510(k) Memorandum #K97-1
DATE: January 10, 1997
FROM: Director, Office of Device Evaluation
Subject: Deciding When to Submit a 510(k) for a Change
to an Existing Device
TO: ODE Review Staff
Through: ODE Branch Chiefs
Purpose
The purpose of this guidance is to provide
direction to manufacturers
on deciding when to submit a 510(k) for
a change to an existing
device.
Background
On April 8, 1994, FDA circulated for comment
the first draft guidance
entitled "Deciding When to Submit a
510(k) for a Change to an Existing
Device." This draft was the subject
of a May 12, 1994, FDA
video conference and it was the subject
of several trade and industry
association meetings. As a result of these
activities, FDA received
over 60 comments on this version of the
guidance. On October 16, 1995
FDA published a Notice of Availability in
the Federal Register
announcing the availability of an August
1, 1995 draft of this
guidance.
Attached is the final version of the guidance
for reference by the
review staff. This guidance is not intended
to supplant existing
definitive guidance for modifications to
specific devices, e.g., daily
wear contact lenses. Moreover, the guidance
is not intended to apply
to combination products, such as drug/device
or biologic/device
combinations, although it may be helpful.
The guidance is also not
intended to address the need for submitting
a 510(k) by
remanufacturers of devices. FDA intends
to develop additional
guidance specific to these situations.
Procedures
The type of modifications addressed in the
draft guidance include
labeling changes, technology or performance
specifications changes,
and materials changes. When making the
decision on whether to submit
a 510(k), the manufacturer's basis for comparison
of any changed
device should be the device described by
the cleared 510(k) or to
their legally marketed preamendments device.
That is, manufacturers
may make a number of changes without having
to submit a 510(k), but
each time they make a change, the device
they should compare it to is
their most recently cleared device (or their
preamendments device).
In effect, manufacturers need to submit
a new 510(k) only when a
change, or the sum of the incremental changes
exceeds the
§807.81(a)(3) threshold, "could
significantly affect the safety or
effectiveness of the device."
Because many simultaneous changes may be
considered in the evolution
of device design, each type of change should
be assessed separately.
When any one change leads the manufacturer
to decide to submit a
510(k), then a 510(k) requesting the change
should compare the
modified device to a legally marketed device
(the manufacturer's
device or a competitor's legally marketed
device). In the instance
where the legally marketed device is the
manufacturer's own device,
the 510(k) should identify previous changes
that did not necessitate a
510(k) submission, to avoid confusion when
we compare the current
510(k) to the previous clearance.
The guidance includes a main flowchart to
help manufacturers through
the logic scheme necessary to arrive at
a decision on when to submit a
510(k) for a change to an existing device.
The flowchart includes the
following three logical breakouts of changes
that might be made to a
device: labeling changes, technology or
performance specifications
changes, and materials changes. To use
the model, the questions posed
in the flowchart should be answered until
the 510(k) holder is
directed to: (1) consider submitting a 510(k)
(including a new 510(k)
labeled "change being effected"),
or (2) document the decision-making.
When contemplating changes to a device,
manufacturers should use the
flowchart for each individual type of proposed
change, e.g.,
performance specification change, material
change, etc. If a
manufacturer's consideration of all proposed
changes results in a
decision merely to document the decision-making,
they should document
the application of the model along with
the necessary records of the
validation of changes to the device. In
those circumstances where the
proposed change is not addressed in the
flowchart or in a
device-specific guidance document, manufacturers
are encouraged to
contact the Office of Device Evaluation
in CDRH to find out whether
other, specific guidance exists or if additional
help is available.
Effective Date:
This guidance is effective immediately.
Susan Alpert, Ph.D., M.D.
On April 8, 1994, FDA circulated for comment the first draft of a document intended to provide guidance to manufacturers on when to submit a new 510(k) for changes to an existing device. That draft was the subject of an FDA/FDLI video conference on May 12, 1994, and also was the subject of discussion at several trade and industry association meetings. Subsequently, in response to comment letters, a second draft of the guidance (dated August 1, 1995) was developed and made available for additional public comment through publication of a Notice of Availability in the Federal Register (60 FR 53624, October 16, 1995). These comments from the second round of public review have led to the current guidance document.
While we are pleased to issue this guidance in final form, we recognize that, as a guidance document, it can and will need to be revised over time as we gain more experience with its application. These revisions will be based on comments and recommendations of its users, both in the industry and in FDA. CDRH continues to look at the 510(k) Program and ways of reengineering the review process. For example, a program to pilot test the third party review of 510(k)s was begun in the summer of 1996. In addition, we will be looking at the better use of consensus standards and special controls in the 510(k) review, as well as ways to better integrate compliance with design controls under the new Quality Systems Regulation with the 510(k) process.
Almost from the enactment of the Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act in 1976, FDA staff have attempted to define with greater accuracy when a change in a medical device would trigger the requirement that a manufacturer submit a new premarket notification (510(k)) to the Agency. The regulatory criteria state that a premarket notification must be submitted when:
(3) The device is one that the person currently has in commercial distribution or is reintroducing into commercial distribution, but that is about to be significantly changed or modified in design, components, method of manufacture, or intended use. The following constitute significant changes or modifications that require a premarket notification:
(i) A change or modification in the device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process.
(ii)A major change or modification in the intended use of the device.1
The key issue here is that the phrase "could significantly affect the safety or effectiveness of the device" and the use of the adjectives "major" and "significant" sometimes lead to subjective interpretations. Because of this, manufacturers have frequently expressed the need for more specific guidance in applying the regulatory standard in their decision-making.
Previous attempts to develop such guidance have focused generally on defining broad issues or principles that should be used in deciding when to submit a 510(k). These attempts have been only partially successful in clarifying the situation. The primary reason for partial success is that the variety of device types currently marketed, as well as the myriad changes that occur as technology evolves, are so diverse that one or two unifying principles cannot possibly account for all possible situations.
To be certain that a decision on when to submit a 510(k) is correct, one would probably need to enumerate all device types and all potential types of changes and then match each combination of device and change with a decision. Given that there are thousands of individual device types and possibly tens or hundreds of enumerable changes, this would be an impossible task. Furthermore, the resultant guidance would fill volumes, would probably be difficult to use, and would be unlikely to keep pace with an ever-changing technology.
Between the two extremes of broad principles and detailed enumeration is the area where models can be developed to assist in the decision-making. If created and used properly, such a model could provide guidance leading toward a rational answer as to whether a 510(k) is necessary in the large majority of circumstances. This document proposes a flowchart model that can be used by manufacturers in their decision-making to analyze how changes in devices may affect safety or effectiveness. In the model, we attempt to address changes to devices at a level detailed enough so that application of the broad principles contained in the regulations would minimize disagreements between manufacturers and the Agency . The goal of the model is to provide guidance in answering a manufacturer's questions on whether a 510(k) should be submitted for a particular type of change and to minimize the number of instances where the answer would be uncertain. Taken as a whole, this guidance, and the model it describes, provides the agency's best definition of when a change to a device could significantly affect safety or
effectiveness.
The 510(k) Process and Good Manufacturing Practices
Any guidance on 510(k)s for changes to a marketed device must consider the role the Good Manufacturing Practice (GMP) regulation plays in changes to device design. For some types of changes to a device, the Agency continues to find that a 510(k) is not necessary and that reliance on existing GMP requirements may continue to reasonably assure the safety and effectiveness of the changed device.
It is important to note that the current 1978 GMP regulation does not directly address the original design of a device. In fact, it was the recognition of the need for this type of control for many types of devices that led to the inclusion of pre-production design controls in the Safe Medical Devices Act of 1990.2 The new GMP and design control regulation, called the Quality Systems regulation, will implement the
new authority
granted by the Safe Medical Devices Act and require design controls for new devices. The Quality Systems regulation 3, will take effect in two stages. The entire regulation, except for design controls, will take effect on June 1, 1997. The design control provisions will take place on June 1, 1998.
The 1978 GMP regulation, however, is not entirely silent on device design. It requires manufacturers to document in the device master record (§820.181) any changes (and internal approval of changes) to device design and any associated testing (§820.100). It also requires process validation to assure that devices meeting the designed quality characteristics will consistently be produced (§820.5 and §820.100). Finally, manufacturers must have a formal approval procedure for any change in the manufacturing process of a device including those dictated by design changes (§820.100(b)(3)).
The Quality Systems regulation has similar requirements relating to design changes, and these requirements will replace the 1978 GMP requirements on June 1, 1998. Under the Quality Systems regulation, manufacturers are required to review and approve any changes to device design and production (new §820.30 and §820.70) and document changes and approvals in the device master record (new §820.181). Any process whose results cannot be fully verified by subsequent inspection and test must be validated (new §820.75), and changes to the process require review, evaluation, and revalidation of the process where appropriate (new §820.75).
The net effect of the 1978 GMP regulation or the new Quality Systems regulation is to require that, when manufacturers make a change in the design of a device, they must have a process in place to demonstrate that the manufactured device meets the change in design specifications (or the original specifications, if no change was intended). They must keep records, and these records must be made available to an FDA
inspector.4 Thus, while the Quality Systems regulation requires design controls for many devices, those controls do not take effect until June 1, 1998. Until then, manufacturers must still comply with the current GMP regulation, which imposes requirements on changes to device design. For many types of changes to a device, it may be found that a 510(k) is not necessary, and the Agency may reasonably rely on good manufacturing practices (either as implemented under the 1978 GMP or the Quality Systems regulation) to continue to assure the safety and effectiveness of the changed device. This reliance is enhanced when manufacturers document their decision-making based on their testing results or other design validation criteria.
The guidance outlined in this document has been developed to aid manufacturers of class I, class II or class III devices (for which premarket approval has not yet been required under section 515(b)) who intend to modify their device and are in the process of deciding whether the modification exceeds the regulatory threshold for submission of a new 510(k). This guidance for changes to an existing device is intended to supplement the general guidance on review of 510(k)s contained in the ODE Bluebook memorandum on the premarket
notification program.5
This document was developed to address all types of modifications, including modifications to device design as well as modifications to device labeling. Furthermore, this guidance can be applied to situations when a legally-marketed device is the subject of a recall and a change in the device or its labeling is indicated. This guidance is not intended to apply, although it may, to combination products, such as drug/device or biologic/device combinations. Furthermore, this guidance is not intended to address the need for submitting 510(k)s by remanufacturers of devices6, who do not hold the 510(k) for the device. FDA intends to develop additional guidance specific to these situations
at a later date.
This document incorporates existing guidance and policy7regarding when 510(k)s are necessary for modifications to a legally-marketed device.8 In some cases, the existing guidance derives from advice given to only a few manufacturers for a limited number of devices. In such instances, we have attempted to generalize the concepts to apply to a broader range of devices. However, special cases exist where both manufacturers and FDA have worked to establish definitive guidance for modifications to specific devices, e.g., daily wear contact lenses. 9 This guidance is not intended to supplant such existing device-specific guidance but may cover areas not addressed in such device-specific guidance.
In developing this guidance for aiding in deciding when to submit a 510(k), a number of assumptions had to be made. Some derive from existing 510(k) policy and are widely known, others are necessary for using the logic scheme contained in this guidance.
Thus, anyone using this guidance needs to bear in mind the following assumptions:
The model uses a flowchart to help manufacturers through the logic scheme necessary to arrive at a decision on whether to submit a 510(k) for a change to an existing device. A single flowchart containing all the logical steps necessary is large and cumbersome and could be quite daunting, Therefore, one is not included in this document. Rather, for ease of use, the single flowchart has been broken down into five smaller flowcharts that include:
· the main types of changes that might be made to a device (Main Flowchart)
· labeling changes (Flowchart A)
· technology or performance specifications changes (Flowchart B)
· materials changes (Flowchart C), and
· materials changes for in vitro devices (IVDs) (Flowchart D).
The reader is referred to the Definitions section (page 22) for the meaning of terms used in the flow charts.
To use the model properly, manufacturers must answer the questions posed in the flow chart for each individual type of change, e.g., performance specification change, material change, etc., until a decision is made either to consider submitting a 510(k) or to document the basis for concluding that a 510(k) is not necessary. Manufacturers should consult the flowchart that applies to the particular change or modification under consideration. When making the decision on whether to submit a 510(k) for changes, the comparison should be to the device described in the last 510(k) clearance, collectively with the presently legally marketed device which incorporated modifications that did not require premarket clearance by the agency. One must keep in mind that what may on the surface appear to be one discrete change to a device may involve multiple changes of various types, triggering submission of a new 510(k).
If any one of the changes that is analyzed results in a manufacturer's decision to submit a 510(k), then the 510(k) should incorporate all of the planned changes, as well as a comparison of the changed device to their legally-marketed device. (If a manufacturer has a cleared 510(k), reference to it will aid in the evaluation of the new 510(k).) If a manufacturer's consideration of all planned changes results in a decision merely to document the decision-making, it should document the application of the model along with the necessary records of the validation of all changes to the device. In addition, a manufacturer may also compare their device to a competitor's legally marketed device.
For those circumstances where the proposed change is not addressed in the flowcharts or in a device-specific guidance document, manufacturers are encouraged to contact the Office of Device Evaluation in CDRH to obtain advice. Note, too, that some elements of the flowchart may not pertain to a particular device, e.g., a software change for an inactive implant; these should be ignored in the application of the model.
Before using the flowcharts, the reader is reminded that specific guidance has been developed for changes to a legally-marketed device that result from a recall. That guidance has been developed separately, but its philosophy is similar to this document in that changes to a device that are intended to bring the device back to its original specifications, and that can be validated under GMPs, do not require a 510(k). On the other hand, changes in specifications that are intended to address the safety or effectiveness problem require a 510(k).11
Note that the flowchart entries, "new 510(k)" and "documentation," are written in this way only for conciseness. The reader should interpret "new 510(k)" as strongly consider submitting a 510(k) and "documentation" as document your analysis and file it for future reference. This is, after all, a guidance document, and it is not intended to be prescriptive. It is intended only to provide the outline of a logic scheme for enhancing the likelihood of good decisions.
Each of the questions listed on the detailed flowcharts are identified by the flowchart letter (A through D) and a sequential number. Those questions on the main spine of the flowcharts relate to major questions to be asked and are identified by a letter and an integer, such as A1, A2, etc. Subsidiary questions that are asked in response to a "yes" answer are identified by the integer for the question, a decimal point, and a sequential integer, e.g., C2.1 in Figure 3 labels a decision point containing the question "Is the device an implant?" which follows the determination made in decision point C2 that a change in material type is
contemplated.
As noted above, the types of changes are divided into labeling changes, technology or performance specifications changes, and materials changes. All labeling changes are handled with a separate logic scheme that concentrates on changes in indications for use as the threshold for contemplating the submission of a 510(k). Other labeling changes are more frequently recommended for documentation only.
Chart A describes the logic scheme to be used when determining when a 510(k) is required for a labeling change. Changes in device labeling often pose the most difficult questions to be addressed by device manufacturers when deciding whether a new 510(k) submission is necessary. Frequently, an apparently subtle change in a device labeling can have a significant impact on the safe and effective use of the device.
Technology, Engineering, and Performance Changes
These types of changes encompass a broad span of design activities from minor engineering changes in a circuit board layout to a change from electromechanical to microprocessor control of device function. Chart B illustrates the decision-making logic scheme for such technology, engineering or performance specifications changes to a device. The key to using this logic scheme is that all changes are evaluated or validated according to the current GMP requirements, and the results of this evaluation/validation are used to guide the decision-making on when to submit a new 510(k).
The types of changes identified at decision points B4 through B8 have frequently been called design changes or engineering changes. They encompass everything from the routine specification changes necessary to maintain or improve device performance as a result of feedback from users,
field or plant personnel, etc., up to and including significant product redesign. The major difficulty lies in sorting out which of these changes is significant enough to trigger the need for a 510(k). The logic scheme that follows is intended to lead a manufacturer through a thought process that will allow routine engineering change orders to occur, while identifying those changes for which a 510(k) would be indicated.
Firms making changes to the materials from which their device is manufactured should first consider the other types of changes discussed above and their impact on the decision regarding the need for a new 510(k). For example, a change of a material type, as discussed below, might also engender a change in the labeling of the device, e.g., the removal of a contraindication or the addition of a new warning, or a change in specifications, e.g., a reduction in the strength of the device. These collateral changes should be considered first, before applying the logic scheme described in this section. See Chart C.
Materials Changes for In vitro Diagnostic Products
The following definitions are provided to clarify the meaning of terms used in the flow chart. Wherever possible, existing definitions from the Food, Drug, and Cosmetic Act, the medical device regulations, or ODE Bluebook memoranda have been used. In some cases, where regulatory definitions are unavailable, we have relied on strict dictionary definitions of terms.
Change: As used in the model, this means a proposed change and not the impact of a proposed change. Important impacts of a proposed change are identified on the flow chart. For example, a manufacturer may propose a change in method of sterilization. This change could impact on performance specifications because of potential chemical or physical damage to the device. The proposed change (in method of sterilization) is the change that should be used in the model.
Contraindications: See "precautions, warnings and contraindications" below.
Control Mechanism: The manner by which the actions of a device are directed. An example of a change in control mechanism would be the replacement of an electro-mechanical control with a microprocessor control.
Dimensional Specifications: The physical size and shape of the device. Such specifications may include the length, width, thickness, or diameter of a device, as well as the location of a part or component of the device.
Documentation: For the purpose of this guidance, documentation means recording the results of applying the model to proposed changes in a device. Consideration of each decision point should be recorded, as well as the final conclusions reached. If testing or other engineering analysis is part of the process, the results of this activity should be recorded or referenced. A copy of this documentation should be maintained for future reference.
Energy Type or Character: The type of power input to or output from the device. Examples of a change in energy type or character would be a change from AC to battery power (input) or a change from ionizing radiation to ultrasound to measure a
property of the body (output).
Environmental Specifications: The (range of) acceptable levels of environmental parameters or operating conditions under which the device will perform safely and effectively. Examples of changes in environmental specifications are expanding the acceptable temperature range in which the device will operate properly or hardening the device to significantly higher levels of electromagnetic interference.
Ergonomics of Patient/User Interface: The way in which the device and the patient/user are intended to interact. Examples of this would be the various audible or visible alarms intended to alert the user to a hazardous condition, the layout of a control panel, or the mode of presentation of information to the user.
Expiration date: The date beyond which there are no data to assure that the product may perform safely or effectively and beyond which the manufacturer states the product should not be used.
Implant: A device that is intended to reside within a surgically or naturally formed channel or cavity of the human body for a period of more than 30 days (excluding dental restoration materials).
Intended Use: Intended use refers to "the objective intent of the persons legally responsible for the labeling of devices. The intent is determined by such persons' expressions or may be shown by the circumstances surrounding the distribution of the article...."24
Indications for use: An indication for use is "a general description of the disease or condition the device will diagnose, treat, prevent, cure, or mitigate, including a description of the patient population for which the device is intended." 25 The indications include all the labeled patient uses of the device, for example:
The indications for use are normally found in the indications section of the labeling, but indications may also be inferred from other parts of the labeling such as the precautions, warnings, or the bibliography sections. In some instances, a change in the indications for use may be a new intended use for the device, in which case, the 510(k) for the changed device would be found not substantially equivalent and a premarket approval application or a reclassification petition would be necessary.26
In vitro Device: Those reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body.27
Label: The term "label" means a display of written, printed, or graphic matter upon the immediate container of any article.28
Labeling: The term "labeling" means all labels and other written, printed, or graphic matter (1) upon any article or its containers or wrappers, or (2) accompanying such article.29 This can include, among other things, any user or maintenance manuals and, in some instances, promotional literature.
Manufacturer: For the purposes of this document, the term manufacturer includes any 510(k) holder, even if that person does not actually fabricate the existing device. The term also includes persons who have a preamendments device or a device that is currently exempt by regulation from the 510(k) requirements of the act.
Material Formulation: The base polymer formulation or the alloy, additives, colors, etc., used to establish a property or the stability of the material. This does not include processing aids, mold release agents, residual contaminants, or other manufacturing aids that are not intended to be a part of the material. An example of a change in material formulation would be a change from a series 300 stainless steel to a series 400 stainless steel.
Material Supplier: The firm supplying the raw material to a finished device manufacturer.
Material Type: The generic name of the material from which the device is manufactured. (Use the generic name in the biomaterials compendium.) An example of a material type change would be the change from natural latex rubber to synthetic
rubber.
Method of Sterilization: The physical or chemical mechanism used to achieve sterility or to achieve a specific sterility assurance level (SAL).
Operating Principle: The mode of operation or mechanism of action through which a device fulfills (or achieves) its intended use. An example of a change in operating principle would be using a new algorithm to compress images in a picture archiving and communications system. For an IVD, an example would be a change from immunofluorescence to ELISA.
Packaging: Any wrapping, containers, etc., used to protect, to preserve the sterility of, or to group medical devices.
Performance Specifications: The performance characteristics of a device as listed in device labeling or in finished product release specifications. Some examples of performance specifications are measurement accuracy, output accuracy, energy output level, and stability criteria.
Preamendments Device: A device legally marketed in the United States prior to May 28, 1976.
Precautions, Warnings, and Contraindications:
Software: The set of instructions used to control the actions or output of a medical device, to provide input to or output from a medical device, or to provide the actions of a medical device. This definition includes software that is imbedded or permanently a part of a medical device, software that is an accessory to a medical device, or software that is itself a medical device.
Warnings: See "precautions, warnings, and contraindications" above.
Material Class
metals
polymers
ceramics
composites
biological origin
Material Subclasses
| Metals | Polymers | Ceramics |
| stainless steel | thermoplastics | Al compound |
| Co & Ni allay | thermoset/elastomers | Ti compound |
| tantalum alloy | absorbable | Zr compound |
| titanium alloy | adhesive | Ca compound |
| zirconium alloy | fluids | carbon |
| precious/noble | glass | |
| amalgam | ||
| miscellaneous |
| Composites | Biologic Origin |
| polymer matrix | tissues |
| metal matrix | cells |
| ceramic matrix | biomolecules |
| antimicrobials |
| Stainless Steels | Co & Ni Alloys | Ti Alloys |
| 316L FeCrNiMo | CoCrMo period | CpTi (grade 1-4) |
| nitrogen strengthened | CoCrWNi | Ti 6Al 4V |
| ferritic | CoNiCrMo | Ti 6Al 7Nb |
| martensitic | CoNiCrMoWFe | Ti 5Al 2.5 Fe |
| austenitic | CoCrNiMoFe | Ti 3.8Al15Mo5Zr |
| Nickel based | Ti 13Nbl3Zr | |
| Ti 12Mo6Zr2Fe | ||
| Ti 15Mo2.8Nb.2Si | ||
| NiTi alloy |
| Zr Alloys | Ta Alloys | Precious/Noble |
| Zr2.5Nb | unalloyed Ta | gold |
| silver | ||
| Amalgams | Miscellaneous | platinum |
| Ag-Hg | aluminum | palladium |
| Cu-Sn | copper | iridium |
| mercury | Pt/Ir |
| Thermoplastics | Thermoset/Elastomer | Absorbable |
| acetal (POM) | bis/GMA | polyester |
| acrylic (hydrogels) | butyl | polyether |
| acrylic (MMA,PMMA) | epoxy | polyanhydride |
| fluorocarbon | EPDM rubber | polyorthoester |
| parylene | hydrogel based | polyetheramide |
| PEO hydrogel | natural latex | |
| poly(aryl)ether ketone | polyesterurethane | |
| poly(aryl)sulfone | polyetherurethane | |
| polyethersulfone | polyurethane (other) | |
| polyamide (nylon) | polyether | |
| polycarbonate (PC) | polyisoprene | |
| polyesters (PET, PBT) | polysulfide rubber | |
| polyester copolymer | rubber-modified acrylic | |
| polyethylene (PE) | silicone gel | |
| polyethylene (UHMWPE) | silicone elastomer | |
| polyimide | ||
| polypropylene (PP) | ||
| polystyrene (PS) | ||
| polyurethane (PU) | ||
| polyvinyl alcohol (PVO) | ||
| polyvinyl chloride (PVC) | ||
| polyvinylidine chloride | ||
| Adhesives | Fluids |
| acrylic based | polyvinylpyrrolidone |
| cyanocrylate | silicone (PDMS) |
| epoxy | |
| polyurethane | |
| silicone | |
| UV curable |
| Al Compounds | Ti Compounds | Zr Compounds | Ca Compounds |
| alumina | TiN | CaO stabilized | Beta-TCP |
| ruby | titanium carbide | MG-PSZ | calcium phosphate |
| sapphire | titanium dioxide | Y-TZP | calcium hydroxyphosphate |
| zirconium dioxide | calcium sulfate | ||
| calcium aluminate | |||
| gypsum | |||
| Carbon | Glass | HA/TCP | |
| fibers | bioactive glass | hydroxylapatite | |
| graphite | silica based | ||
| LTI pyrolytic | |||
| LTI-Si alloy | |||
| ULTI pyrolytic | |||
| vapor deposited | |||
| vitreous |
| Polymer Matrix | Metal Matrix | Ceramic Matrix |
| acrylic glass | Ag-MP35 I? | Calcium hydroxide |
| bis/GMA composites | Ta-Elgiloy wire | carbon-carbon |
| ceramic particle reinforced | glass ionomer cement | |
| CFR epoxy | porcelain | |
| CFR poly(etherketones) | silicate cement | |
| CFR poly(imide) | zinc oxide eugenol | |
| CFR Poly(sulfone) | zinc phosphate cement | |
| CFR UHMWPE | zinc polycarboxylate cement | |
| glass reinforced | ||
| metal fiber reinforced | ||
| PTFE composite | ||
| PU/PC | ||
| urethanedimethacrylate |
| Tissues | Cells | Biomolecules | Antimicrobials |
| blood vessel | adipocyte | agar | aminoglycoside |
| bone | bone marrow | albumin | anti-fungal |
| cartilage | chondrocyte | alginate | anti-mycobacterial |
| coral | endothelial | BMP | cephalosporin |
| cornea | epithelial | cellulose | penicillin |
| dura mater | fibroblast | chitosan/chitan | polymyxin |
| fascia lata | hepacyte | collagen | quinolone |
| fibrous sheath | islet | elastin | sulfonamide |
| heart valve | keratinocyte | fibrin | tetracycline |
| joint | osteoblast | fibrinogen | vancomycin |
| ligament/tendon | renal tubular prog. | fibronectin | |
| pericardium | smooth muscle | gelatin | |
| umbilical cord | growth hormones | ||
| umbilical vein | heparin | ||
| viscera | hyaluronic acid | ||
| hydroxypropylmethyl | |||
| cellulose | |||
| insulin | |||
| molluscan glue | |||
| PHB | |||
| phospholipids | |||
| polyaminoacids | |||
| protein extract | |||
| RDG protein | |||
| saline | |||
| silk | |||
| triglicerides, soybean oil |
Updated January 10, 1997
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