• 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
    High Drug Loading Amorphous Solid Dispersions

    Parenteral Drug Delivery Trends

    Selecting the Right Outsourcing Model for Emerging Biotech

    Inhaled Drug Delivery Technology

    The Future of Biologics: Accelerating Production, Reducing Costs
    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
    Altasciences Contributes to Vibegron Approval

    Cyprium, Sentynl Therapeutics Ink Asset Purchase Agreement

    Pfizer Selects Seven Bridges to Support RNA Sequencing Data

    ACG Launches ACG Laboratories

    Glatt and Aprecia Enter 3D-Printing Collaboration
    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

    Why Increasing Solubility May Not Improve Bioavailability - In Vitro Predictions

    ACG Launches ACG Laboratories

    Glatt and Aprecia Enter 3D-Printing Collaboration

    Catalent Acquires Delphi Genetics

    Almac Group Completes $7M R&D Center
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Centrient Pharmaceuticals to Acquire Astral SteriTech

    Seasonal Vaccine Manufacturing

    PwC Joins Medicines Manufacturing Innovation Centre

    AARDEX Group Partners with Pill Connect

    Phillips-Medsize and Subcuject Collaborate
    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

    Altasciences Contributes to Vibegron Approval

    Cyprium, Sentynl Therapeutics Ink Asset Purchase Agreement

    Why Increasing Solubility May Not Improve Bioavailability - In Vitro Predictions

    Pfizer Selects Seven Bridges to Support RNA Sequencing Data

    ACG Launches ACG Laboratories
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    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

    The Year of COVID: How FDA Coped with a Worldwide Pandemic in 2020 and What to Expect in 2021
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    Baxter BioPharma Solutions

    Almac Group

    Alcami

    Emergent BioSolutions

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

    Baxter BioPharma Solutions

    Adare Pharma Solutions

    test company saurabh

    Syngene
    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
    Online Exclusives

    The FDA Gets Stricter with E&L Oversight, Can the Industry Keep Up?

    Andrew Kolbert of Avomeen discusses FDA oversight of E&L testing, complications that arise, and the expertise needed to keep up with changing quality standards

    The FDA Gets Stricter with E&L Oversight, Can the Industry Keep Up?
    Related CONTENT
    • Legacy Pharma Solutions
    • PCI Pharma Services
    • Catalent Pharma Solutions
    • Trial Runners
    • Mogene
    Kristin Brooks, Contract Pharma07.11.19
    In the past, the FDA focused on Extractables & Leachables (E&L) testing in devices and drug products that had both a low administration risk and low packaging risk, such as topical solutions. Over time, the FDA has moved on to focus on higher risk products with high administration risk and high packaging risk, such as inhalers.
     
    The FDA is now beginning to expand its area of focus for E&L testing outside products and devices with high administration and packing risk to include manufacturing components. For example, if a drug needs to travel through a tube during the manufacturing process, that tube needs E&L testing as well. This often falls outside the area of expertise for many companies, and those companies struggle to keep up with the increasing expectations from the FDA.
     
    Contract Pharma spoke with Andrew C. Kolbert, Ph.D., President and Chief Technology Officer of Avomeen about this recent trend and what the industry is doing to keep pace with expectations.  –KB
     
    Contract Pharma: What is the U.S. FDA’s role in overseeing Extractables and Leachables studies?

    Andrew Kolbert: The FDA approves drug products, and extractables and leachables (E&L) testing is part of the expectation for a drug submission. However, the FDA guidance on E&L testing is generally not prescriptive and is open to interpretation as to its implementation. The United States Pharmacopeia (USP) came out with a guidance monograph, USP 1663 and 1664, and previously the Product Quality Research Institute’s (PQRI) has published comprehensive guidelines, which have for years been the defacto guidance for industry.

    Because the FDA’s guidance on these matters is general, they don’t have to change any regulations to decide if and when prior approaches and standards are no longer acceptable. We usually learn about changing standards because clients start coming forward with a finding from the FDA for something the Agency used to not be concerned with.

    Drug products are considered high risk if they have a high packaging risk and a high route of administration risk. The FDA did not previously focus on E&L for oral tablets and capsules because they require a low-risk form of administration and there is low risk of product-packaging contact. Instead, they were focusing on inhaled drugs because there was a high route of administration risk and risk of dosage and packaging interaction. Over time, industry has been performing E&L studies for high-risk products to products and processes that had lower risk. PQRI developed a matrix detailing these levels of risk 20 years ago to aid industry in self regulation.


    Caption: Products are classified into risk categories for two criteria: the degree of concern with how the product is administered and the risk of product-packaging contact. Products such as inhalation aerosols are considered highest-high risk and products such as oral tablets are considered low-low risk. Over the past few decades, the FDA has begun to increase their oversight for E&L studies moving from concern with the most high-risk products to now also focusing on the lower risk products.



    CP: How has the FDA changed their approach to overseeing E&L testing in recent years?

    AK: A few years ago, you would never have thought that the FDA would be worried about the tubing that a drug product travels through, or a stainless-steel holding tank, as material contact is so transient. This has changed as the FDA has evolved to make sure there is no risk to public health. They have worked their way down the matrix so that now they are concerned about manufacturing equipment, which isn’t on this matrix because it wasn’t on the FDA’s radar 20 years ago. This may include gaskets, tubes and hoses that the drug product touches before the packaging. Much of the concern now is with manufacturing equipment for injectables, but we are also seeing them concerned with manufacturing for oral drugs, which has a very low-risk profile.

    It’s hard to say when this trend started. We just gradually start to see findings come from the FDA through our clients. Ten years ago, you would have never seen these findings.
    For example, in 2011 Ortho-McNeil-Janssen Pharmaceuticals, Inc. recalled 40,000 pill bottles because of a manufacturing concern. There were two consumer reports that the product had an “uncharacteristic odor.” They found that some of the wooden pallets used by suppliers were contaminated with TBA (2,4,6 tribromoanisole), a byproduct of a chemical preservative sometimes applied to wood. The drug product in cartons around boxes contacted those pallets, and the analyte went through the cartons, the product boxes, and the bottles like they weren’t even there. The FDA was previously not focused on E&L in warehousing and manufacturing until recently, so cases like this may have happened occasionally even though manufacturing equipment and warehousing materials are at a low risk for E&L issues. Now they are choosing to focus on these to further improve the overall quality and safety of products.

    CP: What complications arise from this increased focus on manufacturing?

    AK: As mentioned above, there is a low but still potential risk of contaminating a drug product with harmful substances obtained through the manufacturing process. But now that the FDA has chosen to focus on this area, you are likely to get a finding from the FDA, and extending the amount of time to market, if you are not performing E&L studies on these manufacturing components.

    Because the FDA is not making public statements every time its focus areas change, someone has to be the first one to receive this type of finding, and often it is the CRO that hears it from the first client. Then word gets around the industry by way of the CRO. When a company receives a finding from the FDA that they need to look at the E&L in manufacturing process, they may come to a CRO and ask for the work to be done in a compressed time frame. They may have to spend even more money to make sure it gets done quickly and correctly.

    CP: How is the industry reacting to this recent trend?

    AK: E&L work in general is much more frequently outsourced than other areas of drug development, as expertise in polymer science and additives is generally not core to their knowledge base.  Consequently, E&L is highly outsourced, and this area is growing in the pharmaceutical CRO space.

    CP: What expertise is required from analytical CROs to keep up with these changing quality standards?

    AK: While pharmaceutical scientists are experts in drug discovery, they are not experts in rubber, plastics, and polymer additives—the core requirements to interpret the results of E&L testing. Pharmaceutical CROs need to have polymer experts on staff in order to provide state-of-the art interpretation of testing as well as a safety assessment.

    Many pharmaceutical companies also don’t have metals analysis laboratories, so are unable to perform E&L on stainless steel holding tanks or transfer lines. This work would generally need to be outsourced, not to mention USP 232/233 testing on raw materials much of which is being outsourced today as well.

    CP: How are you addressing these changes in your lab?

    AK: Many of our employees come from the plastics and polymers industry. We have employees who worked in other industries or people from General Electric with a resin background. We don’t hire exclusively from the traditional pharmaceutical background.

    With this expertise, we have developed a database that includes 300 to 400 plastic additives. We bought every additive that goes into commercially available plastics and performed tests such as high-performance liquid chromatography and gas chromatography-mass spectrometry. This can help our experts quickly identify what they are finding through these E&L studies. This also means we have specialties other companies do not. For example, we can do metals testing in our elemental analysis unit. This type of expertise, not typically found in pharmaceutical companies, is needed to address the increased expectations from the FDA.
     

    Andrew Kolbert, Ph.D., MTM, is the President and Chief Technology Officer at Avomeen Analytical Services. He has 20 years of experience executing and managing analytical and product development programs, both internally and in external organizations.  His expertise is analytical chemistry in highly regulated areas including pharmaceutical development and testing, extractables and leachables studies, food contact migration studies, food additive and food contact notification testing and registration, and pesticide and insecticide testing under FIFRA. He has served as an expert witness to support litigation in the areas of pharmaceutical development and analytical testing. He has participated in FDA pre-notification conferences, FDA site audits, and trained FDA inspectors on analytical technology.
     
    Related Searches
    • Manufacturing
    • tablets
    • fda
    • it
    Suggested For You
    Legacy Pharma Solutions Legacy Pharma Solutions
    PCI Pharma Services PCI Pharma Services
    Catalent Pharma Solutions Catalent Pharma Solutions
    Trial Runners Trial Runners
    Mogene Mogene
    SGS Life Sciences SGS Life Sciences
    Regis Custom Pharma Regis Custom Pharma
    Softweb Solutions Softweb Solutions
    Vetio Animal Health Vetio Animal Health
    Adare Pharma Solutions Adare Pharma Solutions
    FDA Accepts RedHill Biopharma’s NDA for Talicia FDA Accepts RedHill Biopharma’s NDA for Talicia
    Syndax Pharma Gets IND Clearance for Leukemia Treatment Syndax Pharma Gets IND Clearance for Leukemia Treatment
    FDA Approves J&J FDA Approves J&J's DARZALEX in Multiple Myeloma
    Sierra’s Momelotinib Granted FDA Fast Track Designation Sierra’s Momelotinib Granted FDA Fast Track Designation
    The 20th Annual Salary Survey The 20th Annual Salary Survey

    Related Online Exclusives

    • Analytical Services | Laboratory Testing
      Improving Product Profitability

      Improving Product Profitability

      Using PAT/QbD/CM as tools to increase profitability of products.
      Emil Ciurczak, Contributing Editor 01.21.21

    • Analytical Services | Biologics, Proteins, Vaccines | Drug Development | Drug Discovery | Laboratory Testing
      A Shifting Drug Development Landscape Amid COVID-19 Crisis

      A Shifting Drug Development Landscape Amid COVID-19 Crisis

      Responding to demand for challenging assays and custom solutions required for complex molecules, biologics, vaccines and other innovative therapies.
      Kristin Brooks, Contract Pharma 06.22.20

    • Analytical Services | Bio News | Breaking News | Clinical Trials | CRO News | Drug Discovery | Laboratory Testing
      Streamlining the Clinical Process

      Streamlining the Clinical Process

      Richard Young, vice president at Veeva, shares insight on what companies can do to further expedite the clinical process
      07.12.18


    • Bioanalytical Services | Drug Development | Laboratory Testing
      Biologic Sample Management in R&D

      Biologic Sample Management in R&D

      Vyas of PAREXEL discusses the significance of biologic samples, sample management challenges and the regulatory implications
      Kristin Brooks, Managing Editor 02.15.18

    • Analytical Services | Bioanalytical Services | Biosimilars | Drug Development | Drug Discovery | Inspections | Laboratory Testing | Preclinical Outsourcing | QA/QC | Regulatory Affairs | Serialization
      2015 Contracting & Outsourcing Wrap-up

      2015 Contracting & Outsourcing Wrap-up

      A huge success, with another year of record attendance, sold-out exhibit hall, and a great line up of informative sessions
      Kristin Brooks, Contract Pharma 09.30.15

    • Analytical Services | Bioanalytical Services | Bioassay Development | Capsules | Chemistry | Clinical Trials | Drug Development | Excipients | Formulation Development | GMPs/GCPs | Industry News | Inspections | Laboratory Testing | Methods Development | Process Development | Regulatory Affairs | Solid Dosage/Semi-solids | Toxicology

      Molecular Profiles Hosts Bioavailability Event

      Biannual event attracts scientists, executives
      Gil Roth 02.11.14


    • APIs | Capsules | Extractables and Leachables | Facilities | Fill/Finish | GMPs/GCPs | Industry News | Information Technology | Inspections | Laboratory Testing | Lyophilization | Methods Development | Process Development | QA/QC | Regulatory Affairs | Serialization | Supply Chain | Validation

      FDA Publishes Report on GDUFA

      First-year goals met
      Gil Roth 02.05.14

    • APIs | Aseptic Processing | Capsules | Cleaning Validation | Clinical Trial Materials | Clinical Trials | Extractables and Leachables | Facilities | Fill/Finish | Formulation Development | GMPs/GCPs | Industry News | Information Technology | Inspections | Laboratory Testing | Lyophilization | Methods Development | Microbiology | Process Development | QA/QC | Regulatory Affairs | Serialization | Solid Dosage/Semi-solids | Supply Chain | Validation

      European Medicines Agency Reveals New Structure

      EMA reorganizes to cover drugs' lifecycles
      Gil Roth 09.16.13

    • Analytical Services | Bioanalytical Services | Bioassay Development | Chemistry | Laboratory Testing | Microbiology | Preclinical Outsourcing | Toxicology

      WIL Research Acquires Ricerca Lyon

      CEO David Spaight explains geographic, capacity play
      Gil Roth 08.26.13


    • Clinical Trials | CRO News | Drug Discovery | Laboratory Testing | Preclinical Outsourcing | Validation

      CrownBio-PRECOS Acquisition

      Crown Bioscience's president talks about this preclinical play
      Kristin Brooks 08.21.13

    • Analytical Services | Bioanalytical Services | Bioassay Development | Capsules | Cleaning Validation | Extractables and Leachables | Facilities | Fill/Finish | Formulation Development | GMPs/GCPs | Inspections | Laboratory Testing | Lyophilization | Methods Development | Process Development | Process Validation | QA/QC | Solid Dosage/Semi-solids | Toxicology | Validation | Vials

      Manufacturing Equipment Trends

      Industry perspective from suppliers and manufacturers
      Kristin Brooks, Associate Editor 03.07.12

    Trending
    • Century Therapeutics Significantly Expands Capabilities
    • Catalent Acquires Delphi Genetics
    • Sanofi And Translate Bio Expand Vaccine Collaboration
    • RotaChrom Technologies Partners With Cyclolab
    • Inside A Vaccine Trial
    Breaking News
    • Altasciences Contributes to Vibegron Approval
    • Cyprium, Sentynl Therapeutics Ink Asset Purchase Agreement
    • Pfizer Selects Seven Bridges to Support RNA Sequencing Data
    • ACG Launches ACG Laboratories
    • Glatt and Aprecia Enter 3D-Printing Collaboration
    View Breaking News >
    CURRENT ISSUE

    January/February 2021

    • High Drug Loading Amorphous Solid Dispersions
    • Parenteral Drug Delivery Trends
    • Selecting the Right Outsourcing Model for Emerging Biotech
    • Inhaled Drug Delivery Technology
    • The Future of Biologics: Accelerating Production, Reducing Costs
    • Business Intelligence For (and From) the Lab
    • Communicating Your Contracting Priorities to Your Drug Company Customers
    • COVID-19 Impact Report
    • The Year of COVID: How FDA Coped with a Worldwide Pandemic in 2020 and What to Expect in 2021
    • 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

    Clinical Trial Finds Metabolic Benefits for Polyphenols Formula
    JRF Technology Debuts Elderberry Oral Film Strip
    Danone Adds to Plant-Based Portfolio with Acquisition of Follow Your Heart Brand
    Coatings World

    Latest Breaking News From Coatings World

    Hempel Launches Sustainability Framework: Futureproof
    ChemQuest Hires Rich Gibson
    New Increase in Kynar Fluoropolymer Capacities at Arkema's Chinese Site
    Medical Product Outsourcing

    Latest Breaking News From Medical Product Outsourcing

    Terumo to Purchase Predictive Analytics Firm Health Outcomes Sciences
    Abiomed Leader Michael Minogue Named AdvaMed Board Chairman
    TransEnterix Changes Name to Asensus Surgical
    Contract Pharma

    Latest Breaking News From Contract Pharma

    Altasciences Contributes to Vibegron Approval
    Cyprium, Sentynl Therapeutics Ink Asset Purchase Agreement
    Pfizer Selects Seven Bridges to Support RNA Sequencing Data
    Beauty Packaging

    Latest Breaking News From Beauty Packaging

    Madison Reed Raises $52 Million in Financing Round
    The Estée Lauder Companies Closes Becca Cosmetics
    Afro Sheen Launches New Brand Initiatives
    Happi

    Latest Breaking News From Happi

    PBA Opposes House Bill 2325 in West Virginia
    J.R. Watkins Tackles Pain with New Lines
    RB Launches Vanish Miracle
    Ink World

    Latest Breaking News From Ink World

    Etiflex Enters New Markets with Nilpeter FA-22 Installation
    Hydrocarbon Solvents Market to Surpass $8.1 Billion by 2030
    Lowe-Martin Adds 2 KODAK NEXFINITY Digital Presses
    Label & Narrow Web

    Latest Breaking News From Label & Narrow Web

    Eaglewood Technologies debuts new anilox cleaning system
    INX International and VerifyMe sign supply agreement
    Soma partners with DTM Flexo Services
    Nonwovens Industry

    Latest Breaking News From Nonwovens Industry

    H&V Announces Price Increase
    Fiber Bond VE3 Technology Inactivates SARS-CoV-2 in HVAC Filtration Systems
    Citizens Provides $325 Million Senior Credit Facility to Nice-Pak
    Orthopedic Design & Technology

    Latest Breaking News From Orthopedic Design & Technology

    NuVasive Nabs Simplify Medical for $150M
    SeaSpine Begins Limited Launch of WaveForm TA (TLIF Articulating) 3D-Printed Interbody
    Nexus Spine Implants for Use in Spinal Surgeries Become Available
    Printed Electronics Now

    Latest Breaking News From Printed Electronics Now

    Comercial Kywi Improves Customer Service, Front-Store Operations with Zebra Mobile Solution
    Global Printed Circuit Board Market Projected to Reach $69.32 Billion by 2027
    RFID Locks Market to Reach $9.93 Billion by 2027: Allied Market Research

    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