• 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
    Hygienic Packaging Technology

    Trends in Solid Oral Dosage Delivery

    5 Reasons Paper Has No Place in Contract Manufacturing

    Injectable Drug Delivery Trends

    Pharmaceutical Manufacturing Equipment Trends
    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
    Iontas and Fair Journey Biologics Partner with Quell Therapeutics

    Vetter Establishes Office in China

    AGC Biologics Expands Cell and Gene Facility in Italy

    Celonic to Boost Cell & Gene Therapy Production

    Pharmaron Acquires Biomanufacturing Site in the UK from AbbVie
    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

    Vetter Establishes Office in China

    AGC Biologics Expands Cell and Gene Facility in Italy

    Celonic to Boost Cell & Gene Therapy Production

    Pharmaron Acquires Biomanufacturing Site in the UK from AbbVie

    Fujifilm Breaks Ground on Major Expansion of Biologics Facility in Denmark
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Reed-Lane Facility Virtual Tour

    Hygienic Packaging Technology

    Reshaping the Pharmaceutical Supply Chain

    Serialization: Level 5 Solution

    Covectra Introduces Next-Gen Serialization Solution
    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

    Vetter Establishes Office in China

    Data Management Trends

    AGC Biologics Expands Cell and Gene Facility in Italy

    Celonic to Boost Cell & Gene Therapy Production

    Pharmaron Acquires Biomanufacturing Site in the UK from AbbVie
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    Guide to Maintaining Validation of Older Facilities: Why, When and How

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

    Top BioPharma Form Accumulus Synergy

    Global Biosciences Co. Selects ValGenesis VLMS

    Gene Therapy Co. Selects ValGenesis' SaaS Platform
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    PCI Pharma Services

    Adare Pharma Solutions

    Syngene

    Reed-Lane

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

    Syngene

    Baxter BioPharma Solutions

    Emergent BioSolutions

    Reed-Lane
    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
    • encapsulation
    • solid dosage forms
    • training
    • facility
    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

    • Chemistry | Laboratory Testing
      Back to the Future

      Back to the Future

      All that’s Old is New Again.
      Emil W. Ciurczak, DoraMaxx Consulting 03.01.21

    • 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

    Trending
    • Four Female Leaders Appointed To Cell & Gene CDMO
    • BMS Expands Cell Therapy Manufacturing Capabilities
    • Reed-Lane Facility Virtual Tour
    Breaking News
    • Jubilant Therapeutics Appoints Chief Scientific Officer
    • Iontas and Fair Journey Biologics Partner with Quell Therapeutics
    • Vetter Establishes Office in China
    • AGC Biologics Expands Cell and Gene Facility in Italy
    • Celonic to Boost Cell & Gene Therapy Production
    View Breaking News >
    CURRENT ISSUE

    March 2021

    • Hygienic Packaging Technology
    • Trends in Solid Oral Dosage Delivery
    • 5 Reasons Paper Has No Place in Contract Manufacturing
    • Injectable Drug Delivery Trends
    • Pharmaceutical Manufacturing Equipment Trends
    • Oral Solids: Market & Technology Trends
    • Nutraceutical Manufacturing: Meeting the Challenges of Today, Planning for Tomorrow
    • 2021 Contract Manufacturing Survey
    • Small Molecule Development Trends
    • Challenges & Opportunities Facing Small & Emerging Biopharma Companies
    • 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

    Thymoquinone Inhibits Viral Infection in In Vitro Settings, New Study Finds
    IFT Transitions 2021 Annual Event to Digital Experience
    NY Federal Judge Enters Permanent Injunction Against Dietary Supplement Manufacturer
    Coatings World

    Latest Breaking News From Coatings World

    Sherwin-Williams Announces Resignation of President, COO
    Ashland Completes Expansion, Relocation of Viatel Bioresorbable Polymers Manufacturing Facility
    Evonik Receives Sustainability Award from EcoVadis
    Medical Product Outsourcing

    Latest Breaking News From Medical Product Outsourcing

    Avacta’s Rapid Antigen Test Proves Effective for New Coronavirus Variants
    Cretex CFO Announces Retirement
    New AI-Based Tool Developed for Coronary Artery Analysis, Intervention Planning
    Contract Pharma

    Latest Breaking News From Contract Pharma

    Jubilant Therapeutics Appoints Chief Scientific Officer
    Iontas and Fair Journey Biologics Partner with Quell Therapeutics
    Vetter Establishes Office in China
    Beauty Packaging

    Latest Breaking News From Beauty Packaging

    e.l.f. Cosmetics and Chipotle Collaborate on Burrito-Inspired Makeup Collection
    Weekly Recap: Sephora Expansion, Ulta Partners with Loop, International Women’s Day & More
    Ulta Beauty Opens in Herald Square
    Happi

    Latest Breaking News From Happi

    Batiste Rolls Out Wonder Woman Dry Shampoo
    Erno Laszlo Taps Carina Lau as Global Spokesperson
    It's International Women's Day
    Ink World

    Latest Breaking News From Ink World

    Massilly North America Adds Koenig & Bauer MetalStar 3 Metal Decorating Press
    Hydrocarbon Solvents Market to Surpass $8.1 Billion by 2030
    Access Direct Mail Doubles Revenue with SCREEN's Truepress Jet520HD
    Label & Narrow Web

    Latest Breaking News From Label & Narrow Web

    Epson reveals new ink for ColorWorks C6000-Series label printers
    VPF launches liner made from recycled paper
    Cartes engineers inkjet embellishment technology
    Nonwovens Industry

    Latest Breaking News From Nonwovens Industry

    Kimberly-Clark Names Chief Research and Development Officer
    FPInnovations Develops Biodegradable Mask
    Sani Professional Sanitizing and Disinfecting Products Approved by EPA
    Orthopedic Design & Technology

    Latest Breaking News From Orthopedic Design & Technology

    Colfax Decides to Divide Its Businesses
    Stryker Corp.'s 2020 Sales Slip 3.6 Percent
    Bioventus Appoints Managing Director, China and Asia Pacific
    Printed Electronics Now

    Latest Breaking News From Printed Electronics Now

    Comercial Kywi Improves Customer Service, Front-Store Operations with Zebra Mobile Solution
    Global Smart Glass Market to Register 6.8% CAGR Between 2021-28: Grand View Research
    Global Printed Circuit Board Market Projected to Reach $69.32 Billion by 2027

    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