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Spray-drying as alternative isolation technology for peptides

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peptides. Lonza Kourim focuses on both ISO and cGMP microbially produced peptides. In 2008, Lonza added to this peptide networks with its now established R&D peptide center in Nansha, China. This new FDA approved site supports route selection and process development as well as the production of non-GMP material for pre-clinical or formulation studies. In addition, Nansha is also able to produce large-scale GMP peptide fragments by liquid-phase.

The up-stream part of the peptide synthesis, specifi cally, the assembly of the peptide backbone, can vary between solid-phase (SPPS), liquid-phase (HPPS), and mixed phase (MPPS). However, the down-stream process often uses very similar unit operations. These consist of purifi cation, concentration and isolation.Downstream purifi cation typically needs extensive HPLC capabilities and capacities, for which Lonza is well equipped. Due to the hydrophilic nature of most of the de-protected peptides, reversed-phase chromatography has to be applied to remove side products with similar structures

and characteristics as the fi nal API. In certain cases, purifi cation with crystallization works, but for more diffi cult structures such as long peptides, this process is not easily applied. Lonza’s Braine and Visp facilities are equipped with a variety of small-, mid- and large-scale HPLC equipment ranging from 2 cm up to 60 cm in diameter at pressures of up to 60 bars. The large-sized columns are used to purify commercial peptides with annual demands of up to several

L onza, one of the largest providers for Development and Production Services to the Pharmaceutical Industry, is well-

known for its custom manufacturing offerings in the Mammalian, Microbial and the Small Molecule fi elds. What is sometimes overlooked is Lonza’s custom services for peptides and other hybrid products with peptidic structures. Peptides as well as small molecules are treated differently from a regulatory point of view and differ distinctively from non-peptidic small molecules in terms of production, purifi cation, and stability.

Peptides at Lonza have a long history, starting from the integration of UCB Bioproducts into the network of Lonza’s peptide offering. At the former UCB site at Braine, Belgium, peptide production began in 1980. In addition, Lonza produces peptides at our multi-product facility in Visp, Switzerland. These multiple microbial and chemical approaches to product development and production allow for several robust options, depending on the lengths, amino acid composition and complexity of the given peptide.

Since 2006, Lonza has combined the activities and capabilities of the various sites. Lonza Braine has been slated as the main chemical peptide production site, with Lonza Visp specializing in large-scale solid-phase fragments or API’s and highly-toxic

Monographic supplement series: Oligos & Peptides - Chimica Oggi - Chemistry Today - vol. 32(2) March/April 2014

SKIN CAREPRODUCT FOCUS Chimica Oggi - Chemistry Today customer's publication

Lonza's MDL - 050 Spray Dryer

Dr. Michael MaskusHead of Business Development, Peptides

Lonza Custom ManufacturingMichael.maskus@lonza.com

Spray-drying as alternative isolation technology for peptides

hundred kilograms. Given this capability offering, the purifi cation process typically does not pose a bottleneck for our customers.

The fi nal isolation of peptides is typically performed in a freeze-dryer. This is a streamline way to remove the residual water by sublimation at low temperatures. In order to keep up with the growing portfolio of larger-scale peptides, Lonza decided to expand its isolation capacity. Instead of buying additional freeze-drying equipment, alternatives methods were examined. The drawbacks of lyophilization (freeze-drying) are the high energy consumption (for vacuum pumps and ice condensers), the low productivity (several days cycle time for one batch) and the rather intensive manual labor.

Therefore, Lonza looked at various alternatives, e.g. crystallization, azeotropic distillation, supercritical chromatography with CO2 and also spray drying. After a thorough evaluation phase, the decision was made to support the spray-drying technology. Spray-drying is based on the transformation of an aqueous peptide solution into a powder by “atomizing” (transform the liquid into very small droplets of 10-500µm diameter) the peptide solution through a nozzle into a chamber together with a hot gas in order to remove the liquid.

In order to avoid the decomposition of the peptide during this process, a special spray-drying technology has been adopted. This micro-mist spray drying by Fujisaki, featuring a “four-fl uid” nozzle has allowed the drying temperature to be kept as low as 40°C. During the isolation process no thermal degradation up to 170°C has been observed and the stability of the products is comparable for the old and new methods. Additionally, during spray drying fi ne and dense particles are formed which are less static than the particles formed during

9Monographic supplement series: Oligos & Peptides - Chimica Oggi - Chemistry Today - vol. 32(2) March/April 2014

Spray drying vs. freeze drying: overall comparison

lyophilization and the removal of acetonitrile is improved. The comparison table on this page shows the overall clear advantages compared to lyophilization.

Lonza’s current MDL-50 spray-dryer has become one of its main commercial services, with annual quantities in the multi-ten kilograms, and validated process at >2.5 kg / day capacity.