During the inspection, our investigator observed that many of your computerized systems lacked sufficient controls to ensure the integrity of the data being generated. For example:
Our investigator found “System/Administrator” as the only user role for your [redact] software. There were no restrictions on deleting or modifying data for this user role. [redact] was used for assay and identity testing of finished thyroid, USP API from March 2021 to November 2021.
Our investigator observed numerous deviations to original peak area results for HPLC assays of finished thyroid, USP API validation lots. There was no documentation of these alterations, but your quality unit personnel stated this may have been due to an unapproved update to the [redact] HPLC equipment. This equipment was never qualified according to your quality unit personnel.
A non-validated Excel spreadsheet was utilized to calculate finished thyroid, USP API assay results for all validation lot assay calculations. The formulas and outputs of the spreadsheet were printed at the time of the calculation and not saved. You were unable to provide an electronic copy of the original spreadsheet or master spreadsheet during the inspection.
Manufacturing master batch records held in electronic form on your company’s shared drive do not have restrictions on user access. Your quality unit personnel stated that there are no restrictions for any personnel with login credentials to access new and obsolete master records. Our investigator observed during the inspection multiple versions of batch records were utilized for API lot production.
Review of a spreadsheet of all the complaints [redacted] received from January 2016 through April 2016 revealed that eighty-six (86) out of 233 separate complaint entries were for issue codes that your firm does not routinely review and evaluate. Of these eighty-six (86) complaint entries there were eight (8) entries that describe “high” blood glucose readings. You have stated that unexpected “high” glucose readings are a concern because if the reading is false the patient may administer insulin when it is not needed, which could lead to possible overdose and potential organ failure.
For example, 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.
Additionally, at the Aarti Drug Limited facility (FEI 3009688205), the investigator noticed that the use of the Excel® spreadsheets in analytical calculations are neither controlled nor protected from modifications or deletion. The investigator noticed that the calculation for residual solvent for [redacted] uses an Excel spreadsheet that has not been qualified. We are concerned about the data generated by your QC laboratory from non-qualified and uncontrolled Excel spreadsheets.
One way to prevent unauthorized access to your spreadsheet is to encrypt the spreadsheet. This prevents anyone from opening the spreadsheet without providing the correct password.
To Set a password to open the MS Excel spreadsheet:
Select the File menu option.
On the File menu option, select Info.
On the Info screen, click Protect Workbook and select Encrypt with Password.
Enter the password twice.
Once the password is set, a user will require the password to open the file. If the file is a template, the user will be asked to provide the password to create a new copy of the spreadsheet.
Users can also create a password that will be required to edit the spreadsheet. In this case, if the password is not provided, the spreadsheet can be opened in Read-Only mode. The spreadsheet contents can be viewed, but users cannot change the data without providing the correct password.
To Set a password to edit an MS Excel spreadsheet:
On the File menu option, select Save As.
On the Save As screen, select Tools (it’s in the lower right corner, beside the Save button).
Select General Options from the Tools drop down list.
Enter the desired password in the “Password to Modify” field and confirm the password.
You can also put a password to open the spreadsheet. If the file is a template, the user is not asked for the password to edit the sheet before creating a copy of the spreadsheet.
Remove Excel Password Protection
If you need to remove password protection from an existing spreadsheet, open the spreadsheet in an editable mode. This will require the spreadsheet password. To Remove a password from an MS Excel spreadsheet:
On the File menu option, select Save As.
On the Save As screen, select Tools (it’s in the lower right corner, beside the Save button).
Select General Options from the Tools drop down list.
Clear the passwords from the appropriate fields and save the spreadsheet.
When you add or remove a password, you will be prompted to save the spreadsheet, even if you didn’t change the spreadsheet name. If you do not save the change, the password will not be added or removed.
Excel Passwords and 21 CFR 11
Excel’s password features are a useful tool for preventing unauthorized access to an Excel spreadsheet, but they may not be enough by themselves (to be used) use in FDA regulated environments. 21 CFR 11.10(g) states that computer systems should include “Use of authority checks to ensure that only authorized individuals can use the system”. Placing a password on a workbook does not individually identify the spreadsheet user. A better strategy for using Excel in a FDA regulated environment is to use a tool like ExcelSafe that individually identifies the User and allows them to perform the spreadsheet functions they are authorized to use.
Click here to learn more about spreadsheet validation.
Software specifically intended for managing manufacturing processes and FDA submissions may very well be too complex and expensive for your firm’s needs – commonly available spreadsheet programs like Microsoft Excel could be a much better choice. But how can you create, validate and use off-the-shelf spreadsheet programs in your regulated environment without violating the provisions of Part 11?
Easy-to-create and surprisingly powerful and flexible tools for data storage, spreadsheets are so common they may seem almost invisible. But regardless of the program(s) you use, FDA expects the controls to be in place to ensure that GxP processes are validated and compliant with 21 CFR Part 11. FDA will look at your spreadsheets…it’s critical that you are prepared to prove your own Part 11 compliance.
You can confidently harness the versatility, functionality, ease-of-uses and economy spreadsheets offer – and still remain in compliance with FDA’s regulatory requirements.
On Thursday, February 7 at 1:00pm EST, join FOI Services and Ofni Systems for a 90-minute teleconference for specific, practical advice on creating FDA-compliant spreadsheets, spreadsheet validation methodology and maintaining spreadsheets in GxP environments. You’ll even receive first-hand observations describing how FDA manages their own spreadsheets!
What Others Have Said about the Presenter:
“This course gave us additional insight into what we could be doing be doing better.”
“Super!”
“Instructor was very knowledgeable and put the right emphasis on the key points.”
What You’ll Learn:
How to design your spreadsheets to facilitate compliance and validation
The part of a spreadsheet with the highest regulatory risk – and how to address it
How FDA validates its own spreadsheets
The expected contents of a spreadsheet validation package
How to write spreadsheet requirements and specifications to facilitate good testing
What must be included during spreadsheet validation testing
The most common deviations discovered during spreadsheet validations, and how to focus your testing to detect these common mistakes
What You’ll Get:
Tips to facilitate compliant spreadsheet design
A checklist to determine if your spreadsheets are compliant with 21 CFR Part 11
Practical examples of requirements, specifications and test scripts
Links to a sample spreadsheet validation package, including functional requirements, design specification and executed test scripts.
A copy of the white paper “MS Excel Spreadsheet Validation” prepared by Ofni Systems
A copy of a FDA Laboratory Information bulletin describing their experience with spreadsheet compliance software.
A trial copy of ExcelSafe, which provides audit trails, password protection, user-level security and electronic signatures to MS Excel spreadsheets
An experienced and approachable instructor
Time for questions and answers
Who Will Benefit:
Managers and staff responsible for providing valid GxP data for spreadsheets
Anyone who designs (or is considering designing) spreadsheets for use in GxP environments
Regulatory professionals expected to defend the compliance of spreadsheets
Quality professionals who audit company regulatory compliance or are responsible for the procedural requirements required for spreadsheet compliance
Information technology professionals responsible for the administration of files or network locations storing spreadsheets incorporating GxP data
Computer validation professionals in GxP environments
The executives ultimately responsible for developing and maintaining a corporate culture of compliance, including those overseeing regulatory affairs, compliance, operations and strategic planning
To Register for this Conference:
Click here to register. For more information, or to register over the phone, call FOI Services at 800-654-1147 (+1-301-975-9400 outside the U.S. and Canada).
About Ofni Systems
Ofni Systems is an industry leader for 21 CFR Part 11 compliance. Their products for Part 11 compliant databases and spreadsheets are used by pharmaceutical, biotech, and medical device companies across the globe, while it’s products for computer validation, auditing, and FDA submissions ensure that their clients meet every requirement for electronic records and electronic signatures. The company provides live desktop support for superior customer support and training and has been providing solutions to their clients since 1999. For more information, call (919) 844-2494 or visit www.OfniSystems.com.
Ofni Systems has recently become aware of several FDA warning letter observations relating to spreadsheets. In both cases, the observation related to spreadsheet formulas which were not properly secured. Ofni Systems wants to remind all people working in the FDA regulated industries that all computer systems, including spreadsheets, that are used to make Quality decisions or used to report information to regulatory bodies must be controlled. For spreadsheets, this includes having the ability to track if changes are made to a spreadsheet, who is accessing the spreadsheets and having appropriate spreadsheet validation package to ensure that spreadsheet formulas are appropriate to the task they perform.
Earlier in 2010, the FDA Center for Drug Evaluation and Research (CDER) had been informing members of the pharmaceutical industry that its inspectors will increase enforcement of 21 CFR 11. Specifically, CDER will begin an inspection assignment of 21 CFR 11 requirements. When FDA representatives were distributing this information to members of the pharmaceutical industry, the key point was “Industry has had since August of 2003 to understand how we intend to enforce Part 11 as per the guidance and be in compliance. Therefore, the intention of CDER to take appropriate enforcement action should not be a surprise.”The full text of both warning letters is available on Ofni Systems’ web page Sample FDA 483 and Warning Letters.
21 CFR Part 11 sets forth the criteria under which the FDA considers electronic records, electronic signatures, and handwritten signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper. This regulation, which applies to all FDA program areas, was intended to permit the widest possible use of electronic technology, compatible with FDA’s responsibility to protect the public health.
About Ofni Systems
Ofni Systems is a leader in providing regulatory compliance solutions for pharmaceutical, biotech and medical device companies. They are the creators of ExcelSafe for Excel spreadsheet security and the Part 11 Toolkit for compliant databases. They also are the creators of the FastVal validation software for generating and executing validation documents, and have been providing professional validation servicesusing FastVal since 2006. Their products for Part 11 compliant databases and spreadsheets are used by pharmaceutical, biotech and medical device companies across the globe, while it’s products for computer validation, auditing and FDA submissions ensure that their clients meet every requirement for electronic records and electronic signatures.
Ofni Systems is also highly acclaimed for their expertise with 21 CFR Part 11 compliance. They are frequent speakers on Part 11 at conferences, meetings and webinars, and have provided training for thousands of employees to help implement the requirements. The company provides live desktop support for superior customer support and training, and has been providing solutions to their clients since 1999. For more information, call (919) 844-2494 or visit www.OfniSystems.com.
Media Contact
Tyson Mew
President
Ofni Systems, Inc.
Phone: (919) 844 – 2494
MS Excel is the FDA’s software of choice for processing results, analyzing and presenting scientific data in their chemical and microbiological laboratories. The FDA, like many organizations, uses Excel to record test results and other report data, and needs compliant, password protected spreadsheets. The San Juan District Laboratory wanted to retain the power and flexibility of Excel for their analysts, while transitioning to a paperless environment and remaining compliant with 21 CFR 11. In order to achieve these goals, the San Juan District Laboratory selected ExcelSafe by Ofni Systems.
The FDA publishes an internal Laboratory Investigation Bulletin (LIB) each month that is distributed to all FDA employees. It contains articles written by FDA employees that describe methods, procedures and products that a site has used that have demonstrated a high degree of success or an improvement over an existing method. The goal of these articles is to promote best practices to other sites within the agency. In the June 2012 issue, the San Juan District Laboratory released a Laboratory Information Bulletin 4524 “Evaluation of ExcelSafe to Implement Part 11 Rules in FDA Analyst WorkBook Files” detailing their experiences with ExcelSafe.
Click Here To Download
The San Juan District Laboratory investigation showed that ExcelSafe improved the analytical spreadsheet’s application’s data integrity, security and template accountability by using electronic signatures, audit trails, and other compliance and tracking features. Using ExcelSafe improved laboratory efficiency by decreasing the time required for internal document review. They praised the ease of using ExcelSafe, noting that ExcelSafe had produced significant cost and time savings, and stated they would continue to use ExcelSafe.
Learn more about ExcelSafe
Media Contact
Ty Mew
President
Ofni Systems, Inc.
Phone: (919) 844 – 2494
About Ofni Systems
Ofni Systems is an industry leader for 21 CFR Part 11/Annex 11 compliance and automating the validation process. Started in 1999, their products for compliant databases and spreadsheets are used by the FDA, pharmaceutical, biotech and medical device companies across the globe. They are the creators of ExcelSafe for Excel spreadsheet security and the Part 11 Toolkit for compliant databases. They also are the creators of the FastVal validation software for generating and executing validation documents, and have been providing professional validation services using FastVal since 2006. The company’s products for computer validation, auditing and FDA submissions ensure that their clients meet all requirements for electronic records and electronic signatures. Ofni Systems provides live desktop support for superior customer support and training. For more information, call (919) 844-2494 or visit www.OfniSystems.com.
Click here to learn more about spreadsheet validation.
Tyson Mew, President of Ofni Systems, and Ofni Systems, Validation Manager for Ofni Systems will speak at IVT’s 12th Annual Computer and Software Validation conference in Philadelphia, PA, from April 26 through April 28. Ty and Daniel will present Spreadsheet Validation 101 : Create and Validation FDA Compliant Spreadsheets on Wednesday, April 27 at 8:45 AM – 12:15 PM.
Easy-to-create and surprisingly powerful and flexible tools for data storage, spreadsheets are so common that they can almost seem invisible. However, GxP data stored within spreadsheets must be maintained in accordance with all applicable regulatory rules, especially 21 CFR 11; Electronic Records Electronic Signatures. The FDA is aware of the usefulness of spreadsheets, but expects controls to be in place to ensure that spreadsheets used in GxP processes are compliant with 21 CFR 11 and are validated. As FDA enforcement of 21 CFR 11 increases, uncontrolled spreadsheets represent an area of increased regulatory concern.
IVT’s 12th annual event showcases the validation process for computer systems and software. Computer and software validation (CSV) has remained a FDA hot button over the last decade in the GXP environment (manufacturing, laboratory and clinical). Whether working in traditional pharmaceuticals, emerging biotechnology or the medical device industry, participants take away cutting edge information that can be immediately implemented.
Ty Mew and Ofni Systems will be available throughout the conference to discuss validation.
Spreadsheet Validation 101 : Create and Validation FDA Compliant Spreadsheets will cover:
Spreadsheets in GxP Environments
How the FDA validates their spreadsheets
Scale validation to spreadsheet functionality
Required spreadsheet validation documents
Design spreadsheets that facilitate compliance
Requirements for compliance with 21 CFR 11
Writing Spreadsheet Functional and Design Requirements
Write requirements that facilitate testing and detect common deviations
Document Data Entry, Formulas and Calculations
Documenting Macros
Test Protocols for Spreadsheets
Focused testing
Test spreadsheet inputs, outputs and compliance
Interactive Exercise – Validating a Spreadsheet
Participants examine a spreadsheet, determine the requirements for the spreadsheet and then create a suitable test case which verifies that the requirement has been implemented successfully. Participants are encouraged to bring their own example spreadsheets.
Bonus Materials
All conference participents will receive:
A checklist to determine if spreadsheets are compliant with 21 CFR 11
Sample spreadsheet validation package
Whitepaper — “MS Excel Spreadsheet Validation”
A trial copy of ExcelSafe that provides audit trails, password protection, user-level security and electronic signatures
About the Presentors
Tyson M. Mew is President of Ofni Systems, a software provider and Part 11 consulting firm. He has a strong background in software development and computer system validation, and has spoken at many conferences and workshops on Part 11. He is the creator of ExcelSafe and has worked on hundreds of client spreadsheets and desktop database systems to make them compliant. Mr. Mew regularly conducts training sessions for organizations to educate employees about the specific requirements of the rule and how to incorporate it into daily practices. He is an active member of ISPE, DIA, PDA, SQA and the PEERS Group.
About Ofni Systems
Ofni Systems is an industry leader for 21 CFR Part 11 compliance. Their products for Part 11 compliant databases and spreadsheets are used by pharmaceutical, biotech, and medical device companies across the globe, while it’s products for computer validation, auditing, and FDA submissions ensure that their clients meet every requirement for electronic records and electronic signatures. The company provides live desktop support for superior customer support and training and has been providing solutions to their clients since 1999. For more information, call (919) 844-2494 or visit www.OfniSystems.com.
Software intended for the management of manufacturing processes and FDA submissions may very well be too complex, expensive, and laden with features unnecessary in your environment. Commonly available spreadsheet programs like MS Excel may really be most appropriate – but how can you create, validate and use off-the-shelf programs in your regulated environment without violating the provisions of Part 11?
FDA is well aware of the wide utility of spreadsheets, but expects the controls to be in place to ensure that spreadsheets used in GxP processes are validated and compliant with 21 CFR Part 11. In today’s environment of renewed FDA enforcement of Part 11, uncontrolled spreadsheets represent an area of increased regulatory concern and scrutiny.
You can learn to confidently harness the versatility and functionality of spreadsheets. You, your colleagues and your organization can take advantages of all of the benefits of the ease-of-use and economy spreadsheets offer – and still remain in compliance with FDA’s regulatory requirements. Key points that will be covered include:
How to design your spreadsheets to facilitate compliance and validation
The part of a spreadsheet with the highest regulatory risk – and how to address it
How FDA validates their own spreadsheets
The expected contents of a spreadsheet validation package
How to write spreadsheet requirements and specifications to facilitate good testing
What must be included during spreadsheet validation testing
The most common deviations discovered during spreadsheet validations, and how to focus your testing to detect these common mistakes
Presented by Ofni Systems, Validation Manager, Ofni Systems
Teleconference, Presented by FOI Services
Raleigh North Carolina – Ofni Systems announces ExcelSafe, version 2.1, which provides MS Excel with password protection, user level security, audit trails and electronic signatures. “ExcelSafe is an excellent tool for regulated industry. It provides the technological tools to make MS Excel compliant with 21 CFR Part 11,” said Ofni Systems President Tyson Mew. “ExcelSafe is spreadsheet security made simple.”
ExcelSafe provides users of Microsoft Excel with
User Security – Entry into spreadsheets requires a user name and password. ExcelSafe has configurable user-level security which can restrict which users can open or spreadsheets and apply or remove electronic signatures.
Data Security – All changes to Excel are automatically recorded. The audit trail records the previous and new value of a cell, the date/time of a change, the user making the change and the reason data was changed. The audit trail also records other spreadsheet events, including addition or deletion of a worksheet. Electronic signatures prevent changes within a worksheet. Even deleted records are preserved on an unalterable audit trail.
Traceability – ExcelSafe comes with tools to track all changes to spreadsheets. Users can query results from any spreadsheet.
Simplicity – ExcelSafe works automatically with existing spreadsheets and templates. Once a spreadsheet is opened in ExcelSafe, all compliance tools work automatically. Users operate Excel normally; there is no complicated interface to learn. ExcelSafe supports any number of users and any number of spreadsheets.
Version 2.1 includes additional tools for users to classify spreadsheets, improved compatibility with Excel 2007 file formats and for system administrators to facilitate the use of ExcelSafe across networks. ExcelSafe can be configured to use either an Oracle or a SQL Server for data storage.
About Ofni Systems
Ofni Systems is an industry leader for 21 CFR Part 11 compliance. Their products for Part 11 compliant databases and spreadsheets are used by pharmaceutical, biotech and medical device companies across the globe, while it’s products for computer validation, auditing and FDA submissions ensure that their clients meet every requirement for electronic records and electronic signatures. The company provides live desktop support for superior customer support and training, and has been providing solutions to their clients since 1999. For more information, call (919) 844-2494 or visit www.OfniSystems.com.
Media Contact
Tyson Mew
President
Ofni Systems, Inc.
Phone: (919) 844 – 2494
, version 2.1, which provides MS Excel with password protection, user level security, audit trails and electronic signatures. “ExcelSafe is an excellent tool for regulated industry. It provides the technological tools to make MS Excel compliant with 21 CFR Part 11,” said Ofni Systems President Tyson Mew. “ExcelSafe is spreadsheet security made simple.”
