QMS structure

Susanne Manz MBA, MBB, RAC, CQA , in Medical Device Quality Management Systems, 2019

A Design History File (DHF) per 21 CFR 820.10(e) means a compilation of records, which describes the design history of a finished device. Per 21 CFR 820.30(j), it contains or references all records necessary to establish compliance with the design plan and regulations including design control procedures. The DHF is not only a regulatory requirement but also provides significant value to the manufacturer in understanding development successes and failures, and approaches for new designs. It contains valuable verification and validation protocols that are not in the DMR. Despite the name "file," the documentation does not need to be housed in one continuous filing cabinet. Rather, the compilation of applicable documents can be housed in various locations or an electronic data management system (EDMS), but it must be readily available. Typical documents include:

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Design plans

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Design review meeting minutes

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Drawings, specifications, assembly drawings

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Procedures

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Risk analysis

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Engineering notebooks

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Component qualification

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Biocompatibility

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Verification protocols and reports

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Validation protocols and reports

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Design transfer checklists

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Good manufacturing practice (GMP) for biomaterials and medical devices in the EU and the USA

F. Tarabah , in Regulatory Affairs for Biomaterials and Medical Devices, 2015

8.6.5.2 Design history file

The DHF is a compilation of records describing the design history of a finished device [820.3(e)]. The DHF covers the design activities used to develop the device, accessories, major components, labelling, packaging, and production processes.

The design controls in 820.30(j) require that each manufacturer shall establish and maintain a DHF for each type of device. 'Each type of device' means a device, or family of devices, that is manufactured according to one DMR. That is, if the variations in the family of devices are simple enough that they can be handled by minor variations on the drawings, then only one DMR exists.

The QSR also requires that the DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of this part. As noted, this requirement cannot be met unless the manufacturer develops and maintains plans that meet the design control requirements. The plans and subsequent updates should be part of the DHF. In addition, the QSR specifically requires that:

•

the results of a design review, including identification of the design, the date, and the individual(s) performing the review, shall be documented in the DHF.

Design verification shall confirm that the design output meets the design input requirements. The results of the design verification, including identification of the design, method(s), the date, and the individual(s) performing the verification, shall be documented in the DHF.

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Form Follows Material

Michael Ashby , Kara Johnson , in Materials and Design (Third Edition), 2014

Conclusions

One of the most quoted and influential phrases of design history is "form follows function." Its originator, Louis Sullivan, had a simple point he wished to make, 5 but its brevity, its alliteration, its practicality – its neatness – gives it a compelling quality, seeming to say that the best form for a product is that which best fulfills its function. This reasoning has an obvious appeal to engineers, whose job it is to make things function, and there are many instances in which the pursuit of function has created a thing of beauty: the Golden Gate bridge in San Francisco, the original Volkswagen Beetle, the Concorde aircraft (though the Boeing 747, it could be argued, is nearer to the "form follows function" principle) – all these were designed with technical rather than aesthetic challenges in mind. Perceptions like these have given the phrase the status of a religious dogma.

But can it really be true? Is the best design – the only design – that which best fulfills its function? Form, as just shown, is also influenced by materials; in the case of architecture, the influence is strong; in product design, though sometimes less obvious, it is certainly present. A case could be made for the dictum "form follows material" – it doesn't sound as good but it may be closer to reality. It seems to be a general rule that good design uses materials in ways that make the most efficient, and often visible, use of their properties and the way they can be shaped. Rules, of course, have their exceptions: incongruous use of materials can convey the surreal (a furry watch) or the ridiculous (a knife blade made of rubber) or transfer an association from one object to another (chocolate Eiffel Towers). All have their small place. But at the center of the stage are forms that use materials elegantly, efficiently, and economically.

And function and material are not the only directors of form. Consumers buy things they like; and with many alternatives of nearly equal technical merit, the consumer is influenced by trends in taste, by advertising, and by the things that other people buy. Form, inevitably, follows fashion. There are still other drivers of form. Form follows delight. The near-satiated society of 2000+ is attracted by humor (the Snoopy hair dryer, the banana telephone), by perfection (the immaculate body paint of a new car), by luxury (deep, soft leather-upholstered furniture), and by whimsical novelty (any Philippe Starck design). Product form is influenced by many things, but material and process are among the strongest.

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Design realisation/detailed design

Peter Ogrodnik , in Medical Device Design (Second Edition), 2020

8.3.1 DHF considerations for the "lead designer"

You will have appreciated, from previous chapters, that all regulatory bodies want a Design History File (DHF). Hence one of your main roles as lead designer is to ensure that the DHF is populated and updated. This means that you need to ensure that you receive documentary evidence from all of the participants, and that documentation is in the form you require.

Hence another consideration for the lead designer is contracts. You cannot run this level of project on "word of mouth" instruction; all must be documented. Hence the two external bodies in Table 8.1 need to have been selected on merit (documented); the PDS of their aspect of the project has to be agreed an signed off; and your contract with them must ensure that they provide you with the information you require for your DHF.

A more subtle aspect of dealing with external companies is security. You should always have a Non-Disclosure Agreement with all of your sub-contractors. If the project is highly secret you should ensure that they know it is so and that all is kept secret – do not rely on thinking they know.

The final thing the lead designer needs to do is to organize regular design meetings to review progress and agree any design changes. These need to be regular, and with today's internet availability they can be done using video-conferencing. Again all of this needs documenting, agenda's need to be set, action plans need to be produced and monitored. All needs to go into the DHF.

Even if you are doing the design all by yourself all of the above needs considering as the DHF must exist; you cannot escape the need for a populated DHF no matter how small you company. Whilst it is difficult to have meetings with yourself you WILL have meetings with sub-contractors at some time; you will make design decisions. They ALL need documenting in the DHF.

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Risk management, risk analysis and ISO 14971

Peter Ogrodnik , in Medical Device Design (Second Edition), 2020

9.7 Risk management folder in the technical file

An essential element of the Technical File (for CE marking) or the Design History File (for FDA 510(k) and clinical assessment approval) is a risk management folder (or you may hear the term risk register). In essence it is simple. Before you apply for a CE mark or for an FDA 510(k) this document must be in place. As virtually all regulatory bodies accept ISO14971 as the basis for risk management then the file will always contain the following:

1.

Statement of clinical benefit outweighing residual risk (title page Fig 9.4)

2.

(optional) Pre-assessment of hazards on which risk analysis is performed (e.g. appendix C as presented earlier)

1.

Complete dossier of all individual risk assessments

2.

(optional) Company risk management procedure

Although I have highlighted 2 as optional, it is a good idea to document this step as it points your auditors to the concept of "they have done it properly". Without this section you can be asked "where did this hazard come from?"

Again, I have suggested 4 is optional, bit as every company has its own rules on what is an unacceptable level of risk RPN, or not, means that any auditor will have their own opinion of what is acceptable or not. None of that matters if you present this document in your folder as all the information by which you make decisions on RPN is given within. But note, if you have more than one technical file/DHF then each time you update your risk management procedure you will need to update this section of EACH technical file. Personally I believe it to be more efficient to simply have a statement on the title page that states

this risk analysis was conducted using the risk management procedure XXX

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Introduction to Medical Devices: Design, Manufacturing, Evaluation, and Control

Gary H. Harding , Alice L. Epstein , in Clinical Engineering Handbook, 2004

The authors of the next chapters provide historical and contemporary insights into many aspects of the history, design, manufacturing, costs, and control of medical devices from a clinical engineering perspective. These chapters begin with the evolution and growth of medical device technology, from the early healer's use of sharpened stones to endoscopy, and through the intricate financial aspects of technology acquisition, software development, and the excitement of research and design of new, cutting-edge technology. These chapters examine issues that face medical device manufacturers, as well as hospital-based engineers, innovators, designers, testers, and evaluators. They share interests, concerns, and issues and address them with an interest in providing insight into the information that will prove valuable to a clinical engineer, regardless of the base from which the design, manufacturing, or control is performed.

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Nanomaterials in Design

Daniel L. Schodek , in Materials Experience, 2014

Nanomaterials in Nature and Art

We may not have understood why or appreciated the nanomaterial contribution, but specific types of nanomaterials have been found in nature and have long contributed to many unique artifacts in our art and design history. In nature, one of the most fundamental of life-sustaining processes—photosynthesis—depends on nanoscale pigments that convert light to chemical energy. Also, the famous gecko that can scamper on walls and ceilings can do so because gecko's feet are covered with millions of nanometer-sized hairs that each produces a very small force of attraction due to molecular interactions. The common mussel depends on nanosized filaments to create a remarkable kind of adhesive that sticks underwater to anchor the mussel to solid surfaces beneath waves. Understanding how nanosized elements play a role in nature is not just a matter of curiosity. The issue of how to connect pieces, for example, plays a major role in the design and shaping of many products. Investigators are well under way in developing new classes of superstrong adhesives that can bind in wet conditions that are based on understandings of nano-related behaviors of geckos and mussels.

In the history of art and architecture, phenomena based on nano-related effects are surprisingly common. Many artifacts have rich colors or beautiful metallic sheens that are attributable to nanoparticles. The famous Lycurgus cup celebrating the 324 AD victory of Constantine over Licinius in Thrace has achieved an almost iconic status in the field of nanomaterial studies. Under normal external lighting conditions, the cup appears green, but then assumes a strong red color when lighted from within—a phenomenon attributable to the unique optical effects possible when nanosized particles (in this case gold) are embedded in the glass (Figure 15.1).

FIGURE 15.1. The Lycurgus cup contains gold nanoparticles; it looks green when light shines on it but red when a light shines inside it.

 Figure 2.17 in "Nanomaterials, Nanotechnologies and Design…" Elsevier. Source: The British Museum.

Embedded nanoscale metallic particles, often nanosized gold, are known to have contributed to the ruby-red color of many Medieval era stained glass. The beautiful lusterware produced in Manises, Spain, c. sixteenth century, is prized because of the sheens derived from the firing of metal oxides, which in turn contain nanosized metallic particles. The fabulous intense blues of Mayan wall paintings can be traced to the exact size, shape, and distribution of nanoparticles in the palygorskite clays in the paints used. These phenomena are generally attributable optical effects caused when the diameter of the nanoparticles become very close in size to the wavelength of light. The way light is reflected, scattered, or absorbed is dependent on the size, shape, and distribution of the nanoparticles. Obviously, early users had no science-based idea about why these effects occurred. Despite a seeming endless array of colors now available to designers—often with ridiculous names such as "peach cream"—there is a paucity of products based on colors that can come even close to matching these remarkable historical artifacts and their assured places in our collective memory. With our current abilities to control the size, shape, and distribution of different kinds of nanoparticles, perhaps we can return to thinking more deeply about how color quality can be more effectively utilized in design.

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Regulations for Medical Devices

Markus Schönberger , Marc Hoffstetter , in Emerging Trends in Medical Plastic Engineering and Manufacturing, 2016

2.3.9 21 CFR Part 11

The development, manufacturing, and distribution of medical devices require statutory comprehensive documentation. The legal requirements affect primarily data and documents that are essential to prove safety of the device, such as the design history files, test certificates, work procedures, or tracking and tracing of manufactured materials and products. Nowadays, this takes place close to exclusively with tools for electronic processing of data. External and internal communication happens with e-mail, product development bases on CAD-systems, data from quality inspection are acquired and stored by computers, work instructions are distributed electronically, and the flow of goods is controlled with enterprise recourse planning (ERP) software. Thereby, any action in an FDA-regulated industry is subject to part 11 of the Title 21 of the Code of Federal Regulation that is labeled "electronic records and electronic signatures." This law defines the criteria that make electronic records and signatures—a trustworthy and reliable equivalent to paper-based documentation. And many actions of daily business generate data that are handled ideally electronically. These may include the following:

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The history of device design is documented in CAD-systems

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Risk Management is supported with specialized software

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Data from in-process quality control are stored in databases

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Work instructions are provided as electronic documents

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The flow of goods is managed with ERP software

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Batch numbers and labels are generated automatically

All these actions are subject to the regulations of 21 CFR part 11, if performed electronically. Thereby, the legal requirements are rather challenging and induce many pitfalls. To give some examples: It is a common practice to record data from quality inspection in spreadsheets or minutes of meeting as text files. Both may be manipulated ex post, and thus basically are not compliant to part 11. Usually, login to a computer is controlled by username and password. This enables tracking of any action performed within the system, and consequently this approach is utilized as system for electronic identification, and thus considered as electronic signature. Anyhow, this frequently is not compliant to the FDA regulation that requires any user to be provided a unique ID number and personal PIN number, to avoid feigning a foreign identity. Although implementing electronic records and signatures within the entire company offers great benefits in terms of efficiency and costs, the hurdles induced by part 11 are considerably high. Therefore, it is recommendable to thoroughly examine the advantages and disadvantages.

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Implementing design procedures

Peter Ogrodnik , in Medical Device Design (Second Edition), 2020

4.5.6 Control of documents

It is very important to have a control of documents procedure. This can be written but it must cover:

1.

How long documents are kept.

2.

Who is responsible for maintaining the design history file.

3.

Where the original design history file is kept.

But as you have already seen, the procedures force you to control your documents. However do not forget that all of your standard procedures, pro-forma, templates etc., all need to be approved. Hence each one needs a title, needs a version number, a date of approval, and who approved it.

Document control is hard; do not let anyone tell you otherwise. However there are electronic systems out there to help you. Of course you will have to purchase them, or at least a license … but that expense may be worth it in the end. Most industrial computer aided design packages come with an in-built document control/revision control system: often these link to Microsoft Word ®. But there is nothing stopping you having a good, old fashioned ring-binder on your desk and have paper copies of all documents inside. I am not going to suggest which method is best, or which computer package is best; it is what works best for you. However, as we are all electronic nowadays the ring binder can be replaced with a dedicated memory stick. Whatever you use, a management system, a memory stick, or paper remember to make regular backups 4 – juts in case the worst happens (and it often does and often to me!)

One last word of advice, and it is one I give all my students and all the companies I work with:

If you have not written it down, you have not done it

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Global Optimization Concepts and Methods

Jasbir Singh Arora , in Introduction to Optimum Design (Fourth Edition), 2017

Trajectory Approximation

The random points x R selected for starting a local search, as well as the intermediate points x M during local minimization, are examined for proximity to each stored trajectory. A trajectory is the design history from a starting point to the corresponding local minimum point. There can be many trajectories meeting at one local minimum point. The selected point is rejected if it is near any trajectory. This is done to prevent unnecessary minimization steps that would otherwise lead to already known local minima. The trajectory can be approximated using several techniques. The simplest approximation is a straight line connecting x (0) and the corresponding x*. Experiments have shown that actual trajectories usually do not follow straight lines, especially at the beginning of the search and for nonlinear problems. Other alternatives to approximate the trajectory include:

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Passing least squares straight line through several points along the trajectory.

2.

Passing straight-line segments through selected points along the trajectory.

3.

Passing a quadratic curve through three points.

4.

Passing quadratic segments through groups of three points.

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Constructing higher-order polynomial or spline approximations.

Several issues affect the choice of the technique to use: the number of points needed (which have to be stored), the number of operations, and the accuracy of the approximation. Any technique other than straight-line approximation requires more intermediate points to be saved and more calculations. Therefore, use of a straight-line approximation is suggested.

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