• 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
    Small Innovators & Niche CROs

    Focus on Science

    Rapid and Data Rich Chromatographic Method Development

    Preparing Your Post Pandemic Talent Strategy

    How Modern Near-Infrared Came to Be
    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
    Resilience Acquires Ology Bioservices

    RDIF, Hualan Ink COVID-19 Vaccine Deal

    Kintor, Visum Enter COVID-19 Manufacturing Partnership

    Pfizer, BioNTech Expand COVID-19 Vaccine Agreement with EU

    Evotec Enters Master Service Agreement with Kazia Therapeutics
    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

    Abenza Chooses North Carolina for New Biologics Manufacturing Site

    Catalent Adds Cryogenic Capabilities at Philadelphia Facility

    Recro, Ensysce Expand Development and Manufacturing Partnership

    Metrics Names Stephanie Emory Associate Director of Pharma Development

    Albumedix Completes Commercial-Scale Mfg. Facility Expansion
    Capsules
    Cold Chain Management
    Injectables
    Logistics
    Serialization
    Solid Dosage / Semi-solids
    Supply Chain
    Vials

    Obituary Notice: Russell “Russ” Haines

    Catalent Adds Cryogenic Capabilities at Philadelphia Facility

    Cryoport Acquires Critical Transport Solutions Australia

    PharmParts – This Makes Sense!

    Securing Your API Supply Chain: Three Keys to Success
    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

    Resilience Acquires Ology Bioservices

    RDIF, Hualan Ink COVID-19 Vaccine Deal

    Pfizer, BioNTech Expand COVID-19 Vaccine Agreement with EU

    Evotec Enters Master Service Agreement with Kazia Therapeutics

    Bristol Myers Squibb Expands at Cambridge Crossing
    Filtration & Purification
    GMPs/GCPs
    Inspections
    QA/QC
    Regulatory Affairs
    Validation

    Ensuring Pharma Manufacturing Quality

    What Will Change at FDA for 2021?

    RBQM Comes of Age: COVID as a Catalyst for Change

    Post-Pandemic Regulations

    Enteris BioPharma: Custom Solutions – From Bench to Market
    Companies
    Categories
    Corporate Capabilities
    Add New Company
    Contract Service Directory Companies
    Alcami

    Reed-Lane

    Emergent BioSolutions

    Quotient Sciences

    Baxter BioPharma Solutions
    Companies
    News Releases
    Posters
    Brochures
    Services
    Videos
    Case Study
    White Papers
    Jobs
    Contract Service Directory Companies
    Almac Group

    Baxter BioPharma Solutions

    Adare Pharma 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
    FDA Watch

    Data Integrity: Beyond Electronic Records

    Get your Data Integrity house in order

    Data Integrity: Beyond Electronic Records
    Data Integrity: Beyond Electronic Records
    Figure 1. Example of a Data Map for Testing of a Sample
    Data Integrity: Beyond Electronic Records
    Figure 2. Data Map of the Preparation of Reference Standard Solution
    Tim Rhines, Ph.D., Director, Lachman Consultant Services, Inc.05.05.20
    The global pharmaceutical industry has been grappling with the regulatory agencies’ focus on data integrity for the past several years. Data integrity guidance documents issued by regulatory agencies have resulted in the examination of the lifecycle of data coming from the analytical and microbiological laboratories. For a contract laboratory, reliability and trust in the data delivered to the sponsor are paramount. A contract laboratory cannot afford to be implicated in a breach of data integrity, no matter how small. A breach in data integrity not only impacts the data and standing with regulatory agencies, but also compromises relationships with sponsors, and in turn, the health of the business. The data integrity guidance(s) do not need to be considered an obstacle but a tool to improve the trust in the data. Data integrity is not a new concept: it has been part of science for centuries. However, the technology of today has added complexity to proving that the data is beyond reproach.

    One of the foundational tenets of science that young scientists are introduced to in university studies with respect to data integrity is the consequence of “dry labbing” or falsifying results. Instructors emphasize the importance of accurately recording data by issuing the ultimatum that falsifying laboratory data would be met with immediate failure of the course. As scientists enter the pharmaceutical laboratory work force, the effects of falsifying results become clearer as the impact to patient safety is directly impacted by the laboratory data. In today’s environment, acts that breach data integrity guidance by a laboratory analyst should result in disciplinary action. Each discovered case of data falsification or of an uncontrolled process that could easily allow data falsification, adversely impacts the integrity of the data and degree of trustworthiness in the results from a laboratory.

    The principles that guided the documentation of scientific data in the past, when data was recorded primarily in hardcopy laboratory notebooks, are the same as the ALCOA+ principles used now, there just was no acronym used. These principles and definitions require data to be:1
    • Attributable – Who performed the activity, and when?
    • Legible – Can it be read? Must be human-readable and a permanent record
    • Contemporaneous – Recorded at the time the activity was performed
    • Original – Original record or certified true copy
    • Accurate – Error free
    • Complete – Everything is included, and nothing is missing
    • Consistent – The data should be acquired in a chronological order, with time stamps included for any addition to original data
    • Enduring – Data is on a media that is maintained and protected with an emphasis on ensuring data is readable and available long after it is recorded
    • Available – Records are accessible when needed

    For decades, the documented hardcopy laboratory data in bound notebooks was reviewed, and any discrepancy in the data was easily detectable and could be questioned. However, even with hardcopy data, the validity of the data was directly impacted by the integrity of the bench analyst and laboratory management’s commitment to ensuring the recording of complete and accurate data.

    With the introduction of computerized chromatographic data acquisition systems in 1980s and 1990s, a conundrum was created. Was the printout of the data or the electronic file the raw data? If the raw data was the electronic file, was the electronic file secure from being easily altered? In some systems, the files could be written over, renamed, etc., without any audit trail documenting the action. Subsequently, the integrity assurance of the laboratory data was diminished unless laboratories added configurational or procedural controls over the data acquisition systems.

    Compliance to 21 CFR Part 11 - Electronic Records; Electronic Signatures, has been part of our industry for more than two decades, but data integrity guidances have relatively recently enhanced the control of electronic records. Warning letters that cited data integrity gaps  have emphasized the lack of control of computer systems and associated records. However, the data integrity principles also apply to paper-based records, such as printouts from balances, pH meters, documentation captured on loose forms, and observations written directly into a bound laboratory notebook. While a laboratory can achieve compliance with electronic data record integrity, the job is not complete. Laboratories must find and root out vulnerable data documentation practices beyond electronic records. A useful tool to find areas of vulnerability is data mapping. Data mapping is a type of mapping with an emphasis on the lifecycle of data, considering the following:2
    • Generation and recording of data
    • Processing data into usable information
    • Checking the completeness and accuracy of reported data and processed information
    • Data (or results) being used to make a decision
    • Retaining and retrieval of data which protects it from loss or unauthorized amendment
    • Retiring or disposal of data in a controlled manner at the end of its life
    Figure 1 provides an example of a high-level data map of sample testing, starting with sampling and ending with reporting test results, with a breakdown of one step in the process: sample testing. The map provides the visual assessment of how data is generated, the required supporting records, where data is recorded, and how data is recorded. 


    Figure 1. Example of a Data Map for Testing of a Sample

    Many of the steps/boxes in the sample testing data map can be further detailed to eventually list every document that supports each process. Each of the underlying records must meet ALCOA+ principles. Figure 2 exemplifies how the preparation of the reference standard solution step can be further broken down to list each of the underlying records that support the process of the preparation of the reference standard solution.


    Figure 2. Data Map of the Preparation of Reference Standard Solution

    Each of the supporting records should be assessed to ensure all the records meet the ALCOA+ requirements. For example, the weight data from the balance is commonly printed with the metadata of date, time, and balance ID. However, some older analytical balances allow relatively easy access to the date and time settings which are sent to the printer along with the weight data. In such a case, a procedural control is needed to verify that the time and date was correct when the weight was printed. Similar situations may also be present in other small instruments such as pH meters or Karl Fischer titrators. Integrity of date, time, user, and other metadata can be assured when a laboratory adapts a validated e-notebook system.

    Changes in data lifecycle are inevitable, and when changes are proposed it is important to understand the lifecycle elements for each type of the affected data or record, and ensure controls which are proportionate to data criticality and risk at all stages.2 Data mapping the changes can aid in determining if the change increases the risk on data integrity. For example, in the past the logging of the receipt and use of reference standard may have been recorded on a dedicated form or 3 x 5 card that was kept in a file.

    However, was this document (form or card) tracked? Was the document secure at all times? What is the risk to the products if this document was accidently lost/destroyed? Would an electronic system be better? Not necessarily if the electronic records do not meet the ALCOA+ principles; however, even a bound logbook of the reference standard receipt and use would improve the integrity of the data over a loose form. 

    A new data process may have conveniences over the traditional bound notebook, although if changes are not easily detectable through audit trails, controlled through access control, and accountable to individuals, the new process adversely impacts the integrity of the data. Data mapping would explore these potential shortcomings and allow mitigation to ensure a compliant process.

    Data integrity can impact any stage in the data lifecycle, whether the data is electronic or a hardcopy. Therefore, it is important to understand the lifecycle elements for each type of data or record in terms of criticality and risk. Thoroughly mapping each data acquisition process can be a useful tool to find areas of data integrity risk and a potential risk to products. A map of data acquisition in a laboratory should break down the process so that each step in the map can list out every record supporting each process on the map. Then, each of the records can be assessed individually for the risk to data integrity. 

    References
    1. Pharmaceutical Inspection Convention/Pharmaceutical Inspection Co-operation Scheme. “PIC/S Guidance: Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments”, PI 041-1 (Draft 3), November 30, 2018, available for download from https://picscheme.org/en/publications#selCategory_
    2. European Medicines Agency, “Guidance on good manufacturing practice and good distribution practice: Questions and answers: Data integrity,” August 2016, https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-manufacturing-practice/guidance-good-manufacturing-practice-good-distribution-practice-questions-answers#data-integrity-(new-august-2016)-section


    Tim Rhines, Ph.D., Director,
    Lachman Consultant Services, Inc.

    Timothy Rhines is a director in the science and technology practice at Lachman Consultants. He is a seasoned CMC pharmaceutical/biopharmaceutical professional with more than 27 years directing CMC activities, leading analytical chemistry teams, addressing compliance gaps, compliance department leadership with P&L responsibility, implementing process excellence initiatives, developing pharmaceutical product stability operations, and CMC project management. Dr. Rhines has a strong technical background encompassing both small and large molecules. For more information visit www.lachmanconsultants.com.
    Related Searches
    • Information Technology

    Related FDA Watch

    • Information Technology | Regulatory Affairs
      FDA’s Increased Information Transparency

      FDA’s Increased Information Transparency

      ...
      Ricki A. Chase, Lachman Consultants 03.09.18

    • GMPs/GCPs | Information Technology | Inspections | Regulatory Affairs

      Mobile Medical Apps

      There's an FDA guidance for that
      Kyle Sampson and Allison L. Reschovsky, Hunton & Williams LLP 11.13.13

    • Clinical Trials | GMPs/GCPs | Information Technology | Inspections | Regulatory Affairs

      Physician Payment Transparency

      ...
      Kyle Sampson, Hunton & Williams LLP 06.05.13


    • Fill/Finish | Information Technology | Logistics | Serialization | Supply Chain | Validation

      Ending Pedigrees?

      FDA’s proposal to abolish drug pedigree requirements
      D. Kyle Sampson, J.D., and Brian J. Wesoloski, J.D. 10.11.11

    • GMPs/GCPs | Information Technology | Inspections | Regulatory Affairs

      Are State Aggregate Spend Laws Here To Stay?

      State sunshine laws in a post-federal sunshine law world
      D. Kyle Sampson, J.D. 03.07.11

    Trending
    • Jubilant, Novavax Enter COVID-19 Vaccine Partnership
    • Pfizer, BioNTech Expand COVID-19 Vaccine Agreement With EU
    • Resilience Acquires Ology Bioservices
    • Ensuring Pharma Manufacturing Quality
    • Sartorius Expands In The UK
    Breaking News
    • Resilience Acquires Ology Bioservices
    • RDIF, Hualan Ink COVID-19 Vaccine Deal
    • Kintor, Visum Enter COVID-19 Manufacturing Partnership
    • Pfizer, BioNTech Expand COVID-19 Vaccine Agreement with EU
    • Evotec Enters Master Service Agreement with Kazia Therapeutics
    View Breaking News >
    CURRENT ISSUE

    April 2021

    • Small Innovators & Niche CROs
    • Focus on Science
    • Rapid and Data Rich Chromatographic Method Development
    • Preparing Your Post Pandemic Talent Strategy
    • How Modern Near-Infrared Came to Be
    • Securing Your API Supply Chain: Three Keys to Success
    • 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

    Review Concludes Refined Grains Have a Place in Healthy Eating Patterns
    AstaReal Astaxanthin Ingredient Receives U.S. Patent Approval
    Study on Kemin’s DailyZz Botanical Blend Uncovers Sleep Quality, Next-Day Performance Benefits
    Coatings World

    Latest Breaking News From Coatings World

    SOS '21 Call For Papers
    ICP Acquiring Choice Adhesives
    PPG Brand Olympic Stains Announces 1st Ever 2021 Stain Color of the Year
    Medical Product Outsourcing

    Latest Breaking News From Medical Product Outsourcing

    FDA OKs Canon Medical's One-Beat Spectral Cardiac CT
    NeuroLogica Debuts Next-Generation SmartMSU with OmniTom Elite
    IZI Medical Products Launches Fully Automatic Quick-Core Auto Biopsy System
    Contract Pharma

    Latest Breaking News From Contract Pharma

    Resilience Acquires Ology Bioservices
    RDIF, Hualan Ink COVID-19 Vaccine Deal
    Kintor, Visum Enter COVID-19 Manufacturing Partnership
    Beauty Packaging

    Latest Breaking News From Beauty Packaging

    2021 Perfumed Plume Awards Announces Finalists
    Bésame Cosmetics Unveils Marilyn Monroe Collection
    Procos Opens U.S. Office
    Happi

    Latest Breaking News From Happi

    Hair Luxury Company Expands Availability of Its Vegan Beauty to Walmart Online
    ACI Appoints Director, State Government Affairs
    Jergens Launches Mother’s Day Campaign
    Ink World

    Latest Breaking News From Ink World

    Kumon North America Adds Speedmaster XL 106 from Heidelberg
    SE-DA Invests in Kornit Presto S
    Acrylic Resins Market Worth $21.9 Billion by 2025: MarketsandMarkets
    Label & Narrow Web

    Latest Breaking News From Label & Narrow Web

    Sakata INX and INX International continue sustainability efforts
    TLMI reveals Eugene Singer Award winners at Virtual Spring Summit
    Monadnock Paper Mills joins SGP
    Nonwovens Industry

    Latest Breaking News From Nonwovens Industry

    Andritz to Supply Elliptical Cylinder Pre-Needler in France
    Ahlstrom-Munksjö to be Delisted from Nasdaq Stockholm
    Radienz Living Introduces Sustainable Products
    Orthopedic Design & Technology

    Latest Breaking News From Orthopedic Design & Technology

    AgNovos Healthcare's AGN1 LOEP SV Kit Obtains IDE
    First Surgeries Completed with Globus Medical's CREO ONE Robotic Screw
    BioMagnetic Sciences Names President and CEO
    Printed Electronics Now

    Latest Breaking News From Printed Electronics Now

    SEMI, Center for Automotive Research Collaborate
    Zebra Technologies Introduces New Alliance Track for PartnerConnect Channel Program
    Virtual ASMC 2021 Spotlights Advanced Semiconductor Manufacturing Excellence

    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