Project Planning

Good planning is the basis of any successful endeavor. Planning helps you to make good, well-considered, robust plans, that, when successfully executed gives great products. A good plan will:
* State the current situation.
* Have a clear aim.
* Use the resources available.
* Detail the tasks to be carried out, whose responsibility they are, and their priorities and deadlines.
* Detail control mechanisms that will alert you to difficulties in achieving the plan.
* Identify risks, and plan for contingencies. This allows rapid and effective response to crises.
* Consider transitional arrangements – how to keep things going while implementing the plan.
A product planning cycle looks something like this:

1. Analysis of opportunities gives reality to the plan. It is important to explore and exploit all available opportunities to determine what is to be done. Creativity tools, SWOT Analysis and Risk Analysis can help to identify opportunities for development or improvement.
2. Definition of the aim gives your plan a goal to focus and concentrate its energy on. A well defined plan will prevent wastage of resources on irrelevant issues.
3. Explore options helps to generate as many different ways for achieving the aim as possible. By spending time looking for these you may find a better solution than the obvious one, or may be able to improve the obvious solution with parts of other ones.
4. Selection of the best approach is sometimes a tough call. This can be made easier by considering the resources and time available or with the use of Decision making tools like Grid Analysis or Decision Trees.
5. Detailed planing shows how to implement selected option. It helps to work out the most efficient and effective way of achieving the aim defined. It is the process of determining who will do what, when, where, how and why, and at what cost. Gantt Charts and Critical Path Analysis can be immensely helpful in working out priorities, deadlines and the allocation of resources.
6. Evaluation of this plan makes sure that the plan will be worth implementing. If it is not, return to an earlier stage and either improve the plan or make a different one. If no plan looks to be producing enough benefit to justify the cost, it is best not to make any changes at all.
7. Plan implementation is the next step once a course of action is selected, and has been proven to be viable.
8. Plan closure involves examining results and drawing conclusions. It is important to identify any mistakes, both to rectify them and to learn from them. The feedback is also noted for future planning.

Device Recalls

A recall is a method of removing or correcting marketed products that are in violation of laws administered by the Food and Drug Administration (FDA). Recall does not include a market withdrawal or a stock recovery (removal of un-marketed devices under the manufacturers' control). Medical device recalls are usually conducted by the manufacturer voluntarily using 21 CFR 7, to protect public health. However, if a manufacturer fails to report a malfunctioning device or initiate its recall, the FDA can issue a recall order under 21 CFR 810 and start legal action against the manufacturer.

Medical device recalls may result from manufacturing defects, labeling deficiencies, failure to meet premarketing requirements [PMA, 510(k)], packaging defects or other nonconformance problems. Recalls are of different classes depending on the relative degree of health hazard they pose to the user, class I posing the most hazard.
Class I - reasonable probability that the use of, or exposure to, a violative product will cause serious adverse health consequences or death.
Class II - remote probability that the use of, or exposure to, a violative product may cause temporary or medically reversible adverse health consequences.
Class III - a situation in which use of, or exposure to, a violative product is not likely to cause adverse health consequences.

A manufacturing firm may decide of its own volition and under any circumstances to remove or correct a distributed product. A firm that does so because it believes the product to be violative is requested to notify immediately the appropriate FDA District Office. Such removal or correction will be considered a recall only if the FDA regards the product as involving a violation that is subject to legal action, e.g., seizure.

When a device is found to be in violation of the FDA regulations, it is first subject to a health hazard evaluation by the FDA. Data evaluation is done to detect if the device has caused any diseases or injuries during use, or can contribute to other clinical conditions. Various assessments are conducted to evaluate
* hazards in all segments of population;
* degree of seriousness of the hazard in the exposed population;
* likelihood of hazard occurrence; and
* consequences of the potential hazard.
Based on these results and other evaluations, the FDA assigns a Recall Class to the device being evaluated.

Once the device is assigned for recall, the recall firm develops a recall strategy based on the heath hazard evaluation. The recall firm in most cases is the manufacturer of the device. The recall strategy determines the
* Depth of Recall - level of distribution chain up to which recall is to extend. Can be user level, retail level or wholesale level.
* Public Warning - to alert the public of the violative device being recalled.
* Effectiveness Checks - to verify that all consignees have received notification about the recall and have taken appropriate action.
The recalling firm is to submit periodic recall status reports to the appropriate FDA district office. The FDA assesses the progress of the recall through these reports an their frequency is determined by the relative urgency of the recall and will be specified by the FDA for each recall case. A recalling firm may request termination of its recall based on its progress. A recall will be terminated when FDA determines that all reasonable efforts have been made to remove or correct the product in accordance with the recall strategy, and when it is reasonable to assume that the product subject to the recall has been removed and proper disposition or correction has been made commensurate with the degree of hazard of the recalled product.

Complaint Handling

Any communication that points to some deficiencies in the product identity, quality, durability, consistency, security, efficiency, or performance of a product or device after it is released for distribution, is considered as a complaint. As seen under MDR, complaints concerning device-related deaths, serious injuries, or malfunctions must be reported to the FDA.

Manufacturers are to maintain a detailed record of all complaints and solve them in a timely and efficient manner. The complaint handling system of a company can define the efficiency of its Quality System. Each manufacturer must establish and maintain procedures for receiving, reviewing, and assessing complaints by an officially designated unit. A good complaint handling system can
* Provide a suitable solution to the problem;
* Improve customer relations and customer satisfaction;
* Evaluate weaknesses in the product and help resolve it;
* Increase company's accountability and transparency;
* Reduce medical device reporting;
* Reduce costs and improve production schedules;
* Reduce employee confusion.

The GMP regulations state certain requirements that are to be included in any complaint handling system. All manufacturers should:

1. document, review, evaluate, and file all complaints;
2. formally designate a unit or individual to perform these activities;
3. determine if an investigation is necessary;
4. record the reason if no investigation is made;
5. assign responsibility for deciding when not to investigate; and,
6. determine if the complaint requires an MDR report.

A sample complaint handling system is depicted in the image below:
(Source: http://www.assurx.com/software-solutions/complaint-handling-management.htm)

All complaint records should have some basic details like
* sequential number of the complaint;
* origin of the complaint;
* customer information;
* product information;
* any corrective actions already taken;
* details of the complaint;
* and dates, signatures, assignments, etc.
These records should be maintained by the company for review during FDA audits.

Six Sigma Process

Six Sigma Processes can be of two types depending on the stage of the business. The process used for a developed/developing business is DMAIC, while the process used for new business is DMADV. Both processes are explained in detail.

1.Six Sigma DMAIC: A systematic Six Sigma Process used to perfect business processes already in place.

D: Define M: Measure A: Analyze I: Improve C: Control

Define Phase : Define a goal for the project. This is done by identifying issues causing biggest problems and setting up requirements to define the goal-.

Measure Phase: The goals defined in the previous phase are quantified to make them real and achievable. Pertinent data is collected and stored for future reference.

Analyze Phase: Statistical tests are performed on the data collected. Other six sigma tools are also applied to collect concrete information that undoubtedly shows areas that need improvement. This step involves determining the causes of any errors, evaluation of corrective measures already in place or those that have been planned to be implemented.

Improve Phase: This step aims at implementing the solutions created based on data analysis and brainstorming. The solutions are implemented and the information is disseminated to the employees.

Control phase: This deals with any obstacles that occur and takes care of it properly and promptly.

2. Six Sigma DMADV: A systematic Six Sigma Process used to create and perfect brand new products or services.

D: Define M: Measure A: Analyze D: Design V: Verify

The first three phases, Define, Measure, and Analyze are the same as the DMAIC process.

Design Phase: This step involves design of new processes that will provide stronger support by correction or elimination of the identified error at its root to reach the goals set in the Define phase.

Verify Phase: It involves monitoring and simulation. Simulation is done before the plan or process is implemented to ensure that the error or errors have been eliminated. Once the plan is implemented, the changes are monitored to determine its effectiveness or the necessity for corrections.

Six Sigma

Six Sigma is a quality management methodology that uses different theories and tools to improve upon the processes of a certain business such that greater output is realized with less input. This results in near perfect products and services that meet and/or exceed the expectations of customers or end users, while simultaneously reducing the amount of time, money, and resources put in. In 1980's, the Motorola Corporation first created and implemented this methodology and have profited immensely since then.

Statistically, ‘Sigma’ (σ) is used to represent the statistical term ‘standard deviation’ which measures the deviations from average in a particular business process.
As the deviation from the normal increases, there is an increase in defective products or services. These ‘defects’ require resolution, which costs businesses increased time, money and resources in the long run. It is possible and practical to improve all business processes to 99.9997% perfection with the Six Sigma Methodology. The percentage of defects decreases as the number of sigma increases. The Defects Per Million Opportunities (DPMO) is only 3.4 when 6σ is employed, as opposed to 6,210 using 4σ which is the current industry standard.

Six Sigma = 3.4 DPMO, or 99.99% defect-free
Five Sigma = 233 DPMO, or 99.98% defect-free
Four Sigma = 6,210 DPMO, or 99.4% defect-free
Three Sigma = 66,807 DPMO, or 93.3% defect-free
Two Sigma = 308,538 DPMO, or 69.1% defect-free
One Sigma = 691,462 DPMO, or 30.9% defect-free

One of the most important things to note about the Six Sigma Process is that it does not rely on quick-fix programs to temporarily mask a business problem. It is a systematic methodology of hard work that is fused with a disciplined, factual, data-based and statistical problem-solving method. The amount of guesswork and product testing can be cut to a fraction, saving time and money. Therefore, it affects almost all aspects and levels of a company. Six Sigma can be applied in any field, if there is a process involved, it can be streamlined with Six Sigma.

Steps for manufacturing successful product

According to the FD&C Act, it is required that domestic or foreign manufacturers have a quality system for the design and production of medical devices intended for commercial distribution in the United States. The regulation requires that various specifications and controls be established for devices; that devices be designed under a quality system to meet these specifications; that devices be manufactured under a quality system; that finished devices meet these specifications; that devices be correctly installed, checked and serviced; that quality data be analyzed to identify and correct quality problems; and that complaints be processed. Thus, the QS regulation helps assure that medical devices are safe and effective for their intended use. More details can be obtained from
◦ The Quality System Regulations – 21CFR 820(QSR’s)and
◦ ISO Standard 13485:2003.

The QS consists of four major actions: Design -> Manufacture -> Distribute -> Monitor performance. The FDA's QSR manual shows how any new entrepreneur can start a successful medical device company by sequentially following the steps below.

1. Obtaining information on GMP requirements;
2. Determining the appropriate quality system needed to control the design, production and distribution of the proposed device;
3. Designing products and processes;
4. Training employees;
5. Acquiring adequate facilities;
6. Purchasing and installing processing equipment;
7. Drafting the device master record;
8. Noting how to change the device master records;
9. Procuring components and materials;
10. Producing devices;
11. Labeling devices;
12. Evaluating finished devices;
13. Packaging devices;
14. Distributing devices;
15. Processing complaints and analyzing service and repair data;
16. Servicing devices;
17. Auditing and correcting deficiencies in the quality system; and,
18. Preparing for an FDA inspection.

It is to be noted how each of the steps is a comprehensive process in itself. These steps if followed according to the FDA protocols will ensure production of a successful medical device.

Failure Modes and Effects Analysis (FMEA)

Failure modes and effects analysis (FMEA) is a tool used for identifying all possible failures in a
* design,
* manufacturing or assembly process,
* product or
* service.
It follows a step-by-step approach to detect possible failure modes and based on its priority, corrective actions are applied.

“Failure modes” denotes the ways in which something might fail. Any potential or actual errors or defects that can affect the customer are termed failures. The consequences of those failures are studied and described under “Effects analysis”.

Once the failures are identified they are prioritized according to the seriousness of their consequences are, their frequency and the ease of their detection. The FMEA aims to take actions to eliminate or reduce failures, based on their priority.

The steps involved in the FMEA process are:
1. The scope of the FMEA is identified. The scope can be a design, process or service.
2. Identify key functions of the scope.
3. List potential failure modes of each of the function. (How can this function go wrong)
4. Identify the effects for each failure mode. (How will this failure affect the manufacturer, customer..)
5. Rate the severity(S) of each effect on a scale of 1 to 10, 10 being most severe.
6. Identify the causes of all the failure modes. (Why does the function go wrong)
7. Rate the causes for each failure mode in terms of occurrence (O), 10 denoting the most frequent cause.
8. Identify the controls in the scope to detect the cause.
9. Rate the controls on the basis of detectability (D), 10 denoting extremely weak or no control.
10 Calculate Risk Priority Number (RPN). This is done by multiplying the ranks of severity, occurrence and detection (S*O*D). If, we had a severity of 10 (very severe), occurrence of 10 (happens all the time), and detection of 10 (cannot detect it) our RPN is 1000. This is a serious issue with great priority.
11. Identify the most critical issues by sorting the RPNs.
12. Assign corrective actions and deadlines.
13. Perform corrective actions and re-score the S, O and D numbers as applicable and calculate new RPNs.

A sample FMEA template can be seen in the figure above. It is a template specific for process FMEA as seen in http://lssacademy.com/2007/06/28/10-steps-to-creating-a-fmea

Corrective Action Preventive Action (CAPA)

CAPA focuses on the systematic investigation of non-conformances (failures and/or deviations) to prevent their recurrence or their potential occurrence.

Corrective Action aims to correct any event of non-conformance that has already occurred and to prevent its re-occurance.
Preventive Action is a proactive measure taken to identify and eliminate potential causes of potential non-conformances.

The FDA requires that all manufacturers find their problems, fix them and prevent their recurrence. The procedure for implementing CAPA includes requirements for:
1. Analyses of all sources of quality data to identify existing and potential causes of non-conformance.
2. Investigation of the causes of non-conformance.
3. Development of corrective actions to correct or prevent the occurrence of non-conformance.
4. Verification and validation to ensure effectiveness of corrective and preventive actions. The effect of these actions should not adversely affect the finished device.
5. Implementation of the changes in the methods or procedures needed to correct and prevent the quality problem identified. These changes are also recorded.
6. Dissemination of the CAPA information to the quality team.
7. Submission of relevant information on quality problem identification and the corrective and preventive action for management review.
8. Documentation of all activities required for the CAPA procedure.

The inputs for the CAPA procedure can be obtained from audits, customer complaints, process improvement projects, nonconformance reports, waste/rejection rates, FMEA, etc. The controls in CAPA to handle these inputs are:
* Design control
* Process control
* Facilities control
* Documentation and change control
* Materials control
All closed CAPA procedures should be audited to verify effectiveness.

HFE and Risk Management

Studies show that the frequencies and consequences of use-related hazards of medical devices might far exceed those resulting from device failures. This necessitates the incorporation of Human Factors Engineering (HFE) principles in the device design process. HFE identifies and addresses potential use-related hazards that arise due to interactions between the user and the device.

Most designers only consider the most apparent (e.g., fire) or well-known use problems and thus limit to only relatively few user actions that cause device failure. According to the FDA, use-related hazards occur for one or more of the following reasons:
• Use of devices in ways that were not anticipated,
• Devices are used in an anticipated way, but inadequately controlled,
• The user's physical, perceptual, or cognitive abilities are not sufficient for the device use,
• The user’s expectations or intuition about device operation are inconsistent with actual device use,
• The effects of the use environment on device operation is not understood by the user, or
• The user’s physical, perceptual, or cognitive capacities are exceeded when using the
device in a particular environment.

The device-user system, thus consists of three major components:
1. Use environments,
2. User characteristics and
3. Device user interface characteristics.
The interactions of these components can thus result in a safe, effective, or unsafe and ineffective use of the device. This can be depicted in the following image.

HFE approaches can be incorporated into the design of medical devices within the risk management process to account for the changes in the device-user system. FDA defines risk management as the systematic application of management policies, procedures, and practices to the tasks of identifying, analyzing, controlling, and monitoring risk.
HFE incorporation into risk management can be achieved by four steps:
• Identify use- related hazards that are anticipated (derived analytically) and unanticipated (derived empirically),
• Describe the hazardous use scenarios that can occur,
• Develop and apply strategies that can control these use-related hazards, and
• Demonstrate safe and effective use of the device (validation).
The risk management process by which use-related hazards can be addressed is shown below,

A more detailed description of the process can be found in the FDA document, "Medical Device-Use Safety: Incorporating Human Factors Engineering into Risk Management."

Human Factors

Human factors is a discipline that seeks to improve human performance in the use of a device/equipment by developing a hardware and software design compatible with the user's abilities. It is often referred as human engineering or ergonomics. A medical device can be used safely and effectively only if the interaction between the operating environment, user capabilities, stress levels, and device design is considered when the manufacturer designs the device.

Device design should take into account the basic physical and sensory capabilities, perceptional and cognitive abilities, device expectations, user's mental model of the device capabilities and design, use environments, and all possible categories of users, including the patients themselves.

User interface designing is an important aspect of an ergonomic design. Some basic considerations include,
* Control/Display Layout and Design
* Simple device logic, microprocessing and software design
* Design and code systems to avoid device mis-installation
* Alarms and alert systems
* Device maintenance
* Packaging

The following figure gives a brief outline of the steps involved in usability engineering or human engineering.

Human Factors Standards and Resources
AAMI HE75 – Design Reference
AAMI HE74 – Human Factors Process
IEC 62366 – (Process) Application of usability engineering to medical devices
FDA.gov; FAA.gov

Design Controls

Design controls are a system of checks and balances for systematic assessment of the design during all phases of development. It consists of an interrelated set of practices and procedures that are incorporated into the process of design and development. As a result, discrepancies between user requirements, design and the product can be avoided to create a design that will translate into a successful device. The application of design controls to a design process can be depicted in the figure below.

* Design Input - It consists of physical and performance requirements that are the basis of device design. The design input requirements are unambiguous, self-consistent and expressed with quantitative limits of tolerance. The device use environment is also properly characterized and all requirements are thoroughly reviewed.

* Design Output - It consists of the results of each design phase and the total design effort. The finished design output is usually the device master record. Design output includes production specifications as well as a description of the materials which define and characterize the design. The total finished design output is the device with its packaging, labeling and the device master record.

* Design Review - It consists of a documented, comprehensive, systematic examination of a design to evaluate the adequacy of the design requirements, to evaluate the capability of the design to meet these requirements, and to identify problems. Formal design reviews can be designed to detect problems early in the development process. As the design nears completion, the flexibility of implementing optimal solution decreases and the cost to correct design errors increases.

* Design Verification - It is the confirmation by examination and provision of objective evidence to show that the device meets the manufacturer's requirements. It follows a three-pronged approach employing tests, inspections and analyses and is to be documented systematically.

* Design Validation - It is the process of establishing that the device specifications conforms with user needs and intended use. It usually follows design verification and it provides assurance that the design will conform with user needs and intended uses.

All changes made during the design process are documented as the design history file, which is a compilation of records describing the design history of the finished device. Design validation is followed by design transfer where the device design is translated into production specifications. Manufacturing processes are employed to produce a device based on the production specifications. The device is then sterilized, packaged, labelled and marketed, with the FDA approval.

Good Laboratory Practices (GLP)

GLP's are regulatory guidelines designed to prevent malpractices in research and development. The GLPs are designed to promote the quality and validity of the test data. GLP was imposed on the industry by regulatory authorities, in the same way as good manufacturing practice (GMP) had been before, and followed by good clinical practice (GCP) afterwards. FDA issued mandatory requirements for GLP on June 20, 1979 and they apply for all non-clinical studies used to evaluate safety. It is also instituted by all OECD(Organization for Economic Co-operation and Development) countries.

The fundamental requirements of the GLPs focusses on standardization of 5 categories:
1. Resources: organization, personnel, facilities and equipment.
2. Rules: protocols and written procedures.
3. Characterization: test items and test systems.
4. Documentation: raw data, final report and archives.
5. Quality assurance unit.

The main goal of the GLPs is to make results reliable, repeatable, auditable and recognized by scientists worldwide.

It aims at making False Negatives and False Positives markedly obvious to validate results better and to promote mutual recognition and comparison of study data universally.

Pre-market Notification 510K

The purpose of the 510k is to establish safety and efficacy of the new device by proving its substantial equivalence to a predicate device. The predicate device can be a pre-amendment device (devices prior to May 28, 1976 Medical Devices Amendment) or a post-amendment device that is substantially equivalent (with respect to intended use, component materials, etc.,) to a pre-amendment device. If substantial equivalence is established then the new device is subjected to the same regulations as the device to which substantial equivalence has been established. The comparison with the predicate device should include similarities/differences, identification of materials, design considerations, energy expected to be used or delivered by the device, and a description of the operational principles of the device.

In addition, all 510k submissions also require to state:
device name - proprietary and common name
device classification
device description
its intended use
proposed label, labeling, advertisements, directions of use
sterilization techniques
results of biocompatibility testing

Once submitted, the FDA takes 90 days to process the 510k and it can permit or deny the marketing of the device.

Medical Device Design Process

The process of designing a medical device consists of the following steps:

1. Identifying user needs - This may involve identifying problems with existing diagnostic tools, prosthetic or surgical devices, or recognizing a whole new unexplored market (novel device based solutions for diseases). The primary user of medical devices are physicians who either prescribe or incorporate these devices on/in patients.

2. Reviewing marketed solutions - The next step is to understand the technology and the shortcomings of existing solutions(if any) to the problem.

3. Developing possible solutions - This is the major brainstorming step where solutions are conceived for the problem based on the user needs. Many possible solutions can be obtained to solve the problem.

4. Identifying the best possible solution - In this stage, the results of the previous step are compared and the solution which best satisfies the user needs is selected.

5. Device Design Criteria - The solution selected is translated into design inputs for the design process.

6. Device Design Process - This is a comprehensive step where the design inputs are manipulated to develop a product design.

7. Developing a Prototype - The design is now engineered to produce a working model or prototype of the device.

8. Verification and Validation - This prototype is tested to check its compliance with the design needs and user needs. Based on the outcome of this step, the steps 6-8 might undergo several iterations.

9. Packaging and Marketing - Once the device is ready, it is sterilized and packed according to FDA standards and is ready for marketing.

The FDA regulatory process must also go hand in hand with the device design process. This would enable timely release of device into the market.