Oligonucleotide Trends January 2020

January 30, 2020

MEET US AT ASIATIDES

AsiaTIDES is the premier event in Asia for accelerating promising oligonucleotide and peptide molecules from research to commercialization. The 2020 edition will take place on February 24 – 26 at the Westin Miyako Kyoto, Kyoto, Japan.

AsiaTIDES brings 300+ global oligonucleotide and peptide leaders across Asia, Europe and North America together to present case studies, best practices and to discuss current strategies and trends to accelerate promising molecules to market.

Join our presentation at the Main Conference, on Tuesday, February 25, 11:45am – 12:15pm: Dr. Ralph Schönleber, Vice President for Research & Development, Bachem AG, will present «CMC Development Concept for Synthetic Peptides».

Bachem‘s pipeline contains more than 150 customer projects in preclinical and clinical phases. In the last couple of years, a number of products in phase III trials received marketing authorization and phase II projects progressed to phase III clinical trials. Starting 2019, Bachem is strategically diversifying its technology platform to include the manufacture of therapeutic oligonucleotides and nucleic-acid-based medicine. A full-service oligonucleotide manufacturing facility is being built at the headquarters in Bubendorf, Switzerland.

The Bachem team is excited to meet with you, learn your needs for peptides and oligonucleotides and discuss how Bachem can meet your API custom manufacturing needs. We kindly invite you to drop by our Booth 19 or to contact us  to schedule a meeting in advance.

We look forward to meeting you at AsiaTIDES 2020!

THERAPEUTIC OLIGONUCLEOTIDES

Oligonucleotides for therapeutic purposes gained increased importance during the past 20 years. This was furthered by advances in biomedical research, improving drug properties like degradation stability, target binding and pharmacokinetics.

 Different classes of oligonucleotide therapeutics exist, referring to their mode of interaction with the target molecules. Oligonucleotides binding to mRNA rely on a Watson-Crick base-paring mechanism. The goal is to identify sequences that are highly specific for the target RNA, but do not unintendedly bind homologous RNA. However, also aspects such as tertiary structures and molecular interactions established by RNA under physiological conditions as well as aspects of drug safety and delivery have to be taken into account.

 Two principle modes of action can be discriminated, a target RNA degrading and a target RNA non-degrading. Mechanisms, which decrease the expression levels of specific proteins are referred to as gene silencing. In their degrading pathways, antisense oligomers and small interfering RNAs (siRNAs) bind to corresponding sequences of mRNA and ultimately lead to the degradation of the latter. In consequence, the expression of the coded, eventually medical relevant proteins is reduced.

 In their non-degrading pathways, stretches of mRNA are occupied or a steric block of the recruitment of other factors, e.g. ribosomes, takes place, leading for example to an altered mRNA splicing pattern or to a translation arrest. A further non-degrading pathway antagonizes microRNAs, endogenous small RNAs that can regulate normal physiological processes and which are involved in diseases.

 Oligonucleotide aptamers do not rely on Watson-Crick base-paring, but bind via their three-dimensional structure to, typically, peptides, and consist of short strands of DNA or RNA. An example is Pegaptanib, an RNA aptamer, which received in December 2004 first approval by the US FDA for the treatment of ocular vascular disease.

 Other therapeutic approaches include unmethylated CpG oligodeoxynucleotides, interesting in the context of new adjuvants, or, vaccinations employing mRNA, the latter for example investigated in the search for novel tumor therapies

 Overall, therapeutic oligomers provide new chances for curing a variety of diseases, primarily on basis of information about the human genome, which differentiates them from all classical therapies.

 References

[1] A.A.Levin, Treating disease at the RNA Level with oligonucleotides. N. Engl. J. Med., 380(1), 57-70 (2019)

[2] W.B.Wan and P.P. Seth, The medicinal chemistry of therapeutic oligonucleotides. J. Med. Chem., 59(21), 9645-9667 (2016)

[3] C.F.Bennett and E.E. Swayze, RNA Targeting therapeutics: Molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol., 50(1), 259-293 (2010)

 

PROMISE FOR OLIGONUCLEOTIDES IS RISING

Oligonucleotides have been under development for several decades. Development started with antisense oligonucleotides and aptamers, followed by siRNAs. In total, the U.S. Food and Drug Administration (FDA) has approved eleven oligonucleotide drugs.

 First Approvals

In 1998, Novartis Pharmaceutical’s Vitravene (fomiversen), an antisense oligonucleotide, became the first oligonucleotide to be approved by the FDA. Vitravene was developed for the local treatment of cytomegalovirus (CMV) retinitis afflicting HIV patients. It was formulated as an intravitreal injection, a procedure to place the medication directly in the eye. Ultimately, Vitravene was discontinued in 2004 because HIV treatment led to a reduction in the number of cases of CMV in HIV patients. Macugen (peaptanib sodium), an aptamer, was approved in 2004 for the treatment of wet age related macular degeneration (AMD). Macugen is also formulated as an intravitreal injection.

 Recent Approvals

Over a decade after the approval of Vitravene, FDA approval came for Kynamro (mipomersen sodium) in 2013. This approval was followed by a flurry of activity that resulted in FDA approvals for eight more oligonucleotides.

FDA ApprovalDrug nameCompanyIndicationType
2013 (Withdrawn)Kynamro (mipomersen sodium)Kastle Therapeutics LLCHomozygous Familial HypercholesterolemiaAntisense Oligonucleotide
2016 (Marketed)Defitelio (defibrotide sodium)Jazz Pharmaceuticals PlcHepatic Veno-Occlusive DiseaseOligonucleotide, natural product
2016 (Marketed)Exondys 51 (eteplirsen)Sarepta TherapeuticsDuchenne Muscular DystrophyAntisense Oligonucleotide
2016 (Marketed)Spinraza (nusinersen)BiogenSpinal Muscular AtrophyAntisense Oligonucleotide
2017 (Marketed)Heplisav-B (hepatitis B vaccine, adjuvanted)Dynavax TechnologiesHepatitis BCytidine phospho-guanosine (CpG) oligonucleotide as adjuvant
2018 (Marketed)Tegsedi (inotersen sodium)Akcea TherapeuticsFamilial Amyloid NeuropathiesAntisense Oligonucleotide
2018 (Marketed)Onpattro (patisiran)Alnylam PharmaceuticalsFamilial Amyloid NeuropathiessiRNA
2019 (Marketed)Givlaari (givosiran)Alnylam PharmaceuticalsAcute Hepatic PorphyriasiRNA
2019 (Marketed)Vyondys 53 (golodirsen)Sarepta TherapeuticsDuchenne Muscular DystrophyAntisense Oligonucleotide

Also in 2019, Akcea Therapeutics UK’s Waylivra (volanesorsen sodium), an antisense oligonucleotide, received conditional marketing authorization from the European Commission as an adjunct to diet for patients with familial chylomicronaemia syndrome and high risk of pancreatitis.

 Drugs in Development

The clinical pipeline of oligonucleotide drugs is rich with 157 drugs in Phase I to pre-registration. The therapeutic areas for the drug candidates is diverse spanning oncology, infectious disease, metabolic disorders, genetic disorders, and other areas. Two oligonucleotide drug candidates to watch are in the pre-registration phase including Atlantic Healthcare’s alicaforsen and NS Pharma’s viltolarsen.

Figure 1 Oligonucleotide Clinical Drug Pipeline Phase I to Pre-Registration

 

References

[1] GlobalData (2019)

[2] [email protected]: FDA Approved Drug Products (2019)

MEET BACHEM: ADRIEN NYAKAS

What is your official job title at Bachem?

My job title is Project Manager QC.

 

How long have you been with Bachem? Where did you work before Bachem?

I have been working for Bachem for 5 years, approximately 3 years in the MS-Services group and approximately 2 years as Project Manager QC. Before I did a Post Doc at the University of Bern and another one at the University of Victoria

 

Have you had any particular expectation when you came to Bachem and have these been fulfilled?

For the role of project manager QC I expected a profound knowledge of the aspects of analytical development of NCEs. Yes, my expectations were fully met, not only in the area of peptides but recently also in the field of oligonucleotides

 

Briefly, what do you do at Bachem?

I am involved in the coordination of the analytical development of peptide and oligonucleotide NCE projects.

 

What is your academic background/degrees or training?

I have an MSc in chemistry and a PhD in chemistry. In addition, I have a strong background in mass spectrometry.

 

What makes a perfect day for you?

When a big, concerted team effort results in the on-time delivery of critical data to the customer.

 

What do you like most about your job?

I like the fast-paced environment, close collaboration with other departments within the project teams, involvement in all aspects of a NCE project, and the direct customer contact.

 

What do you like to do outside of work?

I am fond of horseback riding, reading, and playing golf.

 

Thank you very much Adrien.

Oligo highlights

Interesting news about oligonucleotides in basic research and pharmaceutical development:

Milasen: The drug that went from idea to injection in 10 months-Chemical & Engineering News

Possible new treatment strategy against progeria-Science Daily

The discovery of RNA aptamers that selectively bind glioblastoma stem cells-Molecular Therapy Nucleic Acids

Deep genomics identifies AI-discovered candidate for Wilson Disease-Genetic Engineering & Biotechnology News

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.

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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.

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Subscribe to our newsletter

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

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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.

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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.

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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.

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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.

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test theme builder local clear 256mb

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MEET US AT ASIATIDES

AsiaTIDES is the premier event in Asia for accelerating promising oligonucleotide and peptide molecules from research to commercialization. The 2020 edition will take place on February 24 – 26 at the Westin Miyako Kyoto, Kyoto, Japan.

AsiaTIDES brings 300+ global oligonucleotide and peptide leaders across Asia, Europe and North America together to present case studies, best practices and to discuss current strategies and trends to accelerate promising molecules to market.

Join our presentation at the Main Conference, on Tuesday, February 25, 11:45am – 12:15pm: Dr. Ralph Schönleber, Vice President for Research & Development, Bachem AG, will present «CMC Development Concept for Synthetic Peptides».

Bachem‘s pipeline contains more than 150 customer projects in preclinical and clinical phases. In the last couple of years, a number of products in phase III trials received marketing authorization and phase II projects progressed to phase III clinical trials. Starting 2019, Bachem is strategically diversifying its technology platform to include the manufacture of therapeutic oligonucleotides and nucleic-acid-based medicine. A full-service oligonucleotide manufacturing facility is being built at the headquarters in Bubendorf, Switzerland.

The Bachem team is excited to meet with you, learn your needs for peptides and oligonucleotides and discuss how Bachem can meet your API custom manufacturing needs. We kindly invite you to drop by our Booth 19 or to contact us  to schedule a meeting in advance.

We look forward to meeting you at AsiaTIDES 2020!

THERAPEUTIC OLIGONUCLEOTIDES

Oligonucleotides for therapeutic purposes gained increased importance during the past 20 years. This was furthered by advances in biomedical research, improving drug properties like degradation stability, target binding and pharmacokinetics.

 Different classes of oligonucleotide therapeutics exist, referring to their mode of interaction with the target molecules. Oligonucleotides binding to mRNA rely on a Watson-Crick base-paring mechanism. The goal is to identify sequences that are highly specific for the target RNA, but do not unintendedly bind homologous RNA. However, also aspects such as tertiary structures and molecular interactions established by RNA under physiological conditions as well as aspects of drug safety and delivery have to be taken into account.

 Two principle modes of action can be discriminated, a target RNA degrading and a target RNA non-degrading. Mechanisms, which decrease the expression levels of specific proteins are referred to as gene silencing. In their degrading pathways, antisense oligomers and small interfering RNAs (siRNAs) bind to corresponding sequences of mRNA and ultimately lead to the degradation of the latter. In consequence, the expression of the coded, eventually medical relevant proteins is reduced.

 In their non-degrading pathways, stretches of mRNA are occupied or a steric block of the recruitment of other factors, e.g. ribosomes, takes place, leading for example to an altered mRNA splicing pattern or to a translation arrest. A further non-degrading pathway antagonizes microRNAs, endogenous small RNAs that can regulate normal physiological processes and which are involved in diseases.

 Oligonucleotide aptamers do not rely on Watson-Crick base-paring, but bind via their three-dimensional structure to, typically, peptides, and consist of short strands of DNA or RNA. An example is Pegaptanib, an RNA aptamer, which received in December 2004 first approval by the US FDA for the treatment of ocular vascular disease.

 Other therapeutic approaches include unmethylated CpG oligodeoxynucleotides, interesting in the context of new adjuvants, or, vaccinations employing mRNA, the latter for example investigated in the search for novel tumor therapies

 Overall, therapeutic oligomers provide new chances for curing a variety of diseases, primarily on basis of information about the human genome, which differentiates them from all classical therapies.

 References

[1] A.A.Levin, Treating disease at the RNA Level with oligonucleotides. N. Engl. J. Med., 380(1), 57-70 (2019)

[2] W.B.Wan and P.P. Seth, The medicinal chemistry of therapeutic oligonucleotides. J. Med. Chem., 59(21), 9645-9667 (2016)

[3] C.F.Bennett and E.E. Swayze, RNA Targeting therapeutics: Molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol., 50(1), 259-293 (2010)

 

PROMISE FOR OLIGONUCLEOTIDES IS RISING

Oligonucleotides have been under development for several decades. Development started with antisense oligonucleotides and aptamers, followed by siRNAs. In total, the U.S. Food and Drug Administration (FDA) has approved eleven oligonucleotide drugs.

 First Approvals

In 1998, Novartis Pharmaceutical’s Vitravene (fomiversen), an antisense oligonucleotide, became the first oligonucleotide to be approved by the FDA. Vitravene was developed for the local treatment of cytomegalovirus (CMV) retinitis afflicting HIV patients. It was formulated as an intravitreal injection, a procedure to place the medication directly in the eye. Ultimately, Vitravene was discontinued in 2004 because HIV treatment led to a reduction in the number of cases of CMV in HIV patients. Macugen (peaptanib sodium), an aptamer, was approved in 2004 for the treatment of wet age related macular degeneration (AMD). Macugen is also formulated as an intravitreal injection.

 Recent Approvals

Over a decade after the approval of Vitravene, FDA approval came for Kynamro (mipomersen sodium) in 2013. This approval was followed by a flurry of activity that resulted in FDA approvals for eight more oligonucleotides.

FDA ApprovalDrug nameCompanyIndicationType
2013 (Withdrawn)Kynamro (mipomersen sodium)Kastle Therapeutics LLCHomozygous Familial HypercholesterolemiaAntisense Oligonucleotide
2016 (Marketed)Defitelio (defibrotide sodium)Jazz Pharmaceuticals PlcHepatic Veno-Occlusive DiseaseOligonucleotide, natural product
2016 (Marketed)Exondys 51 (eteplirsen)Sarepta TherapeuticsDuchenne Muscular DystrophyAntisense Oligonucleotide
2016 (Marketed)Spinraza (nusinersen)BiogenSpinal Muscular AtrophyAntisense Oligonucleotide
2017 (Marketed)Heplisav-B (hepatitis B vaccine, adjuvanted)Dynavax TechnologiesHepatitis BCytidine phospho-guanosine (CpG) oligonucleotide as adjuvant
2018 (Marketed)Tegsedi (inotersen sodium)Akcea TherapeuticsFamilial Amyloid NeuropathiesAntisense Oligonucleotide
2018 (Marketed)Onpattro (patisiran)Alnylam PharmaceuticalsFamilial Amyloid NeuropathiessiRNA
2019 (Marketed)Givlaari (givosiran)Alnylam PharmaceuticalsAcute Hepatic PorphyriasiRNA
2019 (Marketed)Vyondys 53 (golodirsen)Sarepta TherapeuticsDuchenne Muscular DystrophyAntisense Oligonucleotide

Also in 2019, Akcea Therapeutics UK’s Waylivra (volanesorsen sodium), an antisense oligonucleotide, received conditional marketing authorization from the European Commission as an adjunct to diet for patients with familial chylomicronaemia syndrome and high risk of pancreatitis.

 Drugs in Development

The clinical pipeline of oligonucleotide drugs is rich with 157 drugs in Phase I to pre-registration. The therapeutic areas for the drug candidates is diverse spanning oncology, infectious disease, metabolic disorders, genetic disorders, and other areas. Two oligonucleotide drug candidates to watch are in the pre-registration phase including Atlantic Healthcare’s alicaforsen and NS Pharma’s viltolarsen.

Figure 1 Oligonucleotide Clinical Drug Pipeline Phase I to Pre-Registration

 

References

[1] GlobalData (2019)

[2] [email protected]: FDA Approved Drug Products (2019)

MEET BACHEM: ADRIEN NYAKAS

What is your official job title at Bachem?

My job title is Project Manager QC.

 

How long have you been with Bachem? Where did you work before Bachem?

I have been working for Bachem for 5 years, approximately 3 years in the MS-Services group and approximately 2 years as Project Manager QC. Before I did a Post Doc at the University of Bern and another one at the University of Victoria

 

Have you had any particular expectation when you came to Bachem and have these been fulfilled?

For the role of project manager QC I expected a profound knowledge of the aspects of analytical development of NCEs. Yes, my expectations were fully met, not only in the area of peptides but recently also in the field of oligonucleotides

 

Briefly, what do you do at Bachem?

I am involved in the coordination of the analytical development of peptide and oligonucleotide NCE projects.

 

What is your academic background/degrees or training?

I have an MSc in chemistry and a PhD in chemistry. In addition, I have a strong background in mass spectrometry.

 

What makes a perfect day for you?

When a big, concerted team effort results in the on-time delivery of critical data to the customer.

 

What do you like most about your job?

I like the fast-paced environment, close collaboration with other departments within the project teams, involvement in all aspects of a NCE project, and the direct customer contact.

 

What do you like to do outside of work?

I am fond of horseback riding, reading, and playing golf.

 

Thank you very much Adrien.

Oligo highlights

Interesting news about oligonucleotides in basic research and pharmaceutical development:

Milasen: The drug that went from idea to injection in 10 months-Chemical & Engineering News

Possible new treatment strategy against progeria-Science Daily

The discovery of RNA aptamers that selectively bind glioblastoma stem cells-Molecular Therapy Nucleic Acids

Deep genomics identifies AI-discovered candidate for Wilson Disease-Genetic Engineering & Biotechnology News

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.

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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.

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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.

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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.

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MEET US AT ASIATIDES

AsiaTIDES is the premier event in Asia for accelerating promising oligonucleotide and peptide molecules from research to commercialization. The 2020 edition will take place on February 24 – 26 at the Westin Miyako Kyoto, Kyoto, Japan.

AsiaTIDES brings 300+ global oligonucleotide and peptide leaders across Asia, Europe and North America together to present case studies, best practices and to discuss current strategies and trends to accelerate promising molecules to market.

Join our presentation at the Main Conference, on Tuesday, February 25, 11:45am – 12:15pm: Dr. Ralph Schönleber, Vice President for Research & Development, Bachem AG, will present «CMC Development Concept for Synthetic Peptides».

Bachem‘s pipeline contains more than 150 customer projects in preclinical and clinical phases. In the last couple of years, a number of products in phase III trials received marketing authorization and phase II projects progressed to phase III clinical trials. Starting 2019, Bachem is strategically diversifying its technology platform to include the manufacture of therapeutic oligonucleotides and nucleic-acid-based medicine. A full-service oligonucleotide manufacturing facility is being built at the headquarters in Bubendorf, Switzerland.

The Bachem team is excited to meet with you, learn your needs for peptides and oligonucleotides and discuss how Bachem can meet your API custom manufacturing needs. We kindly invite you to drop by our Booth 19 or to contact us  to schedule a meeting in advance.

We look forward to meeting you at AsiaTIDES 2020!

THERAPEUTIC OLIGONUCLEOTIDES

Oligonucleotides for therapeutic purposes gained increased importance during the past 20 years. This was furthered by advances in biomedical research, improving drug properties like degradation stability, target binding and pharmacokinetics.

 Different classes of oligonucleotide therapeutics exist, referring to their mode of interaction with the target molecules. Oligonucleotides binding to mRNA rely on a Watson-Crick base-paring mechanism. The goal is to identify sequences that are highly specific for the target RNA, but do not unintendedly bind homologous RNA. However, also aspects such as tertiary structures and molecular interactions established by RNA under physiological conditions as well as aspects of drug safety and delivery have to be taken into account.

 Two principle modes of action can be discriminated, a target RNA degrading and a target RNA non-degrading. Mechanisms, which decrease the expression levels of specific proteins are referred to as gene silencing. In their degrading pathways, antisense oligomers and small interfering RNAs (siRNAs) bind to corresponding sequences of mRNA and ultimately lead to the degradation of the latter. In consequence, the expression of the coded, eventually medical relevant proteins is reduced.

 In their non-degrading pathways, stretches of mRNA are occupied or a steric block of the recruitment of other factors, e.g. ribosomes, takes place, leading for example to an altered mRNA splicing pattern or to a translation arrest. A further non-degrading pathway antagonizes microRNAs, endogenous small RNAs that can regulate normal physiological processes and which are involved in diseases.

 Oligonucleotide aptamers do not rely on Watson-Crick base-paring, but bind via their three-dimensional structure to, typically, peptides, and consist of short strands of DNA or RNA. An example is Pegaptanib, an RNA aptamer, which received in December 2004 first approval by the US FDA for the treatment of ocular vascular disease.

 Other therapeutic approaches include unmethylated CpG oligodeoxynucleotides, interesting in the context of new adjuvants, or, vaccinations employing mRNA, the latter for example investigated in the search for novel tumor therapies

 Overall, therapeutic oligomers provide new chances for curing a variety of diseases, primarily on basis of information about the human genome, which differentiates them from all classical therapies.

 References

[1] A.A.Levin, Treating disease at the RNA Level with oligonucleotides. N. Engl. J. Med., 380(1), 57-70 (2019)

[2] W.B.Wan and P.P. Seth, The medicinal chemistry of therapeutic oligonucleotides. J. Med. Chem., 59(21), 9645-9667 (2016)

[3] C.F.Bennett and E.E. Swayze, RNA Targeting therapeutics: Molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu. Rev. Pharmacol. Toxicol., 50(1), 259-293 (2010)

 

PROMISE FOR OLIGONUCLEOTIDES IS RISING

Oligonucleotides have been under development for several decades. Development started with antisense oligonucleotides and aptamers, followed by siRNAs. In total, the U.S. Food and Drug Administration (FDA) has approved eleven oligonucleotide drugs.

 First Approvals

In 1998, Novartis Pharmaceutical’s Vitravene (fomiversen), an antisense oligonucleotide, became the first oligonucleotide to be approved by the FDA. Vitravene was developed for the local treatment of cytomegalovirus (CMV) retinitis afflicting HIV patients. It was formulated as an intravitreal injection, a procedure to place the medication directly in the eye. Ultimately, Vitravene was discontinued in 2004 because HIV treatment led to a reduction in the number of cases of CMV in HIV patients. Macugen (peaptanib sodium), an aptamer, was approved in 2004 for the treatment of wet age related macular degeneration (AMD). Macugen is also formulated as an intravitreal injection.

 Recent Approvals

Over a decade after the approval of Vitravene, FDA approval came for Kynamro (mipomersen sodium) in 2013. This approval was followed by a flurry of activity that resulted in FDA approvals for eight more oligonucleotides.

FDA ApprovalDrug nameCompanyIndicationType
2013 (Withdrawn)Kynamro (mipomersen sodium)Kastle Therapeutics LLCHomozygous Familial HypercholesterolemiaAntisense Oligonucleotide
2016 (Marketed)Defitelio (defibrotide sodium)Jazz Pharmaceuticals PlcHepatic Veno-Occlusive DiseaseOligonucleotide, natural product
2016 (Marketed)Exondys 51 (eteplirsen)Sarepta TherapeuticsDuchenne Muscular DystrophyAntisense Oligonucleotide
2016 (Marketed)Spinraza (nusinersen)BiogenSpinal Muscular AtrophyAntisense Oligonucleotide
2017 (Marketed)Heplisav-B (hepatitis B vaccine, adjuvanted)Dynavax TechnologiesHepatitis BCytidine phospho-guanosine (CpG) oligonucleotide as adjuvant
2018 (Marketed)Tegsedi (inotersen sodium)Akcea TherapeuticsFamilial Amyloid NeuropathiesAntisense Oligonucleotide
2018 (Marketed)Onpattro (patisiran)Alnylam PharmaceuticalsFamilial Amyloid NeuropathiessiRNA
2019 (Marketed)Givlaari (givosiran)Alnylam PharmaceuticalsAcute Hepatic PorphyriasiRNA
2019 (Marketed)Vyondys 53 (golodirsen)Sarepta TherapeuticsDuchenne Muscular DystrophyAntisense Oligonucleotide

Also in 2019, Akcea Therapeutics UK’s Waylivra (volanesorsen sodium), an antisense oligonucleotide, received conditional marketing authorization from the European Commission as an adjunct to diet for patients with familial chylomicronaemia syndrome and high risk of pancreatitis.

 Drugs in Development

The clinical pipeline of oligonucleotide drugs is rich with 157 drugs in Phase I to pre-registration. The therapeutic areas for the drug candidates is diverse spanning oncology, infectious disease, metabolic disorders, genetic disorders, and other areas. Two oligonucleotide drug candidates to watch are in the pre-registration phase including Atlantic Healthcare’s alicaforsen and NS Pharma’s viltolarsen.

Figure 1 Oligonucleotide Clinical Drug Pipeline Phase I to Pre-Registration

 

References

[1] GlobalData (2019)

[2] [email protected]: FDA Approved Drug Products (2019)

MEET BACHEM: ADRIEN NYAKAS

What is your official job title at Bachem?

My job title is Project Manager QC.

 

How long have you been with Bachem? Where did you work before Bachem?

I have been working for Bachem for 5 years, approximately 3 years in the MS-Services group and approximately 2 years as Project Manager QC. Before I did a Post Doc at the University of Bern and another one at the University of Victoria

 

Have you had any particular expectation when you came to Bachem and have these been fulfilled?

For the role of project manager QC I expected a profound knowledge of the aspects of analytical development of NCEs. Yes, my expectations were fully met, not only in the area of peptides but recently also in the field of oligonucleotides

 

Briefly, what do you do at Bachem?

I am involved in the coordination of the analytical development of peptide and oligonucleotide NCE projects.

 

What is your academic background/degrees or training?

I have an MSc in chemistry and a PhD in chemistry. In addition, I have a strong background in mass spectrometry.

 

What makes a perfect day for you?

When a big, concerted team effort results in the on-time delivery of critical data to the customer.

 

What do you like most about your job?

I like the fast-paced environment, close collaboration with other departments within the project teams, involvement in all aspects of a NCE project, and the direct customer contact.

 

What do you like to do outside of work?

I am fond of horseback riding, reading, and playing golf.

 

Thank you very much Adrien.

Oligo highlights

Interesting news about oligonucleotides in basic research and pharmaceutical development:

Milasen: The drug that went from idea to injection in 10 months-Chemical & Engineering News

Possible new treatment strategy against progeria-Science Daily

The discovery of RNA aptamers that selectively bind glioblastoma stem cells-Molecular Therapy Nucleic Acids

Deep genomics identifies AI-discovered candidate for Wilson Disease-Genetic Engineering & Biotechnology News

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