• Login
    • Join
  • FOLLOW:
  • Subscribe Free
    • Magazine
    • eNewsletter
    Checkout
    • Magazine
    • News
    • Manufacturing
    • Packaging
    • Development
    • Compliance
    • Top 20
    • Directory
    • Solution Center
    • Events
    • More
  • Magazine
  • News
  • Manufacturing
  • Packaging
  • Development
  • Compliance
  • Top 20
  • Directory
  • Solution Center
  • Events
  • Current / Back Issue
    Features
    Editorial
    Columns
    Digital Edition
    eNewsletter Archive
    Our Team
    Editorial Guidelines
    Subscribe Now
    Advertise Now
    Top Features
    Reducing the Risk of Comparator Sourcing

    Clinical Data Management

    Leveraging AI/ML Analytics for Better Clinical Development Decisions

    What is a Manufacturing Ecosystem and Why are They Growing?

    Get Smart: Integrating PAT Data into Existing Biotech Data Infrastructures
    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
    Meiji Seika Pharma, Adcock Ingram Pharma Complete Construction of New Manufacturing Facility

    JSR Life Sciences Consolidates KBI Biopharma and Selexis SA

    Charles River, Wheeler Bio Partner to Operate RightSource Laboratory

    Cellular Origins Launches Robotic Platform for Scalable Manufacture of Advanced Therapies

    Waters Corp. Acquires Light Scattering Company Wyatt Technology
    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

    Manufacturing Complex Peptide APIs

    How CDMOs Can Leverage Contract Terms to Facilitate Payment

    Purification – A Bottleneck for Large-Scale Manufacturing of Oligonucleotide API?

    Peptide Aggregation - A Complex Topic

    Meiji Seika Pharma, Adcock Ingram Pharma Complete Construction of New Manufacturing Facility
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Traceability & 2D Barcodes

    Complex in Complex – New Hopes for Better Drug Delivery in Topical Dosage Formulation

    Proactive Resource Group Offers DSCSA Services for Pharma Companies

    Catalent Adds New Cryogenic Capabilities at Japanese Facility

    TraceLink, PharmaLink Partner to Simplify DSCSA Compliance
    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

    Manufacturing Complex Peptide APIs

    How CDMOs Can Leverage Contract Terms to Facilitate Payment

    Meiji Seika Pharma, Adcock Ingram Pharma Complete Construction of New Manufacturing Facility

    JSR Life Sciences Consolidates KBI Biopharma and Selexis SA

    Charles River, Wheeler Bio Partner to Operate RightSource Laboratory
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    Purification – A Bottleneck for Large-Scale Manufacturing of Oligonucleotide API?

    FDA 2023 Inspection Roadmap: Is “Readiness” in Your Annual Objectives?

    FDA Watch: Are You Suitably Staffed?

    FDA Watch: Is Your Supply Chain at Risk?

    FDA Watch: CDER to Launch Guidance Snapshot Pilot Program
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    TaiMed Biologics

    Lannett CDMO

    Syngene International Ltd.

    INCOG BioPharma Services

    Alcami
    Companies
    News Releases
    Posters
    Brochures
    Services
    Videos
    Case Study
    White Papers
    Jobs
    Contract Service Directory Companies
    TaiMed Biologics

    Lannett CDMO

    Syngene International Ltd.

    INCOG BioPharma Services

    Alcami
    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
    • Microsites
      • 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

    Baby Steps Toward the 21st Century

    Mix and match technologies to succeed.

    Baby Steps Toward the 21st Century
    Emil W. Ciurczak, Contributing Editor02.06.23
    When I was part of the US-FDS PAT sub-committee in 2002, Dr. Ajaz Hussain (FDA) brought in people from industries that were using in-process controls (e.g., the automotive industry) to run workshops, using their experience to address “stress-points” in “normal” GMP manufacturing. It was quite informative and helped form the basis of the FDA Guidances and ICH (International Conference on Harmonization) Q8, 9, 10, 11, etc. I was invited largely because of my work using NIRS for incoming raw material qualification, implemented at Sandoz in 1984.

    My only point of dispute with Dr. Hussain was his suggestion to shut down an entire process line, upgrade each step with validated monitors, then validate the whole system on a product-by-product basis. Now, when you buy your first home, unless you were born into money, you start small and, as the family and your income(s) grow, you can move upward in size and cost. My suggestion was to pick a “low-hanging fruit” project, such as blend uniformity—first performed by Pfizer in late 1980s—or drying, both already using NIR monitors at some early-initiator companies. So, when you show management that your first project 1) works and 2) can be validated, and 3) it speeds up production and minimizes waste, and 4) and most important to the “bean-counters,” it saves money, allowing for a larger profit.

    Then, and only then, you can ask for funds to add other monitors along the process stream, slowly building to a full PAT/QbD process line. In other words, you don’t have to buy/build all the monitors before you begin gathering PAT experience, it can be done gradually. Likewise, a company does not (normally) spend millions of dollars/euros for a full-sized, fully automated, Continuous Manufacturing (CM) suite. Just as we have numerous and efficient contract research organizations (CROs), there are a number of locations in the U.S. and Europe where they perform contract PAT/QbD R&D and a number that can generated a continuous manufacturing protocol for you. Figure 1 below shows a small unit at the U. of Eastern Finland, used to perform contract PAT/QbD development.


    Figure 1: A small unit at the U. of Eastern Finland used to perform contract PAT/QbD development.

    Who Can/Should Use/Switch to PAT/QbD and, eventually, CM?

    It is understood that a straight-forward contract producer cannot arbitrarily change the MMF of the client/patent-holder. However, considering the pandemic-inspired supply chain kerfuffle and recent legislation aimed at reducing drug costs to consumers, it is in everyone’s interest to gradually make the shift, for new and legacy products, from GMP to QbD. Some reasons are:

    1.  With difficulties in obtaining timely shipments from traditional raw material vendors (i.e., API, excipients, and packaging materials), validating new sources is far speedier if the process is allowed to vary—QbD sets product specs not rigid manufacturing steps. That means that, instead of a lengthy validation process to integrate a new vendor’s product into an existing MMF (set in stone), the process may be varied to use the new material to generate a product, already defined as “good.” That is, the final product meets established performance criteria.

    2.  Even if the original source becomes easily available again, any alternate source might be a) less expensive, b) closer, therefore, faster to deliver, and c) could help fulfill requests to “buy locally” instead of importing materials. Note: the FDA can more easily inspect a facility in-country than overseas, assuring GMP compliance at those facilities.

    3.  The costs involved with GMP production versus QbD production are strikingly different: OOS lots, alone, can be quite costly due to failure and destruction in-house or the need to have a recall, mandated by the Agency. For a generic product, a recall can be doubly expensive: loss of the income for that lot and potential loss of business, due to bad publicity.

    Operational Cost Savings and Profitability

    A few less obvious savings of CM may be overlooked. Obviously, the major selling point was control over the quality of the product. A few other time and cost savings are also other “selling points” that should be addressed:

    1.  Amounts of API(s) needed during Process Development studies are smaller and require less active. Generating a Design Space (DS), using a Design of Experiments (DoE) study requires “production-sized” batches. Under GMP, generating 20-30 lots of, at least, 500,000 tablets would use up large amounts of (potentially expensive) API and take weeks, involving much equipment, personnel, and waiting for cleaning validation results. A continuously manufactured “batch” is essentially the same for 1,000 or 1,000,000 units. This is important because, for a new product (or updating a legacy product) there is often not an abundance of API in existence.

    2.  Scale-up studies are not required. This is a twin benefit: a) the six or so months that are normally required for scale-up is obviated , since the R&D/clinical sized batches are merely “up-sized” by running the CM equipment as long as needed to generate the required number of units, and b) the ideal final specs already exist from the DoE process, so further development is not needed before commercialization.

    3.  CM improves both the quality and consistency of products. There is, by definition, a steady state of control because the automated process, continuously monitored, assures instant response to any variation. This results in a consistent, high-quality product, obviating OOS (out of specification) products, virtually eliminating any recalled product.

    4.  CM-based products can be expanded or slowed, responding rapidly to changes in market demand. This flexibility allows for a quick rapid response to an increase in product demand, reducing shortage risks or prevents over-stocking when sales slow.

    5.  You can reduce your total cost of supplies. Allowing for the process (under QbD) to use any GMP-generated raw materials, ensures that supply chain shortages do not occur, meaning you needn’t carry an oversized inventory of raw materials, fearing an outage of available product on the market.

    6.  In a similar manner, you can achieve a lowering of COGS (cost of goods sold). This COGS reduction results in increased speed to clinic or market and lowers the cost of delivering a higher quality product.

    All these benefits are largely to flexible batch sizes and speed to market. With government mandated price limits (mainly for Medicare patients) in the U.S. and Europe, lowering the COGS must be the mode of increasing profits. Clearly, merely raising prices will not be the future for fiscal success in the future.

    I may have touched on other cost savings in the past, but the COVID-19 shut-downs, followed by supply chain disasters and a shrinking labor pool (accompanied by increases in salaries) and utility costs (oil prices skyrocketing) have made “normal” GMP production more expensive and prone to outages. Moving to QbD and CM allows for some major cost savings in addition to those outlined above:

    1.  Smaller warehouse space needed.  Using PAT/QbD from the arrival of raw materials to the departure of finished products, the needed warehouse space diminishes for two main reasons (both are based on the GMP “waiting for Godot, er, uh, waiting for QC results” paradigm): a) RM supplies are approved or failed, on-the-spot, so, they can proceed to the active portion of the warehouse or sent back to the supplier. This greatly diminishes needed warehouse space and, b) finished products are, in essence, either passed by PAT monitors (up to 100% of the units) in real time, so they do not need to be stored in a quarantine area, awaiting QC analysis results.

    2. A CM unit has a much smaller footprint than discreet, individual pieces of equipment needed for GMP production. Far more equipment is needed for GMP production, if only because so much stands idle, waiting for cleaning or cleaning validation, CM units may be cleaned as assembled, so fewer units are required.

    3.  Operational/personnel reductions are huge. Switching to CM allows for smaller and fewer buildings which drastically lowers a) electricity costs, b) heating/HVAC costs, c) lower personnel requirements (we already have a smaller labor pool, so this relieves that problem) since moving materials, equipment, and cleaning and validating equipment is lowered, needing fewer operators. Add to that, a smaller overall footprint could lower property taxes and maintenance costs, too.

    In future columns, I will discuss biopharma applications of PAT/QbD. Clearly, there is a greater requirement for sterility and the “API” production is often a large and complex process. The packaging/final dosage form, unlike a solid, small molecule, is less complex and the biochemical process becomes the major focus for the PAT/QbD R&D. We will address the heterogeneity of the process and what water does to the most used technology in CM: Near-Infrared Spectroscopy. 


    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.
    Related Searches
    • Analytical Services
    • Laboratory Testing
      Loading, Please Wait..
      Trending
      • Aurigene Expands Biologics CDMO Capacity
      • Astellas To Transfer Manufacturing Plant To Delpharm
      • Catalent Adds New Cryogenic Capabilities At Japanese Facility
      • Thermo Fisher Expands Steriles Facility In Asia-Pacific Region
      • Lifecore Biomedical Enters Into $150M New Financing Deal
      Breaking News
      • Meiji Seika Pharma, Adcock Ingram Pharma Complete Construction of New Manufacturing Facility
      • JSR Life Sciences Consolidates KBI Biopharma and Selexis SA
      • Charles River, Wheeler Bio Partner to Operate RightSource Laboratory
      • Cellular Origins Launches Robotic Platform for Scalable Manufacture of Advanced Therapies
      • Waters Corp. Acquires Light Scattering Company Wyatt Technology
      View Breaking News >
      CURRENT ISSUE

      May 2023

      • New Modalities Hog the Limelight
      • Cell and Gene Therapy is Coming of Age
      • Demand Surges for Cell and Gene Therapy Contract Manufacturing
      • Embracing a New Reality
      • Japan: A Unique Opportunity for Regenerative Medicines and Cell & Gene Therapies
      • Single-Use Technologies Enable Biologic Scaling
      • Get Smart: Integrating PAT Data into Existing Biotech Data Infrastructures
      • FTEs in Drug Discovery
      • Digital Transformation in Pharma
      • What is a Manufacturing Ecosystem and Why are They Growing?
      • View More >

      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

      Verdure Sciences Receives Award for Sustainable, Ethical Turmeric Sourcing
      BGG Receives Patent for Saw Palmetto ID Method
      Premium Label & Packaging Solutions Receives Safe Quality Food (SQF) Certification
      Coatings World

      Latest Breaking News From Coatings World

      Brand Finance: Post-COVID Recovery Slows for Chemicals Industry Battling Energy Crisis
      BCF Calls for Greater Urgency on REACH Impasse
      MNYCA Hosts Afternoon Baseball Event
      Medical Product Outsourcing

      Latest Breaking News From Medical Product Outsourcing

      CareDx, Miromatrix Collaborate on Bioengineered Organs Research
      Capitainer Releases to Market its Fully Automated Sample Handler
      Titan Medical Licenses Most IP to Intuitive; CEO Steps Down
      Contract Pharma

      Latest Breaking News From Contract Pharma

      Meiji Seika Pharma, Adcock Ingram Pharma Complete Construction of New Manufacturing Facility
      JSR Life Sciences Consolidates KBI Biopharma and Selexis SA
      Charles River, Wheeler Bio Partner to Operate RightSource Laboratory
      Beauty Packaging

      Latest Breaking News From Beauty Packaging

      Stetson Introduces Men’s Grooming Portfolio
      Two Executives Depart from Unilever Amid CEO Transition
      L’Oréal Paris Welcomes Thuso Mbedu as Brand Ambassador
      Happi

      Latest Breaking News From Happi

      Shaz and Kiks Launches at Sephora
      Beautycounter Appoints Board Director Mindy Mackenzie Interim CEO
      Unilever Ventures’ Backs Selva Ventures in $34 Million Fund for Early-Stage CPG Brands
      Ink World

      Latest Breaking News From Ink World

      ACTEGA, Makro Labelling to Advance Signite Technology
      BCF Requests Greater Urgency on REACH Impasse
      Updated Method Published for Entire BASF Product Portfolio
      Label & Narrow Web

      Latest Breaking News From Label & Narrow Web

      ACTEGA teams with Makro Labelling to advance Signite technology
      Constantia Flexibles and SB Packagings commence joint venture
      Inland donates new VersaStudio printer to local high school
      Nonwovens Industry

      Latest Breaking News From Nonwovens Industry

      Mann+Hummel Names President Air Filtration Americas
      KNH Launches Eco-Friendly Menstrual Pads
      Niine Introduces India's First PLA-Based Sanitary Pads
      Orthopedic Design & Technology

      Latest Breaking News From Orthopedic Design & Technology

      Enrollment Completed in Anika Therapeutics' Hyalofast Study
      Exactech Releases Next-Gen GPS Shoulder
      Data Shows Favorable Survivorship of MISHA Knee System & Reduction of Arthroplasty Risk in Patients
      Printed Electronics Now

      Latest Breaking News From Printed Electronics Now

      onsemi Presents Path to Accelerate Revenue Growth
      STMicroelectronics Introduces Waterproof MEMS Pressure Sensor
      Graphene Flagship to Join Euro Nano Forum 2023

      Copyright © 2023 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