- 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
This PPT contains topics on web technologies
1. HTML,XML and CSS
2. INTRODUCTION TO PROGRAMING LANGUAGES
3. INTRODUCTION TO DATABASE
4. PHARMACY DRUG DATABASE
It is very useful for beginners especially for Pharmacy Students.
Application of computers in Pharmacy – Drug information storage and retrieval, Pharmacokinetics, Mathematical model in Drug design, Hospital and Clinical Pharmacy, Electronic Prescribing and discharge (EP) systems, barcode medicine identification and automated dispensing of drugs, mobile technology and adherence monitoring
Diagnostic System, Lab-diagnostic System, Patient Monitoring System, Pharma Information System
this ppt contains information regarding Bioinformatics database. introduction, objectives of database, database management, application of database management, types of database management. Its a part of subject pharmacy, 2nd semester computer application.
Important questions of Human anatomy and physiology 2 Payaamvohra1
This ppt gives you n idea about frequently asked questions In Human Anatomy and Physiology .Do checkout other ppt for more important question of pharmacy subjects according to PCI syllabus
Dynamic data processing tools to minimize time spent on chromatogram review and integration (Dynamic Data Linking, SmartLink, Cobra, SmartPeaks).
Learn more about our chromatography data system Chromeleon: http://www.thermoscientific.com/en/about-us/general-landing-page/chromeleon-resource-center.html?ca=chromeleon
This PPT contains topics on web technologies
1. HTML,XML and CSS
2. INTRODUCTION TO PROGRAMING LANGUAGES
3. INTRODUCTION TO DATABASE
4. PHARMACY DRUG DATABASE
It is very useful for beginners especially for Pharmacy Students.
Application of computers in Pharmacy – Drug information storage and retrieval, Pharmacokinetics, Mathematical model in Drug design, Hospital and Clinical Pharmacy, Electronic Prescribing and discharge (EP) systems, barcode medicine identification and automated dispensing of drugs, mobile technology and adherence monitoring
Diagnostic System, Lab-diagnostic System, Patient Monitoring System, Pharma Information System
this ppt contains information regarding Bioinformatics database. introduction, objectives of database, database management, application of database management, types of database management. Its a part of subject pharmacy, 2nd semester computer application.
Important questions of Human anatomy and physiology 2 Payaamvohra1
This ppt gives you n idea about frequently asked questions In Human Anatomy and Physiology .Do checkout other ppt for more important question of pharmacy subjects according to PCI syllabus
Dynamic data processing tools to minimize time spent on chromatogram review and integration (Dynamic Data Linking, SmartLink, Cobra, SmartPeaks).
Learn more about our chromatography data system Chromeleon: http://www.thermoscientific.com/en/about-us/general-landing-page/chromeleon-resource-center.html?ca=chromeleon
6.COMPUTERS AS DATA ANALYSIS.pptxB.Pharm sem 2 Computer Applications in PharmacyVedika Narvekar
Computers as data analysis in Preclinical development:
Chromatographic dada analysis(CDS), Laboratory Information management
System (LIMS) and Text Information Management System(TIMS)
Semisolid dosage forms: Definitions, classification, mechanisms and factors influencing dermal penetration of drugs. Preparation of ointments, pastes, creams and gels. Excipients used in semi solid dosage forms. Evaluation of semi solid dosages forms
Suspension is made of two phase system, consisting of a finely divided solid particles (Dispersed phase) distributed in a particular manner throughout another medium (Continuous phase).
Bioinformatics: Introduction, Objective of Bioinformatics, Bioinformatics Databases, Concept of Bioinformatics, Impact of Bioinformatics in Vaccine Discovery
HELLO!
THIS PRESENTATION WILL GIVE YOU ALL THE BASIC AND IMPORTANT DETAILS ABOUT" INFORMATION STORAGE AND RETRIEVAL".
SO CHECK IT OUT IF YOU NEED THIS.
Mobile Technology in Medical InformaticJAMES JACKY
1. Mobile Technology in Medical Informatic
2. Mobile Health
3. The Cloud
4. MediHome
5. Itareps
6. Advantages of Mobile Technology in Medical Informatic
7. Problems faced in implementing mobile technology in medical healthcare
8. How does the systems work?
Presentation on data integrity in Pharmaceutical IndustrySathish Vemula
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
6.COMPUTERS AS DATA ANALYSIS.pptxB.Pharm sem 2 Computer Applications in PharmacyVedika Narvekar
Computers as data analysis in Preclinical development:
Chromatographic dada analysis(CDS), Laboratory Information management
System (LIMS) and Text Information Management System(TIMS)
Semisolid dosage forms: Definitions, classification, mechanisms and factors influencing dermal penetration of drugs. Preparation of ointments, pastes, creams and gels. Excipients used in semi solid dosage forms. Evaluation of semi solid dosages forms
Suspension is made of two phase system, consisting of a finely divided solid particles (Dispersed phase) distributed in a particular manner throughout another medium (Continuous phase).
Bioinformatics: Introduction, Objective of Bioinformatics, Bioinformatics Databases, Concept of Bioinformatics, Impact of Bioinformatics in Vaccine Discovery
HELLO!
THIS PRESENTATION WILL GIVE YOU ALL THE BASIC AND IMPORTANT DETAILS ABOUT" INFORMATION STORAGE AND RETRIEVAL".
SO CHECK IT OUT IF YOU NEED THIS.
Mobile Technology in Medical InformaticJAMES JACKY
1. Mobile Technology in Medical Informatic
2. Mobile Health
3. The Cloud
4. MediHome
5. Itareps
6. Advantages of Mobile Technology in Medical Informatic
7. Problems faced in implementing mobile technology in medical healthcare
8. How does the systems work?
Presentation on data integrity in Pharmaceutical IndustrySathish Vemula
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 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.
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)
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.
Calibration, preventative maintenance, Asset Management in Bio-Med Applications. How to comply the FDA validation and Part 11 requirements? computer software for calibration/PM and asset management processes.
To learn about more details, please check out this article.
https://www.qualcy.com/blog/calibration-management-software-asset-management/
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.
Overview of the key requirements ofelectronic data management systems in relation to pharmaceuticals and healthcare facilities. This includes the importance of computerised systems controls and defenitions of data. The presentation includes the importance of validation and quality assurance aspects.
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.
Computerized system validation (CSV) as a requirement for good manufacturing ...Ahmed Hasham
The biopharmaceutical industries has more and more used computers to support and accelrate producing of their
products. Computer systems also are accustomed support routine offer of high quality products to boost production
process performance, scale back production prices, and improve product quality. it's vital that these systems square
measure suitable purpose from a business and restrictive perspective. Regulatory authorities treat a lack of regulatory
computer system compliance as a serious GxP deviation.
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
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.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
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.
Health Education on prevention of hypertensionRadhika kulvi
Hypertension is a chronic condition of concern due to its role in the causation of coronary heart diseases. Hypertension is a worldwide epidemic and important risk factor for coronary artery disease, stroke and renal diseases. Blood pressure is the force exerted by the blood against the walls of the blood vessels and is sufficient to maintain tissue perfusion during activity and rest. Hypertension is sustained elevation of BP. In adults, HTN exists when systolic blood pressure is equal to or greater than 140mmHg or diastolic BP is equal to or greater than 90mmHg. The
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/
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...The Lifesciences Magazine
Deep Leg Vein Thrombosis occurs when a blood clot forms in one or more of the deep veins in the legs. These clots can impede blood flow, leading to severe complications.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
2. - 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
pharmauptoday@gmail.com
Contents
3. Introduction
Chromatography data systems have been in laboratories for many years in many forms:
• integrator
• single PC
• central data system
• client/ server or networked system.
4. Functions of CDS
In outline the process used by most CDS consists of all or most of
the points below:
• Set up the method and analytical run information.
• Instrument control
• Acquire data from each injection, together with injection number
from the auto-sampler and any chromatographic conditions.
• Process the acquired data first into peak areas or heights and
then into analyte amounts or concentrations.
• Store the resultant data files and other information acquired
during the run for reanalysis.
• Interface with other data or information systems for import of
data relating to CDS set-up or export of data for further
processing or collation of results.
5. Validation Package Documentation
Document Name Outline Function in Validation
Validation plan • Documents the intent of the validation effort throughout the whole life cycle
• Defines documentation for validation package
• Defines roles and responsibilities of parties involved
Project plan • Outlines all tasks in the project
• Allocates responsibilities for tasks to individuals or functional units
• Several versions as progress is updated
User requirements
specification (URS)
• Defines the functions that the CDS will undertake
• Defines the scope, boundary and interfaces of the system
• Defines the scope of tests for system evaluation and qualification
System selection report • Outlines the systems evaluated either on paper or in-house
• Summarizes experience of evaluation testing
• Outlines criteria for selecting chosen system
Vendor audit report and
vendor quality certificates
• Defines the quality of the software from vendor’s perspective (certificates)
• Confirms that quality procedures match practice (audit report)
• Confirms overall quality of the system before purchase
6. Validation Package Documentation
Document Name Outline Function in Validation
Purchase order • From vendor quotation selects software and peripherals to be ordered
• Delivery note used to confirm actual delivery against purchase order
• Defines the initial configuration items of the CDS
Installation qualification (IQ) • Installation of the components of the system by the vendor
• Testing of individual components
• Documentation of the work performed
Operational qualification
(OQ)
• Testing of the installed system
• Use of a vendor’s protocol or test scripts
• Documentation of the work performed
Performance qualification
(PQ) test plan
• Defines user testing on the system against the URS functions
• Highlights features to test and those not to test
• Outlines the assumptions, exclusions and limitations of approach
PQ test scripts • Test script written to cover key functions defined in test plan
• Scripts used to collect evidence and observations as testing is performed
7. Validation Package Documentation
Document Name Outline Function in Validation
Written procedures • Procedures defined for users and system administrators
• Procedures written for IT related functions
• Practice must match the procedure
User training material • Initial material used to train super users and all users available
• Refresher or advanced training documented
• Training records updated accordingly
Validation summary report • Summarizes the whole life cycle of the CDS
• Discusses any deviations from validation plan and quality issues found
• Management authorization to use the system
9. Regulations
Main Clauses from EU Annex 11 Applicable for Maintaining the Validation Status of an Operational
CDS.
• validation covers the whole lifecycle (11.2)
• environmental conditions must be within specifications (11.3)
• system description (11.4)
• access control and user account management (11.8)
• audit trails for data quality (11.10)
• change control procedures (11.11)
• data back-up quality and security (11.13)
• data back-up (11.14)
• alternative ways of working (11.15)
• procedures for breakdown (11.16)
• problem identification and resolution (11.17).
10. US FDA Regulatory Requirements for Data Integrity
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
11. US FDA Regulatory Requirements for Data Integrity
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=11
12. FDA Regulatory Requirements for Computer Systems
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
13. FDA Regulatory Requirements for Computer Systems
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
14. FDA Regulatory Requirements for Computer Systems
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
15. FDA Regulatory Requirements for Computer Systems
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
16. FDA Regulatory Requirements for Data Integrity
Reference: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124787.htm
20. Procedures required for computer systems
• Description of responsibilities: the roles and responsibilities of staff supporting the
computer system are defined.
• System description of hardware and change-control procedures: describes how the
hardware components will be maintained (equivalent to the hardware configuration log)
with the procedure to be adopted when the system configuration is changed.
• Preventative maintenance: describes the procedures for preventative maintenance of the
hardware components.
• Prevention, detection and correction of errors: the measures and procedures for finding,
recording and resolving errors in the system. This can be a complex SOP covering many
different aspects of the system and may refer to sections of the technical manuals
provided with the system. This SOP includes good housekeeping such as disk
defragmentation or monitoring the space available on all disks.
21. Procedures required for computer systems
• System boot and shutdown: this is a special SOP that should contain all the specific
instructions for starting up and shutting down the system. This SOP may be required in an
emergency and, therefore, should be well written and be easily available for use.
• Control of environmental conditions: For systems that require a controlled environment,
an SOP should define the acceptable ranges of temperature, humidity and power supply.
Other environmental considerations may be what to do in the situation of electrostatic
discharges, power surges, fire, lightning strikes or the use and maintenance of an
uninterruptable power supply (UPS).
• Contingency plans and emergency operation: this is a disaster-recovery plan and uses
alternative plans until the computer system has been recovered. It is important that any
disaster recovery plan is tested and verified before any disaster occurs.
• Back-up and restore of data: describes the procedures for back-up of data and software
programs and how to restore data to disk.
22. Procedures required for computer systems
• Security: the logical (software) and physical security of the system is covered with the
procedures for setting up and maintaining security.
• Installation and update of software: procedures to be undertaken before, during and after
installing software. This should start with the complete back-up of all disks and then
installation of the software and any testing and validation that may be required.
• Development and update of system software procedures: software can be written to
control the system or help execute functions. This SOP outlines the procedures for the
creation, documentation and modification of these procedures.
• Password policy
• Peak Integration procedure
23. Comparison of FDA and EU Regulations for Audit Trails
The audit trail regulatory requirements from 21
CFR 11 and EU GMP Annex 11 are compared and
contrasted.
In general, the two requirements are similar, but
interpretation is required, as some requirements
are present either in the underlying predicate rule
(for 21 CFR 11) or in other locations (for EU
GMP). It is important when interpreting a specific
section of a regulation to remember that other
parts of the regulations may modify or interact with
it.
The problem is that audit trails in commercial
applications fail to document the second person
review adequately and should highlight when
changes have been made to records.
24. Areas for ensuring CDS Data Integrity
1. Identify each user uniquely
2. Implement adequate password controls
3. Establish different user roles / access privileges
4. Establish and maintain a list of current and historical users
5. Control changes to the system
6. Use only trained staff to operate the system
7. Understand predicate rules for laboratory records
8. Define and document e-records for the system
9. Review the audit trails for each batch set
10. Back the system up regularly
27. 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..
a. The inspection documented that HPLC processing methods (including integration
parameters) and re-integrations are executed without a pre-defined, scientifically valid
procedure.
Your analytical methods are not locked to ensure that the same integration parameters are
used on each analysis.
A QC operator interviewed during the inspection stated that integrations are performed and
re-performed until the chromatographic peaks are “good”, but was unable to provide an
explanation for the manner in which integration is performed.
Moreover, your firm does not have a procedure for the saving of processing methods used
for integration.
Reference : WL: 320-13-22 / Aarti Drugs Limited 7/30/13
28. 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..
c. During the review of the chromatography data, our investigator noticed that the raw data
retained does not include the run sequence or the processing method used to perform the
peak integrations.
Your QC personnel perform peak integrations based on analysts’ experience rather than by
an approved procedure.
Moreover, the chromatography raw data does not include the processing method used to
produce the final analytical results; therefore, during the review of the analytical data, it
would not be possible to detect any modification to the processing method.
Your firm’s response mentions that the QC operations are now under “direct control of
administrator”, but it does not define the roles and responsibilities of the administrator to
ensure the integrity and reliability of all QC laboratory data.
Reference : WL: 320-13-22 / Aarti Drugs Limited 7/30/13
29. 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..
d. The audit trail function for the chromatographic systems was disabled at the time of the
inspection; therefore, there is no record for the acquisition of data or modifications to
laboratory data.
Your response to this deficiency did not discuss how you will ensure that data audit trails
will not be disrupted in the future.
Reference : WL: 320-13-22 / Aarti Drugs Limited 7/30/13
30. Failure to implement access controls and audit trails for laboratory
computer systems.
Your firm failed to have adequate procedures for the use of computerized systems used in
the QC laboratory.
At the time of the inspections, your QC laboratory personnel shared the same username
and password for the operating systems and analytical software on each workstation in the
QC laboratory.
In addition, no computer lock mechanism had been configured to prevent unauthorized
access to the operating system.
The investigator noticed that the current QC computer users are able to delete data
acquired.
In addition, the investigator found that there is no audit trail or trace in the operating system
to document deletions.
Reference : WL: 320-13-22 / Aarti Drugs Limited 7/30/13
31. 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)).
Your firm’s (b)(4) “Jasco LC-Net II” HPLC instruments do not have restrictions in place to
prevent any change or deletion of analytical raw data.
Additionally, there is no audit trail in place to determine any previous deletion of raw data.
Reference : WL: 320-13-26 / Agila Specialties Private Limited 9/9/13
32. Your laboratory control records do not include data derived from all of the tests necessary to establish
compliance with standards.
For example, the inspection found multiple raw data chromatograms in digital files labeled “test” and
“demo,” that were injected prior to the sample injections that were used to conclude that batches were in
conformance with the specification. They were:
a. A “demo” chromatogram injected 3/6/12 and the official organic impurities injection on 4/6/12
for (b)(4)batch (b)(4).
b. A “demo” chromatogram injected 3/6/12 and the official organic impurities injection on 4/6/12
for (b)(4)batch (b)(4).
c. A “test” chromatogram injected 12/9/08 and the official related substances injection on 12/10/08
for (b)(4)batch (b)(4).
d. Two “test” chromatograms injected 12/4/08 and the official related substances injections on 12/5/08
for(b)(4) batch (b)(4).
e. Five “trial” chromatograms injected 7/5/11 between the official related substances injections which
occurred both before and after the “trial” injections for batch (b)(4) of (b)(4). The final injections were
made on 12/6/11 for this batch.
Reference : WL: 320-13-20 / Fresenius Kabi Oncology Ltd 7/1/13
33. Failure to protect computerized data from unauthorized access or changes.
Our inspection found that there were no restrictions to access the laboratory data residing on
the workstations attached to your standalone instrumentation: (b)(4) High Pressure Liquid
Chromatographs (HPLCs), the Fourier Transform Infrared Spectrophotometer (FTIR), the
gas chromatograph (GC) and the drives and portable media used as back-ups.
There was no protection of the data from alteration and deletion and no audit trails to detect if
such alteration or deletion had occurred.
Reference : WL: 320-13-23 / Posh Chemicals Private Limited 8/2/13
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)).
• 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.
Reference : WL: 320-13-17 / RPG Life Sciences Limited 5/28/13
35. Your firm failed to establish and exercise adequate controls over computers to prevent unauthorized
access or changes to electronic data.
• For example, the computers that control your analytical laboratory instruments, including
an HPLC, (b)(4) GCs, and an FTIR, lacked control mechanisms to prevent unauthorized
access to, changes to, or omission of data files.
a. Your analysis of (b)(4) USP batch (b)(4) exceeded the (b)(4) residual solvent limit on
February 29, 2012. Your firm did not report or investigate this OOS result, and deleted the
related electronic records. During our inspection, your analyst admitted that he also deleted
other uninvestigated failing and/or OOS electronic data from the laboratory database in
January 2013 prior to our inspection. Your QC Senior Manager also acknowledged this
laboratory-wide electronic data deletion practice.
b. During our inspection, your analysts demonstrated to our investigators that they could
delete any electronic analytical data files from the laboratory computers and external
backup hard drives.
Reference : WL: 320-13-17 / RPG Life Sciences Limited 5/28/13
36. 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’s laboratory records failed to include complete records of all stability testing
performed. The FDA investigators identified the practice of performing "trial" sample analysis for
High Performance Liquid Chromatography (HPLC) analyses prior to collecting the “official” analytical
data for stability testing. These “trials” were performed on multiple products,
including (b)(4) Tablets (b)(4)mg, (b)(4)mg/(b)(4)ml, and (b)(4)Tablets. These trial runs were not
recorded in the equipment use log, and sample preparation data associated with these analyses
was destroyed, preventing any calculation or analysis of the resulting data. Your response states
that trial runs were conducted using only one of the (b)(4) HPLC instruments located in the stability
laboratory, which happened to be the one instrument that the FDA investigators reviewed during the
inspection. Your response indicates that you have revised procedures and re-trained your staff.
• Additionally, your quality control HPLC raw data files can be deleted from the hard drive using the
common PC login used by all (b)(4) analysts. This deletion eliminates all records of sample
injections and analyses. Your response indicates that this deletion function is only available on the
software used for one of (b)(4) sets of HPLC instruments. You also indicated that you have changed
the access control privileges such that laboratory analysts in a “user” role cannot delete or rename
files.
Reference : WL: 320-13-21 / Wockhardt Limited 7/18/13
37. Your firm failed to record and justify any deviations from required laboratory control mechanisms (21
CFR 211.160(a)).
The FDA investigators identified a memo dated March 12, 2013 (a week before the inspection),
documenting a computer “crash” that occurred on the central back-up and controller PC
for (b)(4) HPLC instruments. The memo describes the loss of instrument activity logs (audit
trails). Our investigators found that several of the HPLCs had the audit trail functions disabled;
therefore, there is no assurance that the data generated using these HPLCs is accurate.
Your response indicates that your firm performed an assessment of the historical HPLC
chromatograms (raw data) generated on each individual HPLC unit prior to March 12, 2013 and
verified it against previously printed chromatograms. Based on this analysis, your firm claimed that
you had confirmed that the backup data is available for each of the analyses and no analytical data
has been lost due to the computer crash. However, your firm failed to provide a risk assessment for
the products tested using the HPLC instruments that had the audit trail functions disabled. This is
especially noteworthy given the fact that prior to the inspection, at least one QC officer had the
ability to delete data on the affected system.
Reference : WL: 320-13-21 / Wockhardt Limited 7/18/13
38. 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, our investigators identified your practice of performing “trial” sample analysis for high
performance liquid chromatography (HPLC) analyses prior to acquiring the “official” analytical data for
release and stability testing.
• The FDA investigators observed your practice of performing “trial” injections for HPLC analyses used to
test content uniformity, assay, and dissolution for release and stability for at least (b)(4) different products.
• The investigator observed that for finished product (b)(4) Tablets (b)(4) mg, batches (b)(4), your firm
performed “trial” injections. The inspection documented that an HPLC run had an injection sequence
named as (b)(4) assay,(b)(4) assay (b)(4), and (b)(4) assay (b)(4) attributed to the “trial” injections. Our
investigators noticed that the injection sequence names used the (b)(4) digits of the previously
referenced batch numbers. During the inspection, your firm’s management was unable to determine
whether the “trial” injections were performed using standard solutions or actual batch samples. Based on
the HPLC data, these “trial” injections occurred on 5/7/13. Later that same day, it appears that the
“official” sample analyses were performed for batches (b)(4). The assigned names for the sequence
injections creates the perception that your QC operator named the vials using the (b)(4)digits of the batch
numbers to link the “trial” injections for the batches with the official assay analyses. We are concerned
because our investigator noticed that the “trial” injection data related to batch (b)(4) rendered an out-of-
specification (OOS) result for the (b)(4) and (b)(4) assays. Therefore, it appears that the batch (b)(4) did
not pass the “trial” analysis but met specifications when the “official” sample was tested shortly thereafter.
Reference : WL: 320-14-01 / Wockhardt Limited 11/25/13
39. 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)).
• In addition, our investigator discovered that some of the “trial” injection data was not kept
on the HPLC hard drives because your firm deleted it. Your firm’s management confirmed
that the files were deleted as part of an internal audit.
• Our investigators found similar instances of the use of “trial” injections stored in default
folders on the HPLC hard drive for at least four drug products. The inspections
documented that both sites have SOPs that allow the use of “trial” injections. For example,
SOP QA/GLP/08 “HPLC Analysis” mentions that standard and sample injections are
allowed to ensure system equilibration before the system suitability runs are
performed. Neither the International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use (ICH) document Q2R,
“Validation of Analytical Procedure: Text and Methodology,” nor the United States
Pharmacopoeia General Chapter <1058> , “Analytical Instrument Qualification,” includes
instructions for performing “trial” injections for a method that is validated.
Reference : WL: 320-14-01 / Wockhardt Limited 11/25/13
40. 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)).
• The inspection documented that all of your QC laboratory computerized instruments ((b)(4) HPLCs)
were found to be stand-alone, and laboratory personnel demonstrated that they can delete
electronic raw data files from the local hard drive. Your firm deleted multiple HPLC data files
acquired in 2013 allegedly to clear up hard drive space without creating back-ups. Your QC
management confirmed that there is no audit trail or other traceability in the operating system to
document the deletion activity. Furthermore, your analysts do not have unique user names and
passwords for the computer and laboratory information systems; your QC analysts use a single
shared user identifier and password to access and manipulate multiple stand-alone systems.
• The (b)(4) HPLC systems in operation at the Waluj facility are also stand-alone, and during our
inspection, an employee demonstrated to the investigator that data can be deleted through the local
hard drive of the data acquisition system. As with the Chikalthana facility, all Waluj facility employees
use a shared password to access the operating system. During the inspection, your firm’s
management informed our investigator that (b)(4) back-ups of data are performed. However, we are
concerned that your system and procedures permit deletion of HPLC files and that (b)(4) backed up
data may not represent all the original data generated.
Reference : WL: 320-14-01 / Wockhardt Limited 11/25/13
42. Your firm frequently performs “unofficial testing” of samples, disregards the results, and reports results
from additional tests. For example, during stability testing, your firm tested a batch sample six times
and subsequently deleted this data
• Our investigators found your practice of performing initial “trial” sample high performance liquid
chromatography (HPLC) analyses prior to acquiring the “official” analyses. The “trial” sample results
were subsequently discarded. “Trial” HPLC analyses for (b)(4) USP ((b)(4)) were apparently run as
part of the 12-month long-term stability studies on batch #(b)(4) for related substances.
• The inspection revealed that on August 26, 2011, your employee ran an HPLC analysis sequence
with the sample names (b)(4) and subsequently deleted the raw data files. It was noted that the
assigned names for the sequence injections indicates that your quality control staff named the
samples using the last three digits of the batch numbers to link the "trial" injections for the batches
with the official assay analyses.
• Your Senior Quality Control (QC) Officer confirmed that these were analyses of batch
samples. Furthermore, we found that on August 27, 2011, this batch was analyzed for unknown
impurities and the results were reported to be within specifications. However, the chromatographic
data showed that the "trial" injection data for this batch failed the unknown impurities specification
of (b)(4)% in multiple cases.
Reference : WL: 320-14-08 / Sun Pharmaceutical Industries Limited - Karkhadi 5/7/14
43. Your firm frequently performs “unofficial testing” of samples, disregards the results, and reports results
from additional tests. For example, during stability testing, your firm tested a batch sample six times
and subsequently deleted this data
• Similar unacceptable data handling practices were observed in your laboratory’s conduct of gas
chromatography (GC) analyses. The FDA investigators reviewed what appear to be data from
“unofficial” injections for GC analyses for recovered (b)(4) raw material batch #(b)(4). On February
11, 2012, your analyst performed testing on recovered (b)(4) raw material batch #(b)(4) and the
sample was within specifications. The following day, February 12, 2012, your analyst ran a GC
analysis sequence with the sample names (b)(4) and subsequently deleted the raw data files. Your
staff performed calculations during the inspection, at our request, that showed that these samples
did not meet the (b)(4) impurity specification for this material. Therefore, it appears that out-of-
specification data for batch #(b)(4) was considered to be “unofficial,” while passing data were
reported as the "official" results for the batch.
• In addition, the inspection revealed numerous examples of deleted GC electronic raw data files on
the computer controlling the GC instruments that were replaced with identical “official”
chromatogram file names. The identically named GC data files that were deleted had been created
at different times and contained disparate data. Also, it appeared that data was not consistently
archived to the central server.
Reference : WL: 320-14-08 / Sun Pharmaceutical Industries Limited - Karkhadi 5/7/14
44. Failure to maintain complete data derived from all testing and to ensure compliance with established
specifications and standards pertaining to data retention and management.
• Your firm did not retain complete raw data from testing performed to ensure the quality of your
APIs. Specifically, your firm deleted all electronic raw data supporting your high performance liquid
chromatography (HPLC) testing of all API products released to the U.S. market.
• In addition, your firm failed to retain basic chromatographic information such as injection sequence,
instrument method or integration method for the tests. Your firm’s lack of data control causes us to
question the reliability of your data.
• In addition, your laboratory management was unaware of, and therefore did not follow, the written
procedure detailing the review of analytical data.
• Furthermore, your management confirmed that the review of analytical data did not include
evaluating the system suitability parameters to ensure proper column performance.
Reference : WL: 320-14-10 / Trifarma S.p.A. 7/7/14
45. Failure to prevent unauthorized access or changes to data and to provide adequate controls to prevent
omission of data
• Your firm did not have proper controls in place to prevent the unauthorized manipulation of your
laboratory’s raw electronic data.
• Specifically, your laboratory systems did not have access controls to prevent deletion or alteration of
raw data.
• The inspection noted that all laboratory employees were granted full privileges to the computer
systems.
• In addition, prior to January 7, 2014, HPLC and gas chromatograph (GC) computer software lacked
active audit trail functions to record changes to data, including information on original results, the
identity of the person making the change, and the date of the change.
Reference : WL: 320-14-10 / Trifarma S.p.A. 7/7/14
46. 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
47. 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
52. EU Non Compliance Reports
Firm Name Observation
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.
• 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.
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.
54. EU Non Compliance Reports
Firm Name Observation
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.
59. Data Integrity – Rebuilding Trust
• Know the Regulations & Intensity of Data integrity related to CDS
• Perform a GAP Analysis
• Determine the scope of the problem / Detect the integrity related to CDS
• Implement a corrective action plan (global) & Prevent the Integrity related to CDS
• Remove individuals responsible for problems from CGMP positions
• Complete a satisfactory inspection
60. GAP Analysis
• Perform GAP analysis by
brainstorming with cross
functional team to identify and
prevent the issues related to
CDS.
Review
System
Identify gap
Change
control
process
Develop,
Training &
implement
ion
Implications
Recommen
dations
61. 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
62. Detecting & Preventing CDS issues
• CDS should not be file based (easy to delete data), it should be with
an integrated database.
• Don’t use standalone workstations (easy to change date), use only
networked systems.
• Don’t use local workstation, acquire data on networked server.
• Restrict access to networked server except via CDS application.
• Follow the backup and recovery process.
• CDS application should be configured with full audit trails, Electronic
signatures, user types with access privileges.
• Document the complete software configuration.
ConfigurationofCDS
63. Detecting & Preventing CDS issues
• Define a clear policy / procedure on various activities (e.g.
Password policy, Project creation & back-up)
• 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
64. Detecting & Preventing CDS 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 the 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
65. Detecting & Preventing CDS issues
• Equilibrate chromatographic systems before they are ready for analysis.
• The time taken for equilibration shall be established during the method
development/validation/verification/transfer work performed in the laboratory and
this should be documented in the analytical procedure.
• Train the users and Follow good chromatographic practices and good start-up
procedures. Refer : http://www.slideshare.net/skvemula/good-chromatographic-
practices
• Follow proper change over procedures for mobile phase and modes (Normal
phase & Reverse phase).
• Inject the sample only after the system suitability criteria is met.
• Upon completion of the analysis, document the number of system evaluation
injections as part of the analytical report for the run.
TrialInjections
66. Detecting & Preventing CDS issues
• Roles provide administrators with straight forward method for managing user
privileges.
• Administrator can define roles based on job responsibilities.
• User types / groups should be defined based on the structure of the laboratory.
• Have independent User ids for the computer systems and CDS.
• Users should not have privilege to delete / modify / overwrite the data.
• Audit trails for access (System audit trails) shall be checked frequently.
• Data security shall be maintained.
AccessControls
67. HPLC - Peak Integration for Chromatography
Have a defined procedure on peak integration.
The presentation on “Peak Integration for Chromatography” is accessible form
the link : http://www.slideshare.net/skvemula/hplc-peak-integration-for-
chromatography-38032765
Contents:
- Introduction - Definitions
- How Peaks appear
- ApexTrack Integration
- Timed Events
- Peak Integration Events
- Peak Labels
- Manual Integration
- Warning letter Citations
69. Conclusion
• A structured and systematic evaluation of current compliance state can go a long way to ensuring
that your next CDS implementation is truly compliance-ready and maintains that compliant state.
• Lessons from past FDA warning letters
• Ensure that users are uniquely identified and that records of their access privileges are maintained.
• Have controls on re-integrations & methods.
• Understand the predicate rule in relation to computer systems
• Don’t delete / don’t give access privilege to delete raw data.
• Trial injections are not allowed.
• Stand alone systems are not allowed.
• Define electronic records and electronic working practices
• Review the CDS audit trails
• Vendors of CDS systems must ensure that audit trails are easy-to-use and actually contain information
that is useful to the users to determine the quality and integrity of data.
71. pharmauptoday@gmail.com
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