58. Available from: https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm455345.htm Specifically, the advantages and complications of three major categories of DBMS are compared, see Figure 2. This perspective will clarify the concept of DI, identify its implications for business owners, and the link between data governance and industry best practices. To ensure knowledge retention of the training provided, constant refreshers are needed, be it refresher courses or incentivize maintaining DI with company culture, otherwise, such knowledge might be forgotten if infrequently used [121]. 2018 [homepage on the Internet]. Not only does data integrity compliance safeguard the patient safety, but protects the organization from serious financial consequences of FDA's enforcement action such as facility shutdown, product recalls, import and/or distribution bans, delayed or denied drug approvals, substantial remediation costs, and loss of customers due to a damaged reputation. In the future, the importance of implementing measures and practices that frame the integrity of the collected data through the whole life cycle of a product will increase.
Available from: https://www.pda.org/pda-letter-portal/columns/regulation-snapshot#di-code Guidance in the form of questions are available to help companies find the best DBMS options available for them [75]. color: #00649d;
color: #fff; On the other hand, overly frequent internal audits may inefficiently use the companys manpower. 50. [cited 2020 Sep 15]. April 2016 [homepage on the Internet]. Handbook of research on Strategy Process, 2010. Privett N, Gonsalvez D. The top ten global health supply chain issues: perspectives from the field.
A survey on security issues in Big Data and NoSQL, Advances in Computer Science: an International Journal.
background-image: url(/sites/default/files/assets/images/strategic-plan/strategic-plan-banner1900x400.jpg?v=123); To be compliant, it is essential to gain a deep knowledge and understanding of the most recent Data Integrity related standards, guides, and regulations. [cited 2020 Sep 15]. /* fix file name width */ Gudivada VN, Rao D, Raghavan V. Renaissance in Data Management Systems: SQL, NoSQL, and NewSQL [thesis]. To mitigate part of the cost, a representative could be trained, before training their fellow colleagues, causing a multiplying effect.
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75. To ensure the success of drug manufacturers, there is a need to adopt a holistic view of the business operations that encompasses processes, culture, and technology.3 Furthermore, manufacturers may form associations together, getting group discounts from DI training providers [120]. [cited 2020 Sep 15]. Furthermore, the outsourcing of pharmaceutical manufacturing activities to improve productivity and business efficiency continues unabatedly [20]. Big Data solutions for RDBMS problems a survey, Int J Adv Res Comp Sc Software Eng. Outsourcing trends in biopharmaceutical manufacturing. A database management system (DBMS) stores data [69] and presents them in an understandable format when accessed [112]. In other words, the data quality determines the possibility for companies to guarantee the quality of their products. The audit can be streamlined by tagging relevant items to allow the auditor to quickly sieve them out for scrutiny [132, 133]. Security issues in NoSQL Databases. PharmTech. @media (max-width: 860px) { } 68. Autor D, Kaufman Z, Tetzlaff R, Gribbin M, Dole M, Glover D, et al. Is GMP quality system auditing fundamentally flawed? 69. 11. Also, from Tables 2(a) and 2(b), it is noted that most of the DI violations cited pertain to manual, automatic, mechanical and electronic equipment, which includes failure to calibrate and maintain written records and failure to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in production and control records, laboratory records or other records [31].
Creating excellence.
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Blockchain technology
GAMP 5 guide: compliant GxP computerized systems.
2018. Contact the publisher to obtain permission before redistributing. In short, data must be complete, consistent, and accurate. In the future, blockchain could even be used to supplement guidance documents [106, 107]. 99. Rx-360 Best Practices Quality Agreement Guide. Only when data is reliable can business owners make the best suitable choices for their organizations, improve the quality of their products and contribute to their overall success. It should be maintained to ensure accuracy and consistency over its entire life-cycle.
2005 [homepage on the Internet]. Available from: https://ec.europa.eu/health/documents/eudralex/vol-4_en } Blockchain ICBC 2018: First International Conference, Held as Part of the Services Conference Federation, SCF 2018 Seattle, WA, USA, 25-30 June 2018, Proceedings. display:none; [cited 2020 Sep 15]. 129. .section-about .region--featured-bottom form { Chandrasekhar R. Object Oriented DBMS (OODBMS). .flex.flex-3-col { /* view for ispeak top filter */ Directive 2011/62/EU of The European Parliament and of The Council of 8 June 2011 [homepage on the Internet]. flex-direction: column; Moniruzzaman ABM, Hossain SA. 124. J Intellectual Property Law & Practice. A survey on data quality: classifying poor data. div.js-form-item.form-item.js-form-type-select.form-item-year.js-form-item-year { 2013. Where hybrid approaches are used, appropriate controls for electronic documents, such as templates, forms and master documents, that may be printed, should be available.
A products efficacy, quality and safety can be ensured with reliable and accurate data provided through data integrity.
Agarwal AK, Srivastava A. U.S. 21 Code of Federal Regulations 210, 1978.
Data altered such that it no longer fulfils these criteria is considered as falsified, regardless of it being due to human error or generated deliberately [2, 4]. 2019;37(3):180-4. DiPalma D, Vannest J. Hence, data are known to be falsified to decrease the rejection of manufactured batches, with some companies deleting non-compliant records [3236], or even churning out records without legitimately performing relevant tests to expedite regulatory approval [28, 34]. Medicines and Healthcare products Regulatory Agency. @media (max-width: 860px) { 49. Aalto University; 2016.
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Why pharmaceutical Data Integrity is more important than ever. 21 CFR 212 and 600 regulate specifically radiological [44] and biological pharmaceutical products [45], respectively. Ranbaxy whistleblower reveals how he exposed massive pharmaceutical fraud, CBS This Morning. On the other hand, overly frequent internal audits may inefficiently use the companys manpower. Bernstein D. Todays Tidbit: VoltDB. Consequently, ingraining DI into your processes now will improve the efficiency and productivity of your organization in the future while striving towards high-quality products.
GxP Data Integrity Guidance and Definitions.
2020;9(4):171-82DOI: 10.5639/gabij.2020.0904.028, Author byline as per print journal: Adjunct Associate Professor Sia Chong Hock1, BSc (Pharm), MSc; Vernon Tay1, BSc (Pharm) (Hons); Vimal Sachdeva2, MSc; Associate Professor Chan Lai Wah1, BSc (Pharm) (Hons), PhD. More detailed sessions should be conducted for employees with access to modify processes, systems and records, further explaining their responsibilities [114, 118]. padding: 1.5rem; However, during on-site inspections of the laboratory systems, it has been discovered that data were being falsified on an industrial scale, using a variety of means, such as copy and paste, manipulation of weights, and unauthorized manual integration of chromatograms. 2017;41(7):6-10. ,4
Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co- operation Scheme. There are also guidance that clarify specific portions of the GMP, including PIC/S Good Practices for Computerized Systems in Regulated GxP Environment [55], FDA Standardization of Data and Documentation Practices for Product Tracing Guidance for Industry [56], FDA Contract Manufacturing Arrangements for Drugs: Quality Agreements Guidance for Industry [57], and ICH Q9 Quality Risk Management [58]. Comments having links would not be published. As DI in pharmaceutical manufacturing is strongly associated with GMP, it is important to understand the GMP regulatory framework and its impact on DI.
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display:none; 98. [cited 2020 Sep 15]. 82. Pharmaceutical companies are often under pressure to improve their key performance indicators (KPIs), especially during economic downturns.
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7. Editable Pharmaceutical Documents in MS-Word Format.
2014.
Ready to use SOPs, Protocols, Master Plans, Manuals and more Worldwide Regulatory Updates Where hybrid approaches are used, appropriate controls for electronic documents, such as templates, forms and master documents, that may be printed, should be available. /* style Affiliate/Chapter Officer/Board submission Update form fields */ } 2nd FDA/PQRI Conference on Advancing Product Quality; 5-7 October 2015; North Bethesda, Maryland
border-top: 1px solid #d2d2d2; Although the legislation of different countries generally overlaps [125, 126], individual countries may not accept specific documents that originate from another country, exacerbating DI issues. border-right: 1px solid #d2d2d2; Kumarian Press; 2013. Although more than 90% found this guidance helpful in promoting DI, some remarked that a culture of integrity is required to truly attain DI [62], Incentives, including recognition for companies if no DI issues have been found for a consecutive number of years, could be introduced to encourage companies to follow the guidance. ", New ISPE GAMPB. As audits are limited in duration, meaningful and efficient audits should be conducted [124].
Therefore, DI is essential for reshaping the pharmaceutical industry and triggering significant innovation for ensuring the reliability and trustworthiness of the information. 2016;31:1-6. The WHO, PIC/S and FDA further provide clarification on CAPA to be taken when DI violations are found [9, 59], with PIC/S providing added clarification on outsourced processes and promotion of quality culture [59]. 2015.
Finally, it outlines actionable steps for integrating big data and DI into existing operations and will provide an understanding why the ability to generate value by identifying useful information from digital detritus will be a key indicator of business longevity in the pharmaceutical industry. 87.
39. In the global business environment, advancements in technology and digital platforms are changing how business operations are being carried out. Relational and non-relational database management system Revue Des Droits De lHomme. According to a study by Yang, Sun and Eppler, for any strategy to be implemented successfully, the formulation needs to be of a certain standard, and inter- and intra-department relationships should be cordial [62].
Practical data migration. [cited 2020 Sep 15].
55. 103. 72. 116.
113. 67. Data Integrity Pharmaceutical Training Course, RSSL. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attac hment_data/file/687246/MHRA_GxP_data_integrity_guide_March_edited_Final.p df U.S. 21 Code of Federal Regulations 11, 1997.
Kumar S, Tanwar D, Arora N. The role of regulatory GMP audit in pharmaceutical companies. 94. Available from: https://www.fdanews.com/ext/resources/files/Conference/FIS13Presentations/DIncertiEU-and-US-Joint-Inspections-Data-as-The-Cornerstone-for-The-Future.pdf 12. [cited 2020 Sep 15]. 1994;33:280-99. doi:10.1147/sj.332.0280. 70. padding: 1rem;
Pharma Technol. https://www.ipqpubs.com/wp-content/uploads/2014/04/2013-_-Wockhardt-Limited-7_18_13.pdf CQAs are the characteristics or properties that can harm patients if not properly controlled [, Finally, it must be emphasized that a reliance on periodic audits from the regulator is grossly inadequate to address DI issues. Some guidance documents also help companies to understand the legal requirements. Available from: https://www.researchgate.net/profile/Ron_Snee/publication/282879414_Data_Int egrity_Validation/links/5684106b08aebccc4e0fdadb.pdf Author for correspondence: Adjunct Associate Professor Sia Chong Hock, BSc (Pharm), MSc, Senior Consultant (Audit and Licensing) and Director (Quality .homepage-feature-banners .field-items .field-item:nth-child(2) .banner-text::before {
A lack of synergy and good data management between companies increases the difficulty in standardizing protocols and procedures to assure DI [21], regardless of the legislation and guidance in place [22].
Middle management is noted to be the main drivers for implementation [62], and close collaboration with the top management increases its effectiveness [62]. 80. Data Integrity. These include the Data Integrity and Compliance with cGMP Guidance for Industry from FDA [9], GxP Data Integrity Guidance and Definitions from the UK Medicines and Healthcare products Regulatory Agency (MHRA) [10], and Guidance on Good Data and Record Management Practices from WHO [1], which were published in recent years.
Thus, they may release the product without following internal protocols requiring them to seek approvals from authorized personnel [33], or alter records if given access to the database [35, 39]. Hence, legislation and guidance must be supplemented with other approaches to promote and assure DI at a higher level. Comments shall be published after review. One section specifically provides examples on how DI would be maintained using ALCOA+ as a guide. U.S. Food and Drug Administration. .homepage-feature-banners .field-items .field-item:hover .banner-text:before { } Data should be safe and no one should be allowed to modify, delete or disturb it.
The Drug Data Management Standard of China, as translated by the China Working Group of Rx-360, provides regulations to promote DI [48].
15. Avoid being the Turkey: how big data analytics changes the game of strategy in times of ambiguity and uncertainty. 2007 [homepage on the Internet]. What is Data Integrity training?, Spectroscopy. A review on creation and handling of data in accordance with cGMP requirements in pharmaceuticals. 2018;42(5):6-8. .section-about .region--featured-bottom .form-submit { 132. van Rijmenam M, Erekhinskaya T, Schweitzer J, Williams M-A.
Data integrity is a common issue found during the most of the regulatory audits. /* contact form */ 2018;13:531-3. } Ernst & Young LLP: India; 2015.
Contract Pharma.
ISA Trans. It is a decentralized record of digital events, with validation by the participants occurring before it is recorded [98], making manipulation of previously verified transactions including data entry or movement very hard, and cannot be deleted [99]. These indicators include multiple login attempts and read and write errors [135]. Pharmaceutical News Updates It is also important to emphasize that DI violations are also routinely cited by FDA during inspections of domestic manufacturers as well. British Standards Institution.
Boogaard P, Haag T, Reid C, Rutherford M, Wakeham C. Data Integrity here, large, and not going away, here, large, and not going away. In general, guidance documents encourage voluntary compliance and can be adapted to suit the companys culture and manufacturing processes. The regulatory bodies have published guidance documents. [cited 2020 Sep 15]. padding: 2rem 5rem; Audit trails may be divided into two different types: Data Audit Trail (DAT), which covers the raw data recorded, and System Audit Trails (SAT), which covers the systems in place to maintain DI during documentation.
2017; 50(3):14-5. 2016 [homepage on the Internet]. 2016;6(4):1392-9. For SAT, an approach based on the risks and implications of DI breaches and the Good Automated Manufacturing Practices (GAMP 5) Software Category [, Pharmaceutical and biopharmaceutical manufacturers should validate their computerized systems such that they are fit for their intended purpose, and to ensure that adequate controls are in place to facilitate tracking and detection of deleted or altered data. 2016. Available from: https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm608713.htm
Warning letter. margin: 0; 2013;2:493-8. 2017. } Wentworth S. How will blockchain impact pharma? Ruth A. .homepage-feature-banners .field-items .field-item:nth-child(3) .field-name-field-banner-heading { Wolfgang W, Ludwig H. Part 3: Ensuring data integrity in electronic records. 2015;4:69-72.
12th ed. Data should be retained in the form of true copies, original records and accurate reproductions with credits.
Available from: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM598734.pdf
35.
2018 [homepage on the Internet]. Good practices for data management and integrity in regulated GMP/GDP environments. 2016. U.S. 21 Code of Federal Regulations. PDA J Pharma Sci Technol. 40. 5. Companies can only prove the quality of their products by showing data produced during their production processes.
Available from: http://www.thefdagroup.com/hubfs/Downloads/The_Emergency_Guide_to_FDA_ Warning_Letters_and_FDA_483.pdf } }
} #webform-submission-officer-submission-form-add-form table th { [cited 2020 Sep 15].
/* style Affiliate/Chapter Officer or Headshot Submission Update form fields */ Lopez O. It regulates documentation of various processes such as training of personnel, validation of computerized systems and data management, and CAPA when DI violations are found.
36.
Commission Directive 2003/63/EC. 66. A risk-based approach to Data Integrity. Left unchecked, it can completely seize the engine.
Conoscenti M, Vetro A, Martin JCD. margin-bottom: 15px; 2018. 2015;3(6):119-27. Available from: https://www.tga.gov.au/sites/default/files/manuf-pics-gmp-medicines-part1.pdf It is not easy to analyse the root causes of DI violations as the increasing prevalence of DI issues and efforts to manage them appear to be a recent development [28]. 135. 2017. Edlich S. Choose the Right Database and NewSQL: NoSQL Under Attack, InfoQ. Once a block is added, it is added to all the copies of the verified blockchain across the entire network [101], hence remaining in the system indefinitely.
Burns M. Management of narrow therapeutic index drugs.
Specifically, the advantages and complications of three major categories of DBMS are compared, see, Relational database management systems store data in either a two-dimensional table or a three-dimensional object [, With a wide variety of DBMSchoices currently in the market, adopting one that keeps data ALCOA+ throughout its lifespan would minimize the cost required to maintain it manually [, Blockchain is hypothesized as the next pharmaceutical manufacturing DBMS innovation [, Furthermore, by using blockchain-utilizing smart contracts, DI can be enforced [, However, handling large volumes of information and simultaneous transactions is slow with current blockchain technology [, In general, having a good DBMS promotes DI as it streamlines audits. Watanabe H, Fujimura S, Nakadaira A, Miyazaki Y, Akutsu A, Kishigami JJ. display: block;
[cited 2020 Sep 15].
45.