Project 1 - Device Master File

Device Master File provides confidential information related to about facilities, manufacturing processes, sterilization, packaging materials, and contract packaging and storing of the products, as well as nonclinical and clinical study data] associated with device regulatory submissions to a specific country. This file may contain general description of the device, its variance, intended purpose, & accessories in combination with other device, Warnings, mode of action scientifically demonstrated with description and novel features of the device. They may also include, device specifications, for example, drawings, calculations, components relevant GSPR information, tissues of human and animal origin, toxicity, biological safety and biocompatibility with stability, storage, analytical performance with verification and validation information with clinical data risk management analysis, including risk minimizing measures.

A device master file (DMF) is a document that contains confidential, detailed information about a medical device or pharmaceutical product. It is submitted to regulatory authorities, such as the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA), to provide information about the design, manufacture, and testing of the product.

DMFs are typically used for products that are difficult to describe in a traditional regulatory submission, such as products with complex designs or those that use new technologies. DMFs can also be used to provide information about raw materials, component parts, and finished products that are used in the manufacture of a medical device or pharmaceutical product.

Regulatory authorities may require that companies submit a DMF as part of the process of obtaining marketing authorization for a product. DMFs are typically kept confidential and are not made available to the public. However, regulatory authorities may share information from a DMF with other regulatory agencies or with other interested parties, such as academic researchers or manufacturers of related products, in order to promote the safe and effective use of the product.

Design output means the results of a design effort at each design phase and at the end of the total design effort. The finished design output is the basis for the device master record. The total finished design output consists of the device, its packaging and labeling, and the device master record.

For some devices, many of the design output documents are the same as the device master record documents. Other device output information is used to create a DMR drawing such as for a test or an inspection procedure. Figure 6.1 shows the close relationship between design output and the device master record.

The DMR for each type of device shall include, or refer to the location of, the following information:

(a)  Device specifications including appropriate drawings, composition, formulation, component specifications, and software specifications;

(b)   Production process specifications including the appropriate equipment specifications, production methods, production procedures, and production environment specifications;

(c)  Quality assurance procedures and specifications including acceptance criteria and the quality assurance equipment to be used;

(d)  Packaging and labeling specifications, including methods and processes used; and

(e) Installation, maintenance, and servicing procedures and methods.

The definition for Design Output 820.3(g) and requirements for Design Output 820.30(d) do not apply to most Class I devices. Therefore, the requirements for the DMR for most Class I devices are in 820.181 Device Master Record. Of course, a manufacturer of Class I devices may use the design output sections of the GMP as guidance.

However, almost all sections of the QS regulation have requirements related to the device master record. The device master record contains specifications for the device, accessories, labeling, and packaging, and contains a full description of how to procure the components and manufacture the device including specifications for facilities, environment, and production equipment. In addition to the device specifications, a device master record contains documents that cover typical manufacturing activities such as: 

procurement,

assembly,

labeling,

test and inspection,

packaging, and

where applicable, sterilization.

Note that the listed activities and records or documents are required to produce any product ‑‑ medical, industrial, or consumer. There is nothing special about device master records except the name. Also, note that in common usage, the term "device master record" refers to the total record or any of its individual records. Therefore, the term is singular for the total record, singular for a single document, and plural for a group of single documents. The term also may refer to an original record or a copy of a record.

Device master records should be technically correct, contain and/or reflect the approved device and process designs, be under change control, contain the release or other control date, contain an approval signature, and be directed toward the intended user. These requirements are in the QS regulation because the device master record is the "beginning and end" of a product ‑‑ errors in the device master record will have a serious impact on the state‑of‑control of the manufacturing operation and may have a serious impact on the safety and performance of the device. The device master record should be accurate and complete because the essence of the QS regulation is a quality system based on designing a device to meet user needs, documenting the design and production procedures in the device master record and then producing a finished device that meets the device master record requirements. Thus, the device master record shall accurately reflect the device intended to be produced by a manufacturer.

Technical specifications

Flow rate programmable range atleast from 0.1 nl/hr to 1000ml/hr.

Saves last infusion rate even when the AC power is switched off.

Bolus rate should be programmable to approx, 500ml, with infused volume display.

Selectable occulusion pressure trigger levels selectable from 300, 500 and 900 mmHg.

Accuracy of +-2% or better for set parameters.

Maximum pressure generated 20 psi.

Pause infusion facility required.

Self-check carried out on powering on.

Comprehensive alarm package required including: occlusion alarm, near end of infusion pre-alarm and alarm, volume limit pre-alarm and alarm, low battery pre-alarm and alarm, AC power failure, drive disengaged.

It should be open system

Physical Characterstics

Dimensions: NA

Weight: 150gms

Configuration: Tamper resistant case made of impact resistant material. Securely mountable on tabletop, IV stand or bed fitting.

Noise: Noise free

Mobility: Yes

Energy Source

Voltage: 220V, 60Hz

Battery operated: Yes, backup of 50 hours

Tolerance: +-10%

Protection: Battery powered alarm for power failure or disconnection

 

Regulatory Bodies Approvals, Market history and Price Range

So there are several comapnies out there who sell infusion pumps to the customers. Some of the companies who sell infusion pumps are Smiths Medical, Becton etc. these companies have to follow certain laws in order for their infusion ppumps to sell in the market. The certificates that the manufacturers of this medical device should obtain is ISO 13485 and relevant IEC 60601- Part 1 and 2 certificates by the notified bodies. The market cap for this device has been elevating. The market cap for this device in 2020 was USD 4.4 Bn and expected market cap for 2030 is USD 6.6 BN. The CAGR for 202 to 2030 is 5 percent. The products sell for anywhere between 20000 to 1.5 lakh INR. The market of the infusion pump comes mostly from the NICU and PICU departments of the hospitals as well as small nursing homes who house inn sick patients for large hospitals and need to work according to the standards of the hospital

Adequate Information

Although a manufacturer tries to document for the intended employees, there is a need to audit periodically to see how well the goal is being met. There are various means of determining if information in the device master record, production tools, and other production elements are adequate for a given operation and associated employees. These include analyzing the: 

assistance required by new employees;

assistance required when a new device is introduced into production;­

confusion and hesitation;

information exchanged among employees;

"homemade" documentation drafted by the line employees;

rework;

products produced (productivity);

complaints from departments that subsequently process the device; and

customer complaints.

If any of these factors persist and are out of line with industry norms or with the previous production experience, then the manufacturer should take corrective action. Management shall review the quality system as directed by 820.20 and, thus, be aware of device quality problems or quality system problems such as listed above. The corrective action may include changes in supervision or documentation, adding new documentation, modifying the design, using different tools, modifying the environment, etc.

The process for obtaining market clearance for medical devices in India generally involves the following steps:

1. Classification of the medical device: Medical devices are classified into four categories based on their intended use and potential risk to the user. Class A devices are considered low-risk and do not require any regulatory clearance, while Class B, C, and D devices are considered to have increasing levels of risk and require progressively more stringent regulatory clearance.

2. Registration of the device: Manufacturers of Class B, C, and D devices must register their products with the CDSCO before they can be sold in India. This involves submitting a registration application and supporting documentation, including information about the device's design, intended use, and manufacturing process.

3. Testing and certification: Manufacturers of Class B, C, and D devices must also obtain a certificate of conformity from the CDSCO, which confirms that the device meets the relevant quality, safety, and performance standards. This may involve submitting the device for testing at an accredited laboratory.

4. Marketing authorization: Manufacturers of Class C and D devices must also obtain marketing authorization from the CDSCO before they can be sold in India. This involves submitting a marketing authorization application and supporting documentation, including clinical data demonstrating the safety and effectiveness of the device.

Essential Principle Checklist:

The main principle of the glucometer is to determine the amount of "sugar" in the blood. There are two variations of this action. The first option is photometric determination, and the second one is electromechanical.

Modern glucometers allow us to show the exact content of human sugar. Thus, the photometric principle of operation is based on the determination of glucose by changing the shade of the reagent. The electrochemical form shows the sugar level by measuring the current that appears during the process.

Devices of modern types for measuring glycemia consist of a system with adjustable ejection of blades in order to pierce the skin, an electronic unit that is equipped with a liquid crystal display and test strips.

Initially, nothing is particularly clear, the device seems strange and it's not at all clear how to use it. In fact, there is nothing wrong with that. Modern instruments allow you to quickly use them. After all, this device should be in the house of every person suffering from diabetes.

Many people are interested in how the glucometer work and how to measure the glucose level. So, as mentioned above, there are two principles of action. One of them is called photometric, the second - electromechanical.

So, the first option works as follows. In the interaction of blood glucose and a special reagent that will be applied to the test strip, the latter stains blue. So the intensity of the shade depends on the concentration of glucose. The optical system of the device carries out color analysis and, from these data, determines the level of sugar. The truth is, this device has its disadvantages. Too fragile, and it requires special care, and the results obtained have a great error.

The next device is electromechanical. In this case, glucose interacts with the test strip, resulting in a small electrical current. The device, in turn, fixes this value and determines the level of sugar. In this case, the results can be considered more accurate.

MANUFACTURING AND DESIGN:

One way that diabetics monitor blood glucose concentration is by testing blood samples several times throughout the day and injecting the appropriate dose of insulin. Upon doctors' recommendations and using such products, patients typically measure blood glucose level several (three to five) times a day. Generally these blood samples are taken from the finger, but can be taken from other places. A finger-stick comprised of a lancet is used to prick the finger and withdraw a small amount of blood that is placed on a test strip. The test strip is placed in a monitoring kit typically based on the electroenzymatic oxidation of glucose. While there is no known cure for diabetes, studies show that patients who regularly monitor their blood glucose levels and work closely with their healthcare providers have fewer complications in relation to the disease.

Using a typical glucometer and lancing device, the sampling and measurement process is generally as follows. First, the user prepares the meter for use by removing a test strip from a protective wrapper or vial and inserting it in to the meter. The glucometer may confirm the proper placement of the test strip and indicate that it is prepared for a sample. Some glucometers also may require a calibration or reference step at this time. The user prepares the lancing device by removing a cover from the lancing device, placing a disposable lancet in the lancing device, replacing the cover, and setting a spring-like mechanism in the lancing device that provides the force to drive the lancet into the skin. These steps may happen simultaneously (e.g., typical lancing devices set their spring mechanisms when one installs the lancet). The user then places the lancing device on the finger. After positioning the lancing device on the finger, the user presses a button or switch on the device to release the lancet. The spring drives the lancet forward, creating a small wound.

After lancing, a small droplet of blood appears at the lancing site. If adequate, the user places the sample on a test strip according to manufacturer's instructions. The meter then measures the blood glucose concentration (typically by chemical reaction of glucose with reagents on the test strip).

Raw Materials

There are many raw materials used to produce a glucose monitoring kit. The test strips consist of a porous fabric or material such as polyamide, polyolefin, polysulfone, or cellulose. There is also a water-based hydroxyl eslastomer with silica and ground titanium dioxide. Water, tramethylbenzidine, horseradish peroxidase, glucose oxidase, carboxymethylcellulose, and dialyzed carboxylated vinyl acetate ethyl copolymer latex are also used.

The meter itself is composed of a plastic case that houses the printed circuit board and sensors. There is a liquid crystal display (LCD) that will show the readings of the blood glucose.

The lancet is composed of a stainless steel needle encased in a plastic housing.

Design

There are many different forms of glucose test kits. Some glucometers have needles al-ready installed. The user only presses the release button and the meter ejects the needle prick and withdraws a sample. Others require a separate lancet and test strips. These are the most commonly used forms of glucose kits.

The meter itself typically has a LCD display at the top of the machine. In the middle towards the bottom is a horseshoe-shaped slot in which to fit the test strip. Underneath this slot is a sensor that transmits the readout from the blood sample. The device runs off of batteries and usually has a short term memory built in to remember past glucose readings. Some devices can be hooked up to computer programs to track these readings and printout charts and diagrams depicting drastic shifts.

Verification and validation are important processes in the development and manufacture of pharmaceutical and medical devices. These processes are used to confirm that a product meets the requirements for its intended use and is safe and effective for its intended population.

Verification is the process of confirming that a product, process, or system meets specified requirements. This may involve reviewing the product's design and manufacturing processes to ensure that they are in compliance with relevant regulations and standards, as well as testing the product to confirm that it meets the specified performance, safety, and quality requirements.

Validation is the process of demonstrating that a product, process, or system is capable of consistently meeting its specified requirements. This may involve conducting clinical trials or other studies to demonstrate the safety and effectiveness of the product, as well as ongoing testing to confirm that the product remains safe and effective over time.

Analytical performance reports are documents that provide detailed information about the analytical methods and testing procedures used to evaluate a product's quality and performance. These reports may include information about the accuracy, precision, and sensitivity of the analytical methods, as well as the results of the testing.

Clinical performance reports are documents that provide detailed information about the clinical studies conducted to evaluate a product's safety and effectiveness. These reports may include information about the study design, population, and results, as well as any adverse events or other clinical outcomes observed during the study.

Stability is an important consideration in the development and manufacture of medical devices. It refers to the ability of a product to maintain its quality and performance over time, under specified storage and handling conditions.

Shelf-life is the period of time during which a product is expected to remain stable and suitable for use, when stored under the conditions specified by the manufacturer. Shelf-life is typically determined through stability testing, which involves storing the product under specified conditions and periodically evaluating its quality and performance over time.

In-use stability refers to the ability of a product to maintain its quality and performance when it is being used or administered. This may be influenced by factors such as the product's handling and storage conditions, as well as the duration of use.

Shipping stability refers to the ability of a product to maintain its quality and performance during transportation. This may be influenced by factors such as the product's packaging, handling, and storage conditions, as well as the duration of transportation and the environmental conditions encountered during shipping.

Stability testing is an important part of the regulatory process, as it helps to ensure that products are safe and effective for their intended use. Manufacturers are typically required to provide stability data as part of the process of obtaining market clearance for their products. This may include data on the product's shelf-life, in-use stability, and shipping stability, as well as any relevant storage and handling instructions.

Risk Analysis

The risk analysis of the machine is done by keeping the machine charging for beyond capability hours. The batteries and PCB are check for short circuiting anf is made sure that both are fire proof and do not cause any internal fire on their own. Also it checked if the PCB will discharge charge onto the person touching the machine while it has been charge continuously. Also it is checked if anything that is used on this machine will harm the patient in any way.

Risk Management

For making sure that the things checked above do not happen, several things have been kept in mind during the designing of the machine. The materials that are used in the machine are electric proof, will prevent the fire from happening and are temperature sensitive and can easily disperse the heating that happens from overcharing the device and also its continuous use. Also sensors are added to the design to make sure the machine does not pull the blood out of the patient if the nurse accidentally puts the infusion set in reverse.

Labelling and Packaging

The device is labelled as Class B since the machine will be using invasing procedure to provide the medicine to the patient. the packaging of the material is made in a way that the package does not get damaged during the delivering procedure. The packaging is made out of 100% recyclable material and several layers are used so that the packaging is quite sturdy when it comes to bumps and slight nudging during the delivering. The shelf-life of the product is quite good since the machine needs to be put on patients for use. The shelf life of the material outlasts the shelf life other products in the market. Also the PCB is sturdy and better at handling heat as well as the components used are of good quality.

Post Market Surveillance

PMSPs are documents that outline the specific post-market surveillance activities that a manufacturer plans to undertake in order to monitor and evaluate the safety and performance of a medical device. PMSPs may include activities such as clinical follow-up studies, analysis of adverse event reports, or monitoring of product performance.

Post-market surveillance reports (PMSRs): PMSRs are documents that provide a summary of the results of post-market surveillance activities. Manufacturers are typically required to submit PMSRs to regulatory authorities on a regular basis, in order to provide updates on the safety and performance of their products.

Post-market surveillance is an important part of the regulatory process, as it helps to ensure that medical devices continue to meet the relevant regulatory requirements and remain safe and effective for their intended use. Manufacturers should work closely with regulatory affairs professionals to ensure that their post-market surveillance activities are in compliance with all relevant regulations.

The device has been found with minimum complaints from the consumers. The device has been running good and the after sale service respond has been good from the customers. The complaints seen generally from the customer side is of the battery backup. The batteries of all the infected pieces has been changed and the devices have been up and running. All of the data regarding it is also attached in the form of booklets.