• 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
    Piramal Pharma Solutions New API Plant in Canada Now Online

    MG America Appoints Claudio Radossi as President

    Catalent Invests $175M to Expand Mfg. Capabilities at Winchester, KY

    Sartorius Expands Manufacturing Site in Tunisia

    BioMoti Partners with Pharma Company to Develop Ovarian Cancer Treatment
    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

    Piramal Pharma Solutions New API Plant in Canada Now Online

    Selecting a CMO Partner for Sterile Injectable Manufacturing

    Catalent Invests $175M to Expand Mfg. Capabilities at Winchester, KY

    Grand Opening of Kodiak Sciences’ Bioconjugation Facility

    Vertex Expands Cell and Gene Therapy Footprint
    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

    Selecting a CMO Partner for Sterile Injectable Manufacturing

    BioMoti Partners with Pharma Company to Develop Ovarian Cancer Treatment

    WCG Appoints Sam Srivastava CEO

    AffyXell Expands Manufacturing Partnership with GenScript ProBio

    ABL and Odimma Therapeutics Enter Development Agreement
    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
    Kyongbo Pharmaceutical

    Vector Partners Limited

    Quotient Sciences

    Biosynth Carbosynth

    CMC Pharmaceuticals
    Companies
    News Releases
    Posters
    Brochures
    Services
    Videos
    Case Study
    White Papers
    Jobs
    Contract Service Directory Companies
    Kyongbo Pharmaceutical

    Vector Partners Limited

    Quotient Sciences

    Biosynth Carbosynth

    CMC Pharmaceuticals
    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
    Columns

    A Potential “Marriage”

    Initiator companies and generics/CMOs working together.

    A Potential “Marriage”
    Related CONTENT
    • Taros Chemicals GmbH & Co. KG
    • DPT
    • W. R. Grace FCMS
    • Ackley Machine Corporation
    • SGS Health Science
    Emil W. Ciurczak, DoraMaxx Consulting11.17.20
    For centuries, armies obtained needed supplies from newly conquered areas as they advanced. Since they carried their swords, shields, etc. with them, all they needed was food and firewood to survive and continue forward. As we “progressed,” our needs became more complex and a supply-chain needed to be maintained for success. Some prime examples are the British army in Continental U.S., Napoleon in Russia, and, my favorite, Rommel in N. Africa. These powerful forces were stalled by lack of resources, not necessarily an overpowering opponent. So, substitute the COVID pandemic for the Russians burning Moscow and you see some parallels. [My $40 Timex, getting five years on a battery, demonstrates that, sometimes, simpler is better.]

    Last month, I ended with a thought or two about cooperative projects between initiator companies and (usually) smaller generic or contract manufacturing firms with, of course, the proviso that such “marriages” do not violate anti-trust laws. Before you say this cooperative is impossible, let me give you an example—albeit much smaller—of such an effort.

    Back in the late1980s, early 1990s, companies were beginning to take an interest in measuring processes in real time. The control methods, at that time, for example, consisted of such methods as using a “sample thief” to extract a number of samples from a blending bin, send them to QC and, based on the results, declare the blend mixed, or not. I had published a paper using a fiber optic probe, pushed into the bed to determine uniformity by Near-Infrared Spectroscopy. Pfizer went quite a bit farther.

    Understanding that any one of their blockbuster drugs (Lipitor, for example) had sales in excess of the combined sales of all instrument companies, worldwide, they realized they could not ask a much smaller instrument company to invest a significant portion of its time and fortune in developing a specialized instrument that a Pfizer might or might not buy, after all. So, they came up with a plan that has become a “new normal” in PAT/QbD circles.

    The first (“PAT-type”) in-process instrument was a joint project between Pfizer (Sandwich, UK) and Zeiss optics (Zurich, CH). A lab-style near-infrared spectrometer was mounted on a v-blender with a window in one end cap. Since no R&D was done prior to the experiment, there were still wires coming from the instrument: one from a power source and another to the computer. The blender was rotated a single one-half spin in one direction, the one-half spin in the other direction to avoid breaking or binding the wires. When it appeared to be giving meaningful results, Zeiss developed the unit with an internal power source and wireless capacity. The device/technique was patented, but not “defended,” allowing all companies to use the procedure in their processes. This process monitoring device changed the entire paradigm of the powder blending step in a manufacturing process.

    This big/small company cooperative model can work in many ways:
    1. An initiator company would develop the dosage form/process as usual and, as the successful product increases in sales, it can clone its process equipment and distribute them to subsidiary companies (either co-ops or wholly-owned), quickly validate them, and proceed to produce the drug at multiple sites.
    2. The initiator company can develop the process and sub-let it to a contract manufacturing company. This would be an exclusive license and all the products produced are sold under the initiator’s name. When the patent expires, the contract would end and a new paradigm would need to be negotiated.
    3. Then, we have the concept of a sponsor-company subsidizing an entire PAT/QbD process(es) at a contract location, with the CRO/CMO developing everything from the clinical supplies, through the final dosage form, through actual production and distribution of the commercial supplies.

    The best part of this (these) situation(s) is that any or all of the contract locations would not be dependent on a single supply source for raw materials. Since the overall scope of QbD is to modify the process to affect the outcome, variances in raw materials are overcome through changing the settings/parameters of the Design Space—all previously validated, accepted changes to the process, which allows the intermediate and final product to meet specifications. The reason that we have specified excipients from specific vendors is that, under the cGMP (batch) manufacturing paradigm, processes (and amounts of materials, e.g., lubricants, such as magnesium stearate) cannot be legally varied even though some experienced operators make “corrections” to the batches to “assure” they meet specs.

    This does not mean that all standards for raw materials will be discarded, but that two things are (painfully) apparent:
    1. Current specifications are based on purity, not performance. Since almost all the specs (as in USP, EP, etc.) were formulated decades ago when pharmacists made small batches of pills or capsules in the back rooms of their pharmacies, easy tests, such as tap density, color, heavy metals, and sieve size were all that were needed, since there was no processing as we know it today. This assumed that the supplies were all locally obtained (or from a small number – or one – nationally based vendor(s)), so only id and purity needed to be tested. Manually blended small batches didn’t need physical parameters specified.
    2. Since modern pharmaceutical manufacturing is so dependent on the physical structure of the ingredients, the two choices are to sit down with vendors and agree upon delivery of tightly controlled materials or, the companies can adopt a true QbD program, which allows physical variation (of course, still maintaining chemical purity), which allows manufacturers to use local vendors, saving inter-state and inter-country shipping of materials.

    This ability to not be held captive by a supply chain is step one. Now, we can look at quality. Quality isn’t a vague concept; it is rather easily defined. Some of the hallmarks of a quality product (and its process) are:
    1. Obviously, a product that consistently meets product performance criteria in physical and chemical tests (assay, dissolution, etc.).
    2. Monitoring each step to avoid waste and shorten the time between steps (minimum PAT set-up). This leads to a faster through-put, making better use of manufacturing equipment.
    3. Quality, from a somewhat selfish point of view, means avoiding the hassle of recalls and or destroyed batches that do not meet standards.
    4. All these (1-3) points lead to a reduced COGS and assuring that their orders to distributers are met (especially since, if a generic product, there are many competitors waiting to step in).

    Now that we have the ingredient difference problem addressed, we can look at the manufacturing sites. The traditional (a.k.a., “old-fashioned”) production process has been:
    1. Do the preliminary formulation work. (Including clinical batches)
    2. Do a scale-up (batch process) on the chosen formulation and write the SOPs for the process.
    3. Begin producing the final product, using traditional multi-step processes, at the site of origin.
    4. If the product is successful, attempt to mirror the process at your other sites or, as we are seeing in recent years, contract the (GMP) process to CMOs around the world.

    At this point of a successful product, the traditional approaches as the patent life expires were:
    1. Drop prices during the patent’s last year, hoping to sell a percentage of the product, based on name recognition and reputation.
    2. Change the product design at the last minute, hoping to delay generic competition.
    3. Invent (excuse me), “discover” new uses for the older product to extend its patent life—think a lower dose Proscar (non-cancerous prostate tumors) being marketed as Propecia (male pattern baldness).

    Now, in the time of continuous manufacturing, built on sound scientific principles (QbD, Design of Experiments, real-time process monitoring instruments), it is possible and economically sound to reproduce the same manufacturing conditions in multiple locations: including contract manufacturing sites.

    This is where creative business decisions are needed. Getting back to the three scenarios, where CM units may be “cloned” and placed in subsidiaries to help keep up with demand, or placed on CMOs to either use them as contract producers with short-term contracts, ending or re-negotiated upon patent expiry date.

    The truly imaginative companies will find ways to “partner” with contract manufacturers. These solutions will range from outright paying them to produce the product(s) on equipment owned by and installed by the proprietary company to loaning the CMO the equipment for the duration of the product’s patent life to working out a plan wherein the CMO takes a portion of its fees towards eventually owning the continuous manufacturing unit(s).

    Clearly, there are positive aspects and speed-bumps in each case. The one clear positive that exists in all cases is that the speed and cost-savings and consistency of CM-made product will bring the ever-sought-after “quality” to the product. The scenario wherein the CM unit is merely “lent” to the CMO is the lowest cost to the contract facility, allowing smaller producers to bid successfully for the contract.

    Where the CMO is allowed to purchase the hardware (and expertise and training), either on a lay-away plan or through some profit-sharing method, it sets them up for being able to easily accept more contracts for CM-produced drugs. Ultimately, these well-equipped facilities can be used as resources for DoE experiments (virtual scale-ups) and potentially, with assistance, actual formulation work. A great advantage to that scenario is that all the R&D would be performed with locally sourced raw materials, obviating the need to modify the work performed by a central R&D facility.

    Since I am merely a humble chemist, I cannot even suggest methods for the financial structure of these proposals, nor can I imagine how the distribution of finished products could be integrated into the existing structure. But, all in all, I am sure that the financial wise people in both companies can work out something that will both lower costs and improve quality.


    Emil W. Ciurczak
    DoraMaxx Consulting

    Emil W. Ciurczak has worked in the pharmaceutical industry since 1970 for companies that include Ciba-Geigy, Sandoz, Berlex, Merck, and Purdue Pharma, where he specialized in performing method development on most types of analytical equipment. In 1983, he introduced NIR spectroscopy to pharmaceutical applications, and is generally credited as one of the first to use process analytical technologies (PAT) in drug manufacturing and development.
    Suggested For You
    Taros Chemicals GmbH & Co. KG Taros Chemicals GmbH & Co. KG
    DPT DPT
    W. R. Grace FCMS W. R. Grace FCMS
    Ackley Machine Corporation Ackley Machine Corporation
    SGS Health Science SGS Health Science
    MedPharm MedPharm
    PCI Pharma Services PCI Pharma Services
    Sekisui Sekisui
    PCI Synthesis PCI Synthesis
    Seqens CDMO North America Seqens CDMO North America
    pHOXBIO Unveils Trial Results from COVID Prophylactic Nasal Spray pHOXBIO Unveils Trial Results from COVID Prophylactic Nasal Spray
    Immunic Inc. Signs In-License Agreement with University Medical Center Goettingen, Germany Immunic Inc. Signs In-License Agreement with University Medical Center Goettingen, Germany
    Naobios to Manufacture FluGen’s M2SR Flu Vax Candidate  Naobios to Manufacture FluGen’s M2SR Flu Vax Candidate
    Clean Cells Expands Bioproduction Capabilities Clean Cells Expands Bioproduction Capabilities
    CEO Spotlight: Gaston Salinas, Botanical Solution Inc. CEO Spotlight: Gaston Salinas, Botanical Solution Inc.

    Related Content

    • Taros Chemicals GmbH & Co. KG

      ...
      Dimitrios Tzalis, Manager Executive Projects 12.07.21

    • R&D
      DPT

      DPT

      With a specialized focus on semi-solids and liquids, DPT offers pharmaceutical companies the broadest range of capabilities in the industry. From R&D formulation to commercial-scale manufacturing, small batches to large, liquids to emulsions, sterile or non-sterile, we offer clients of all sizes the most effective resources for meeting challenges.
      Stacy London, Senior Manager, Marketing & Communications 12.02.21

    • W. R. Grace FCMS

      W. R. Grace FCMS

      ...
      Stella Ip, Director Marketing Health and Life Sciences 11.23.21


    • Ackley Machine Corporation

      ...
      Liv, Marketing Manager 11.03.21

    • Chemistry | Extractables and Leachables | Microbiology
      SGS Health Science

      SGS Health Science

      ...
      Jessica Martin, Marketing Director 10.26.21

      Trending
      • Cellipont Bioservices Expands Cell Therapy Facility | Contract Pharma
      • Biopharma Manufacturing Facility Construction | Contract Pharma
      • Next-Gen Lab Services | Contract Pharma
      • Pharma Development & Manufacturing Trends | Contract Pharma
      • Reviving Local Production Of Antibiotic Powders | Contract Pharma
      Breaking News
      • Piramal Pharma Solutions New API Plant in Canada Now Online
      • MG America Appoints Claudio Radossi as President
      • Catalent Invests $175M to Expand Mfg. Capabilities at Winchester, KY
      • Sartorius Expands Manufacturing Site in Tunisia
      • BioMoti Partners with Pharma Company to Develop Ovarian Cancer Treatment
      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

      GOED Creates Infographic Highlighting Omega-3 Health Claims Approved in Europe
      Kyowa Hakko Appoints Dr. Colin Hill to Immuse Scientific Advisory Board
      Expert Consensus Statement: Diet is Best Primary Intervention to Achieve Diabetes Remission
      Coatings World

      Latest Breaking News From Coatings World

      What Are You Reading?
      Teknos Receives EcoVadis Gold Medal for Sustainability Performance
      AkzoNobel and Partners Team Up to Hack Carbon Reduction Challenges
      Medical Product Outsourcing

      Latest Breaking News From Medical Product Outsourcing

      MPO's Most-Read Stories This Week—May 21
      Iterative Scopes Expands its Senior Leadership Team
      Viz.ai Raises $100 Million in Series D Funding
      Contract Pharma

      Latest Breaking News From Contract Pharma

      Piramal Pharma Solutions New API Plant in Canada Now Online
      MG America Appoints Claudio Radossi as President
      Catalent Invests $175M to Expand Mfg. Capabilities at Winchester, KY
      Beauty Packaging

      Latest Breaking News From Beauty Packaging

      Authentic Beauty Concept Launches Second-Generation ‘Refill Bar’
      HASK Beauty Enters Exclusive Partnership with Amazon
      Garance Doré Launches Made in France Skincare Line
      Happi

      Latest Breaking News From Happi

      P&G Closes HQ Due To Security Threat, Launches New Hair Care Line
      SPF Setting Spray, Lip Contour and Knotless Braids Are Hot Trends: Spate
      Nutrafol Launches Collagen Infusion
      Ink World

      Latest Breaking News From Ink World

      Weekly Recap: Zeller+Gmelin, Sun Chemical and Kornit Top This Week’s News
      Nazdar Celebrates 100 Years with a New Look
      hubergroup Chemicals Exhibits at Paint India for First Time
      Label & Narrow Web

      Latest Breaking News From Label & Narrow Web

      Brook + Whittle's new acquisition, SunDance goes to HP and more
      Specialty announces move to new facility
      Mark Andy hosts dealer's open house in Warsaw
      Nonwovens Industry

      Latest Breaking News From Nonwovens Industry

      Weekly Recap: Kimberly-Clark to Expand Diaper, Wipes Production in Brazil; The Honest Company to Sell Diapers, Wipes at Walmart & More
      3M to Expand in Nebraska
      Nicely Offers Nonwoven Slitters, Winders
      Orthopedic Design & Technology

      Latest Breaking News From Orthopedic Design & Technology

      ODT's Most Read Stories This Week—May 21
      FDA Clears Anika Therapeutics' X-Twist Knotless Fixation System
      Paragon 28 Rolls Out TenoTac 2.0 Hammertoe and Soft Tissue Repair
      Printed Electronics Now

      Latest Breaking News From Printed Electronics Now

      Weekly Recap: Graphene Flagship, Japan Display and LG Display Top This Week’s Stories
      Evonik Launches New Processing Aids for PV Wafer Cutting
      NREL Creates Highest Efficiency 1-Sun Solar Cell

      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