What are somatostatin and somatostatin analogues?

July 01, 2021
Light micrograph of oesophageal cancer

Somatostatin (SST) was isolated and characterized by researchers working in the laboratory of Guillemin at the Salk Institute in 19731Burgus, R et al. Proc. Natl. Acad. Sci. U. S. A. 70(3), 684–688 (1973). Somatostatin is a hormone produced by the hypothalamus and some other tissues such as the pancreas and the gastrointestinal tract. It is an inhibitor of growth hormone release from the anterior pituitary gland and suppresses the release of a variety of other hormones involved in the regulation of important physiological functions of the gastrointestinal tract.

 

What does somatostatin look like?

Somatostatin is a cyclic polypeptide containing a disulfide bridge, between Cys-3 and Csy-14 for somatostatin-14 (SST-14) and between Cys-17 and Cys-28 for somatostatin-28 (SST-28). Somatostatin peptides are derived from a precursor protein of 116 amino acids (Figure 1). The precursor is processed into several peptide hormones, including SST-14, SST-28 at the N-terminal, and neuronostatin, which is a 13-residue amidated peptide flanked with the signal peptide.

Schematic structure of somatostatin
Figure 1 – Somatostatin precursor molecule and location of the disulfide bridges

What role does somatostatin play in the body?

 

In the body, there exists five somatostatin receptor (SSTR) subtypes, SSTR1 to SSTR5 to which their natural ligands SST-14 and SST-28 bind. SST-14 and SST-28 bind with equal affinity to SSTRs 1–4. However, SST-28 has a 10- to 30-fold higher affinity for SSTR5 than other SSTs, whereas SST-14 has reduced affinity at SSTR5.

The two somatostatin forms are together considered a global counter regulatory hormone, with inhibitory effects in multiple target tissues. Somatostatin inhibits gastric acid secretion and motility, intestinal absorption, pancreatic bicarbonate and enzyme secretion, and selectively decreases splanchnic and portal blood flow in dogs and humans without affecting mucosal blood flow. Moreover, somatostatin inhibits the secretion of growth hormone (GH), prolactin (PRL), thyrotropin (TSH), cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin, motilin, neurotensin, secretin, glucagon, insulin, and pancreatic polypeptide (PP)2Brown, M at al. Fed. Proc. 40(11), 2565–2569, (1981).

SST-14 is the predominant form in the central nervous system and in most peripheral organs, including the gastrointestinal tract, where it can be found in the stomach, duodenum, colon, and pancreas. In contrast, SST-28 is produced mainly by intestinal enteroendocrine cells and represents >50% of the somatostatin content in the small intestine. Furthermore, SST-28 could be used to treat a range of disorders, mostly relating to hormone hypersecretion.

Somatostatin is characterized as a regulatory-inhibitory peptide with exocrine secretion; for example, of gastric acid, intestinal fluid and pancreatic enzymes and endocrine secretion, or for example, of growth hormone, insulin, glucagon, gastrin, cholecystokinin, vasoactive intestinal peptide (VIP) and secretin. Somatostatin has great potential for the treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. The short half-life of somatostatin however limits its usefulness as an efficient therapeutic modality. Therefore, research has been conducted in the development of new tuned somatostatin derivatives to offer patients a more efficient treatment.

Somatostatin analogues: What role do they play for patients?

 

A somatostatin analogue (SSA) is a synthetic version of somatostatin. It slows down the production of hormones, especially the growth hormone and serotonin. This helps to control the symptoms of carcinoid syndrome such as diarrhoea and flushing of the skin. Furthermore, SSAs are of considerable utility in the diagnosis and treatment of gastroentero-pancreatic neuroendocrine tumors (NETs). These synthetic analogs of somatostatin have longer half-lifes. To date, three of them have been approved by the agencies: lanreotide and octreotide are considered first-generation SSAs, and pasireotide is considered a second-generation SSA.

The first synthetic SSA that was approved by the Food and Drug Administration (FDA) was the octapeptide octreotide (SMS 201-995) marketed as Sandostatin®. Octreotide (scheme 1) shows high affinity for SSTR2 and inhibits the proliferation of the cells expressing SSTR2 gene by activating the tyrosine phosphatase pathway3Buscai, l L et al. Proc. Natl. Acad. Sci. U. S. A. 91(6), 2315–2319 (1994). Octreotide acts through four mechanisms to decrease abnormal growth hormones (GH) secretion in acromegaly. First, octreotide suppresses GH secretion from the pituitary gland and from GH-secreting adenomas. Second, it decreases GH binding to hepatocytes. Third, it inhibits hepatic IFG-1 production and finally it controls tumor growth4Murray, R D et al. J. Clin. Invest. 114(3), 349–356 (2004).

Octreotide or Sandostatin® was approved for use in the United States in 1988. It is used for the reduction of growth hormone and insulin-like growth factor 1 (somatomedin C) in adults with acromegaly who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses. In addition, Sandostatin® is applied for the treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors in adults as well as profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas) in adults.

Chemical structure of octreotide
Scheme 1 Structure of octreotide
Lanreotide (scheme 2) is a cyclic octapeptide that was developed in the 1990s with the intent to develop a longer acting SSA5Morange, I et al. J. Clin. Endocrinol. Metabol. 79(1), 145–151 (1994). Like octreotide, lanreotide is used in adults to treat acromegaly that cannot be treated with surgery or radiation, carcinoid syndrome and a certain type of pancreatic or digestive tract tumor that may spread to other parts of the body. First approved for use in the United States by the FDA in 2007, lanreotide is marketed under the trade name Somatuline®.
Chemical structure of lanreotide
Scheme 2 Chemical structure of lanreotide
Pasireotide, a novel SSA, that is sold under the brand name Signifor®, is an orphan drug approved by the FDA in 2014 for the treatment of Cushing’s disease in patients who fail or are ineligible for surgical therapy. Pasireotide activates a broad spectrum of somatostatin receptors, and binds with higher affinity to SSTR1 (30-fold), SSTR3 (5-fold), and SSTR5 (39-fold), and with the same affinity to SSTR2 (three-fold) when compared with octreotide; and with higher affinity to SSTR1 (19-fold), SSTR3 (nine-fold), and SSTR5 (106-fold), but with the same affinity to SSTR2 (two-fold) when compared with lanreotide6Bruns, C et al. Eur. J. Endocrinol.146(5), 707–716 (2002); Hofland, LJ et al. Eur. J. Endocrinol. 152(4), 645–654 (2005). The binding and activation of the somatostatin receptors causes inhibition of ACTH secretion and results in reduced cortisol secretion in Cushing’s disease patients. Also this agent is more potent than somatostatin in inhibiting the release of human growth hormone (HGH), glucagon, and insulin.
Chemical structure of pasireotide
Scheme 3 Chemical structure of pasireotide

For these drugs to be efficient, they require delivery methods such as infusion, frequent injections, implantable devices, or intramuscular injection of large drug volumes, which are not always preferred by health care providers and patients.

A huge improvement for diagnosis and treatment of tumors

So far, three SSAs have been approved and launched in the market for treatment of tumors secreting vasoactive intestinal peptide, carcinoid tumors, glucagonomas and various pituitary adenomas, and acromegaly in where there is over secretion of growth hormone in an adult. Furthermore, they are an invaluable therapeutic option in the diagnosis of these diseases.

The formulations of somatostatin analogues have been improved over time and new longer acting versions were introduced, Sandostatin LAR® Depot for octreotide and Somatuline® Depot or Autogel for lanreotide.

In the case of Sandostatin LAR® octreotide is encapsulated in microspheres that are formed with a biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer. Sterile mannitol is added to the microspheres to improve suspensibility.

Somatuline® Depot contains lanreotide acetate in a prefilled syringe that is fitted with an automatic needle guard. The formulation is based on the peptide self-assembly, which provide an innovative solution to sustain a therapeutic dose over a long period of time. Indeed, Somatuline® Depot is the first marketed sustained-release formulation produced via peptide self-assembly.

Somatuline® and Sandostatin® are used as treatment for symptoms and slow tumor progression in patients with neuroendocrine tumors (NETs), carcinoid syndrome and to reduce hormone secretion and reduce pituitary tumor volume in patients with acromegaly. These are chronic conditions requiring long-term treatment7Oberg, K et al. Endocr. Relat. Cancer. 23, 551–566 (2016). Therefore, optimizing patients’ treatment experience is essential to improve their quality of life. These highly complex formulations also depend on an API of the highest quality. At Bachem, we have the experience with these complex compounds that allow us to deliver them with consistently high specifications.

The latest development, and still under investigation, are non-parenteral formulations. They will help to further facilitate the therapy. For these formulations the availability of large volumes of API at competitive price is of vital importance. At Bachem, we have strong expertise in API manufacturing. In our pipeline we have lanreotide, octreotide and somatostatin with the compiled documentation for Drug Master File and Certificates of Suitability. We work with passion and dedication to support our customers in achieving breakthrough medical advances that will significantly improve the life of patients.

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Infographic Bachem Smart Factory
Figure 1 - Bachem's smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

Bachem Amino Acid Loading Unit
Figure 2 - Robot's roles in the SPPS

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

watch our video to learn more about our digital transformation

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Automation Pyramid
Figure 3 - The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Implementation of Industry 4.0 concepts for the manufacturing of "Tides"

Watch the full presentation exclusively on Bachem360.

Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_section]

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

[/et_pb_post_content]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Infographic Bachem Smart Factory
Figure 1 - Bachem's smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

Bachem Amino Acid Loading Unit
Figure 2 - Robot's roles in the SPPS

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

watch our video to learn more about our digital transformation

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Automation Pyramid
Figure 3 - The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Implementation of Industry 4.0 concepts for the manufacturing of "Tides"

Watch the full presentation exclusively on Bachem360.

Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]
[/et_pb_row]

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

[/et_pb_column]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Figure 1 - Bachem's smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

watch our video to learn more about BALU

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Figure 3 - The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Implementation of Industry 4.0 concepts for the manufacturing of "Tides"

Watch the full presentation exclusively on Bachem360.

Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

[/et_pb_column]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Figure 1 - Bachem's smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

watch our video to learn more about BALU

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Figure 3 - The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Implementation of Industry 4.0 concepts for the manufacturing of "Tides"

Watch the full presentation on Bachem360.

Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

[/et_pb_column]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Figure 1 - Bachem's smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

watch our video to learn more about BALU

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Figure 3 - The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Watch the full presentation on Bachem360.
Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]
[/et_pb_column]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Figure 1 - Bachem's smart production of peptides via SPPS
Figure 1 - Bachem's smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

watch our video to learn more about BALU

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Figure 3 - The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]
[/et_pb_column]

test theme builder local clear 256mb

[/et_pb_row]
Light micrograph of oesophageal cancer

Somatostatin (SST) was isolated and characterized by researchers working in the laboratory of Guillemin at the Salk Institute in 19731Burgus, R et al. Proc. Natl. Acad. Sci. U. S. A. 70(3), 684–688 (1973). Somatostatin is a hormone produced by the hypothalamus and some other tissues such as the pancreas and the gastrointestinal tract. It is an inhibitor of growth hormone release from the anterior pituitary gland and suppresses the release of a variety of other hormones involved in the regulation of important physiological functions of the gastrointestinal tract.

 

What does somatostatin look like?

Somatostatin is a cyclic polypeptide containing a disulfide bridge, between Cys-3 and Csy-14 for somatostatin-14 (SST-14) and between Cys-17 and Cys-28 for somatostatin-28 (SST-28). Somatostatin peptides are derived from a precursor protein of 116 amino acids (Figure 1). The precursor is processed into several peptide hormones, including SST-14, SST-28 at the N-terminal, and neuronostatin, which is a 13-residue amidated peptide flanked with the signal peptide.

Schematic structure of somatostatin
Figure 1 – Somatostatin precursor molecule and location of the disulfide bridges

What role does somatostatin play in the body?

 

In the body, there exists five somatostatin receptor (SSTR) subtypes, SSTR1 to SSTR5 to which their natural ligands SST-14 and SST-28 bind. SST-14 and SST-28 bind with equal affinity to SSTRs 1–4. However, SST-28 has a 10- to 30-fold higher affinity for SSTR5 than other SSTs, whereas SST-14 has reduced affinity at SSTR5.

The two somatostatin forms are together considered a global counter regulatory hormone, with inhibitory effects in multiple target tissues. Somatostatin inhibits gastric acid secretion and motility, intestinal absorption, pancreatic bicarbonate and enzyme secretion, and selectively decreases splanchnic and portal blood flow in dogs and humans without affecting mucosal blood flow. Moreover, somatostatin inhibits the secretion of growth hormone (GH), prolactin (PRL), thyrotropin (TSH), cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin, motilin, neurotensin, secretin, glucagon, insulin, and pancreatic polypeptide (PP)2Brown, M at al. Fed. Proc. 40(11), 2565–2569, (1981).

SST-14 is the predominant form in the central nervous system and in most peripheral organs, including the gastrointestinal tract, where it can be found in the stomach, duodenum, colon, and pancreas. In contrast, SST-28 is produced mainly by intestinal enteroendocrine cells and represents >50% of the somatostatin content in the small intestine. Furthermore, SST-28 could be used to treat a range of disorders, mostly relating to hormone hypersecretion.

Somatostatin is characterized as a regulatory-inhibitory peptide with exocrine secretion; for example, of gastric acid, intestinal fluid and pancreatic enzymes and endocrine secretion, or for example, of growth hormone, insulin, glucagon, gastrin, cholecystokinin, vasoactive intestinal peptide (VIP) and secretin. Somatostatin has great potential for the treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. The short half-life of somatostatin however limits its usefulness as an efficient therapeutic modality. Therefore, research has been conducted in the development of new tuned somatostatin derivatives to offer patients a more efficient treatment.

Somatostatin analogues: What role do they play for patients?

 

A somatostatin analogue (SSA) is a synthetic version of somatostatin. It slows down the production of hormones, especially the growth hormone and serotonin. This helps to control the symptoms of carcinoid syndrome such as diarrhoea and flushing of the skin. Furthermore, SSAs are of considerable utility in the diagnosis and treatment of gastroentero-pancreatic neuroendocrine tumors (NETs). These synthetic analogs of somatostatin have longer half-lifes. To date, three of them have been approved by the agencies: lanreotide and octreotide are considered first-generation SSAs, and pasireotide is considered a second-generation SSA.

The first synthetic SSA that was approved by the Food and Drug Administration (FDA) was the octapeptide octreotide (SMS 201-995) marketed as Sandostatin®. Octreotide (scheme 1) shows high affinity for SSTR2 and inhibits the proliferation of the cells expressing SSTR2 gene by activating the tyrosine phosphatase pathway3Buscai, l L et al. Proc. Natl. Acad. Sci. U. S. A. 91(6), 2315–2319 (1994). Octreotide acts through four mechanisms to decrease abnormal growth hormones (GH) secretion in acromegaly. First, octreotide suppresses GH secretion from the pituitary gland and from GH-secreting adenomas. Second, it decreases GH binding to hepatocytes. Third, it inhibits hepatic IFG-1 production and finally it controls tumor growth4Murray, R D et al. J. Clin. Invest. 114(3), 349–356 (2004).

Octreotide or Sandostatin® was approved for use in the United States in 1988. It is used for the reduction of growth hormone and insulin-like growth factor 1 (somatomedin C) in adults with acromegaly who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses. In addition, Sandostatin® is applied for the treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors in adults as well as profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas) in adults.

Chemical structure of octreotide
Scheme 1 Structure of octreotide
Lanreotide (scheme 2) is a cyclic octapeptide that was developed in the 1990s with the intent to develop a longer acting SSA5Morange, I et al. J. Clin. Endocrinol. Metabol. 79(1), 145–151 (1994). Like octreotide, lanreotide is used in adults to treat acromegaly that cannot be treated with surgery or radiation, carcinoid syndrome and a certain type of pancreatic or digestive tract tumor that may spread to other parts of the body. First approved for use in the United States by the FDA in 2007, lanreotide is marketed under the trade name Somatuline®.
Chemical structure of lanreotide
Scheme 2 Chemical structure of lanreotide
Pasireotide, a novel SSA, that is sold under the brand name Signifor®, is an orphan drug approved by the FDA in 2014 for the treatment of Cushing’s disease in patients who fail or are ineligible for surgical therapy. Pasireotide activates a broad spectrum of somatostatin receptors, and binds with higher affinity to SSTR1 (30-fold), SSTR3 (5-fold), and SSTR5 (39-fold), and with the same affinity to SSTR2 (three-fold) when compared with octreotide; and with higher affinity to SSTR1 (19-fold), SSTR3 (nine-fold), and SSTR5 (106-fold), but with the same affinity to SSTR2 (two-fold) when compared with lanreotide6Bruns, C et al. Eur. J. Endocrinol.146(5), 707–716 (2002); Hofland, LJ et al. Eur. J. Endocrinol. 152(4), 645–654 (2005). The binding and activation of the somatostatin receptors causes inhibition of ACTH secretion and results in reduced cortisol secretion in Cushing’s disease patients. Also this agent is more potent than somatostatin in inhibiting the release of human growth hormone (HGH), glucagon, and insulin.
Chemical structure of pasireotide
Scheme 3 Chemical structure of pasireotide

For these drugs to be efficient, they require delivery methods such as infusion, frequent injections, implantable devices, or intramuscular injection of large drug volumes, which are not always preferred by health care providers and patients.

A huge improvement for diagnosis and treatment of tumors

So far, three SSAs have been approved and launched in the market for treatment of tumors secreting vasoactive intestinal peptide, carcinoid tumors, glucagonomas and various pituitary adenomas, and acromegaly in where there is over secretion of growth hormone in an adult. Furthermore, they are an invaluable therapeutic option in the diagnosis of these diseases.

The formulations of somatostatin analogues have been improved over time and new longer acting versions were introduced, Sandostatin LAR® Depot for octreotide and Somatuline® Depot or Autogel for lanreotide.

In the case of Sandostatin LAR® octreotide is encapsulated in microspheres that are formed with a biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer. Sterile mannitol is added to the microspheres to improve suspensibility.

Somatuline® Depot contains lanreotide acetate in a prefilled syringe that is fitted with an automatic needle guard. The formulation is based on the peptide self-assembly, which provide an innovative solution to sustain a therapeutic dose over a long period of time. Indeed, Somatuline® Depot is the first marketed sustained-release formulation produced via peptide self-assembly.

Somatuline® and Sandostatin® are used as treatment for symptoms and slow tumor progression in patients with neuroendocrine tumors (NETs), carcinoid syndrome and to reduce hormone secretion and reduce pituitary tumor volume in patients with acromegaly. These are chronic conditions requiring long-term treatment7Oberg, K et al. Endocr. Relat. Cancer. 23, 551–566 (2016). Therefore, optimizing patients’ treatment experience is essential to improve their quality of life. These highly complex formulations also depend on an API of the highest quality. At Bachem, we have the experience with these complex compounds that allow us to deliver them with consistently high specifications.

The latest development, and still under investigation, are non-parenteral formulations. They will help to further facilitate the therapy. For these formulations the availability of large volumes of API at competitive price is of vital importance. At Bachem, we have strong expertise in API manufacturing. In our pipeline we have lanreotide, octreotide and somatostatin with the compiled documentation for Drug Master File and Certificates of Suitability. We work with passion and dedication to support our customers in achieving breakthrough medical advances that will significantly improve the life of patients.

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Infographic Bachem Smart Factory
Figure 1 – Bachem’s smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

Bachem Amino Acid Loading Unit
Figure 2 – Robot’s roles in the SPPS

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

watch our video to learn more about our digital transformation

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Automation Pyramid
Figure 3 – The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Implementation of Industry 4.0 concepts for the manufacturing of “Tides”

Watch the full presentation exclusively on Bachem360.

Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]
[/et_pb_row]

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

[/et_pb_column]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Figure 1 – Bachem’s smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

watch our video to learn more about BALU

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Figure 3 – The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Implementation of Industry 4.0 concepts for the manufacturing of “Tides”

Watch the full presentation exclusively on Bachem360.

Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

[/et_pb_column]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Figure 1 – Bachem’s smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

watch our video to learn more about BALU

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Figure 3 – The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Implementation of Industry 4.0 concepts for the manufacturing of “Tides”

Watch the full presentation on Bachem360.

Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

[/et_pb_column]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Figure 1 – Bachem’s smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

watch our video to learn more about BALU

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Figure 3 – The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

Watch the full presentation on Bachem360.
Visit the CMC development section inside the live area.

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]
[/et_pb_column]

Industry 4.0, or the fourth industrial revolution, refers to the automation and digitalization of traditional industrial processes through smart technology and integration. Within this concept, a “smart factory” is characterized by machines which are interconnected, and interoperable, and can process data autonomously. Such “smart factories” require only limited human decision-making or intervention and are therefore sometimes referred to as “intelligent automation.”

Innovation and operational excellence are two important pillars of Bachem’s success. Thus, to keep technological leadership and high-quality services, it was essential to start our digital transformation and to enter the Industry 4.0 area. This will benefit our customers, as we will be able to increase our capacity with a more agile and flexible production, simplify and improve our GMP documentation, and provide a safe, reliable, and scalable manufacturing process delivering consistently high quality API.

Why are we automating and digitalizing SPPS at Bachem?

Optimizing production is crucial to us to help and support our customers in their drug development and manufacturing processes. We have started our journey to Industry 4.0 by automating and digitalizing one of our core business processes, the solid phase peptide synthesis (SPPS) (Figure 1).

Figure 1 – Bachem’s smart production of peptides via SPPS
Figure 1 – Bachem’s smart production of peptides via SPPS

We have automated our SPPS process so that operations can be carried out with minimal human intervention, thus improving the reliability of the process, reproducibility of results and safety, while significantly increasing the cost-effectiveness of operations. Thanks to automation, we are able to optimize equipment utilization and reduce operating times and personnel time down to a fraction. This reduction enables a higher capacity, efficiency and agility of production and brings more flexibility to take on new projects. Bachem has also invested in digitalization of the production process so that documentation can be conducted in a paper-free way. Furthermore, we can attain improved first-time-right (FTR) rates, data analytics by implementing a plant information (PI) system, and higher data safety and integrity.

Our process innovations

As first steps towards our “smart factory”, we have introduced some major innovations. The first Bachem robot-operator, BALU, was designed and programmed to support commercial scale of SPPS. BALU handles the containers with the amino acid powders and is able to perform the powder transfer into the activator vessels for our 150L SPPS reactors. And the robot does so without the involvement of an operator. BALU can perform other critical tasks, such as cleaning the amino acid transfer port to prevent cross-contamination. A barcode scanner that reads the labels placed on the amino acid containers ensures correct handling.

watch our video to learn more about BALU

Another innovative feature of this new fully automated SPPS process is Process Analytical Technology (PAT), which performs inline analytics after key steps. PAT removes the need for manual In-Process Controls (IPC) and provides a better control of Critical Process Parameters (CPP). Additionally, this automated process enables data recording and analytics as well as paper-free cGMP documentation. Implementing PAT to our process control decreases human contributions and cost of goods. Indeed, manual tasks are no longer required and frees resources for other tasks and projects. Furthermore, PAT leads to a higher reproducibility with minimized chemical side reactions. Ultimately, we utilize our assets more efficiently and streamline our production scheduling for a higher capacity and flexibility.

Our digitalization strategy

Our digitalization of the SPPS process was tackled in the following way: the control system of the production floor (Levels 1 and 2 of the Automation Pyramid, see Figure 2) has been integrated with the Manufacturing Execution System (MES, Level 3 in Figure 2). The MES has three critical tasks:

  • lead the process control system by defining the sequence of operations that have to be performed (as written in the MES recipe, also called Master Batch Record, MBR)
  • record all events, process values, alarms, as they happen during the process, and finally generate the electronic Batch Report, eBR
  • manage equipment without the need of physical logbooks.

MES documentation is thus completely paperless while fully GMP compliant!

Full digitalization is reached by connecting the MES to our ERP system, SAP (Level 4 in Figure 2). Executions of process orders, automatic take-out and stock creations, material flow and inventory control are in this way also fully automated and paperless. Finally, our digitalization strategy includes logging in real time and long-term archiving of data on a Historian platform. This PI system allows for real-time and remote monitoring of the factory floor and easy access to data for trending and batch-to-batch comparisons. This provides the basis for future predictive and prescriptive data analytics.

Figure 3 – The automation pyramid

Bachem will embrace a “smart” future together with our customers

Bachem as a CDMO has implemented a new level of automation and digitalization to fulfill the predicted rise in demand of capacity and compliance. We boosted our processes efficiency regarding time, cost, supply and distribution. Entering industry 4.0 and developing our “smart factory” represents a big step forward for our customers in ensuring swifter interaction and more flexibility in manufacturing and in documentation sharing.

Digitalization and automation initiatives are quickly growing, and, in the coming years, thanks to our experiences in SPPS, a growing number of processes will be transformed this way. With these innovations, we keep our technological leadership and set a high industry standard for the best interests of our customers!

About Bachem

Bachem is a leading, innovation-driven company specializing in the development and manufacture of peptides and oligonucleotides.
With over 50 years of experience and expertise Bachem provides products for research, clinical development and commercial application to pharmaceutical and biotechnology companies worldwide and offers a comprehensive range of services.
Bachem operates internationally with headquarters in Switzerland and locations in Europe, the US and Asia. The company is listed on the SIX Swiss Exchange.

[/et_pb_column]
[/et_pb_column]

test theme builder local clear 256mb

[/et_pb_row]
[/et_pb_column]
Light micrograph of oesophageal cancer

Somatostatin (SST) was isolated and characterized by researchers working in the laboratory of Guillemin at the Salk Institute in 19731Burgus, R et al. Proc. Natl. Acad. Sci. U. S. A. 70(3), 684–688 (1973). Somatostatin is a hormone produced by the hypothalamus and some other tissues such as the pancreas and the gastrointestinal tract. It is an inhibitor of growth hormone release from the anterior pituitary gland and suppresses the release of a variety of other hormones involved in the regulation of important physiological functions of the gastrointestinal tract.

 

What does somatostatin look like?

Somatostatin is a cyclic polypeptide containing a disulfide bridge, between Cys-3 and Csy-14 for somatostatin-14 (SST-14) and between Cys-17 and Cys-28 for somatostatin-28 (SST-28). Somatostatin peptides are derived from a precursor protein of 116 amino acids (Figure 1). The precursor is processed into several peptide hormones, including SST-14, SST-28 at the N-terminal, and neuronostatin, which is a 13-residue amidated peptide flanked with the signal peptide.

Schematic structure of somatostatin
Figure 1 – Somatostatin precursor molecule and location of the disulfide bridges

What role does somatostatin play in the body?

 

In the body, there exists five somatostatin receptor (SSTR) subtypes, SSTR1 to SSTR5 to which their natural ligands SST-14 and SST-28 bind. SST-14 and SST-28 bind with equal affinity to SSTRs 1–4. However, SST-28 has a 10- to 30-fold higher affinity for SSTR5 than other SSTs, whereas SST-14 has reduced affinity at SSTR5.

The two somatostatin forms are together considered a global counter regulatory hormone, with inhibitory effects in multiple target tissues. Somatostatin inhibits gastric acid secretion and motility, intestinal absorption, pancreatic bicarbonate and enzyme secretion, and selectively decreases splanchnic and portal blood flow in dogs and humans without affecting mucosal blood flow. Moreover, somatostatin inhibits the secretion of growth hormone (GH), prolactin (PRL), thyrotropin (TSH), cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin, motilin, neurotensin, secretin, glucagon, insulin, and pancreatic polypeptide (PP)2Brown, M at al. Fed. Proc. 40(11), 2565–2569, (1981).

SST-14 is the predominant form in the central nervous system and in most peripheral organs, including the gastrointestinal tract, where it can be found in the stomach, duodenum, colon, and pancreas. In contrast, SST-28 is produced mainly by intestinal enteroendocrine cells and represents >50% of the somatostatin content in the small intestine. Furthermore, SST-28 could be used to treat a range of disorders, mostly relating to hormone hypersecretion.

Somatostatin is characterized as a regulatory-inhibitory peptide with exocrine secretion; for example, of gastric acid, intestinal fluid and pancreatic enzymes and endocrine secretion, or for example, of growth hormone, insulin, glucagon, gastrin, cholecystokinin, vasoactive intestinal peptide (VIP) and secretin. Somatostatin has great potential for the treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. The short half-life of somatostatin however limits its usefulness as an efficient therapeutic modality. Therefore, research has been conducted in the development of new tuned somatostatin derivatives to offer patients a more efficient treatment.

Somatostatin analogues: What role do they play for patients?

 

A somatostatin analogue (SSA) is a synthetic version of somatostatin. It slows down the production of hormones, especially the growth hormone and serotonin. This helps to control the symptoms of carcinoid syndrome such as diarrhoea and flushing of the skin. Furthermore, SSAs are of considerable utility in the diagnosis and treatment of gastroentero-pancreatic neuroendocrine tumors (NETs). These synthetic analogs of somatostatin have longer half-lifes. To date, three of them have been approved by the agencies: lanreotide and octreotide are considered first-generation SSAs, and pasireotide is considered a second-generation SSA.

The first synthetic SSA that was approved by the Food and Drug Administration (FDA) was the octapeptide octreotide (SMS 201-995) marketed as Sandostatin®. Octreotide (scheme 1) shows high affinity for SSTR2 and inhibits the proliferation of the cells expressing SSTR2 gene by activating the tyrosine phosphatase pathway3Buscai, l L et al. Proc. Natl. Acad. Sci. U. S. A. 91(6), 2315–2319 (1994). Octreotide acts through four mechanisms to decrease abnormal growth hormones (GH) secretion in acromegaly. First, octreotide suppresses GH secretion from the pituitary gland and from GH-secreting adenomas. Second, it decreases GH binding to hepatocytes. Third, it inhibits hepatic IFG-1 production and finally it controls tumor growth4Murray, R D et al. J. Clin. Invest. 114(3), 349–356 (2004).

Octreotide or Sandostatin® was approved for use in the United States in 1988. It is used for the reduction of growth hormone and insulin-like growth factor 1 (somatomedin C) in adults with acromegaly who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses. In addition, Sandostatin® is applied for the treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors in adults as well as profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas) in adults.

Chemical structure of octreotide
Scheme 1 Structure of octreotide
Lanreotide (scheme 2) is a cyclic octapeptide that was developed in the 1990s with the intent to develop a longer acting SSA5Morange, I et al. J. Clin. Endocrinol. Metabol. 79(1), 145–151 (1994). Like octreotide, lanreotide is used in adults to treat acromegaly that cannot be treated with surgery or radiation, carcinoid syndrome and a certain type of pancreatic or digestive tract tumor that may spread to other parts of the body. First approved for use in the United States by the FDA in 2007, lanreotide is marketed under the trade name Somatuline®.
Chemical structure of lanreotide
Scheme 2 Chemical structure of lanreotide
Pasireotide, a novel SSA, that is sold under the brand name Signifor®, is an orphan drug approved by the FDA in 2014 for the treatment of Cushing’s disease in patients who fail or are ineligible for surgical therapy. Pasireotide activates a broad spectrum of somatostatin receptors, and binds with higher affinity to SSTR1 (30-fold), SSTR3 (5-fold), and SSTR5 (39-fold), and with the same affinity to SSTR2 (three-fold) when compared with octreotide; and with higher affinity to SSTR1 (19-fold), SSTR3 (nine-fold), and SSTR5 (106-fold), but with the same affinity to SSTR2 (two-fold) when compared with lanreotide6Bruns, C et al. Eur. J. Endocrinol.146(5), 707–716 (2002); Hofland, LJ et al. Eur. J. Endocrinol. 152(4), 645–654 (2005). The binding and activation of the somatostatin receptors causes inhibition of ACTH secretion and results in reduced cortisol secretion in Cushing’s disease patients. Also this agent is more potent than somatostatin in inhibiting the release of human growth hormone (HGH), glucagon, and insulin.
Chemical structure of pasireotide
Scheme 3 Chemical structure of pasireotide

For these drugs to be efficient, they require delivery methods such as infusion, frequent injections, implantable devices, or intramuscular injection of large drug volumes, which are not always preferred by health care providers and patients.

A huge improvement for diagnosis and treatment of tumors

So far, three SSAs have been approved and launched in the market for treatment of tumors secreting vasoactive intestinal peptide, carcinoid tumors, glucagonomas and various pituitary adenomas, and acromegaly in where there is over secretion of growth hormone in an adult. Furthermore, they are an invaluable therapeutic option in the diagnosis of these diseases.

The formulations of somatostatin analogues have been improved over time and new longer acting versions were introduced, Sandostatin LAR® Depot for octreotide and Somatuline® Depot or Autogel for lanreotide.

In the case of Sandostatin LAR® octreotide is encapsulated in microspheres that are formed with a biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer. Sterile mannitol is added to the microspheres to improve suspensibility.

Somatuline® Depot contains lanreotide acetate in a prefilled syringe that is fitted with an automatic needle guard. The formulation is based on the peptide self-assembly, which provide an innovative solution to sustain a therapeutic dose over a long period of time. Indeed, Somatuline® Depot is the first marketed sustained-release formulation produced via peptide self-assembly.

Somatuline® and Sandostatin® are used as treatment for symptoms and slow tumor progression in patients with neuroendocrine tumors (NETs), carcinoid syndrome and to reduce hormone secretion and reduce pituitary tumor volume in patients with acromegaly. These are chronic conditions requiring long-term treatment7Oberg, K et al. Endocr. Relat. Cancer. 23, 551–566 (2016). Therefore, optimizing patients’ treatment experience is essential to improve their quality of life. These highly complex formulations also depend on an API of the highest quality. At Bachem, we have the experience with these complex compounds that allow us to deliver them with consistently high specifications.

The latest development, and still under investigation, are non-parenteral formulations. They will help to further facilitate the therapy. For these formulations the availability of large volumes of API at competitive price is of vital importance. At Bachem, we have strong expertise in API manufacturing. In our pipeline we have lanreotide, octreotide and somatostatin with the compiled documentation for Drug Master File and Certificates of Suitability. We work with passion and dedication to support our customers in achieving breakthrough medical advances that will significantly improve the life of patients.

Subscribe to our newsletter

  • Hidden
    :
  • This field is for validation purposes and should be left unchanged.

[/et_pb_section]
[/et_pb_column]
[/et_pb_column]