Tag Archives: medical devices

Eliminating Informed Consent on Human Experimentation with Vaccines and Drugs

The 21st Century Cure Act would demand that the Food and Drug Administration (FDA) add an exemption from informed Consent requirements for those clinical trials that pose no more than minimal risks and the appropriate safeguards protecting the right, safety and welfare of subjects.

Informed Consent Waiver

The above can be found in section 3024 – Informed Consent Waiver or Alterations for Clinical Investigations.

So what they are saying now they don’t have to obtain informed consents to test vaccinations or drugs on humans beings if it has been determined that the proposed pose no more than minimal risks.

Let’s review the Exemption  for Devices for Investigational Use

(g)(1) The purpose of this section to encourage to the extent consistent with the protection of public health and safety and ethical standards, the discovery and development of useful devices intended for human use and to that end to maintain optimum freedom for scientific investigators in their pursuit of that purpose.

In other words, you can get an exemption for certain conditions.

Question: if you don’t have informed consent in clinical trials experimentation on people, then how does anyone knows you are not part of an experiment?

If sponsors and clinical researchers not longer has to tell you that you are part of it or get your consent to informed you what they are doing? That may sound a little crazy.

Further source of research:

The 21st Century Cures Act Implications

Say Goodbye to Vaccine Safety Science by Barbara Loe Fisher

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How to Avoid Electronic Data Integrity Issues: 7 Techniques for your Next Validation Project

The idea of this article was taking (with permission from the original authors) from Montrium:  how-to-avoid-electronic-data-integrity-issues-7-techniques-for-your-next-validation-project

Regulatory agencies around the globe are causing life science companies to be increasingly concerned with data integrity.  This comes with no surprise given that Guidance Documents for Data Integrity have been published by the MHRAFDA (draft), and WHO (draft).  In fact, the recent rise in awareness of the topic has been so tremendous that, less than two years after the original publication, the MHRA released a new draft of its guidance whose scope has been broadened from GMP to all GxP data.

Is data integrity an issue of good documentation practices? You can read GCP information about this topic here.

Good Documentation Practices for SAS / EDC Developers

Are you practising GCP?

In computerised systems, failures in data integrity management can arise from poor or complete lack of system controls.  Human error or lack of awareness may also cause data integrity issues.  Deficiencies in data integrity management are crucial because they may lead to issues with product quality and/or patient safety and, ultimately may manifest themselves through patient injury or even death.

I recently was at the vendor qualification tool that uses a hand held device to read data while the physician or expert manually put pressure on someone’s body parts (e..g. pain related). I was not impressed. Even though it seems like a nice device with its own software, the entire process was manual and therefore, questionable data integrity. The measurement seems to be all over the place and you would need the right personnel at the clinical site to perform a more accurate reading since again, it was all manual and dependent of someone else used of the device.

I also questioned the calibration of this device. The sale’s person answer ? “Well, it is reading 0 and therefore, it is calibrated.”….Really? You mean to tell me you have no way of proving when you perform calibration? Where is the paper trail proving your device is accurate? You mean to tell me I have to truth your words? Or your device’s screen that reads ‘0’? Well, I have news for you. Tell that to the regulators when they audit the trial.

What is Data Integrity?

Data can be defined as any original and true copy of paper or electronic records.  In the broadest sense, data integrity refers to the extent to which data are complete, consistent and accurate.

To have integrity and to meet regulatory expectations, data must at least meet the ALCOA criteria. Data that is ALCOA-plus is even better.

Alcoa

 

What is a Computerised System?

computerised system is not only the set of hardware and software, but also includes the people and documentation (including user guides and operating procedures) that are used to accomplish a set of specific functions.  It is a regulatory expectation that computer hardware and software are qualified, while the complete computerised system is validated to demonstrate that it is fit for its intended use.

How can you demonstrate Electronic Data Integrity through Validation?

Here are some techniques to assist you in ensuring the reliability of GxP data generated and maintained in computerised systems.

Specifications

What to do

Why you should do this

Outline your expectations for data integrity within a requirements specification.

For example:

  • Define requirements for the data review processes.
  • Define requirements for data retention (retention period and data format).
Validation is meant to demonstrate a system’s fitness for intended use.  If you define requirements for data integrity, you will be more inclined to verify that both system and procedural controls for data integrity are in place.
Verify that the system has adequate technical controls to prevent unauthorised changes to the configuration settings.

For example:

  • Define the system configuration parameter within a configuration specification.
  • Verify that the system configuration is “locked” to end-users.  Only authorized administrators should have access to the areas of the system where configuration changes can be made.
The inspection agencies expect you to be able to reconstruct any of the activities resulting in the generation of a given raw data set.  A static system configuration is key to being able to do this.

 

Verification of Procedural Controls

What to do

Why you should do this

Confirm that procedures are in place to oversee the creation of user accounts.

For example:

  • Confirm that user accounts are uniquely tied to specific individuals.
  • Confirm that generic system administrator accounts have been disabled.
  • Confirm that user accounts can be disabled.
Shared logins or generic user accounts should not be used since these would render data non-attributable to individuals.

System administrator privileges (allowing activities such as data deletion or system configuration changes) should be assigned to unique named accounts.  Individuals with administrator access should log in under his named account that allows audit trails to be attributed to that specific individual.

Confirm that procedures are in place to oversee user access management.

For example:

  • Verify that a security matrix is maintained, listing the individuals authorized to access the system and with what privileges.
A security matrix is a visual tool for reviewing and evaluating whether appropriate permissions are assigned to an individual. The risk of tampering with data is reduced if users are restricted to areas of the system that solely allow them to perform their job functions.
Confirm that procedures are in place to oversee training.

For example:

  • Ensure that only qualified users are granted access to the system.
People make up the part of the system that is most prone to error (intentional or not).  Untrained or unqualified users may use the system incorrectly, leading to the generation of inaccurate data or even rendering the system inoperable.

Procedures can be implemented to instruct people on the correct usage of the system.  If followed, procedures can minimize data integrity issues caused by human error. Individuals should also be sensitized to the consequences and potential harm that could arise from data integrity issues resulting from system misuse.

Logical security procedures may outline controls (such as password policies) and codes of conduct (such as prohibition of password sharing) that contribute to maintaining data integrity.

 

Testing of Technical Controls

What to do

Why you should do this

Verify calculations performed on GxP data.

For example:

  • Devise a test scenario where input data is manipulated and double-check that the calculated output is exact.
When calculations are part of the system’s intended use, they must be verified to ensure that they produce accurate results.
Verify the system is capable of generating audit trails for GxP records.

For example:

  • Devise a test scenario where data is created, modified, and deleted.  Verify each action is captured in a computer-generated audit trail.
  • Verify the audit trail includes the identity of the user performing the action on the record
  • Verify the audit trail includes a time stamp
  • Verify the system time zone settings and synchronisation.
With the intent of minimizing the falsification of data, GxP record-keeping practices prevent data from being lost or obscured.  Audit trails capture who, when and why a record was created, modified or deleted.  The record’s chronology allows for reconstruction of the course of events related to the record.

The content of the audit trails ensures that data is always attributable and contemporaneous.

For data and the corresponding audit trails to be contemporaneous, system time settings must be accurate.

 

 

 

Who can delete data?

Adequately validated and have sufficient controls to
prevent unauthorized access or changes to data.

Implement a data integrity lifecycle concept:

  • Activate audit trail and its backup
  • Backup and archiving processes
  • Disaster recovery plan
  • Verification of restoration of raw data
  • Security, user access and role privileges (Admin)

Warning Signs – Red Flags

  • Design and configuration of systems are poor
  • Data review limited to printed records – no review
    of e-source data
  • System administrators during QC, can delete data (no proper documentation)
  • Shared Identity/Passwords
  • Lack of culture of quality
  • Poor documentation practices
  • Old computerized systems not complying with part 11 or Annex 11
  • Lack of audit trail and data reviews
  • Is QA oversight lacking? Symptom of weak QMS?
I love being audited

 

 

 

 

 

 

Perform Self Audits

  • Focus on raw data handling & data review/verification
  • Consider external support to avoid bias
  • Verify the expected sequence of activities: dates,
    times, quantities, identifiers (such as batch,
    sample or equipment numbers) and signatures
  • Constantly double check and cross reference
  • Verify signatures against a master signature list
  • Check source of materials received
  • Review batch record for inconsistencies
  • Interview staff not the managers

FDA 483 observations

“…over-writing electronic raw data…..”

“…OOS not investigated as required by SOP….”

“….records are not completed contemporaneously”

“… back-dating….”

“… fabricating data…”

“…. No saving electronic or hard copy data…”

“…results failing specifications are retested until
acceptable results are obtained….”

  • No traceability of reported data to source documents

Conclusion:

Even though we try to comply with regulations (regulatory expectations from different agencies e.g. EMA, MHRA, FDA, etc), data integrity is not always easy to detect. It is important the staff working in a regulated environment be properly trained and continuous refresher provided through their career (awareness training of new regulations and updates to regulations).

Companies should also integrate a self-audit program and develop a strong quality culture by implementing lesson learned from audits.

Sources:

You can read more about data integrity findings by searching the followng topics:

MHRA GMP Data Integrity Definitions & Guidance for the Industry,
MHRA DI blogs: org behaviour, ALCOA principles
FDA Warning Letters and Import Alerts
EUDRA GMDP database noncompliance

The Mind-Numbing Way FDA Uncovers Data
Integrity Laps”, Gold Sheet, 30 January 2015

Data Integrity Pitfalls – Expectations and Experiences

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ICH is coming to Town – European Medicines Agency (EMA)

The International Conference on Harmonization (ICH)  is involved in promoting public health, improve efficiency of new drug development and registration process among other objectives. In order to accomplish this, ICH has developed and implemented harmonized guidelines and standards, also known as ICH6.

ICH Steps

Over 50 guidelines on technical requirements on:
Quality, Safety and Efficacy
Efficacy – 14 topics/17 guidelines
Safety – 8 topics/16 guidelines
Quality – 9 topics/23 guidelines

  • Maintenance of ICH Controlled Terminology Lists
  • Medical dictionary for adverse event reporting and coding
    of clinical trial data (MedDRA)
  • Electronic Standards for the Transfer of Regulatory
    Information
  • Common Technical Document (CTD & eCTD)

The European Medicines Agency (EMA) is a decentralised body of the EU. EMA is responsible for centralised procedure and co-ordination of EU network + plays a role in stimulating innovation and research in the pharmaceutical sector.

EMA is not an FDA for Europe

EMA responsibility does not include:

  • Evaluation of all medicines in the EU
  • Research/development of medicines
  • Clinical trial approval
  • Medical devices
  • EU healthcare policies
EMA Regulatory Process

 

 

Conclusion: ICH-GCP guidelines brought forth public awareness that there was a need to control and regulate clinical trials dealing with drugs and human subjects.

ICH main goal is to provide a unified standard for the European Union (EU), Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.

Source:

Guidelines on good clinical practice (European Community and within the ICH regions)  – https://ec.europa.eu/

Presentation – ICH and EU regulatory – www.ema.europa.eu

 

Recommended Posts:

https://edcdeveloper.wordpress.com/2015/05/11/are-you-practicing-gcp/

https://edcdeveloper.wordpress.com/2011/11/17/21-cfr-part-11-cheat-sheet-for-the-edc-developer/

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Medical Device Safety and Recalls: Hamilton Recalls G5 Ventilator Because of Ventilation and Alarm Failure

Medical Device Safety and Recalls: Hamilton Recalls G5 Ventilator Because of Ventilation and Alarm Failure

A recall has been issued for the G5 Ventilator. The ventilator may stop working, without sounding an alarm, when the device operator presses the oxygen enrichment key to attach the ventilator mask to the patient (suctioning maneuver).

This problem can occur during the following conditions:

* When pressing the oxygen enrichment key a second time within 50 milliseconds after the disconnection is detected, or,
* When disconnection is detected immediately before the oxygen enrichment period automatically ends, so that detection of disconnection and termination of O2-enrichment occur within 50 milliseconds of each other.

If the device operator does not intervene, the patient may not receive enough oxygen and could suffer serious adverse health consequences, including injury or death.

The firm has received a total of 1 report of device malfunction. No injuries or deaths were reported. For more information, please see: http://www.fda.gov/MedicalDevices/Safety/ListofRecalls/ucm471717.htm

Voluntary Recall Of Chariot Guiding Sheath

Voluntary Recall Of Chariot Guiding Sheath

You are subscribed to Recalls, Market Withdrawals and Safety Alerts for U.S. Food & Drug Administration (FDA).

This information has recently been updated and is now available.

Boston Scientific (NYSE: BSX) has voluntarily recalled the Chariot™ Guiding Sheath globally. These devices are intended for the introduction of interventional devices during peripheral vascular procedures, and were recalled on November 19th due to the risk of shaft separation.

For detailed information pertaining to this Recalls, Market Withdrawals and Safety Alerts message, please click the link at the beginning of this bulletin.

CDRH Industry: Medical Device Export Certificates: Revised FDA Fees

CDRH Industry: Medical Device Export Certificates: Revised FDA Fees

Today the FDA issued a Federal Register (FR) Notice announcing revised fees for medical device export certificates that will go into effect on September 1, 2015. This is the first time the FDA has changed the fees for these certificates since the start of the export certification program in 1996.

Since February 2003, the FDA’s costs to process medical device export certificates have increased. Because of this, the agency is revising the formula used to calculate the number of original and subsequent device export certificates issued and raising the fee for subsequent certificates. These changes are necessary to ensure that the program remains self-sustaining.

More information about exporting medical devices and the fees for export certificates for all FDA-regulated products are available on the FDA’s website.

Source: FDA.Gov

Device Approvals: Edwards SAPIEN 3 Transcatheter Heart Valve

Device Approvals: Edwards SAPIEN 3 Transcatheter Heart Valve

The FDA has recently approved the Edwards SAPIEN 3 Transcatheter Heart Valve to be marketed.  The Edwards SAPIEN 3 Transcatheter Heart Valve (often referred to as SAPIEN 3 THV) consists of a catheter-based artificial aortic heart valve and accessories used to implant the valve without open-heart surgery. The valve is made of cow tissue attached to a balloon-expandable, cobalt-chromium frame for support. The SAPIEN 3 THV is the third generation of the SAPIEN THV that FDA originally approved in 2011. The device has a major design change that adds a skirt at the base of the valve frame to minimize leakage around the valve.

Disclaimer: The EDC Developer blog is “one man’s opinion”. Anything that is said on the report is either opinion, criticism, information or commentary. If making any type of investment or legal decision it would be wise to contact or consult a professional before making that decision

Device Approvals: activL® Artificial Disc

The FDA recently approved the activL® Artificial Disc to be marketed.  The activL® Artificial Disc is an implant that replaces the function of a damaged or diseased spinal disc. The activL® consists of two metal (cobalt-chromium with a titanium coating) endplates surrounding a plastic (polyethylene) insert. The endplates attach to the patient’s vertebrae, and the plastic insert fits between them. The insert is designed to move during daily activities.

For more information check FDA.com

Disclaimer: The EDC Developer blog is “one man’s opinion”. Anything that is said on the report is either opinion, criticism, information or commentary. If making any type of investment or legal decision it would be wise to contact or consult a professional before making that decision