility in water and degrade rapidly during compounding, filling and freeze-drying. Smart formulations and manufacturing processes to safeguard the efficacy of the finished drug product are therefore required.

PJP’s long lasting experience and comprehensive know-how of lyophilisation from various kinds of solvent systems enables our customers to follow new paths in process technology for highly potent drugs. Customers will benefit from safer products with optimized impurity profile and reduced manufacturing costs.

Joint Development of a novel lyophilized Dual Chamber Prefillable Syringe System

Tokyo (Japan) and Munich/Martinsried (Germany), June, 2012

Arte Corporation and ProJect Pharmaceutics have been working closely on the development of a new type of dual chamber prefillable syringe for freeze-dried pharmaceuticals.

The two companies have joined together with the objective to provide innovative dual chamber syringes for the global pharmaceutical market. This type of device, called Lyo- DCPS, will be delivered in standard nests and tubs to comply with the industrial standard for aseptic filling of nested syringes. The abbreviation Lyo-DCPS stands for lyophilized dual chamber prefillable syringe.

Teamed-up in new concept development

Arte Corporation contributes its manufacturing expertise on high quality pharmaceutical packaging systems specifically in the field of prefillable syringes. ProJect Pharmaceutics, for its part, adds its know-how in developing filling and freeze drying processes and adapts the Lyo-DCPS design to enable GMP-conformity and efficient manufacturing processes for clients’ drug products.

Nested Dual Chamber Syringes for Filling and Freeze Drying on Common Filling Lines

Like conventional mono chamber syringes Lyo-DCPS will be delivered in standardized nests and tubs and can be filled on widely used nested syringe fillers. The diluent is filled first and can be autoclaved as required by international guidelines. The drug solution is filled into the second chamber and completely sealed on the filling line before entering the freeze drier. Due to its special design, the system opens by itself within the freeze drier enabling lyophilization of the drug solution in presence of the diluent.

The development has reached pilot scale and lyophilization of first customers ́ products in the new device has been performed successfully. Sterile nested Lyo-DCPS for GMP manufacturing of drug product will be available early 2013.

About Arte Corporation

Arte Corporation based in Tokyo and Takahagi City, Japan, is Japan ́s leading manufacturer of pharmaceutical glass packaging systems like ampoules, vials, cartridges and PrefillableTM syringes.

For more information please visit: www.artecorp.co.jp or contact:
Arte Corporation Headquarters/Sales Office:
5F NK Bldg.
2-8-12, Iwamoto-cho, Chiyoda-ku
Tokyo, 101-0032 Japan
+81-(0)3-3861-2881

About ProJect Pharmaceutics GmbH

ProJect Pharmaceutics, based in Martinsried/Munich, Germany, develops pharmaceutical formulations freeze drying cycles and manufacturing processes for biopharmaceutical dug products.

For more information please visit: www.project-pharmaceutics.com or contact:
ProJect Pharmaceutics GmbH
Fraunhoferstraße 22
D-82152 Martinsried
+49 (0) 89 452289700

Check your Lyo Cycle!

Have you ever calculated the drawback on direct and opportunity costs when your freeze dryer is blocked by lyophilization cycles which take several days?

Take this opportunity and have your cycle parameters checked for 2,000 € only. Just send us your lyophilization process parameters, a printout of an actual lyo run and some samples.

Our experts will carefully analyze the data and identify any potential for process risk and process time reduction through:

  • product quality risk assessment
  • detection of technical weaknesses
  • scale-up risk assessment
  • potential product quality improvement
  • potential cycle length reduction

Call on us to optimize the freeze drying cycle in our pilot lab and transfer a high speed cycle back to your GMP facility. New paths in program design empower us to quickly and efficiently generate a dry and elegant lyophilizate without compromising process reliability and product stability.

To safeguard transferability of the results we analyze the technical design and resulting capabilities of your production freeze dryer and adapt our advanced and highly flexible pilot freeze dryers to these conditions.

Moreover, we determine critical lyophilization parameters and explore the design space, for those parameters, in a well-defined robustness program according to ICH Q8. This approach significantly reduces the technology transfer risk from pilot scale to commercial scale production.

Formulations for clinical trials and beyond

Budget is often scarce for pharmaceutical development projects before the drug has even shown proof of concept in first clinical trials. In that early stage, many drug developing companies are hesitant to spend the money for a fully-fledged pharmaceutical development of the formulation.

Thus, quite often formulations in preclinical studies and clinical stages I and II are far from being rationally designed. Particularly when it comes to therapeutic proteins, where formulation development is highly challenging due to the structural complexity and instability of the compound, pharmaceutical quality issues are the likely consequence.

Once proof of concept has been established with the rudimentary formulation, pharmaceutical companies are reluctant to change this formulation due to concerns of jeopardizing the data obtained so far in preclinical and early clinical testing.

As a result, formulations reflecting an early preclinical development status often find their way into pharmaceutical dossiers, and authorities frequently deny approval of numerous drug applications due to the lack of pharmaceutically sound data documenting state-of-the-art formulation and process development.

The key to overcome this dilemma is Predictive Formulation Analytics offered by ProJect Pharmaceutics: Plying state-of-the-art analytical methods permits us to characterize the protein molecule and analyze its response to certain excipients with regard to its intra and intermolecular physicochemical properties. This allows us to quickly and reliably identify those combinations of pH value, ionic strength, ion types, detergents and other stabilizing agents, which preserve the active 3 dimensional structure of the protein in an ideal manner.

Costs, timelines and the amount of API required for this highly efficient approach towards a rational and reliable formulation for clinics and beyond is surprisingly low.

Our deliverable will be a science-based formulation for a freeze dried product of your drug, and a conventional lyophilization cycle, ready for tech transfer to GMP manufacturing.

Once your drug has mastered critical milestones in early clinical development, call on us to carefully work out the final formulation of your drug, by means of an in-depth experimental program, to verify or optimize the quantitative composition of the drug product tailored to the route of application, the delivery system and the pharmaceutical manufacturing process.

ProJect Pharmaceutics introduces Predictive Formulation Analytics for a rational design of optimized biopharmaceutical formulations.

Munich/Martinsried, December, 2011

Protein drug formulation is particularly challenging due to structural complexity and instability. The biological activity of most recombinant proteins emanates specifically from their 3-dimensional structure which needs to remain unaltered throughout the shelf-life of the product. However, cleavage or aggregation incidents may not only reduce efficacy but also produce adverse immunologic effects.

The current industry standard for the formulation development of biopharmaceutical drugs is a time consuming, trial-and-error driven process which requires accelerated stability testing to identify the best out of many formulation alternatives. Occasionally, the large number of formulation options is tested by means of high throughput screening, yet accepting the potential drawback of a highly artificial testing environment.

Predictive Formulation Analytics from ProJect Pharmaceutics offers an innovative scientific approach for designing optimized protein formulations and reduces the need for extensive stability testing.

Plying state-of-the-art analytical methods to characterize the physicochemical state of proteins and analyze their response to certain excipients allows us to quickly and reliably identify promising formulation candidates.

The stability of proteins in solution is mainly determined by intramolecular and intermolecular interactions. Intramolecular stability is characterized by protein thermodynamics which are measured by means of nano differencial scanning calorimetry (nanoDSC). Intermolecular stability is represented by the attractive or repulsive interaction between protein molecules which is quantified via composition gradient static light scattering (2nd virial coefficient).

A systematic algorithm based on design of experiments (DOE) is used to determine the most favorable composition for the native structure of a given protein with regard to its intra- and intermolecular physicochemical properties. Beneficial effects resulting from pH value, ionic strength, ion types, detergents and other stabilizing agents can be identified and quantified without stability testing.

The data obtained from our research provide the basis for a drug product composition that is tailored to the protein, its packaging system and its application. A final stability test program, carried out on samples filled into the final packaging system under genuine pharmaceutical manufacturing conditions, serves to confirm the suitability and stability of the composition and provides trustworthy data for initiating clinical trials.

For more information please visit: www.project-pharmaceutics.com or contact:

ProJect Pharmaceutics GmbH
Fraunhoferstraße 22
D-82152 Martinsried
+49 (0) 89 452289700

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