• Login
    • Join
  • FOLLOW:
  • Subscribe Free
    • Magazine
    • eNewsletter
    Checkout
    • Magazine
    • News
    • Manufacturing
    • Packaging
    • Development
    • Compliance
    • Top 20
    • Directory
    • Microsites
    • Events
    • More
  • Magazine
  • News
  • Manufacturing
  • Packaging
  • Development
  • Compliance
  • Top 20
  • Directory
  • Microsites
  • Events
  • Current / Back Issue
    Features
    Editorial
    Columns
    Digital Edition
    eNewsletter Archive
    Our Team
    Editorial Guidelines
    Subscribe Now
    Advertise Now
    Top Features
    SARS-CoV-2 R&D: Is It Over?

    Sustainability: A New Threat or Opportunity for CDMOs?

    Advanced Therapy Manufacturing

    Advanced Therapy Packaging Trends

    CEO Spotlight: Darren Head
    Breaking News
    Online Exclusives
    Industry News
    Collaborations & Alliances
    Promotions & Moves
    Trials & Filings
    Financial Reports
    Bio News & Views
    Custom Sourcing News
    Packaging & Tracking
    CRO News
    Live From Shows
    Top News
    Piramal Pharma Solutions New API Plant in Canada Now Online

    MG America Appoints Claudio Radossi as President

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

    Sartorius Expands Manufacturing Site in Tunisia

    BioMoti Partners with Pharma Company to Develop Ovarian Cancer Treatment
    APIs
    Aseptic Processing
    Cleaning Validation
    Clinical Trial Materials
    Cytotoxics and High Potency Manufacturing
    Equipment
    Excipients
    Extractables and Leachables
    Facilities
    Fill/Finish
    Lyophilization
    Parenterals
    Process Development
    Process Validation
    Risk Management
    Scale-up/ Technology Transfer
    Solid Dosage/ Creams/ Ointments

    Piramal Pharma Solutions New API Plant in Canada Now Online

    Selecting a CMO Partner for Sterile Injectable Manufacturing

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

    Grand Opening of Kodiak Sciences’ Bioconjugation Facility

    Vertex Expands Cell and Gene Therapy Footprint
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Selecting a CMO Partner for Sterile Injectable Manufacturing

    Royalty Pharma and Jefferies Invest $111M in ApiJect

    Cryoport Acquires Cell&Co BioServices for €6.2M

    Challenges of Developing Large Volume Drug/Device Combination Products for Parenteral SC Delivery

    Yourway Adds Capacity for Controlled Ambient Storage
    Analytical Services
    Bioanalytical Services
    Bioassay Developement
    Biologics, Proteins, Vaccines
    Biosimilars
    Chemistry
    Clinical Trials
    Drug Delivery
    Drug Development
    Drug Discovery
    Formulation Development
    Information Technology
    Laboratory Testing
    Methods Development
    Microbiology
    Preclinical Outsourcing
    R&D
    Toxicology

    Selecting a CMO Partner for Sterile Injectable Manufacturing

    BioMoti Partners with Pharma Company to Develop Ovarian Cancer Treatment

    WCG Appoints Sam Srivastava CEO

    AffyXell Expands Manufacturing Partnership with GenScript ProBio

    ABL and Odimma Therapeutics Enter Development Agreement
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    FDA Inspection Trends Update

    Phase-Appropriate cGMP Considerations for Cell and Gene Therapy

    Sustainability: A New Threat or Opportunity for CDMOs?

    In Pursuit of Sustainability: How the Biopharma Industry Can Contribute

    Conducting Clinical Trials During the Pandemic: What Did We Learn?
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    IDT Biologika

    Quotient Sciences

    Qosina

    Baxter BioPharma Solutions

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

    Quotient Sciences

    Qosina

    Baxter BioPharma Solutions

    CMC Pharmaceuticals
    Webinars
    Live From Shows
    • Magazine
      • Current / Back Issue
      • Features
      • Editorial
      • Columns
      • Editorial Guidelines
      • Subscribe Now
      • Advertise Now
      • Enewsletter Archive
      • Digital Edition
    • Directory
      • Companies
      • Categories
      • Corporate Capabilities
      • Add Your Company
    • Manufacturing
      • APIs
      • Aseptic Processing
      • Cleaning Validation
      • Clinical Trial Materials
      • Cytotoxics and High Potency Manufacturing
      • Equipment
      • Excipients
      • Extractables and Leachables
      • Facilities
      • Fill/Finish
      • Lyophilization
      • Parenterals
      • Process Development
      • Process Validation
      • Risk Management
      • Scale-up/ Technology Transfer
      • Solid Dosage/ Creams/ Ointments
      • cGMP Manufacture
    • Packaging
      • Capsules
      • Cold Chain Management
      • Injectables
      • Logistics
      • Serialization
      • Solid Dosage / Semi-solids
      • Supply Chain
      • Vials
    • Development
      • Analytical Services
      • Bioanalytical Services
      • Bioassay Developement
      • Biologics, Proteins, Vaccines
      • Biosimilars
      • Chemistry
      • Clinical Trials
      • Drug Delivery
      • Drug Development
      • Drug Discovery
      • Formulation Development
      • Information Technology
      • Laboratory Testing
      • Methods Development
      • Microbiology
      • Preclinical Outsourcing
      • R&D
      • Toxicology
    • Compliance
      • Filtration & Purification
      • GMPs/GCPs
      • Inspections
      • QA/QC
      • Regulatory Affairs
      • Validation
    • Top 25 Pharma & BioPharma
    • Contract Pharma Direct
    • Breaking News
    • Online Exclusives
    • Slideshows
    • Experts Opinions
    • Surveys
      • Outsourcing Survey
      • Salary Survey
    • Glossary
    • Videos
    • White Papers
    • Podcasts
    • Infographics
    • Supplier Microsite
      • Companies
      • News Releases
      • Posters
      • Brochures
      • Services
      • Videos
      • Case Study
      • White Papers
    • Contract Pharma Conference
      • Contract Pharma Conference
      • Speakers
      • Exhibitors
      • Conference Sessions
    • eBook
    • Webinars
    • Events
      • Industry Events
      • Live from Show Events
      • Webinars
    • Classifieds / Job Bank
      • Classifieds
      • Job Bank
    • About Us
      • About Us
      • Contact Us
      • Advertise With Us
      • Privacy Policy
      • Terms of Use
    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
    • SGS Health Science
    • PCI Pharma Services
    • Coriolis Pharma
    • Catalent Pharma Solutions
    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
    • Development
    • Dosage
    • contract pharma
    • CRO
    Suggested For You
    Legacy Pharma Solutions Legacy Pharma Solutions
    SGS Health Science SGS Health Science
    PCI Pharma Services PCI Pharma Services
    Coriolis Pharma Coriolis Pharma
    Catalent Pharma Solutions Catalent Pharma Solutions
    Trial Runners Trial Runners
    Mogene Mogene
    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

    Related Content

    • Legacy Pharma Solutions

      Legacy Pharma Solutions

      ...
      Nathan Bender, Director, Sales & Marketing 12.07.21

    • Chemistry | Extractables and Leachables | Microbiology
      SGS Health Science

      SGS Health Science

      ...
      Jessica Martin, Marketing Director 10.26.21

    • Drug Development
      PCI Pharma Services

      PCI Pharma Services

      ...
      Jessica Kloster, Marketing Manager 10.20.21


    • Coriolis Pharma

      Coriolis Pharma

      ...
      Daniel Weinbuch, Dr. 07.01.21

    • Drug Delivery
      Catalent Pharma Solutions

      Catalent Pharma Solutions

      ...
      Christopher, Director, Global Communications and Marketing 11.25.20

      Trending
      • Catalent Invests $175M To Expand Mfg. Capabilities At Winchester, KY | Contract Pharma
      • Sartorius Expands Manufacturing Site In Tunisia | Contract Pharma
      • Grand Opening Of Kodiak Sciences’ Bioconjugation Facility | Contract Pharma
      • Vertex Expands Cell And Gene Therapy Footprint | Contract Pharma
      • Emergex COVID-19 Vaccine Candidate Successfully Coated Onto Zosano Micro-Needle Patch | Contract Pharma
      Breaking News
      • Piramal Pharma Solutions New API Plant in Canada Now Online
      • MG America Appoints Claudio Radossi as President
      • Catalent Invests $175M to Expand Mfg. Capabilities at Winchester, KY
      • Sartorius Expands Manufacturing Site in Tunisia
      • BioMoti Partners with Pharma Company to Develop Ovarian Cancer Treatment
      View Breaking News >
      CURRENT ISSUE

      May 2022

      • Sustainability and the Biopharma Industry
      • Contract Manufacturing During COVID
      • Orphan Drugs in the United States
      • CEO Spotlight: Peter DeYoung
      • CEO Spotlight: Darren Head
      • Advanced Therapy Packaging Trends
      • Advanced Therapy Manufacturing
      • Sustainability: A New Threat or Opportunity for CDMOs?
      • SARS-CoV-2 R&D

      Cookies help us to provide you with an excellent service. By using our website, you declare yourself in agreement with our use of cookies.
      You can obtain detailed information about the use of cookies on our website by clicking on "More information”.

      • About Us
      • Privacy Policy
      • Terms And Conditions
      • Contact Us

      follow us

      Subscribe
      Nutraceuticals World

      Latest Breaking News From Nutraceuticals World

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

      Latest Breaking News From Coatings World

      Teknos Receives EcoVadis Gold Medal for Sustainability Performance
      AkzoNobel and Partners Team Up to Hack Carbon Reduction Challenges
      Five PPG Facilities in Ohio Recognized for Sustainability, Health, Safety Practices
      Medical Product Outsourcing

      Latest Breaking News From Medical Product Outsourcing

      Iterative Scopes Expands its Senior Leadership Team
      Viz.ai Raises $100 Million in Series D Funding
      FDA Clears Arterys' AI Mapping and Quantification Tools
      Contract Pharma

      Latest Breaking News From Contract Pharma

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

      Latest Breaking News From Beauty Packaging

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

      Latest Breaking News From Happi

      SPF Setting Spray, Lip Contour and Knotless Braids Are Hot Trends: Spate
      Nutrafol Launches Collagen Infusion
      ÄZ Craft Luxury Haircare Products Support All Hairstyles
      Ink World

      Latest Breaking News From Ink World

      Nazdar Celebrates 100 Years with a New Look
      hubergroup Chemicals Exhibits at Paint India for First Time
      Award for Sustainability: Evonik Receives Platinum Rating Again
      Label & Narrow Web

      Latest Breaking News From Label & Narrow Web

      Specialty announces move to new facility
      Mark Andy hosts dealer's open house in Warsaw
      Nazdar celebrates 100th anniversary with refreshed brand identity
      Nonwovens Industry

      Latest Breaking News From Nonwovens Industry

      3M to Expand in Nebraska
      Nicely Offers Nonwoven Slitters, Winders
      'Right' Hygiene Conference to be Held in June
      Orthopedic Design & Technology

      Latest Breaking News From Orthopedic Design & Technology

      FDA Clears Anika Therapeutics' X-Twist Knotless Fixation System
      Paragon 28 Rolls Out TenoTac 2.0 Hammertoe and Soft Tissue Repair
      Cionic Expands Scientific Advisory Board
      Printed Electronics Now

      Latest Breaking News From Printed Electronics Now

      Evonik Launches New Processing Aids for PV Wafer Cutting
      NREL Creates Highest Efficiency 1-Sun Solar Cell
      eMagin Wins People’s Choice Award at Display Week 2022

      Copyright © 2022 Rodman Media. All rights reserved. Use of this constitutes acceptance of our privacy policy The material on this site may not be reproduced, distributed, transmitted, or otherwise used, except with the prior written permission of Rodman Media.

      AD BLOCKER DETECTED

      Our website is made possible by displaying online advertisements to our visitors.
      Please consider supporting us by disabling your ad blocker.


      FREE SUBSCRIPTION Already a subscriber? Login