• Login
    • Join
  • FOLLOW:
  • Subscribe Free
    • Magazine
    • eNewsletter
    Checkout
    • Magazine
    • News
    • Manufacturing
    • Packaging
    • Development
    • Compliance
    • Top 20
    • Directory
    • Microsites
    • Events
    • More
  • Magazine
  • News
  • Manufacturing
  • Packaging
  • Development
  • Compliance
  • Top 20
  • Directory
  • Microsites
  • Events
  • Current / Back Issue
    Features
    Editorial
    Columns
    Digital Edition
    eNewsletter Archive
    Our Team
    Editorial Guidelines
    Subscribe Now
    Advertise Now
    Top Features
    SARS-CoV-2 R&D: Is It Over?

    Sustainability: A New Threat or Opportunity for CDMOs?

    Advanced Therapy Manufacturing

    Advanced Therapy Packaging Trends

    CEO Spotlight: Darren Head
    Breaking News
    Online Exclusives
    Industry News
    Collaborations & Alliances
    Promotions & Moves
    Trials & Filings
    Financial Reports
    Bio News & Views
    Custom Sourcing News
    Packaging & Tracking
    CRO News
    Live From Shows
    Top News
    DFE Pharma Opens India CoE for Fast-Track Formulation Services

    Helsinn Establishes New R&D Hub in the U.S.

    CureVac, myNEO Partner on Antigen Targets for mRNA-Cancer Vax Development

    Mirum Pharmaceuticals Acquires San Diego-based Satiogen

    Catalyst Biosciences Sells Complement Portfolio to Vertex Pharmaceuticals
    APIs
    Aseptic Processing
    Cleaning Validation
    Clinical Trial Materials
    Cytotoxics and High Potency Manufacturing
    Equipment
    Excipients
    Extractables and Leachables
    Facilities
    Fill/Finish
    Lyophilization
    Parenterals
    Process Development
    Process Validation
    Risk Management
    Scale-up/ Technology Transfer
    Solid Dosage/ Creams/ Ointments

    DFE Pharma Opens India CoE for Fast-Track Formulation Services

    Risk Assessment for a Nitrosamine Contamination of Peptide APIs Manufactured by SPPS

    Clinigen Expands U.S. Site Capacity

    Corealis CDMO Completes Deal with ArchiMed

    Piramal Pharma Solutions Upgrades Oral Solid Dose Capabilities
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Selecting a CMO Partner for Sterile Injectable Manufacturing

    Royalty Pharma and Jefferies Invest $111M in ApiJect

    Cryoport Acquires Cell&Co BioServices for €6.2M

    Challenges of Developing Large Volume Drug/Device Combination Products for Parenteral SC Delivery

    Yourway Adds Capacity for Controlled Ambient Storage
    Analytical Services
    Bioanalytical Services
    Bioassay Developement
    Biologics, Proteins, Vaccines
    Biosimilars
    Chemistry
    Clinical Trials
    Drug Delivery
    Drug Development
    Drug Discovery
    Formulation Development
    Information Technology
    Laboratory Testing
    Methods Development
    Microbiology
    Preclinical Outsourcing
    R&D
    Toxicology

    DFE Pharma Opens India CoE for Fast-Track Formulation Services

    Helsinn Establishes New R&D Hub in the U.S.

    CureVac, myNEO Partner on Antigen Targets for mRNA-Cancer Vax Development

    How Can Automation Optimize Immunohistochemistry?

    Corealis CDMO Completes Deal with ArchiMed
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    FDA Inspection Trends Update

    Phase-Appropriate cGMP Considerations for Cell and Gene Therapy

    Sustainability: A New Threat or Opportunity for CDMOs?

    In Pursuit of Sustainability: How the Biopharma Industry Can Contribute

    Conducting Clinical Trials During the Pandemic: What Did We Learn?
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    Qosina

    Kyongbo Pharmaceutical

    Baxter BioPharma Solutions

    Aphena Pharma Solutions

    Quotient Sciences
    Companies
    News Releases
    Posters
    Brochures
    Services
    Videos
    Case Study
    White Papers
    Jobs
    Contract Service Directory Companies
    Qosina

    Kyongbo Pharmaceutical

    Baxter BioPharma Solutions

    Aphena Pharma Solutions

    Quotient Sciences
    Webinars
    Live From Shows
    • Magazine
      • Current / Back Issue
      • Features
      • Editorial
      • Columns
      • Editorial Guidelines
      • Subscribe Now
      • Advertise Now
      • Enewsletter Archive
      • Digital Edition
    • Directory
      • Companies
      • Categories
      • Corporate Capabilities
      • Add Your Company
    • Manufacturing
      • APIs
      • Aseptic Processing
      • Cleaning Validation
      • Clinical Trial Materials
      • Cytotoxics and High Potency Manufacturing
      • Equipment
      • Excipients
      • Extractables and Leachables
      • Facilities
      • Fill/Finish
      • Lyophilization
      • Parenterals
      • Process Development
      • Process Validation
      • Risk Management
      • Scale-up/ Technology Transfer
      • Solid Dosage/ Creams/ Ointments
      • cGMP Manufacture
    • Packaging
      • Capsules
      • Cold Chain Management
      • Injectables
      • Logistics
      • Serialization
      • Solid Dosage / Semi-solids
      • Supply Chain
      • Vials
    • Development
      • Analytical Services
      • Bioanalytical Services
      • Bioassay Developement
      • Biologics, Proteins, Vaccines
      • Biosimilars
      • Chemistry
      • Clinical Trials
      • Drug Delivery
      • Drug Development
      • Drug Discovery
      • Formulation Development
      • Information Technology
      • Laboratory Testing
      • Methods Development
      • Microbiology
      • Preclinical Outsourcing
      • R&D
      • Toxicology
    • Compliance
      • Filtration & Purification
      • GMPs/GCPs
      • Inspections
      • QA/QC
      • Regulatory Affairs
      • Validation
    • Top 25 Pharma & BioPharma
    • Contract Pharma Direct
    • Breaking News
    • Online Exclusives
    • Slideshows
    • Experts Opinions
    • Surveys
      • Outsourcing Survey
      • Salary Survey
    • Glossary
    • Videos
    • White Papers
    • Podcasts
    • Infographics
    • Supplier Microsite
      • Companies
      • News Releases
      • Posters
      • Brochures
      • Services
      • Videos
      • Case Study
      • White Papers
    • Contract Pharma Conference
      • Contract Pharma Conference
      • Speakers
      • Exhibitors
      • Conference Sessions
    • eBook
    • Webinars
    • Events
      • Industry Events
      • Live from Show Events
      • Webinars
    • Classifieds / Job Bank
      • Classifieds
      • Job Bank
    • About Us
      • About Us
      • Contact Us
      • Advertise With Us
      • Privacy Policy
      • Terms of Use
    Features

    Making Medicines: Speeding the Path from Idea to Patient

    Speeding the path from idea to patient

    Making Medicines: Speeding the Path from Idea to Patient
    Making Medicines: Speeding the Path from Idea to Patient
    FIGURE 1. It costs more than a billion U.S. dollars to bring a drug from the discovery stage to commercialization and only about 1 in 5,000 new drug candidates make it through the whole process to become a marketable product. However, the reward is worth the risk.
    Making Medicines: Speeding the Path from Idea to Patient
    FIGURE 2. Although the number of new drug approvals per year fluctuates, there is a constant supply of new products to the market.
    Related CONTENT
    • Biosynth Carbosynth
    • MedPharm
    • Coriolis Pharma
    • Asymchem
    • Vetio Animal Health
    Dan Bowles and Michael Tracey, Cambrex 10.11.17
    In the past century, small molecules drugs have revolutionized human healthcare. From antibiotics to anticancer drugs, allied to medicines designed to treat chronic conditions as diverse as epilepsy and diabetes, the skills of the organic chemist have had a huge impact on both life expectancy and quality of life. Despite the successes, bringing a new small molecule drug to market is far from a trivial exercise. It typically takes 15 years and costs in excess of a billion dollars, and the attrition rate is high—one estimate is that just one in 5,000 promising chemical entities will actually reach the market (see Figure 1).

    But the reward is worth the risk: the size of the global pharmaceutical market topped $1 trillion in 2016 (see Figure 2). In the 40 years from 1977-2016, the U.S. FDA approved around 4,000 small molecule products for commercialization. Annual fluctuations aside, there is a constant supply of new drugs to the market, and with many unmet medical needs remaining, the potential for success is great if these hurdles can be overcome.

    Once a new biological target has been identified that might have potential for altering the course of a disease, medicinal chemists can get to work on creating a molecule that might interfere with that target’s activity. Only small amounts of these molecules are required for early biological assays and screens, and through an iterative cycle of design–make–test, an optimized compound is identified for further progression.

    At this point, the project has usually been up and running for a number of years, and it is only at this stage that larger quantities of prospective active pharmaceutical ingredient (API) will be required. The medicinal chemistry route to the molecule is rarely appropriate for large-scale manufacturing—medicinal chemists are more interested in speed than cost, because time is of the essence when determining its potential biological activity. The sooner a molecule gets into clinical trials, the sooner it will reach the market if it proves efficacious and safe.

    Medicinal chemists will, therefore, routinely use reagents and reactions that process chemists try to avoid, because they allow a new molecule to be accessed quickly. These might be organolithium bases that must be used at very low temperatures, perhaps, or a reaction that gives a complex mix of products that require separation using solvent-heavy column chromatography.

    This is the first point along the development pathway for a small molecule drug that a contract manufacturing organization (CMO) is likely to get involved. Scale up and route optimization is an art in itself, and if in-house expertise is not available, the skills of the CMO can be invaluable. The CMO can be a complement to a Big Pharma company’s own process development team and, in the case of a biotech company with no in-house capabilities, can offer the means to design an appropriate large-scale synthesis.

    It is also important to get a good synthetic route early on in the development cycle. It is rarely altered past phase IIa, but where the demands for API increase throughout the clinical stages, and then further into commercial manufacturing, the synthetic route is scrutinized, and process chemists and engineers look to adapt it.

    Route evaluation is common for CMOs once the market has been established for a drug, as late as a number of years after launch. Although there are regulatory costs involved in changing the route post launch, there are occasions when it can be worthwhile. This is particularly the case if the new route is very much faster or very much cheaper, and may even help to reduce the impact of generic competition once patent expiry occurs.

    Early stage support
    The following two case studies illustrate support provided for API manufacturing demand across the drug development spectrum.

    Case Study No. 1: Early process development and rapid progression to first GMP bulk manufacture. A client had developed a 13-step route for a new molecule and initially required sub-kilogram quantities to be manufactured under non-GMP conditions, followed by a scale up to 5kg batches that would be manufactured in accordance with cGMP.

    Cambrex was able to design a new route to replace that original medicinal chemistry route, and at the same time increase the overall reaction yield significantly from 2% to 18%. In addition, downstream development was completed in parallel with plant production of the API to minimize the timeline for the process.

    Two steps were shaved off the route, bringing the total number down to 11. Furthermore, a hazardous diazotization step was evaluated and risk-mitigated, and solubility and final form issues were resolved to provide the desired polymorph.

    Case Study No. 2: Process development and process validation studies. In some cases, full time equivalent (FTE)-based R&D is a more appropriate way to approach a problem. In this example, Cambrex provided FTE-based R&D to support a client’s medicinal chemistry/structure-activity-relationship studies. The result was a second-generation process that was developed in collaboration with the client, and sufficient API was delivered to satisfy an early toxicity study program. This was quickly followed up by the first kilogram-scale GMP batch of API to meet the demands of clinical trials.

    During the development process, an issue with water sensitivity was identified. To meet the stringent purity requirements, refinements to the process were made, in collaboration with the client, to ensure its robustness at scale. Further process improvements resulted in an efficient and streamlined route that also dramatically reduced the cost of the API. Full analytical and process validation was successfully completed, enabling the API to be manufactured at a 40kg batch scale.

    Supporting API demand at late clinical phase and commercial launch
    Late-stage development requires specific skills that a CMO may be better placed to provide than a company’s in-house team. Biotech companies are unlikely to be able to do these tasks themselves, and therefore will look for a CMO with extensive experience in supporting API manufacturing for late-stage development and commercial launch.

    Case Study No. 3. Internal development and transfer. A customer synthesis project for a generic API project was originated by Cambrex at the company’s R&D site in Tallinn, Estonia, and a number of scouting runs performed to establish the synthetic route and initial development procedures. The development and technical transfer teams from the company’s Charles City site became involved early on in the project to help direct development, which included design of experiment (DoE) studies.

    The process transfer was undertaken in Estonia, so the U.S. staff were able to see the process being implemented and discuss progress with the Estonian development team. This early involvement resulted in very little process development being required after the campaign was transferred back to Cambrex Charles City for full-scale commercial manufacture.

    Case Study No. 4: Process development. A client approached Cambrex with an 8-step process that required further development and CMO support for production and commercial launch of an API. A previous CMO had made 50kg of the API with an overall yield of 9%. By understanding and optimizing two key reaction steps, Cambrex was able to develop a process that gave a substantially improved overall yield of 49%. DoE being used to determine a proven acceptable range (PAR) for each critical process parameters (CPP), and fate/purge of impurities. Analytical method development and validation included chiral chromatography and UPLC-MS.

    Case Study No. 5: Technology transfer. A U.S. client that had developed a complex 4-step process was looking for a domestic supplier of the product. Cambrex had considerable knowledge of the client’s process, having previously manufactured it at pilot scale, and developed a suite of analytical methods that enabled the chemical process to be monitored.

    Cambrex committed to building and qualifying a new large-scale manufacturing facility for the process in Charles City. This was achieved in less than one year, and only one laboratory-scale run was required before the process was transferred to the pilot plant. Furthermore, just two validation pilot runs were required prior to the scale up of the process to 15,000-litre equipment. The application of Six Sigma techniques has allowed an increase in production year-on-year, and more than 60 tons of this API have now been manufactured by Cambrex over the past four years.

    What makes a good small molecule CMO?
    For a partnership with a CMO to succeed, there are multiple factors that will be important. The CMO should have extensive expertise in process chemistry and engineering, with a reputation for quality and reliability in its manufacturing operations. As well as a strong safety record, it should offer advanced chemical manufacturing technology, and flexibility that allows it to manufacture small molecules from milligram through to ton scales, and be able to adapt as the molecule moves through the development pipeline.

    Perhaps the most critically important factor, however, is that the CMO should offer dedicated support throughout the whole route through development, from compound selection to commercial launch and beyond. Speed is of the essence, and any delay in the development process will shave weeks, months or even years off the time a drug will have on the market before it is subject to generic competition on patent expiry. A good CMO will play a key role in getting the drug to the market in a timely fashion, so it can start to recoup those huge development costs. 


    About the Authors: Dr. Dan Bowles is senior director of chemical development at Cambrex High Point, North Carolina. Dr. Michael Tracey is principal scientist for new product development at Cambrex Charles City, Iowa.
    Related Searches
    • api manufacturing
    • pipeline
    • technology transfer
    • study
    Suggested For You
    Biosynth Carbosynth Biosynth Carbosynth
    MedPharm MedPharm
    Coriolis Pharma Coriolis Pharma
    Asymchem Asymchem
    Vetio Animal Health Vetio Animal Health
    Know the Challenges of Biosimilar Manufacturing Know the Challenges of Biosimilar Manufacturing
    CEO Spotlight:  Samsung Biologics CEO Spotlight: Samsung Biologics
    Sterile Manufacturing: Future Trends and Challenges Sterile Manufacturing: Future Trends and Challenges
    Contracting & Outsourcing Session Highlights and Key Takeaways Contracting & Outsourcing Session Highlights and Key Takeaways
    Know the Challenges of  Biosimilar Manufacturing Know the Challenges of Biosimilar Manufacturing
    Outsourcing Partnerships:  Trends in the CDMO Sector Outsourcing Partnerships: Trends in the CDMO Sector
    Serialization Validation: Right Fitting Your Strategy With a CMO Serialization Validation: Right Fitting Your Strategy With a CMO
    Cambrex Expands NC Facility Cambrex Expands NC Facility
    Cancer Trials in the New Age of Drug Development Cancer Trials in the New Age of Drug Development
    Senate Passes FDA Reauthorization Act Senate Passes FDA Reauthorization Act

    Related Content

    • Biosynth Carbosynth

      Biosynth Carbosynth

      ...
      Aimee Cossins, Marketing 03.01.22

    • MedPharm

      MedPharm

      ...
      Andie Woodson, Marketing Manager 10.21.21

    • Coriolis Pharma

      Coriolis Pharma

      ...
      Daniel Weinbuch, Dr. 07.01.21


    • Asymchem

      Asymchem

      ...
      Mandy Boyd, Asymchem 12.01.20

    • Vetio Animal Health

      Vetio Animal Health

      ...
      John Kane, CEO 10.24.19

      Trending
      • How Can Automation Optimize Immunohistochemistry? | Contract Pharma
      • Catalyst Biosciences Sells Complement Portfolio To Vertex Pharmaceuticals | Contract Pharma
      • Corealis CDMO Completes Deal With ArchiMed | Contract Pharma
      • Mirum Pharmaceuticals Acquires San Diego-based Satiogen | Contract Pharma
      • CureVac, MyNEO Partner On Antigen Targets For MRNA-Cancer Vax Development | Contract Pharma
      Breaking News
      • CPDC Enters Clinical Manufacturing Deal with CellBion
      • Olon to Build New R&D Center in Italy
      • Hanmi Fine Chemical Launches CDMO Business
      • DFE Pharma Opens India CoE for Fast-Track Formulation Services
      • Helsinn Establishes New R&D Hub in the U.S.
      View Breaking News >
      CURRENT ISSUE

      May 2022

      • Sustainability and the Biopharma Industry
      • Contract Manufacturing During COVID
      • Orphan Drugs in the United States
      • CEO Spotlight: Peter DeYoung
      • CEO Spotlight: Darren Head
      • Advanced Therapy Packaging Trends
      • Advanced Therapy Manufacturing
      • Sustainability: A New Threat or Opportunity for CDMOs?
      • SARS-CoV-2 R&D

      Cookies help us to provide you with an excellent service. By using our website, you declare yourself in agreement with our use of cookies.
      You can obtain detailed information about the use of cookies on our website by clicking on "More information”.

      • About Us
      • Privacy Policy
      • Terms And Conditions
      • Contact Us

      follow us

      Subscribe
      Nutraceuticals World

      Latest Breaking News From Nutraceuticals World

      Thorne Relaunches Gut Health Test with Microbiome Wipe
      Alkemist Labs Announces Alkemist Assured Seal and Next Generation Transparency Reports
      GC Rieber Foundations Expand Philanthropic Efforts
      Coatings World

      Latest Breaking News From Coatings World

      ICP Receives ASC Innovation Award for Spray Foam That Meets Changing Environmental Regulations
      Pylon Coatings Uses Polygiene Biomaster & Verimaster for Antimicrobial Surface Protection
      Sto Corp. Recognized with Multiple Honors at the EIFS Hero Awards
      Medical Product Outsourcing

      Latest Breaking News From Medical Product Outsourcing

      New Breast Implant Surgery Guidelines to Enhance Patient Safety
      Rhythm Management Group Debuts RhythmSynergy Tech Platform
      FDA Approves Trial Completion for Virtual Incision's MIRA Platform
      Contract Pharma

      Latest Breaking News From Contract Pharma

      DFE Pharma Opens India CoE for Fast-Track Formulation Services
      Helsinn Establishes New R&D Hub in the U.S.
      CureVac, myNEO Partner on Antigen Targets for mRNA-Cancer Vax Development
      Beauty Packaging

      Latest Breaking News From Beauty Packaging

      Shellworks Raises $6.2 Million in Seed Funding
      Ulta Beauty Reports Record First Quarter 2022 Results
      Carlyle To Acquire HCP Packaging
      Happi

      Latest Breaking News From Happi

      Honeywell Addresses Critical Issues Such as Sustainability, Workforce Training and Digitalization
      Monat Global Wins Four Stevie Awards in the 20th Annual American Business Awards
      Coty Expands Vegan Beauty Portfolio With New Rimmel Mascara
      Ink World

      Latest Breaking News From Ink World

      UK-Based Caps Cases Installs World’s First EFI Nozomi 14000 LED Digital Corrugated Press
      Sonoco Announces Transition of Chief Financial Officer
      Azelis Expands Presence in India
      Label & Narrow Web

      Latest Breaking News From Label & Narrow Web

      Labelexpo Asia 2022 postponed
      Teklynx software helps Top Clean Injection validate labels
      Zeller+Gmelin named Berry Global’s 2021 Ink Supplier of the Year
      Nonwovens Industry

      Latest Breaking News From Nonwovens Industry

      Rael Raises $35M in Series B Funding
      Schobertechnologies Offers Rotary Web-fed Converting Solutions
      Thorne Relaunches Gut Health Test with Microbiome Wipe
      Orthopedic Design & Technology

      Latest Breaking News From Orthopedic Design & Technology

      Toetal Solutions Raises $1.02 Million in New Financing
      ManaMed's ManaSport Wearable Ultrasound Earns FDA Nod
      Ekso Bionics Names Jerome Wong as Interim CFO
      Printed Electronics Now

      Latest Breaking News From Printed Electronics Now

      onsemi Recognized by Fortune 500 for Its Transformation Journey
      LG Display Presents AI-Driven NFT Artwork on Transparent OLED
      Joe Stockunas Joins SEMI as Americas President

      Copyright © 2022 Rodman Media. All rights reserved. Use of this constitutes acceptance of our privacy policy The material on this site may not be reproduced, distributed, transmitted, or otherwise used, except with the prior written permission of Rodman Media.

      AD BLOCKER DETECTED

      Our website is made possible by displaying online advertisements to our visitors.
      Please consider supporting us by disabling your ad blocker.


      FREE SUBSCRIPTION Already a subscriber? Login