Presentation on data integrity in Pharmaceutical Industry
Contents:
- Definition & Basics
- Criteria for integrity of laboratory data
- Regulatory Requirements
- Barriers to Complete Data
- Possible data integrity problems
- Previous observations
- FDA Warning Letters – 2013
- FDA Warning Letters – 2014
- FDA 483’s related to data integrity
- EU – Non compliance Reports
- WHO - Notice of Concern
- Summary of Data Integrity issues
- Consequences- Rebuilding Trust
- Conclusion
Data integrity, Pharmaceutical industry, Good Manufacturing Practice, GMP, Guidelines, Data management, DI and GMP Compliance, paper and electronic data, Archive and back up
Trends changed from Non compliance to RR --> Gap to RR --> Data Integrity --> DIB --> Smart Audit & Smart Data.
RR = Regulatory Requirements
DIB = Data Integrity Breach
Take a serious Note for Data Integrity whether you are small or big organization. Your Data is the Heart of your business. Regulatory bodies are highly conscious about such issues. For beginners in this path, my small note can help you a lot.
Data integrity, Pharmaceutical industry, Good Manufacturing Practice, GMP, Guidelines, Data management, DI and GMP Compliance, paper and electronic data, Archive and back up
Trends changed from Non compliance to RR --> Gap to RR --> Data Integrity --> DIB --> Smart Audit & Smart Data.
RR = Regulatory Requirements
DIB = Data Integrity Breach
Take a serious Note for Data Integrity whether you are small or big organization. Your Data is the Heart of your business. Regulatory bodies are highly conscious about such issues. For beginners in this path, my small note can help you a lot.
Data integrity is a Fundamental in a pharmaceutical quality system. It ensures that medicines are of required quality. This presentation is based on MHRA Guidance and provides MHRA expectations. Guidance complements existing EU GMP relating to active substances and dosage forms. This guidance should be d in conjunction with national medicines legislation and the GMP standards published in Eudralex volume 4.
CCK Discussion Forum held at ICCBS, University of Karachi, attended by over hundred of registered experienced pharmaceutical professionals participants belonging from dozen of pharmaceutical manufacturing facilities
www.3-14.com
Source Data expectations for the life sciences industry. Data integrity refers to the completeness, consistency, and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate.
Data Integrity app Link: https://play.google.com/store/apps/details?id=com.innovativeapps.dataintegrity&hl=en
One Step Ahead in Pharma Compliance
Across the internet, there are millions of resources are available which provide information about Computer System Validation.
Refer above Data Integrity app which helps you to understand current regulatory agencies thinking on Data Integrity.
Data integrity is critical throughout the CGMP data life cycle, including in the creation, modification, processing, maintenance, archival, retrieval, transmission, and disposition of data after the record’s retention period ends. It would be helpful for data management.
This presentation describes approaches for software validation used to automate laboratory research procedures, consolidate data collection and analysis and/or run sophisticated QC or manufacturing operations.
Several approaches to software validation exist and may be appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Size and complexity of the software,
Origin of the software (custom vs. off-the-shelf) and
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources can be reduced while meeting regulatory requirements.
Risk assessment for computer system validationBangaluru
A risk assessment is a process to identify potential hazards and analyze what could happen if a hazard occurs.
Computer system validation (sometimes called computer validation or CSV) is the process of documenting that a computer system meets a set of defined system requirements.
Data Integrity in pharmaceutical laboratories is a must, the attached ppt shall help the QC members to understand and develop an integral analytical culture
Data Integrity Issues in Pharmaceutical CompaniesPiyush Tripathi
Data integrity refers to maintaining and assuring the accuracy and consistency of data over its entire life-cycle, and is a critical aspect to the design, implementation and usage of any system which stores, processes, or retrieves data.
Data Integrity II - Chromatography data system (CDS) in PharmaSathish Vemula
- Introduction
- Functions of CDS
- Validation of CDS
- Regulatory requirements
- Procedures required
- Areas for ensuring CDS Data Integrity
- Previous observations
- FDA Warning Letters – 2013
- FDA Warning Letters – 2014
- FDA 483’s related to CDS
- EU – Non compliance Reports
- WHO - Notice of Concern
- How to avoid observations ?
- Conclusion
Data Integrity in a GxP-regulated Environment - Pauwels Consulting AcademyPauwels Consulting
On Tuesday, December 6, 2016, our colleague Angelo Rossi, Senior Regulatory Compliance Consultant, gave an interesting presentation about “Data Integrity in a GxP-regulated Environment” at the Brussels Office of Pauwels Consulting in Diegem.
In his presentation, Angelo covered definitions and concepts of data integrity, the change in regulatory focus, lessons learned from recent FDA warning letters, importants highlights of regulations and guidelines. Angelo also presented a practical example of data integrity for a computerized system.
Please contact us at contact@pauwelsconsulting.com or +32 9 324 70 80 if you have any further questions regarding our consulting services in this area.
Data integrity is a Fundamental in a pharmaceutical quality system. It ensures that medicines are of required quality. This presentation is based on MHRA Guidance and provides MHRA expectations. Guidance complements existing EU GMP relating to active substances and dosage forms. This guidance should be d in conjunction with national medicines legislation and the GMP standards published in Eudralex volume 4.
CCK Discussion Forum held at ICCBS, University of Karachi, attended by over hundred of registered experienced pharmaceutical professionals participants belonging from dozen of pharmaceutical manufacturing facilities
www.3-14.com
Source Data expectations for the life sciences industry. Data integrity refers to the completeness, consistency, and accuracy of data. Complete, consistent, and accurate data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate.
Data Integrity app Link: https://play.google.com/store/apps/details?id=com.innovativeapps.dataintegrity&hl=en
One Step Ahead in Pharma Compliance
Across the internet, there are millions of resources are available which provide information about Computer System Validation.
Refer above Data Integrity app which helps you to understand current regulatory agencies thinking on Data Integrity.
Data integrity is critical throughout the CGMP data life cycle, including in the creation, modification, processing, maintenance, archival, retrieval, transmission, and disposition of data after the record’s retention period ends. It would be helpful for data management.
This presentation describes approaches for software validation used to automate laboratory research procedures, consolidate data collection and analysis and/or run sophisticated QC or manufacturing operations.
Several approaches to software validation exist and may be appropriate for a specific project.
The scope of any validation effort depends upon a number of factors
Size and complexity of the software,
Origin of the software (custom vs. off-the-shelf) and
Whether the functions are critical or non-critical in nature.
By effectively planning the process, validation time and resources can be reduced while meeting regulatory requirements.
Risk assessment for computer system validationBangaluru
A risk assessment is a process to identify potential hazards and analyze what could happen if a hazard occurs.
Computer system validation (sometimes called computer validation or CSV) is the process of documenting that a computer system meets a set of defined system requirements.
Data Integrity in pharmaceutical laboratories is a must, the attached ppt shall help the QC members to understand and develop an integral analytical culture
Data Integrity Issues in Pharmaceutical CompaniesPiyush Tripathi
Data integrity refers to maintaining and assuring the accuracy and consistency of data over its entire life-cycle, and is a critical aspect to the design, implementation and usage of any system which stores, processes, or retrieves data.
Data Integrity II - Chromatography data system (CDS) in PharmaSathish Vemula
- Introduction
- Functions of CDS
- Validation of CDS
- Regulatory requirements
- Procedures required
- Areas for ensuring CDS Data Integrity
- Previous observations
- FDA Warning Letters – 2013
- FDA Warning Letters – 2014
- FDA 483’s related to CDS
- EU – Non compliance Reports
- WHO - Notice of Concern
- How to avoid observations ?
- Conclusion
Data Integrity in a GxP-regulated Environment - Pauwels Consulting AcademyPauwels Consulting
On Tuesday, December 6, 2016, our colleague Angelo Rossi, Senior Regulatory Compliance Consultant, gave an interesting presentation about “Data Integrity in a GxP-regulated Environment” at the Brussels Office of Pauwels Consulting in Diegem.
In his presentation, Angelo covered definitions and concepts of data integrity, the change in regulatory focus, lessons learned from recent FDA warning letters, importants highlights of regulations and guidelines. Angelo also presented a practical example of data integrity for a computerized system.
Please contact us at contact@pauwelsconsulting.com or +32 9 324 70 80 if you have any further questions regarding our consulting services in this area.
TGA presentation: Data Integrity - an international regulatory perspectiveTGA Australia
An exploration of the topic of Data Integrity including consequences of international regulatory collaboration on the subject, highlights of recent overseas and international guidance documents, as well as common misconceptions.
Quick Overview: Pharmaceutical Data IntegrityPeter Dellva
Brief overview of the most important aspects of pharmaceutical data integrity. Slideshare includes pharmaceutical and biopharmaceutical industry key resources.
An brief introduction to the clinical data management process is described in this slides. These slides provides you the information regarding the data evaluation in the clinical trials , edit checks and data review finally data locking,then the data is submitted to the concerned regulatory body.
Process and Regulated Processes Software Validation ElementsArta Doci
Medical device manufacturers operate in a competitive marketplace with increasing end-user demands for features and usability and in a highly regulated environment.
Regulatory bodies look for evidence that medical devices are developed under a structured, quality-oriented development process. By following software validation and verification best practices, one can not only increase the likelihood that they will meet their compliance goals, they can also enhance developer productivity.
Study start up activities in clinical data managementsoumyapottola
Study start-up (SSU) is so much more than a one-time document management exercise. It’s a global, strategic operation that can get new drugs approved faster – and it’s ripe for innovation – from Site Selection to Site Activation and Site Training.
Many SSU tech solutions deployed by sponsors don’t deliver the results promised because they add burden without benefits to clinical research sites. The result? Site staff simply avoid using them.
When that happens, document exchange and tracking falls back to paper, email and Excel formats – with CRAs holding the processes together. The tools that were supposed to solve a problem become part of the problem – and consume preThe implementation and conduct of a study can be a complex process that involves a
team from various disciplines and multiple steps that are dependent on one another. This
document offers guidance for navigating the study start-up processcious clinical trial budget.
A successful clinical study start-up is a crucial first step and an important factor for the overall success of the trial. For this reason, SCRO has experienced study start-up teams, offering customized services depending on your needs, whether it be fuWhile the definition varies across companies, study startup typically includes the process of identifying and qualifying sites, collecting essential documents at the study and site level, and submitting these documents for ethics approval. Successful study startup requires coordination between sites, sponsors, and contract research organizations (CROs) to achieve critical milestones in a compliant manner.ll-service or single activities.
How to achieve better time management in EDC start up
Clinical data management requires strict time management processes, especially in study start up within an electronic data capture (EDC) system. Three steps that clinical data management teams can take to outline the planning and executing of each task that needs to be considered are as follows:
Make a List: Create a daily or weekly task list and schedule when each task will be completed. This strategy will assist you in maintaining focus and staying organized.
Set realist goals: Be realistic about what you can finish in the amount of time you have. When setting unrealistic goals, failure is almost certain to follow.
Explore time-saving techniques: Examples of techniques that could help save time include grouping similar tasks together or using a timer to stay focused.
To help get started, here is a list of EDC considerations for Study Start-Up deadlines:
Protocol finalization and study enrollment
Split go-live considerations
eCRF Specification meetings (this will ensure proper collaboration and minimize any back-and-forth communication)
EDC add-on modules (which will be required and need validation?)
ePRO/eCOA used with licensed questionnaires.
IRB requirements for add-on modules (eConsent/ePRO)
Clinical Data Management Plan_Katalyst HLSKatalyst HLS
Introduction to Data Management Plan in Clinical Data Management in Clinical Trials of Pharmaceuticals, Bio-Pharmaceuticals, Medical Devices, Cosmeceuticals and Foods.
Looking for expertise or support on Data Integrity? Contact us today.
Recently, the pharmaceutical industry has been challenged with the regulatory requirements to provide complete, consistent and accurate data, throughout all GMP regulated processes.
Moreover, during audits the regulatory bodies have observed a level of inconsistency in the application of the predicate rules in GMP processes. This has become a growing concern and has led to a set of new (draft) guidances from different market authorities.
Index:
Data Integrity – Why / What
Data life cycle
Core Data Integrity concepts & building blocks
Short & mid-term actions enabling a focused road to compliance
Providing SharePoint Solutions in an FDA Regulated EnvironmentDeb Walther
This talk explains to the IT Professional the reasons behind the FDA regulations and what must be considered when implementing SharePoint in a GxP environment.
Data integrity is assuming greater importance in current Good Manufacturing Practices in FDA regulated industry with increased emphasis by other regulatory agencies like the EMA. Data integrity and security infractions are not only 21 Code of Federal Regulations (CFR) Part 11 issues but also severe CGMP violations. As FDA increases its focus on data integrity and reliability, inspectors are examining data based on multiple regulations and standards including CGMP, Good Laboratory Practices (GLP), Good Clinical Practices (GCP) and the Application Integrity Policy (AIP) in addition to FDA-recognized consensus standards.
This presentation discusses data integrity regulations and enforcement trends that have led to increased scrutiny of pharmaceutical laboratories by inspectors.
Presentation: Data Integrity – an international regulatory perspectiveTGA Australia
This presentation will provide an overview of the international regulatory perspective on data integrity and discuss some of the key points highlighted in recently released guidance documents from across the globe.
Similar to Presentation on data integrity in Pharmaceutical Industry (20)
Pharma Uptoday Monthly Magazine Volume 22; Issue Jan 2016Sathish Vemula
To recap the previous month's pharma highlights, Monthly magazine Volume 22 has been released with the following content.
News Uptoday
New Guidance
Audit Findings
Warning Letters
- Warning letter: Sun Pharmaceutical Industries Ltd.
- Warning letter: One Way Drug, LLC
- Warning letter: Thomas S. Tooma, M.D.
EU Non Compliance Report
- Non Compliance Report: Iason Italia SRL, Italy
- Non Compliance Report: AstraZeneca Pharma India Ltd., India
Regulations of the Month
- Sec. 211.48 Plumbing (b)
- Sec. 211.50 Sewage and refuse
- Sec. 211.52 Washing and toilet facilities
- Sec. 211.56 Sanitation (a)
Pharma Uptoday Monthly Magazine Volume 21; Issue Dec 2015Sathish Vemula
News Uptoday
New Guidance
Audit Findings
- Diabetes Corporation of America
- Pine Pharmaceuticals
Warning Letters
- Warning letter: American Family Pharmacy
- Warning letter: Dr. Reddy's Laboratories Limited
- Warning letter: Sandoz Private Limited
Article of the Month
- Data Integrity Checklist related to Electronic Records and Electronic Signatures.
Regulations of the Month
- Sec. 211.46 Ventilation, air filtration, air heating and cooling
- Sec. 211.48 Plumbing
Top 20 observation series # 7 21 CFR 211.42 (Subpart C-Buildings and Facili...Sathish Vemula
- US FDA inspectional observations - 2014- List of “Top 20 – CFR parts to know”- Sec. 21 CFR 211.42- 483 observations- Warning Letters- Other Guidance- How to avoid observations related to 21 CFR 211.42 ?
To recap the previous month's pharma highlights to members, Monthly magazine Volume 20 has been released with the following content.
News Uptoday
New Guidance
Audit Findings
- Pernix Receives Form 483 for cGMP Violations
- FDA Hits Pfizer Subsidiary With Second Form 483 in Five Years
- Galena Hit With 10-Item Form 483 Over Unresolved Issues
Warning Letters
- Warning letter: Unimark Remedies Ltd., Mumbai, India
- Warning letter: SSM Health Care St. Louis DBA SSM St. Clare Health Center
Health Canada Non Compliance Report
- Non Compliance Report: Unilever Canada Inc.
EMA Non-Compliance Report
- GlaxoSmithKline (Tianjin) Company Limited (Teda), China
- CARGILL FRANCE
Regulations of the Month
- Sec. 211.42 Design and construction features (c)(5) to (c)(10)
- Sec. 211.44 Lighting
To recap the previous month's pharma highlights, Monthly magazine Volume 19 has been released with the following content.
News Uptoday
New Guidance
Audit Findings
483 Observations (Millers of Wyckoff, Inc., NJ, - Producer of Sterile Drugs & InvaGen Pharmaceuticals, Inc., NY
Warning Letters (Pan Drugs Ltd., India & Jaychem Industries Ltd, New Zealand)
Health Canada Non Compliance Report (MS Pharma, Inc, Canada.)
WHO Notice of Concern (NOC)Report (Svizera Labs Private Limited, India)
Article of the Month - Warning Signs of a Weak Quality Culture
Regulations of the Month - Sec. 211.42 Design and construction features (c)(1) to (c)(4)
To recap the August 2015 month's pharma highlights to Pharma Uptoday members, Monthly magazine Volume 18 has been released with the following content.
News Uptoday
New Guidance
Audit Findings
483 Observations
- 483 of PharMEDium Services, LLC (Outsourcing facility)
- 483 of "Walgreens Home Care, Inc. dba Walgreens Infusion Services
EU Non Compliance Report
- EU Non-Compliance Report: TXCELL - BESANCON, France Warning Letters
- Warning letter : Sipra Labs Limited, Hyderabad
- Warning letter : Mylan Laboratories Limited, India
Health Canada Non Compliance Report
- Procter & Gamble Inc., Canada.
Regulations of the Month
- Sec. 211.28 Personnel responsibilities (b) & (c)
- Sec. 211.42 Design and construction features (a) & (b)
To recap the previous month's pharma highlights to Pharma Uptoday followers, Monthly magazine Volume 17 has been released with the following content.
News Uptoday
New Guidance
Audit Findings
483 Observations
EU Non Compliance Report
- INTEGRA LIFE SCIENCES CORP, United States
- JINAN JINDA PHARMACEUTICAL CHEMISTRY CO., LTD., China
- WUXI JIDA PHARMACEUTICAL CO., LTD, China
- PARABOLIC DRUGS LIMITED, India
Warning Letters
- Mahendra Chemicals, India
Regulations of the Month
- Sec. 211.25 Personnel qualifications
- Sec. 211.28 Personnel responsibilities
News Uptoday
New Guidance
Audit Findings
483 Observations
EU Non Compliance Report
- Polydrug Laboratories PVT. LTD., Ambernath, Maharashtra, India
- ZHUHAI UNITED LABORATORIES CO., LTD, China
Health Canada Non Compliance Report
- Pharmax Limited, Ontario Canada.
Warning Letters
- VUAB Pharma a.s., Czech Republic
- Attix Pharmaceuticals, Canada
Regulations of the Month
- Sec. 211.22 Responsibilities of quality control unit
Top 20 observation series # 6 21 CFR 211.165 - Testing and release for dist...Sathish Vemula
- 2014 inspectional observations- List of Top observations in 2014- Sec. 21 CFR 211.165- 483 observations- Warning Letters- Other Guidance- How to avoid observations
Subpart I--Laboratory ControlsSec. 211.165 Testing and release for distribution. 21 CFR 211.165(a), (b) , (c) , (d) , (e) &(f)
Top 20 observation series # 5 21 CFR 211.100Sathish Vemula
- 2014 inspectional observations
- List of Top observations in 2014
- Sec. 21 CFR 211.100
- 483 observations
- Warning Letters
- Other Guidance
- How to avoid observations
Top 20 observation series # 4 : 21 CFR 211.67Sathish Vemula
- 2014 inspectional observations
- List of Top observations in 2014
- Sec. 21 CFR 211.67
- 483 observations
- Warning Letters
- Other Guidance
- How to avoid observations
Top 20 observation series # 3 21 CFR 211.192Sathish Vemula
- 2014 inspectional observations
- List of Top observations in 2014
- Sec. 21 CFR 211.192
- 483 observations
- Warning Letters
- Other Guidance
- How to avoid observations
- Batch Record Review - Investigations
Top 20 observation series 2: 21 CFR 211.22Sathish Vemula
- 2014 inspectional observations- List of Top observations in 2014- Sec. 21 CFR 211.22 (a) 21 CFR 211.22 (b) 21 CFR 211.22 (c) 21 CFR 211.22 (d) - 483 observations- Warning Letters- Other Guidance- How to avoid observations
Pharma Uptoday Monthly Magazine Volume 12; Issue Mar 2015Sathish Vemula
To recap the previous month's pharma highlights to Pharma Uptoday members, Monthly magazine Volume 12 has been released with the following content.
News Uptoday
New Guidance
Audit Findings
483 Observations
- India's Lupin says FDA raises concerns over plant at Pithampur
Warning Letters
- Micro Labs Limited, Bangalore
- Apotex Research Private Limited
- Oregon Compounding Centers, Inc. dba Creative Compounds
- Cantrell Drug Company
- Warning Letters on Data Integrity: What does the FDA expect from Third Party Auditors and Consultants?
Regulations of the Month
- § 211.194 Laboratory records (a)(5)(6)(7)(8) & (b)
Top 20 observation series 1 21 CFR 211.160Sathish Vemula
The module Consult Yourself.... “Know Regulation - No Observation” deals with most common (top 20) basic CFR regulations having frequent violations and previous observations for better understanding.
#1 dealing with Regulation "21 CFR 211.160 " enclosed with the following content
- 2014 inspectional observations
- List of Top observations in 2014
- Sec. 211.160 General requirements.
21 CFR 211.160 (a)
21 CFR 211.160 (b)
- 483 observations
- Warning Letters
- Other Guidance
- How to avoid observations
- Message from Experts
3 News Uptoday
35 New Guidance
42 Audit Findings
483 Observations
- Top Drug 483 Observations
46 EMA Non-Compliance Reports
- Wockhardt Limited, Aurangabad
- AGEPHA, Austria
- North China Pharmaceutical Group Semisyntech Co., Ltd, China
48 Regulations of the Month
- § 211.188 Batch production and control records
- § 211.192 Production record review
- § 211.194 Laboratory records.
To recap the previous month's (Dec- 2014) pharma highlights to Pharma Uptoday members, Monthly magazine Volume 10 has been released with the following content.
3 News Uptoday
24 New Guidance
34 Audit Findings
483 Observations
- Teva Parenteral Medicines Inc (Jul-2009)
- Hovione API facility in Portugal
- Impax Hit With Another FDA 483
38 Warning Letters
- Novacyl Wuxi Pharmaceutical Co., Ltd.
40 EMA Non-Compliance Reports
- Medreich Limited – Unit V
- Sri Krishna Pharmaceuticals Ltd., Hyderabad, India
43 Regulations of the Month
§ 211.188 Batch production and control records
3 News Uptoday
22 New Guidance
28 Audit Findings
483 Observations
- Caraco Pharmaceutical Laboratories
- Hospira Inc
- Novartis Consumer Health
- McNeil Consumer Healthcare
Warning Letters
- Hikma Farmaceutica, (Portugal) S.A.
- Cadila Pharmaceuticals Limited
- Sharp Global Limited
- Wells Pharmacy Network LLC
EMA Non-Compliance Reports
- Taishan City Chemical Pharmaceutical Co. Ltd., China
- Zhejiang Apeloa Kangyu Bio-Pharmaceutical Co. Ltd., China
- MANUEL RIESGO S.A., Spain
- Ranbaxy Laboratories Limited, Dewas, India
36 Regulations of the Month
§ 211.186 Master production and control records
§ 211.188 Batch production and control records
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
QA Paediatric dentistry department, Hospital Melaka 2020Azreen Aj
QA study - To improve the 6th monthly recall rate post-comprehensive dental treatment under general anaesthesia in paediatric dentistry department, Hospital Melaka
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
We understand the unique challenges pickleball players face and are committed to helping you stay healthy and active. In this presentation, we’ll explore the three most common pickleball injuries and provide strategies for prevention and treatment.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
2. - Definition & Basics
- Criteria for integrity of laboratory data
- Regulatory Requirements
- Barriers to Complete Data
- Possible data integrity problems
- Previous observations
- FDA Warning Letters – 2013
- FDA Warning Letters – 2014
- FDA 483’s related to data integrity
- EU – Non compliance Reports
- WHO - Notice of Concern
- Summary of Data Integrity issues
- Consequences
- Rebuilding Trust
- Conclusion
pharmauptoday@gmail.com
Contents
3. Definition of Data Integrity
• Integrity as being the quality or condition of being whole or undivided;
completeness.
• In the context of laboratory data integrity within a GMP environment, this can be
defined as…
―generating, transforming, maintaining and assuring the accuracy, completeness
and consistency of data over its entire life cycle in compliance with applicable
regulations.‖
4. Why is Data Integrity Important?
• Undermines the safety and efficacy and/or assurance of quality of the drugs that
consumers will take.
• Data integrity problems break trust.
• We rely largely on trusting the firm to do the right thing when no one is seeing.
5. Data Integrity – What Regulators See
• Not recording activities contemporaneously
• Backdating
• Fabricating data
• Copying existing data as new data
• Re-running samples
• Discarding data
• Releasing failing product
• Testing into compliance
• Not saving electronic or hard copy data
6. Criteria for integrity of laboratory data
• Attributable — who acquired the data or performed an action and when?
• Legible — can you read the data and any laboratory notebook entries?
• Contemporaneous — documented at the time of the activity
• Original — written printout or observation or a certified copy thereof
• Accurate — no errors or editing without documented amendments
• Complete — all data including any repeat or reanalysis performed on the sample
• Consistent — all elements of the analysis, such as the sequence of events, follow on and are dated
or time stamped in expected sequence
• Enduring — not recorded on the back of envelopes, cigarette packets, Post-it notes or the sleeves of
a laboratory coat, but in laboratory note books and / or electronic media in the CDS or LIMS
• Available — for review and audit or inspection over the lifetime of the record
Analytical scientists need to understand these criteria and apply them in their respective analytical
methods.
8. GMP Regulatory Requirements for Data Integrity
Derived from the laboratory data integrity definition and the applicable 21 CFR 211 GMP regulations there
are some of the following points:
• Instruments must be qualified and fit for purpose [§211.160(b), §211.63]
• Software must be validated [§211.63]
• Any calculations used must be verified [§211.68(b)]
• Data generated in an analysis must be backed up [§211.68(b)]
• Reagents and reference solutions are prepared correctly with appropriate records [§211.194(c)]
• Methods used must be documented and approved [§211.160(a)]
• Methods must be verified under actual conditions of use [§211.194(a)(2)]
• Data generated and transformed must meet the criterion of scientific soundness [§211.160(a)]
• Test data must be accurate and complete and follow procedures [§211.194(a)]
• Data and the reportable value must be checked by a second individual to ensure accuracy,
completeness and conformance with procedures [§211.194(a)(8)]
9. US FDA Regulatory Requirements for Data Integrity
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
10. US FDA Regulatory Requirements for Data Integrity
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=11
11. FDA Regulatory Requirements for Data Integrity
Reference: http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm073837.htm
12. FDA Regulatory Requirements for Data Integrity
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
13. FDA Regulatory Requirements for Data Integrity
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
14. European Council Regulatory Requirements
Reference: ec.europa.eu/health/files/eudralex/vol-4/annex11_01-2011_en.pdf
15. European Council Regulatory Requirements
Reference: http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000027.jsp#section9
16. MHRA Regulatory Requirements for Data Integrity
Reference:
http://www.mhra.gov.uk/Howweregulate/Medicines/Inspectionandstandards/GoodManufacturingPractice/News/CON355490
19. MHRA Regulatory Requirements for Data Integrity
Designing systems to assure data quality and integrity
Systems should be designed in a way that encourages compliance with the principles of data
integrity. Examples include:
• Access to clocks for recording timed events
• Accessibility of batch records at locations where activities take place so that ad hoc data recording
and later transcription to official records is not necessary
• Control over blank paper templates for data recording
• User access rights which prevent (or audit trail) data amendments
• Automated data capture or printers attached to equipment such as balances
• Proximity of printers to relevant activities
• Access to sampling points (e.g. for water systems)
• Access to raw data for staff performing data checking activities.
21. Health Canada – Letter to stakeholders
Reference: http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/docs/notice-avis-ltr-obligations-eng.php
22. Health Canada – Letter to stakeholders
Reference: http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/docs/notice-avis-ltr-obligations-eng.php
23. Application Integrity Policy (AIP)
• The Application Integrity Policy is what FDA pulls up when it has questions about a
manufacturer’s electronic data.
• Electronic information includes everything, such as emails, adverse events reports,
complaints, batch records, and quality control records—everything that’s stored
electronically.
Reference: http://www.fda.gov/downloads/ICECI/EnforcementActions/ApplicationIntegrityPolicy/ucm072631.pdf
24. Barriers to Complete Data
However, data integrity and the lack of complete data over the record retention period can be
compromised in a number of ways, such as:
• Human errors
when data is entered by mistake (an uncorrected fat finger moment),
stupidity (not being aware of regulatory requirements or poor training) or
willfully (falsification or fraud with the intent to deceive)
• Selection of good or passing results to the exclusion of those that are poor or failing
• Unauthorized changes to data made post-acquisition
• Errors that occur when data is transmitted from one computer to another
• Changes to data through software bugs or malware of which the user is not aware
• Hardware malfunctions, such as disk crashes
• Changes in technology, where one item is replaced when it becomes obsolete or no longer
supported, making old records unreadable or inaccessible.
25. Possible data integrity problems
According to the FDA, the following are possible data integrity problems in the laboratory
that have been observed in the past:
• Alteration of raw, original data and records (e.g., the use of correction fluid)
• Multiple analyses of assay with the same sample without adequate justification
• Manipulation of a poorly defined analytical procedure and associated data analysis in
order to obtain passing results
• Backdating stability test results to meet the required commitments
• Creating acceptable test results without performing the test
• Using test results from previous batches to substitute testing for another batch
28. Failure to record all quality activities at the time they are performed.
a. On October 26, 2012, the investigator noticed that during an inspection of the packaging area
for (b)(4) #(b)(4) a production employee had recorded the final packed quantity of the batch in
Step (b)(4), even though the quantity was not yet known because the operator had not yet weighed
the batch.
Immediately after observing the incident, the investigator requested a copy of page 6 of the batch record
containing Step (b)(4) and was given a photocopy. A full batch record provided later that day did not
include the original page 6. Instead it included a new version of page 6.
b. The investigator observed at least two examples when a manufacturing step was recorded in the
batch record before it occurred:
i. The production operator had already recorded the start time for step (b)(4) for (b)(4) #(b)(4) as 12:15
PM on October 26, 2012, although it was still 11:00 AM when our investigator noticed this situation.
ii. For the (b)(4) # (b)(4), at approximately 11:00 AM on the same date, a production officer had already
recorded (b)(4) of (b)(4) used for (b)(4) the API (b)(4) in the (b)(4) at step (b)(4) in the batch production
record, although the (b)(4) step had not yet occurred. The (b)(4) had not been pre-weighed or otherwise
measured out in advance.
Reference : WL: 320-13-22 / Aarti Drugs Limited 7/30/13
29. Failure to record all quality activities at the time they are performed.
c. On October 27, 2012, our investigator noticed that a QC analyst was performing a Loss on Drying
(LOD) analysis for (b)(4) Lot # (b)(4) and had recorded the completion time as "(b)(4)" and total time
as "(b)(4)" in the usage log book for the LOD oven usage logbook although the step was not yet
completed.
d. The investigator observed that a QC analyst had recorded completion times of laboratory analyses
that had not yet occurred. Specifically, a Loss on Drying (LOD) analysis was performed for (b)(4) Lot
#(b)(4) and (b)(4) Lot #(b)(4) at approximately 10:55 AM.
The investigator noted that the analyst had already recorded the completion time as "(b)(4)" for
two (b)(4) samples and "(b)(4)" for one (b)(4)sample although the step was not yet completed.
Our investigator asked the analyst why he recorded the completion time for each of the three
samples if the step was still in progress.
The analyst did not offer an explanation. Moreover, our investigator also found that weights for these
three samples were recorded on blank pieces of paper and not directly onto the test data sheets.
Reference : WL: 320-13-22 / Aarti Drugs Limited 7/30/13
30. Failure to maintain laboratory control records with complete data derived from all
tests conducted to ensure compliance with established specifications and
standards, including examinations and assays..
b. The inspection at this facility documented that there is no raw data for the related
substance preparation of (b)(4) testing for lots (b)(4) of (b)(4) USP and there is no raw
data for the standard and sample preparation for the residual solvent testing of the same
lots.
When weighing samples, reagents, and other laboratory materials, QC analysts write weight
values on small pieces of paper, transcribe the values onto the analytical worksheets, and
then destroy the original paper on which the weights are written.
This was reported to be a normal practice within the laboratory. Our investigator also
observed the practice of writing the weight values for samples on a small piece of paper
and not on the analytical worksheet. This is an inappropriate documentation practice.
Reference : WL: 320-13-22 / Aarti Drugs Limited 7/30/13
31. We observed and documented practices during the inspection that kept some
samples, data and results outside of the local systems for assessing quality. This
raises serious concerns regarding the integrity and reliability of the data generated.
For example,
a. Our review of the Chromeleon and Empower II software found that your firm was testing
samples unofficially, and not reporting all results obtained. Specifically, ―test,‖ ―trial‖ and
―demo‖ injections of intermediate and final API samples were performed, prior to performing
the tests that would be reported as the final QC results.
b. Out-of-specification or undesirable results were ignored and not investigated.
c. Samples were retested without a record of the reason for the retest or an
investigation. Only passing results were considered valid, and were used to release
batches of APIs intended for US distribution.
d. Unacceptable practices in the management of electronic data were also noted. The
management of electronic data permitted unauthorized changes, as digital computer
folders and files could be easily altered or deleted.
Reference : WL: 320-13-20 / Fresenius Kabi Oncology Ltd 7/1/13
32. Failure to follow and document quality-related activities at the time they are
performed.
• During this inspection, your QC Chemist admitted that, under the direction of a senior colleague, he
had recorded false visual examination data in the logbooks for reserve samples. This QC Chemist
was responsible for multiple entries in the (b)(4) API logbooks.
• Your firm’s failure to prevent, detect, and rectify the falsification of your GMP documentation is
concerning. In response to this letter, describe your investigation into this misconduct and clearly
explain how you determined the extent of the data falsification. Describe the role of the senior
colleague who advised the QC Chemist during this incident. Also describe your plans for and
outcome of a thorough investigation into data integrity at your facility, both in documents produced
by the QC Chemist involved in this incident and by all other personnel at your site.
• Our inspection also found that your laboratory failed to take note of a trend in the total impurity test
results reported for this API. A striking number of the long term room temperature stability results
show a drop in the total impurities result (for the most recent test) regardless of whether that is the
12, 24, 36, 40 or 48 month test interval.
Reference : WL: 320-13-23 / Posh Chemicals Private Limited 8/2/13
33. Your firm failed to ensure that laboratory records included complete data derived from
all tests necessary to assure compliance with established specifications and
standards (21 CFR 211.194(a)).
• For example, your firm did not retain any raw data related to sample weights and sample
solution preparations for the HPLC assays of (b)(4) tablet batches (b)(4) and (b)(4) that
you conducted on July 18, 2012. In addition, you did not include those results in the
calculation of the final assay values. Instead, you repeated the analysis the next day using
a new set of sample solutions, and reported the retest results on the certificates of analysis
(COAs). Other examples were also noted during the inspection.
• In response to the FDA-483, you conducted a retrospective investigation and concluded
that the analyst realized he recorded the initial data incorrectly in the HPLC ―trial folder‖
instead of the regular folder. Thus, he repeated the test the next day using the same
sample solutions. However, your QC manager stated during the inspection that the initial
injections were trial runs, and that performing trial standard and sample analysis prior to
official analysis is a standard practice in your QC laboratory. Moreover, our review of the
final QC worksheet revealed that you prepared the new retest samples on July 19, 2012,
the day after you performed the trial injections. (Continued …)
Reference : WL: 320-13-17 / RPG Life Sciences Limited 5/28/13
34. Your firm failed to ensure that laboratory records included complete data derived from
all tests necessary to assure compliance with established specifications and
standards (21 CFR 211.194(a)).
• Our investigator also observed (b)(4) trial HPLC injections during the period of January 5,
2012 to November 16, 2012. Your response acknowledged that a number of these trial
injections involved sample testing. However, you provided no evidence that your firm
retained laboratory records and raw data associated with these sample tests.
• Additionally, during an audit of the data submitted in support of
the (b)(4) regarding (b)(4) tablets USP (b)(4) mg, our investigator requested to review the
electronic analytical raw data to compare the values for (b)(4) assay and degradation
products. However, your firm provided only the printed copies of the raw data because
your firm did not have the software program available to view the electronic raw data.
Reference : WL: 320-13-17 / RPG Life Sciences Limited 5/28/13
35. Your firm failed to exercise appropriate controls over computer or related systems to assure that only
authorized personnel institute changes in master production and control records, or other records (21
CFR 211.68(b)).
• For example, you analyzed (b)(4) API lot (b)(4) on February 14, 2011, at 2:55 a.m., and then
retested it at 2:05 p.m. using a new sample solution. You did not maintain any raw data associated
with the initial test.
• In your response, you stated that the retest was performed due to data deletion of the original
analysis. You concluded that the analyst misused the administrator password to delete and overwrite
the actual data logged in the audit trail. The ability of your analysts to alter and delete electronic
analytical data raises serious concerns regarding laboratory controls in place at your facility.
• During the inspection, our investigator also identified a backdated QC worksheet in the analytical
report of (b)(4)API raw material batch (b)(4). When your analyst affixed the related substance and
IR weight printouts to the Format for Blank Sheet for Printout (Format No. F2/QCD/F/026-00), he
signed and dated this worksheet as July 29, 2011. A second analyst, who reviewed this worksheet,
also signed and dated it as July 29, 2011. However, your QA department did not issue this
worksheet until July 31, 2011. Your analyst acknowledged during the inspection that he backdated
this worksheet on July 31, 2011.
Reference : WL: 320-13-17 / RPG Life Sciences Limited 5/28/13
36. Your firm failed to exercise appropriate controls over computer or related systems to assure that only
authorized personnel institute changes in master production and control records, or other records (21
CFR 211.68(b)).
• For example, you analyzed (b)(4) API lot (b)(4) on February 14, 2011, at 2:55 a.m., and then retested it at
2:05 p.m. using a new sample solution. You did not maintain any raw data associated with the initial test.
• In your response, you stated that the retest was performed due to data deletion of the original
analysis. You concluded that the analyst misused the administrator password to delete and overwrite the
actual data logged in the audit trail. The ability of your analysts to alter and delete electronic analytical
data raises serious concerns regarding laboratory controls in place at your facility.
• During the inspection, our investigator also identified a backdated QC worksheet in the analytical report
of (b)(4)API raw material batch (b)(4). When your analyst affixed the related substance and IR weight
printouts to the Format for Blank Sheet for Printout (Format No. F2/QCD/F/026-00), he signed and dated
this worksheet as July 29, 2011. A second analyst, who reviewed this worksheet, also signed and dated it
as July 29, 2011. However, your QA department did not issue this worksheet until July 31, 2011. Your
analyst acknowledged during the inspection that he backdated this worksheet on July 31, 2011.
• Your response stated that the analyst incorrectly dated the worksheet as July 29, 2011, instead of July
31, 2011, and that there was no intention to deliberately backdate the document. However, your response
contradicted your analyst’s backdating admittance during the inspection. In addition, your response did
not explain the reviewer’s signature which was also dated July 29, 2011. Backdating documents is an
unacceptable practice and raises doubt about the validity of your firm's records.
Reference : WL: 320-13-17 / RPG Life Sciences Limited 5/28/13
37. Your firm failed to follow written procedures for production and process control designed to assure that
the drug products you manufacture have the identity, strength, quality, and purity they purport or are
represented to possess, and to document same at the time of performance (21 CFR 211.100(b)).
• Poor documentation practices during in-process testing. Specifically, an operator
performed the in-process tablet (b)(4) testing for the (b)(4) mg tablet batch #(b)(4)without
the batch record or a manufacturing form to document the results contemporaneously. The
FDA investigator was informed that the pre-test and post-test weight values are
documented in the batch record located in a separate manufacturing room rather than in
the same room where the actual weights are measured. Moreover, your operator stated
that he records the two weights with (b)(4) significant figures into the batch record from
memory.
• Additionally, the investigator noticed that the balance used in production was not level,
which can result in inaccurate weights. The investigator asked how long the balance had
not been level, and you indicated that you would investigate the matter and respond to the
investigator. To date, you have not responded to FDA explaining your resolution of this
matter.
Reference : WL: 320-14-01 / Wockhardt Limited 11/25/13
39. Your firm failed to exercise appropriate controls over computer or related systems to assure that only
authorized personnel institute changes in master production and control records, or other records (21
C.F.R. §211.68(b))
• Your firm failed to have adequate procedures for the use of computerized systems in the
quality control (QC) laboratory. Our inspection team found that current computer users in
the laboratory were able to delete data from analyses. Notably, we also found that the
audit trail function for the gas chromatograph (GC) and the X-Ray Diffraction (XRD)
systems was disabled at the time of the inspection. Therefore, your firm lacks records for
the acquisition, or modification, of laboratory data.
• Moreover, greater than (b)(4) QC laboratory personnel shared (b)(4) login IDs
for (b)(4) high performance liquid chromatographs (HPLC) units. In addition, your
laboratory staff shared one login ID for the XRD unit. Analysts also shared the username
and password for the Windows operating system for the (b)(4) GC workstations and no
computer lock mechanism had been configured to prevent unauthorized access to the
operating systems. Additionally, there was no procedure for the backup and protection
of data on the GC standalone workstations.
Reference : WL: 320-14-03 / USV Limited 2/6/14
40. Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance
with established specifications and standards.
• Your firm failed to prevent raw data from being deleted from the Atomic Absorption
Spectrophotometer (AAS) used for elemental analysis testing.
• Specifically, our investigation found laboratory analysts had access to delete and overwrite
AAS raw data. This instrument did not have sufficient controls to prevent unauthorized
access to, changes to, or omission of data files and folders.
• This is especially concerning because our inspection uncovered only 38 raw data files on
the hard drive of the AAS, while analysts stated that the AAS had been used for over 400
analyses. Your firm failed to store the raw data elsewhere.
• Therefore, all AAS testing results for which no raw data exists are in doubt. Your firm’s
improper control over the laboratory records raises concerns about the quality of the APIs
your firm has released.
Reference : WL: 320-14-04 / Canton Laboratories Pvt. Ltd. 2/27/14
41. Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance
with established specifications and standards.
• Your firm lacked accurate raw laboratory data records for API batches shipped by your firm. The
inspection revealed that batch samples were retested until acceptable results were obtained. In
addition, your quality control (QC) laboratory failed to include complete data on QC testing
sheets. Failing or otherwise atypical results were not included in the official laboratory control
records, not reported, and not investigated. For example,
• A review of the Gas Chromatograph (GC) electronic records from July 13, 2013, for (b)(4) USP
batch #(b)(4)revealed an out-of-specification (OOS) result for the limit of residual solvents that was
not reported. However, the QC test data sheet included passing results obtained from samples
tested on July 14, 2013 and July 15, 2013. The inspection documented that your firm discarded
sample preparation raw data related to the OOS results. In your response you indicate that the
electronic chromatographic data and the weighing log books were available and reviewed during the
inspection. However, the raw data and sample preparation information used for the calculation of the
test results that were found OOS or disregarded were not in fact available for review.
Reference : WL: 320-14-11 / Apotex Pharmachem India Pvt Ltd. 6/16/14
42. Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance
with established specifications and standards.
• A review of the High Performance Liquid Chromatograph (HPLC) electronic records from July 3,
2013, for (b)(4)batch #(b)(4) revealed an Out-of-Trend (OOT) result. The sample preparation raw
data was discarded and not reported. A QC analyst indicated that these results were discarded due
to some small extra peaks identified in the chromatogram fingerprint and an unexpected high assay
result. The QC test data sheet reported two new results that were obtained from samples tested on
July 4, 2013 and July 5, 2013, using a different HPLC instrument.
• A review of the Karl Fischer electronic records from November 21, 2013, for (b)(4) EP batch
#(b)(4) revealed an OOS result that was not reported. The passing results reported on the data
sheets were generated from another sample tested an hour after the initial OOS results were
obtained on the same day, November 21, 2013.
Reference : WL: 320-14-11 / Apotex Pharmachem India Pvt Ltd. 6/16/14
43. Failure to record activities at the time they are performed.
• Specifically, your staff used ―finished product reports review data‖ worksheets to document critical laboratory
information days after the actual testing was performed. The worksheets reported observations from your firm’s
secondary reviewer, and next to each of these listed observations the analyst marked them as corrected. A
review of these worksheets revealed that your analysts did not always record data in the laboratory records in a
contemporaneous manner as noted in the following examples:
• (b)(4) USP batch #(b)(4) worksheet dated September 18, 2013, reports ―sample wt. taken wrongly." However,
the correction to the stability data sheet for this lot gives the appearance that sample weighing was performed
on August 10, 2013.
• (b)(4) USP batch #(b)(4) worksheet dated September 19, 2013, reports ―all tests completed but appearance not
reported.‖ However, the correction to the test record indicates the test was performed on September 15, 2013,
the date of the original testing.
• (b)(4)% batch #(b)(4) worksheet dated June 11, 2013, reports ―resolution b/t (b)(4) & (b)(4) in ID std not in
working std & it is (b)(4) not (b)(4).‖ However, the correction to the stability test data sheet for this lot gives the
appearance that the resolution was performed on June 9, 2013
Reference : WL: 320-14-11 / Apotex Pharmachem India Pvt Ltd. 6/16/14
44. Failure to manage laboratory systems with sufficient controls to ensure conformance to established
specifications and prevent omission of data.
• Our inspection revealed serious deficiencies related to your documentation practices, including
missing raw data. It is a basic responsibility of your quality unit to ensure that your firm retains the
supporting raw data that demonstrates your APIs meet specifications that they are purported to
possess.
• For example, during the inspection, our investigator found a chromatogram related to (b)(4), API in
the trash, dated October 15, 2013, which reported an additional chromatographic peak when
compared to the standard. During the inspection, your firm stated that the analyst discarded the
chromatogram because it was present in the blank injection. However, the analyst was unable to
retrieve the blank chromatogram from the system because it was overwritten by a subsequent
injection.
Reference : WL: 320-15-04 / Novacyl Wuxi Pharmaceutical Co., Ltd. 12/19/14
45. Failure to manage laboratory systems with sufficient controls to ensure conformance to established
specifications and prevent omission of data.
• In addition, the inspection documented that your firm made changes to integration parameters for the impurities
test without appropriate documentation or justification. Your firm relied upon hand written notes on a
chromatogram discovered in a drawer at the laboratory as the documentation for this change. Furthermore,
your firm implemented this change without an audit trail that would have captured the date of the change and
who made the change.
Other significant deficiencies noted in your laboratory system include:
a) Failure to have a written procedure for manual integration despite its prevalence.
b) Failure to use separate passwords for each analyst’s access to the laboratory systems.
c) Use of uncontrolled worksheets for raw analytical data in your laboratory.
d) Presence of many uncontrolled chromatograms, spreadsheets and notes of unknown origin found in a
drawer.
• The lack of controls on method performance and inadequate controls on the integrity of the data collected raise
questions as to the authenticity and reliability of your data and the quality of the APIs you produce.
Reference : WL: 320-15-04 / Novacyl Wuxi Pharmaceutical Co., Ltd. 12/19/14
46. Failure to document manufacturing operations at the time they are performed.
• When reviewing the entries in your (b)(4) use, cleaning, and maintenance logbook for the days immediately
prior to the inspection, our investigator found missing entries. Your operators stated that lines were left blank to
later add information about cleaning events that may have occurred during a previous shift.
• During the inspection, our investigator found other similar instances of missing data or belated data entry in
your manufacturing records. These practices are not consistent with CGMP.
• Operators acknowledged that there is no system in place to report these lapses in the documentation system;
documentation errors of this type did not require deviation investigations or notification to the Quality Unit.
• In addition, during the inspection, one of your quality unit employees presented the investigator with a batch
record containing his signature, stating that he had performed the review of this batch record.
• The employee later admitted that he had falsified this CGMP record and stated that he in fact had not
performed the review, despite having signed the batch record as the QA reviewer and having released the
batch. This data falsification and the record-keeping deficiencies described above raise doubt regarding the
validity of your firm’s records.
Reference : WL: 320-14-12 / Zhejiang Jiuzhou Pharmaceutical Co., Ltd. 7/9/14
52. EU Non Compliance Reports
Firm Name Observation
Smruthi Organics Limited Feb
2014
• There was no raw data available in the Quality control laboratory for the verification of
compendial analytical methods.
Smruthi Organics Limited Jan
2014
• Manipulation and falsification of documents and data were observed in different
departments ;
Medreich Limited – Unit V • 1 deficiency related to data falsification has been classified as "critical" .
IND-SWIFT LIMITED, Punjab;
Mar 2014
• It was not possible to confirm the validity of stability testing data. Several falsified and
inaccurate results had been reported in long term stability and batch testing.
• Discrepancies between electronic data and those results formally reported were
identified.
• Established processes to verify data accuracy and integrity had failed and there had
been no formal investigation raised by the company.
• The company provided commitments to address the data integrity concerns and initiated
a wider review of quality critical data. Additional discrepancies were identified in process
validation and release data.
• During on-going communications with the licensing authority regarding the data review,
the company failed to disclose data integrity issues for all products. No satisfactory
explanation was given for this discrepancy.
53. EU Non Compliance Reports
Firm Name Observation
Zeta Analytical Ltd, UK; Jan
2014
• It could not be confirmed who had conducted the testing or when because of
discrepancies in the raw data; consequently staff competence could not be confirmed.
• Raw data were not being recorded contemporaneously nor by the performing analyst.
• Failed HPLC injections of QC standards in place to demonstrate the correct operation
of the HPLC were deleted, repeated many hours after the original analysis and re-
inserted into the analytical sequence without explanation invalidating the batch
data. The company provided commitments to address the data traceability concerns.
Seikagaku Corporation,
Japan; Apr 2014
• The critical deficiency concerns systematic rewriting/manipulation of documents,
including QC raw data.
• The company has not been able to provide acceptable investigations and explanations
to the differences seen in official and non-official versions of the same documents.
Renown Pharmaceuticals Pvt.
Ltd., Gujarat, India; Aug 2014
• Record integrity and veracity: some records were made up or altered.
• Defects on deviation recording and investigation.
• Lack of mechanisms to ensure integrity of analytical data.
54. EU Non Compliance Reports
Firm Name Observation
North China Pharmaceutical
Group Semisyntech Co., Ltd,
China, Jan 2015
• Lack of data integrity in the QC laboratory (No access control, inadequate traceability
and archiving practices, no audit trail, no restriction on the deleting of data, etc.) and
falsification of the analytical results for residual solvents;
Zhejiang Apeloa Kangyu Bio-
Pharmaceutical Co. Ltd.,
China; Nov 2014
• The company failed to establish a procedure to identify and validate GMP-relevant
computerized systems in general.
• Two batch analysis reports for Colistin Sulfate proved to be manipulated.
• HPLC chromatograms had been copied from previous batches and renamed with
different batch and file names.
• Several electronically stored HPLC runs had not been entered into the equipment log
books. The nature of these data could not finally been clarified.
• Neither the individual workstation nor the central server had been adequately protected
against uncontrolled deletion or change of data.
• The transfer of data between workstations and server showed to be incomplete.
• No audit trail and no consistency checks had been implemented to prevent misuse of
data.
Hebei Dongfeng
Pharmaceutical Co., Ltd,
China; Sep 2014
• Data recording and integrity in the QC laboratory
55. EU Non Compliance Reports
Firm Name Observation
Sri Krishna Pharmaceuticals
Ltd., Hyderabad, India, Dec
2014
1. Drug products failing to meet established quality control criteria are not rejected. In
particular:
a) analysts routinely use the PC administrator privileges to set the controlling time and date
settings back to over-write previously collected failing and/or undesirable sample results.
This practice is performed until passing and/or desirable results are achieved;
b) Analysts routinely perform ―trial‖ injections of sample aliquots prior to performing the
official/reported analysis. There are no documented sample preparation details for these
trial analyses. The results of these trial injections are not reported, and were found to
differ significantly from the subsequent reported results;
c) Analysts routinely perform ―trial‖ injections of sample aliquots prior to performing the
official/reported analysis. The resulting raw data chromatogram files were often found to
have been deleted and unavailable for review;
d) Analysts delete undesirable and/or failing results (entire sample sequences) and retest
samples until desirable results are achieved.
56. EU Non Compliance Reports
Firm Name Observation
Taishan City Chemical
Pharmaceutical Co. Ltd.,
China, Nov 2014
• Insufficient securisation of the electronic raw data in the Quality Control laboratory (No
limitation of access levels, no restriction on the deleting of data, no audit trail, inadequate
traceability and archiving practises);
Fujian South Pharmaceutical,
China, Oct 2014
• The inspection team tried to verify some regulatory information requested during the
assessment of the dossier and reached the conclusion that fundamental GMP and
regulatory requirements such as loss of data integrity, combined with insufficient
management of data, change control system, supplier qualification, laboratory controls
as well as the accuracy of data submitted, were not adequately implemented/considered
because of a weakness of the QA system and regulatory affairs department;
• Severe GMP violations related to the implementation of sound computerised systems in
the quality control facilities were committed, that could lead/could have led to the
falsification of data. It was impossible to verify that the decision to approve raw material
and final API was based on valid and accurate data;
57. EU Non Compliance Reports
Firm Name Observation
Wockhardt - NANI
DAMAN, India Oct 2013
• Quality Control deficiencies including; inadequate records, lack of specificity in analytical
methods, failure to investigate unknown peaks and non-compliance with MA details.
Wockhardt Limited, India,
Jun 2014
• The deficiency related to data integrity, deleted electronic files with no explanation, the
running of ―trial testing‖ prior to performing system suitability and the formal testing and a
loss of control of reconciliation of samples such as those used for additional testing could not
be traced.
Wockhardt Limited, Nani
Daman, India Oct 2014
• Issues were identified which compromised the integrity of analytical data produced by the QC
department. Evidence was seen of data falsification.
• A significant number of product stability data results reported in the Product Quality Reviews
had been fabricated. Neither hard copy nor electronic records were available.
• In addition issues were seen with HPLC electronic data indicating un-authorised manipulation
of data and incidents of unreported trial runs prior to reported analytical runs.
Wockhardt Limited,
Aurangabad, Jan 2015
• A critical deficiency was cited with regards to data integrity of GMP records, entries were
seen to be made when personnel were not present on site, documentation was seen that
was not completed contemporaneously despite appearing to be completed in this manner.
61. Summary of Data Integrity issues
• Employees signing as completing manufacturing steps were not on
premises at the time the steps were completed
• Data was removed and new data was added
• Employee scraped off entries with hand-made tool
• Making up Batch records during an FDA inspection
BPR’s
• Making up Training records during an FDA inspection
• Firm had no CGMP training
Training
• Testing conducted late but recorded as being tested on time
• No samples available, however testing data was generated
Stability
62. Summary of Data Integrity issues
• Employee used same sample for identity testing on a regular basis
• Unlabeled or partially labeled vials dumped down the drain
• No samples available, however testing data was generated
Samples
• Test results for one batch were used to release other batches
• Releasing product with known contaminants
• Repacking failed product without assessing impact of failure; Repacked product was released
• Data supporting test results was missing
Quality
control
• Growth on microbiological plates was observed and recorded as no growth
Microbiol
ogy
63. Summary of Data Integrity issues
• Employee used same sample for identity testing on a regular basis
• Unlabeled or partially labeled vials dumped down the drain
• No samples available, however testing data was generated
Samples
• Test results for one batch were used to release other batches
• Releasing product with known contaminants
• Repacking failed product without assessing impact of failure; Repacked product was released
• Data supporting test results was missing
Quality
control
• Growth on microbiological plates was observed and recorded as no growthMicrobiology
64. Summary of Data Integrity issues
• No raw data for Standard preparation
• No raw data for Sample weights
• No raw data for Sample solution preparation and sample dilutions
• Sample and reagent weights are written on small pieces of paper and
transcribed onto analytical worksheets Then, small pieces of paper were
discarded
• Destruction of raw data not meeting specification
• Missing raw data
• Re-writing laboratory notebooks
• Unjustified invalidation of data and re-testing without a laboratory investigation
• Raw data found in the garbage
RawData
65. Summary of Data Integrity issues
• Pre / post dating of the records.
• Failure to use approved procedures.
• Recording / Signing for others
• Re-writing the records without authorization.
• Failure to report / document a discrepancy.
• Failure to retain raw data / records.
Documentation
66. Summary of Data Integrity issues
• Out-of-specification or undesirable results were ignored and not
investigated
• – Re-testing without justification
• – Product released despite failing sterility testing
• – Failing or suspect HPLC assay results are overwritten
• Evidence did not support the reason to invalidate the dissolution test
results
• Dissolution data discarded with no investigation
InvestigationData
67. Summary of Data Integrity issues
• HPLC integration parameters were changed and re-run until passing
results were obtained
• Audit trail function was disabled.
• Unofficial testing of samples with file names like test, trial, or demo
• There are no controls to prohibit unauthorized changes to electronic
data / inadequate access controls.
• Files were saved on personal computers instead of a network
• Sharing passwords / unauthorized access.
• Lack of security on electronic data systems.
• Failure to maintain back-up of electronic data.
ElectronicData
69. Consequences of Data Integrity
• Loss of Trust
• Recalls
• Form – 483
• Warning or Untitled Letter
• Import Alert
• Injunction
• Seizure
• Application Integrity Policy Invocation
• Non-compliance Report
• Notice of Concern
• Loss of job
• Loss of business
• Loss of Money
71. Data Integrity – Rebuilding Trust
• Know the Regulations & Intensity of Data integrity
• Perform a GAP Analysis
• Determine the scope of the problem / Detect the integrity
• Implement a corrective action plan (global) & Prevent the Integrity
• Remove individuals responsible for problems from CGMP positions
• Complete a satisfactory inspection
72. GAP Analysis
• Perform GAP analysis by
brainstorming with cross
functional team to identify and
prevent the data integrity
issues.
Review
System
Identify gap
Change
control
process
Develop,
Training &
implement
ion
Implications
Recommen
dations
73. Detecting & Preventing Data Integrity issues
• Increase the frequency of review
• Do surprise / spot checks
• Have a procedure & check list for review mechanism
• Compare hand writing styles / signatures.
• Verify attendance / presence of the person.
• Verify the traceability & log book entries.
• Internal / external audits.
• Trend the observations & provide the training
ReviewSystem
74. Detecting & Preventing Data Integrity issues
• Define a clear policy / procedure on various activities (e.g.
Password policy)
• Have clear procedure and controls over the electronic data /
software administration.
• Cross check Privileges Vs. Job responsibilities.
• Check the adequacy of the procedures.
Policies&Procedures
75. Detecting & Preventing Data Integrity issues
• Strategic planning
• Determine the level of compliance that we are seeking
• Identify the weaknesses and strengths in our computerized
systems
• Conduct an inventory of our systems
• Determine if the system must comply with Part 11
• Conduct the assessment using a checklist or spreadsheet
• Provide documented justification if certain system are exempt
from Part 11
• Implement and execute a remediation plan
• Conduct the required follow-up as warranted.
Part11GAPAssessment
77. Conclusion
• The integrity of data generated by any regulated laboratory is a prime factor in
determining the credibility of that laboratory.
• The finding of a single instance where data integrity is compromised casts a shadow
over the whole of the data generated.
• Remember that inspections and audits can only sample, finding one instance of
falsification raises the question of how many more instances of non-compliances exist?
Therefore, ensuring data integrity is of major importance to analytical scientists,
managers and quality assurance of any organization, as the consequences of getting it
wrong are very costly and it will take a long time to rebuild regulatory trust.
78. Conclusion
• The extended FDA regulation and draft guidance now also impact the laboratory data
integrity issue, as failure to provide complete records means that any drugs are now
classified as adulterated under the new extension of the Food Drug and Cosmetic Act as
amended in 2012.
• Data integrity issue is prevalent globally and not merely India centric. If the pharmaceutical
industry in the country is engaged in the production of life-saving drugs then it cannot afford
to be negligent.
• We need to be careful and it is absolutely fair by global regulators to keep tabs on this.
• Therefore it is not that India pharmaceutical companies are targeted by the global regulators
79. pharmauptoday@gmail.com
Data Integrity Part II is continued …. as
Presentation on Chromatography Data System (CDS)
http://www.slideshare.net/skvemula/chromatography-data-system-cds-in-pharma
80. pharmauptoday@gmail.com
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