SPECIAL SYSTEM / PROCESS REQUIREMENTS FOR ISO 13485

Risk management system –

In the design and development of safe, effective medical devices, reducing risk and ensuring reliability are a manufacturer’s primary responsibility. The advanced technology inherent in medical devices and their production means that all aspects of the system–including mechanics, electronics, soft­ware, and hardware–must be evaluated for reliability. These standards may apply not only to manufacturers, but also to vendors, suppliers, contractors, OEMs, third parties, and others in product development and distribution.  When risks are discovered, they must be evaluated for their severity and probability of occurrence, and eliminated or mitigated as appropriate. Then, medical devices must be monitored throughout their useful lives to ensure that no new or unexpected risks arise; and, if they do, additional risk analysis and control measures must be implemented.

Medical devices–which may be defined as any equipment used to diagnose, treat, or monitor patient health–are subject to a variety of complex quality and safety analyses due to the potential significant impact on human lives. According to this stan­dard, risk management involves the systematic application of policies, procedures, and practices to the task of analyz­ing, evaluating, controlling, and monitoring the risk inherent in medical devices. Risk management is an iterative process that should evaluate all aspects of the product’s lifecycle and must be implemented and documented over the course of the design, development, prototyping, manufacture, and even postproduction phases of a product’s lifecycle to ensure that no new or unexpectedly severe risks go unmanaged.

1. Phase 1- Establishing acceptable and unacceptable levels of risks.  
2. Phase 2 – Identifying and analyzing the risks associated with the device from all potential sources. 
3. Phase 3 – Evaluating these risks in light of the definitions of risk acceptability defined in Phase 1. 
4. Phase 4 – Implementing control measures to eliminate risks or mitigate their effects, and monitoring the effectiveness of these controls once they are implemented

Numerous standards throughout the medical device industry require the use of a documented process to identify, analyze, and eliminate or control the risks associated with medical device hardware, software, and electronics. This process, known as risk management, must address potential risks throughout the entire product lifecycle of medical device products, including development, manufacture, maintenance, and disposal or decommissioning. Assessing and reducing the risks associated with medical devices also helps to reduce the total impact of wide-ranging product recalls, including financial costs as well as reduced customer satisfaction and a damaged company reputation.

1. Part failures – The failure of one part or component of a medical device can lead to system failure and may result in patient injury or death. 
2. Process failures – Fully operational devices can inflict harm when used improperly, such as X-ray machines when proper measures are not taken to protect the patient.
3.  Human impact – The potential harm caused by a part or process failure may extend not only to the patient but to the device operator and others in the environment, as in the case of a highly flammable oxygen source. 
4. Device application – Each device may have many different applications, uses, or environments.  These devices require different risk controls when used by different operators. 
5. Complex technology – The advanced technology used in medical devices and in their production requires that all aspects of the system–including mechanics, electronics, software, and hardware–must be evaluated for reliability. 
6. Product lifecycle – Every aspect of the product development lifecycle for a medical device–from design, prototyping, and manufacture through distribution, decommissioning, and disposal–must adhere to strict quality standards that are documented and traceable. 
7. Industry-wide standards – These standards may apply not only to device manufacturers, but also to their suppliers, contractors, OEMs, third-party manufacturers, and others associated with product development and distribution. 
8. Significant stakeholders – A wide range of potential stakeholders are affected by the reliability of a medical device, including medical practitioners, healthcare institutions, government, industry, patients, their family members, and others.

Clinical evaluations –

Clinical evaluation is the assessment and analysis of clinical data pertaining to a medical device in order to verify the clinical safety and performance of the device. Clinical evaluation is an ongoing process conducted throughout the life cycle of a medical device. It is first performed during the conformity assessment process leading to the marketing of a medical device and then repeated periodically as new clinical safety and performance information about the device is obtained during its use. This information is fed into the ongoing risk analysis and may result in changes to the Instructions for use.

When placing a medical device on the market the manufacturer must have demonstrated through the use of appropriate conformity assessment procedures that the device complies with the relevant Essential Requirements covering safety and performance. Generally, from a clinical perspective, it is expected that the manufacturer has demonstrated the device achieves its intended performance during normal conditions of use and that the known and foreseeable risks, and any adverse events, are minimized and acceptable when weighed against the benefits of the intended performance, and that any claims made about the device’s performance and safety (e.g. product labeling and instructions for use) are supported by suitable evidence.

To conduct a clinical evaluation, a manufacturer needs to - 

1. Identify the Essential Requirements that require support from relevant clinical data.
2. Identify available clinical data relevant to the device and its intended use.
3. Evaluate data in terms of its suitability for establishing the safety and performance of the device.
4. Generate any clinical data needed to address outstanding issues.
5. Bring all the clinical data together to reach conclusions about the clinical safety and performance of the device.

The results of this process are documented in a clinical evaluation report. The clinical evaluation report and the clinical data on which it is based serve as the clinical evidence that supports the marketing of the device.

Product cleanliness and contamination control –

In the medical device sector, the surfaces of implant devices are of critical importance as they control many clinical properties including the immediate response from the biological host. Surfaces are becoming more complex both in terms of chemistry and geometric form. For example, new-generation cardiovascular stents need to accept drug-loaded polymer coatings and orthopaedic implants, for knee and hip replacement, have complex shapes with beaded or porous surfaces which are coated with hydroxy-apatite to aid tissue adhesion. This makes cleanliness critical in order to optimize coating performance.

 Company requires –

1. Characterization of product surface cleanliness.
2. Validation of new or existing cleaning equipment. 
3. Provision of a validated turnkey installation or continued process monitoring.

A typical cleaning validation project would include the following –

1. Chemical characterization of contaminants.
2. Effects of each manufacturing process stage on surface condition.
3. Production of finalized cleaning specification.
4. Characterization of detergents to be used.
5. Assess Cleaning Stages and Final validation.
6. Continued System Monitoring.

Regulatory bodies, such as the FDA, increasingly require companies to submit general procedures on how cleaning processes will be validated and contamination controlled. The following objectives should be met –

1. Identification of residues to be removed, detection and sampling method.
2. Effectiveness of the steps used to clean the product.
3. Identification of detergent residues deposited in cleaning stages.
4.  Effectiveness of final cleaning stages to remove detergent residues if any.

Requirement for implantable device –

The field of biomaterials is of immense importance for the mankind as the very existence and longevity of some of the less fortunate human beings. Their works at the laboratory were first tested on animals which led to the birth of the ultimate biomaterials that could be accepted by the human system. The first and foremost requirement for the choice of the biomaterial is its acceptability by the human body. The implanted material should not cause any adverse effects like allergy, inflammation and toxicity either immediately after surgery or under post operative conditions. Secondly, biomaterials should possess sufficient mechanical strength to sustain the forces to which they are subjected so that they do not undergo fracture and more importantly, a bio implant should have very high corrosion and wear resistance in highly corrosive body environment and varying loading conditions, apart from fatigue strength and fracture toughness. A biomaterial should remain intact for a longer period and should not fail until the death of the person. This requirement obviously demands a minimum service period of from 15 to 20 years in older patients and more than 20 years for younger patients. The success of a biomaterial or an implant is highly dependent on three major factors

1. The properties of the biomaterial in question.
2. Biocompatibility of the implant.
3. The health condition of the recipient and the competency of the surgeon.

Proper communication of advisory notice –

Medical Device Industry has continued to evolve, so has the role and importance of public relations and corporate communications. Effective external communications activities help organizations build strong stakeholder relationships and marketplace success. The external communications function is the public voice of an organization. Internal communications is a small but important group that delivers information to an organization’s employees on issues such as corporate initiatives and benefits. As the conduit between a company and its workforce, internal communications keeps employees informed about issues that impact corporate success. At many organizations, these two communication groups are separate, but both play crucial roles in educating employees and employees on corporate goals and objectives.

Additional research and developments requirements –

For rare diseases, efforts to accelerate research and product development clearly focus on drugs and biological products. Devices and the need for devices are much less frequently mentioned in articles or conversations. When devices for rare conditions are discussed, it is generally in connection with pediatric populations. To acknowledge the emphasis on drugs for rare diseases is not to imply that devices are not important for many people with rare medical conditions. Some people depend critically on devices targeted at distinctive features of their condition. No pharmaceutical or biological product can provide the mechanical support afforded by this implant. Genetic tests that are necessary for the diagnosis and treatment of certain rare conditions are, in certain cases, regulated as medical devices. In addition, people with rare conditions benefit from a large number of medical devices that are used generally in connection with complex surgery, anesthesia, respiratory support, nonsurgical cardiac procedures, administration of certain medications, diagnostic and therapeutic imaging of various kinds, laboratory testing, and other services.