Project 1 - Device Master File

Project 1

Device Master File: It gives all the information pertaining to the device, its manufacturing process, sterilization, and packaging materials as well as clinical study data associated with device regulatory submissions to India, as per MDR 2017.

Device class identification:

Broadly, the device must be determined if it is an IVD or a medical device other than IVD. Then as per MDR 2017, devices are classified based on risk class as below:

• Class A: low risk
• Class B: low-medium risk
• Class C: medium-high risk
• Class D: high-very high risk

Regulatory policies requiring information about device master file

Device Master file for medical devices other than IVD information is specified in Appendix II and for IVD medical devices the information is specified in Appendix III.

Device master file Information:

• Executive summary: It contains the introductory descriptive information about device, intended use, indications for use, class of device, shelf life, sterilization information, risk management plan.
  • It also contains information about clinical evidence, regulatory information of similar product, design examination certificate, marketing history, price and safety information
• Device description and product specifications: working principle, description of accessories
  • Features, dimensions and key functional elements of device
• Labelling: labelling as per chapter VI
  • Copy of original label of device including accessories
  • Promotional material
• Design and manufacturing information: Device design and manufacturing process
  • Device design to give general understanding of design stages
• Essential principles checklist: essential principles
  • Methods of conformity
• Risk analysis
  • Description of risks and benefits of device
• Validation and verification of device
  • It includes reports of verification and validation
  • Biocompatibility testing, software verification and validation is also included

Requirements of market clearance of devices in Indian market

All the medical devices and IVD devices are regulated by CDSCO (Central Drugs Standard Control Organization).

For registration or distribution or sale of medical device

Step 1: Classify the device as per CDSCO and Apply for the licence through online portal through Form MD-3 or 5 along with the fee prescribed in second schedule.

Step 2: For Class A or Class B device, SLA will offer the licence. For class C and Class D device CLA will offer the licence

Step 3: For Class B, C, D devices before grant of licence audit will take place by notified bodies

Step 4: For new medical device without predicate device, clinical performance evaluation is mandatory.

Step 5: After all the careful examination by CLA or SLA, it will grant the licence.

For imported device

Step 1: Apply through online prtal

Step 2: Appoint Authorized agent to interact with CDSCO through power of attorney

Step 3: Class B, C, D devices require in-country performance testing through nationally accredited laboratories.

Step 4: Compile information like clinical performance reports and safety

Step 5: After necessary documents, we will get the licence

Risk analysis

Risks identified during risk analysis process and how these risks have been controlled to an acceptable level. This risk analysis should be based on standards and complexity and risk class of the device. The technique used to analyze the risk has to be specified and ensure that the technique used is appropriate for the medical device.

The risk analysis submitted will have a periodic updating of risks identified as per risk management plan.

Characteristics of verification & validation

Verification: it involves ensuring each element of device meets the appropriate specifications and standards. It is an internal process

Validation: it is the systematic and objective evaluation of device that examines if the device meets the specifications. It is an external process.

Verification and validation of medical devices include following

• Engineering test reports
• Laboratory tests
• Animal tests for demonstrating feasibility or proof of concept
• Biocompatibility testing: It evaluates the device for its compatibility with human tissue
• Medicinal substances: the identity of medicinal substances and intended use and its safety and performance
• Biological safety: list of all materials of animal or human origin used in the device.
• Sterilization: if the device is supplied sterile then sterilization method is evaluated
• Software verification and validation: information on the software design and development process and evidence of validation of software.

Analytical performance: It tests for the ability of a device to correctly detect or measure a particular analyte. The following characteristics are measured-

• Accuracy of measurement
• Reproducibility
• Analytical sensitivity
• specificity

Clinical performance: it is the ability of a device to produce results in correlation with a particular clinical condition.

It is the justification for clinical evidence. It gives details about intended purpose of device. Clinical performance evaluation is performed for new medical devices as per CLA procedure.

Clinical Performance evaluation report demonstrates the conformity to essential principles that are applicable to it.

Stability

Stability of a medical device is the extent to which the device maintains its integrity under environmental conditions like temperature, humidity, light, moisture, pH.

For supporting the stability of a medical device, a real-time aging data shall be submitted to support the claimed shelf life of a medical device if available. However, if real-time data is not available, an accelerated stability data is submitted.

A provisional claimed shelf life may be approved if manufacturer immediately initiates real-time stability testing to validate the claimed shelf life. Once the real-time stability analysis is completed, data may be submitted in support of the claimed shelf life.

Claimed shelf life: testing should be performed on at least three different lots . the claimed shelf life report should contain the study report including protocol, number of lots and testing intervals.

In use stability: this includes open vial stability for automated instruments, on board stability. In case of automated instrumentation, calibration stability can be claimed.

Shipping stability: it is to evaluate the tolerance of products to the anticipated shipping conditions.

Labeling of medical devices

All class medical devices require labeling. The following particulars must be printed in a permanent ink on the label, on the shelf pack or on the outer cover namely-

• Name of the medical device
• Necessary details to identify the device and its use
• Name and address of manufacturer and manufacturing premises
• Details of net quantity in terms of weight, volume
• Month and year of manufacture and expiry
• Indicate if device contains medicinal or biological substance
• Indicate distinctive batch number or lot number
• Indicate if any special care or storage method is essential
• Indicate if the product is already sterile or else mention the method of sterilization method
• Indicate any warnings or precautions if required
• If the device needs to be used only for single time, indicate it appropriately
• If the device is for distribution to medical professional, then mention “Physician’s sample-Not to be sold”
• In case of imported devices, mention import licence number, name, address of actual manufacturing premises

Labeling for IVD medical devices

For any new medical device or IVD medical device manufactured for the purpose of clinical investigation, it shall be kept in containers indicating labels, name of the product, code number, date of manufacturing, expiry date and the purpose of it manufacturing.

Post-Marketing Surveillance Report (PMSR): It is a systematic process to collect and analyze the information from devices that have been placed in the market.

After the product has been approved for the market use, the manufacturer has to conduct post-marketing surveillance with objective of safety and performance as per CLA protocol.

Device master file contains a Post-marketing surveillance report that has data collected by manufacturer, details of complaints received and corrective &preventive actions taken for its improvement. Post-marketing surveillance report is also called as vigilance report

Manufacturers have to conduct a post marketing clinical investigation for testing the safety and performance for the new medical devices that do not have any predicate device. This post marketing clinical investigation includes studies on

• Drug-device interaction
• Safety studies
• Mortality and morbidity studies

PSUR-Periodic Safety Update Record

PSUR is a must for all class of devices

It is a record for clinical safety. It summarizes all clinical and non-clinical safety data periodically. For new approved devices, PSUR is submitted every 6 months for two years. For subsequent two years, it is submitted annually. PSUR contains the following information-

• Title page: Name of the device, its approval date, date of marketing, licence name and address
• Introduction: it mentions the reporting period, device’s intended use, working principle and risk class
• Current worldwide marketing authorization status: details of countries currently device has been approved along with approval date
• Actions taken for safety reasons: A description of the action taken and its reporting
• Changes to reference: it gives the details of any significant changes implemented during reporting period
• Estimated patient exposure: it provides the estimation of size and nature of the population that is exposed to the device
• Studies: it gives a brief summary of clinically important efficacy or effectiveness findings