• Login
    • Join
  • FOLLOW:
  • Subscribe Free
    • Magazine
    • eNewsletter
    Checkout
    • Magazine
    • News
    • Manufacturing
    • Packaging
    • Development
    • Compliance
    • Top 25
    • Directory
    • Microsites
    • Events
    • More
  • Magazine
  • News
  • Manufacturing
  • Packaging
  • Development
  • Compliance
  • Top 25
  • Directory
  • Microsites
  • Events
  • Current / Back Issue
    Features
    Editorial
    Columns
    Digital Edition
    eNewsletter Archive
    Our Team
    Editorial Guidelines
    Subscribe Now
    Advertise Now
    Top Features
    Bye-Bye China?

    Decentralized Trials Fuel AI Revolution in Clinical Research

    Self-Medication: Flexibility for Patients and Drug Manufacturers

    The Single-Use Mixing Landscape: Evaluating Your Options

    DCAT President Talks COVID-19, Drug Manufacturing and Innovation
    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
    Global Biosciences Co. Selects ValGenesis VLMS

    Eisai Appoints Chief Clinical Officer of Oncology Biz

    Nexelis Acquires GSK Vax Lab in Marburg

    Bone Therapeutics, Rigenerand Ink Cell Therapy Deal

    NovaQuest Private Equity Acquires CoreRx
    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

    Lonza to Exit Pharma Softgels and Liquid-Filled Hard Capsules

    Cognate BioServices Announces Major Expansion

    Sanofi Unveils EUROAPI as Name of New European API Company

    Precision Medicine Group Acquires Project Farma

    Cytiva Delivers Modular Biologics Factory to Lonza
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Catalent Acquires Acorda’s INBRIJA Manufacturing Operations

    Varcode, PL Developments Form Strategic ‘Smart Tag’ Pact

    COVID-19 Vaccine Distribution: The Air Cargo Industry’s Greatest Challenge

    Thermo Fisher Expands Clinical Supply Services in Europe

    Schreiner MediPharm Joins DoseID Consortium
    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

    Global Biosciences Co. Selects ValGenesis VLMS

    Nexelis Acquires GSK Vax Lab in Marburg

    The Future of Clinical Trials Series: Part I

    JS Bio and Etta Biotech Advancing Partnership

    Intravacc Completes Project for Provention Bio’s Vax Candidate
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    Global Biosciences Co. Selects ValGenesis VLMS

    Gene Therapy Co. Selects ValGenesis' SaaS Platform

    The Year of COVID: How FDA Coped with a Worldwide Pandemic in 2020 and What to Expect in 2021

    Samsung Biologics Adopts Veeva Vault QMS to Unify Quality Management

    CDMO Cognate BioServices Teams Up with L7 Informatics
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    Cytovance Biologics

    Reed-Lane

    Flow Sciences

    PCI Pharma Services

    Alcami
    Companies
    News Releases
    Posters
    Brochures
    Services
    Videos
    Case Study
    White Papers
    Jobs
    Contract Service Directory Companies
    Adare Pharma Solutions

    Cytovance Biologics

    PCI Pharma Services

    Aphena Pharma Solutions

    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
    • Podcasts
    • White Papers
    • Infographics
    • Contract Pharma Conference
      • Contract Pharma Conference
      • Speakers
      • Exhibitors
      • Conference Sessions
    • Supplier Microsite
      • Companies
      • News Releases
      • Posters
      • Brochures
      • Services
      • Videos
      • Case Study
      • White Papers
    • 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

    Re-Open Your Tool Chest

    There’s no longer an excuse NOT to start “PAT-ing” your products

    Re-Open Your Tool Chest
    Related CONTENT
    • MedPharm
    • Mogene
    • Softweb Solutions
    • Vetio Animal Health
    • 06 Merck
    Emil W. Ciurczak, DoraMaxx Consulting07.15.19
    When I was a youngster my dad gave me some good advice: “If you don’t want to do something, you’ll always find a reason not to do it. If you WANT to do something, you’ll FIND a WAY to do it.” This applies to converting from same-old, same-old GMP batch processing—and testing a miniscule portion of the final product—to real-time testing and a de facto examination, if not actual analysis of the entire lot of product.

    I have already on multiple occasions discussed the cost savings due to a speedier time to completion, less warehousing needed for intermediates, better quality control leading to fewer customer complaints and FDA/EMA mandated recalls, and so forth. The reasons were logical and based on quality, as well as financial return. However, I may have overlooked the familiarity of the personnel at smaller companies (CMOs, CROs, and smaller generic companies) with the latest hardware and software for doing PAT/QbD. No, I am not going to expound upon the wonders and rewards of continuous manufacturing or merely point out that the revolution, begun almost two decades ago, is now far easier than ever to join.

    I understand that the professionals who work at these smaller companies are as bright and educated as those at the “Big Boys.” What is different is the “loose change” available for them to attend professional meetings and seminars. As much as one can learn from websites and Google, actually attending seminars, meetings and conferences allows professionals to see the equipment and meet with their peers and exchange ideas on how to utilize the newer instruments, what they disclose, and how to use the information to control and improve a product’s manufacture.

    Certainly, a column this size cannot replace hand-on experience or even a full-sized primer; but I will highlight several pieces of new and relatively new hardware and software that can allow even the novice to dip his/her toe in the (PAT) water. Spoiler alert: you install a PAT program much as you would eat an elephant—one bite at a time.

    When the PAT (draft) Guidance was unveiled in 2004, the author (Ajaz Husaain, CDER, FDA) envisioned a company shutting down an entire production line, re-fitting all the equipment, calibrating and validating the line, training the operators and, after a year or so off-line, restarting the line under PAT. At the time, I was very, very cynical about a mass conversion to the process. Unfortunately, I was correct. However, I had a slightly different idea of how to convert the masses.

    Unknown to me at the time, I was taking the first steps into the PAT-world in 1983, when I instituted a 100% qualification of all incoming raw material containers. Looking at existing wet and instrumental methods in the USP, BP, etc., I knew that even the major Pharma company that employed me (Sandoz) would be hard-pressed to expand the QC department, buy enough equipment for the process, and absorb the costs.

    Happily, I was able to work with the foremost NIR supplier in the world at that time to develop qualitative software, generate equations, validate them, and institute NIRS for 100% of all batches of all materials entering our facility. One simple example of the time and cost savings would be a single lot of Lactose, USP. We generally received about 220 bags of the material per load—sometimes, several times a month. To check all the bags would entail:

    1. Quarantine the lot and place red/orange stickers on each bag;
    2. Open each bag;
    3. Using a sample thief, sample each bag;
    4. Label a whirl-pack and insert the sample;
    5. Bring the samples to the QC lab;
    6. Log the samples;
    7. Assign the samples (220, on the average) to an analyst;
    8. Run the wet tests and the Infrared/UV comparisons with a standard;
    9. Report the results;
    10. Have a supervisor check the results;
    11. Label each bag with an appropriate sticker (green = OK to use); and
    12. Move the bags to the part of the warehouse where approved materials reside.

    While steps 2-5 existed until portable analyzers were developed, the other steps were neatly eliminated. The materials could be sampled where they were delivered and, as we found through experience, a typical Lactose, USP lot could be sampled, bagged, brought to the lab, scanned, and approved or rejected, all before lunch. Yes, the new method, performed with newly written software on a 1982 instrument, could analyze more than 200 samples in four hours! The wet and instrumental methods, aside from requiring an entire shift to be hired, would have taken up to two weeks to analyze the same samples While not a true PAT step—this is eight years before the PAT Guidance was even written—it was the first step towards accessing information needed for a QbD program (avg. particle size, moisture, polymorphic form, crystallinity, etc.).

    These parameters were formerly measured by compendial methods, if only for checking that the correct materials were delivered. I discovered micronized API where it should have been 100-120 mesh by NIR and several bags of lactose were above the moisture limit, so 100% testing worked well. When this ability is extended to a formal SOP, we have the first under-pinning of PAT: characterization of raw materials so that we can control the process better.

    Now, we can attach a wireless spectrometer (NIR for 2% => and LIF [light-induced fluorescence] for less than 2% API) to our blender. You say you’ve never done this before? No problem, the technique and technology has been around since approximately 1990, so the instrument suppliers have the wherewithal to assist you in choosing, installing, and validating their blend uniformity equipment. Now you have step one (raw material qualification) and step two (blending), so we move on to step three (drying/granulating).

    Most major suppliers of fluid bed driers routinely supply extra ports, besides the traditional sampling port, to accommodate fiber optic probes from NIR or Raman instruments. Literature is available and the suppliers of both the driers/granulators and spectroscopic instruments are able and willing to assist with your timed conversion, then analyzed to monitor and dry/granulate to an appropriate endpoint. Since the PAT Guidance asserts that, in lieu of the minimum three “demonstration lots,” then fix your blend/granulation time via SOP, each batch is a validation batch. That is, the process continues, not to a fixed time point, but to completion.

    So, through steps three/four, depending on whether you count drying as separate from granulation, we have now finally met the legal requirement for GMP (as seen in the CFR): that “meaningful” in-process tests must be performed. Considering many of the “traditional” tests for solid dosage forms (hardness, friability, and disintegration, along with loss on drying, all off-line), with these monitors we would have control and the required measurements. That leaves the penultimate, or final, step: compression, or encapsulation.

    If the previous steps were not meaningfully checked, then the final dosage forms really, really miss the stated requirement: “a statistically significant number of final dosage forms must be tested.” Now, I’m just a simple, country chemist, but I don’t believe that analyzing 20-30 tablets from a batch of 1,000,000 to 5,000,000 units is in any way “statistically significant.” Here’s where several vendors come to the rescue. Several commercial instruments are available, and for far less than the cost of one rejected or recalled batch of product, that are capable of fully analyzing up to 100,000 tablets or capsules per hour, per line. According to military standards of testing, a batch of over 500,000 should have at least 25,000 of its units checked. Ask yourself: “which is cheaper and faster: HPLC or NIRS?”

    For those of you that coat your tablets, the prior step may be used to assure the core integrity, and a separate spectroscopic unit (NIR, Raman) may be used to measure the coating levels, in real time, assuring the proper time to completion. So, it seems that PAT is not only allowed under GMP, but aside from the money and time saved over current methods, aligns your process more closely with cGMP rules. And, as I mentioned at the start, all these need not be done in one bite, which is expensive and time-consuming. Taking one “nibble at a time” is a better approach.

    In truth, other than raw materials analysis, whichever of the other steps you update does not matter. You need not go in order. In fact, see which step is giving your operators the most trouble and start there. 

    Author’s note: specific suppliers may be obtained by contacting me via email. The column is not meant to be a commercial for specific suppliers.


    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.
    Related Searches
    • tablets
    • training
    • quality
    • Pharma
    Suggested For You
    MedPharm MedPharm
    Mogene Mogene
    Softweb Solutions Softweb Solutions
    Vetio Animal Health Vetio Animal Health
    06	Merck 06 Merck
    Artificial Intelligence and Machine Learning in Healthcare Artificial Intelligence and Machine Learning in Healthcare
    Getting PAT into Bioprocessing CMOs Getting PAT into Bioprocessing CMOs
    Merck to Restructure Manufacturing Ops Merck to Restructure Manufacturing Ops
    Eisai, Purdue Pharma Amend Lemborexant Alliance Eisai, Purdue Pharma Amend Lemborexant Alliance
    Merck & NJII Receive NIIMBL Award Merck & NJII Receive NIIMBL Award
    Pharmaceutical Excipients Trends Pharmaceutical Excipients Trends
    Career Inflection Points Career Inflection Points
    Solid Dose Manufacturing: It’s Time to Trade-in Your 1952 Studebaker Solid Dose Manufacturing: It’s Time to Trade-in Your 1952 Studebaker
    Are We Embracing FDA’s Messages? Are We Embracing FDA’s Messages?

    Related Columns

    • Analytical Services
      What Happens When the All-Clear Signal is Given?

      What Happens When the All-Clear Signal is Given?

      Maybe 3M had some good ideas?
      Emil W. Ciurczak, DoraMaxx Consulting 06.04.20

    • Analytical Services | Laboratory Testing
      The Supply Chain, as Developed by IKEA (some assembly required)

      The Supply Chain, as Developed by IKEA (some assembly required)

      Pick One from Column A, Two from Column B, etc.
      Emil W. Ciurczak, DoraMaxx Consulting 03.04.20

    • Analytical Services | Laboratory Testing
      Solid Dose Manufacturing: It’s Time to Trade-in Your 1952 Studebaker

      Solid Dose Manufacturing: It’s Time to Trade-in Your 1952 Studebaker

      Making a solid case for PAT, QbD and continuous manufacturing in the pharma industry
      Emil W. Ciurczak, DoraMaxx Consulting 03.06.19


    • Analytical Services | Laboratory Testing
      The Great Diaspora of the Pharma Industry

      The Great Diaspora of the Pharma Industry

      Or, good things come in small(er) packages
      Emil W. Ciurczak, DoraMaxx Consulting 11.14.18

    • Analytical Services | Laboratory Testing
      Possibly Time for a New Paradigm

      Possibly Time for a New Paradigm

      Or, why the chicken should cross the road
      Emil W. Ciurczak, DoraMaxx Consulting 10.10.18

    • Analytical Services | Laboratory Testing
      The Times, They Are a-Changin’

      The Times, They Are a-Changin’

      For contract organizations and generics, for sure
      Emil W. Ciurczak, DoraMaxx Consulting 07.20.18


    • Analytical Services | Bioanalytical Services | Laboratory Testing
      The Final Frontier

      The Final Frontier

      A look at contract bioprocessing and PAT/QbD
      Emil W. Ciurczak, DoraMaxx Consulting 06.12.18

    • Analytical Services | Laboratory Testing
      We Need to Get Back to Basics

      We Need to Get Back to Basics

      In life, and the lab, the calculator/computer is a blessing and a curse!
      Emil W. Ciurczak, DoraMaxx Consulting 05.08.18

    • Chemistry | Laboratory Testing
      When Your Product is Neither a Liquid or a Solid

      When Your Product is Neither a Liquid or a Solid

      And you need to analyze/control it, in real time
      Emil W. Ciurczak, DoraMaxx Consulting 01.30.18


    • Analytical Services
      Finding the “Missing Link”

      Finding the “Missing Link”

      Outsourcing and the supply chain
      Emil W. Ciurczak, DoraMaxx Consulting 10.11.17

    • Analytical Services | Laboratory Testing
      Analytical Equipment Technology for the 21st Century

      Analytical Equipment Technology for the 21st Century

      A look at some more toys available for CMOs, CROs and generics to boost their analytical capabilities
      Emil W. Ciurczak, DoraMaxx Consulting 05.09.17

    • Analytical Services
      Quality Risk Management

      Quality Risk Management

      It’s not just for the big guys anymore
      Emil W. Ciurczak, DoraMaxx Consulting 04.03.17


    • Analytical Services | R&D
      Trends in Pharma Analysis

      Trends in Pharma Analysis

      A look at how pharma analysis technology continues to evolve to meet market needs
      Emil W. Ciurczak, DoraMaxx Consulting 03.07.17

    • Analytical Services | Drug Development | Laboratory Testing

      Orphan Drug Development & Production: Turning Lemons into Lemonade

      Forming a “win-win-win” paradigm for large pharma companies, contract service providers and generics
      Emil W. Ciurczak, DoraMaxx Consulting 01.26.17

    • Analytical Services | Bioanalytical Services | Chemistry | Laboratory Testing

      Hyperspectral Imaging

      It’s not just for the Big Boys anymore
      Emil W. Ciurczak, DoraMaxx Consulting 11.09.16

    Trending
    • Lonza To Exit Pharma Softgels And Liquid-Filled Hard Capsules
    • Roche Canada To Invest $500M To Create 500 Jobs In Ontario
    • Grifols Begins COVID-19 Plasma Treatment Trial
    • Fujifilm To Invest $2B In US Manufacturing Site
    • Virtual Clinical Trials: The Future Of Dermatology Studies
    Breaking News
    • Global Biosciences Co. Selects ValGenesis VLMS
    • Eisai Appoints Chief Clinical Officer of Oncology Biz
    • Nexelis Acquires GSK Vax Lab in Marburg
    • Bone Therapeutics, Rigenerand Ink Cell Therapy Deal
    • NovaQuest Private Equity Acquires CoreRx
    View Breaking News >
    CURRENT ISSUE

    November/December 2020

    • Modeling Process Safety Workflows in Pharmaceutical Manufacturing Scale-Up
    • Ensuring Quality During the Transfer and Scale Up of Rx Drugs
    • Inspecting the Unexpected
    • Cold Chain Trends
    • Catering for the Complex
    • Biopharma Contract Manufacturing: Robust Growth Ahead
    • DCAT President Talks COVID-19, Drug Manufacturing and Innovation
    • The Single-Use Mixing Landscape: Evaluating Your Options
    • Self-Medication: Flexibility for Patients and Drug Manufacturers
    • Decentralized Trials Fuel AI Revolution in Clinical Research
    • 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

    Study Highlights Differences Between EPA's and DHA's Effect on Sleep
    BGG Obtains U.S. Patent on AstaZine Natural Astaxanthin for Heart Function During Exercise
    Qualitas Health/iwi Raises $10 Million in Investment Round
    Coatings World

    Latest Breaking News From Coatings World

    IGL Coatings Launches Graphene Reinforced Dual System Ceramic Coating
    Miller Paint Declares Simple Serenity its 2021 Color of the Year
    TAUBMANS Paint by PPG Releases ‘Chromatic Joy’ Palettes
    Medical Product Outsourcing

    Latest Breaking News From Medical Product Outsourcing

    Researchers Successfully ‘Fine Tune’ New Thermoplastic Biomaterial
    RSIP Vision Announces Versatile Medical Image Segmentation Tool
    Vance Street Capital Adds Operating Partner
    Contract Pharma

    Latest Breaking News From Contract Pharma

    Global Biosciences Co. Selects ValGenesis VLMS
    Eisai Appoints Chief Clinical Officer of Oncology Biz
    Nexelis Acquires GSK Vax Lab in Marburg
    Beauty Packaging

    Latest Breaking News From Beauty Packaging

    Top Beauty Brands in the World—And Most Loved Fragrances
    P&G Reports Q2 Results
    A Lacquering Technique Makes Very Good Girl by Carolina Herrera Shine
    Happi

    Latest Breaking News From Happi

    Colonial Chemical Announces New Facility
    Ashland Acquires Schülke & Mayr's Personal Care Business
    FDA Issues New Guidance On Pharmaceutical Alcohol
    Ink World

    Latest Breaking News From Ink World

    Morancé Soudure France Adds Comexi F2 MC 10-color Flexo Press
    THIMM Group Installs 1st Koenig & Bauer CorruFLEX
    Cowan Graphics Adds Fujifilm Inca OnsetX3 HS
    Label & Narrow Web

    Latest Breaking News From Label & Narrow Web

    Domino grows installation and service teams
    ABG keeps pace with demand with recruitment drive
    Acucote expands FSC-certified portfolio
    Nonwovens Industry

    Latest Breaking News From Nonwovens Industry

    First Quality Launches Incognito by Prevail
    Essity Launches Reusable Underwear Product
    Honeywell Delivered 225 Million Masks in December
    Orthopedic Design & Technology

    Latest Breaking News From Orthopedic Design & Technology

    DJO Acquires Trilliant Surgical
    FDA Breakthrough Device Designation Granted to Spiderwort's Spinal Cord Technology
    Bioventus Appoints SVP of Operations
    Printed Electronics Now

    Latest Breaking News From Printed Electronics Now

    UDC Subsidiary Adesis' Website Wins 2020 MarCom Platinum Award
    Roadsimple Modernizes Warehouse Ops with Zebra Technologies
    Graphene Flagship Launches Redesigned Website

    Copyright © 2021 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