HTF and modified HTF are intended for the retrieval, culture, transport, storage and transfer of human gametes and embryos.
Device Story
HTF and Modified HTF are synthetic media formulated to mimic human fallopian tube fluid. HTF uses a sodium bicarbonate buffer requiring a CO2 incubator for embryo culture and fertilization. Modified HTF uses a sodium bicarbonate/HEPES buffer, allowing use without a CO2 incubator for sperm washing, oocyte retrieval, and embryo transport/implantation. These media are used in clinical assisted reproductive technology (ART) laboratories by embryologists and clinicians. The media provide a physiological environment (pH 7.2–7.4) to support gamete and embryo viability during various stages of ART procedures. By maintaining optimal conditions outside the body, the media facilitate successful fertilization, development, and subsequent transfer of embryos, potentially improving patient outcomes in fertility treatments.
Clinical Evidence
No clinical data. Performance is supported by mouse embryo assay (MEA) to confirm functionality and lack of toxicity, alongside endotoxin and sterility testing. Historical use in clinical settings is cited as evidence of suitability.
Technological Characteristics
Synthetic media mimicking human tubal fluid. HTF: sodium bicarbonate buffer. Modified HTF: sodium bicarbonate/HEPES buffer. Form factor: liquid or powder. Sterilization: not specified. Connectivity: N/A. Software: N/A.
Indications for Use
Indicated for assisted reproductive technology procedures involving manipulation of human gametes or embryos. HTF is for embryo culture post-fertilization (requires CO2 incubator) and in vitro fertilization. Modified HTF is for sperm washing, oocyte retrieval, embryo transport, and embryo implantation support.
Regulatory Classification
Identification
Reproductive media and supplement are products that are used for assisted reproduction procedures. Media include liquid and powder versions of various substances that come in direct physical contact with human gametes or embryos (including water, acid solutions used to treat gametes or embryos, rinsing solutions, sperm separation media, supplements, or oil used to cover the media) for the purposes of preparation, maintenance, transfer or storage. Supplements are specific reagents added to media to enhance specific properties of the media (e.g., proteins, sera, antibiotics, etc.).
Special Controls
*Classification.* Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, biocompatibility testing, and clinical testing). The device, when it is phosphate-buffered saline used for washing, and short-term handling and manipulation of gametes and embryos; culture oil used as an overlay for culture media containing gametes and embryos; and water for assisted reproduction applications, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.
Predicate Devices
Notice of Final Rule, 63 FR 48428, Docket number 97N-0335
Submission Summary (Full Text)
{0}------------------------------------------------
K93586
October 9, 1998
Image /page/0/Picture/2 description: The image shows the logo for Irvine Scientific. The logo consists of a stylized, white "IS" monogram set against a black square. Below the square, the words "IRVINE SCIENTIFIC" are printed in a simple, sans-serif font, with the word "IRVINE" stacked directly above "SCIENTIFIC".
# 510(k) SUMMARY AS REQUIRED BY SECTION 807.92(c)
Submitted by: Irvine Scientific Sales Co., Inc. 2511 Daimler Street Santa Ana, CA 92705-5588
> Telephone: (800) 437-5706 Facsimile: (949) 261-6522
Contact: Roberta L. Johnson
Date Submitted: October 9, 1998
### Device Identification:
| Trade Name: | HTF Medium<br>Modified HTF Medium-HEPES<br>HTF Powder (without antibiotics)<br>Modified HTF Powder-HEPES<br>(without antibiotics)<br>Modified HTF Powder-HEPES |
|----------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | Gamete and embryo retrieval, storage and<br>transfer medium |
| Classification Name: | Reproductive Media (21 CFR, 886.6180) |
#### Predicate Device:
Notice of Final Rule, 63 FR 48428, Docket number 97N-0335
### Description:
HTF and Modified HTF (mHTF) are synthetic, defined media intended for use in assisted reproductive technology procedures. Both have been formulated
Human Tubal Fluid (HTF
{1}------------------------------------------------
to mimic the composition of the fluid found in human fallopian tubes. Modified HTF differs from HTF by the buffer system used. HTF uses a sodium bicarbonate buffering system, and is appropriate for those procedures requiring the use of a carbon dioxide atmosphere during incubation. Modified HTF utilizes a combined sodium bicarbonate/HEPES ([4-(2-hydroxyethyl)-1piperazineethanesulfonic acid]) buffer. This buffering system provides maintenance of physiological pH (7.2 to 7.4), and does not require the use of a carbon dioxide incubator.
#### Intended Use:
HTF and modified HTF are intended for the retrieval, culture, transport, storage and transfer of human gametes and embryos.
#### Technological Characteristics:
Modified HTF is has utility for a variety of assisted reproductive procedures. It has been used for a number of years as a sperm-washing medium. During sperm wash procedures, viable sperm cells are separated from the other constituents of seminal fluid in an effort to concentrate the viable sperm and increase the number available for fertilization. A culture medium, such as modified HTF is used to suspend the semen, the sample is centrifuged to pellet the viable sperm, and, after the supernatant is decanted, the pellet is resuspended in fresh medium. After a brief incubation during which motile sperm "swim-up" into the fresh medium, the sperm are aspirated and used for the desired fertilization procedure. Modified HTF is also used as an oocyte retrieval medium, in procedures that flush oocytes from the patient's fallopian tubes. Once the oocyte has been retrieved, it is placed into a culture dish with an appropriate amount of culture medium, and fertilized. After fertilization, the embryo is allowed to develop in the culture medium, until an appropriate developmental stage is reached. At that time, the embryo is removed from the incubation dish, placed into an suitable amount of mHTF for transport and
{2}------------------------------------------------
October 9, 1998
implantation into the patient. Modified HTF is therefore intended for use as a sperm-washing medium, an oocyte retrieval medium, and as a transport and storage medium.
HTF intended for use as a culture medium, with appropriate protein supplementation, for the support of fertilized embryos. Fertilization is also allowed to occur in HTF when in vitro fertilization techniques are used. The fertilized gamete is then allowed to grow in the media and supplement, which are replenished as needed, until the desired state of development, usually up to three days post fertilization. Since HTF utilizes a sodium bicarbonate buffer system, it is intended to be used in those procedures that require a carbon dioxide atmosphere, as is found in the incubators used by assisted reproductive laboratories. Therefore, HTF is primarily used as a medium to support embryo growth, development, and culture in vitro.
#### Performance Data:
HTF and modified HTF are assaved by mouse embryo assay prior to their release to market. This assay assures that the product is both functional for its intended use, the support of embryonic growth, and that no toxic components are present in the formulation. HTF and modified HTF have been used in a variety of clinical settings, for their intended use, for a number of years. In that time, the products have become the standard media used for the retrieval, growth, storage and transport of human gametes and embryos.
### Additional Information:
Mouse embryo testing will be performed as a condition of release for these products, as well as endotoxin and sterility testing. Results of all release assays performed will be reported on a lot-specific certificate of analysis, and will be indicated on the labeling.
{3}------------------------------------------------
# Conclusion:
The conclusion from performance testing, as well as a review of the historical information contained in professional literature shows that HTF and modified HTF are suitable for their intended use, and meet the criteria outlined in the Notice of Final Rule, 63 FR 48428, Docket number 97N-0335.
Human Tubal Fluid (HTF) Modified Human Tubal Fluid (mHTF)
{4}------------------------------------------------
## PROPOSED LABELING
Three copies of the proposed labeling for HTF and modified HTF are enclosed with this submission, beginning on the following page. These labels include vial/bottle labels, and the proposed package insert. Some information, such as results of endotoxin tests and mouse embryo assays, will be included in the lot-specific certificate of analysis provided with the product. An example of the format for these certificates of analysis, and of the information supplied in them, may be found in Appendix E to this submission.
{5}------------------------------------------------
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
FEB 1 8 1999
Roberta L. Johnson Manager, Regulatory Affairs Irvine Scientific 2511 Daimler Street Santa Ana, CA 92705
Re: K983586 HTF Medium, Modified HTF Medium-Hepes, HTF Powder Dated: January 14, 1999 Received: January 19, 1999 Regulatory Class: II 21 CFR 884.6180/Procode: 85MQL
Dear Ms. Johnson:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmelic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or dass III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or requlations.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4613. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its intemet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours.
Capt. Daniel G. Schultz, M.D. Acting Director, Division of Reproductive, Abdominal, Ear, Nose and Throat, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
{6}------------------------------------------------
Irvine Scientific
#### INDICATIONS FOR USE STATEMENT (page 1 of 1)
510(K) Number:
Device Name: HTF Medium and Modified HTF Medium - HEPES.
Indications for Use:
HTF and Modified HTF are intended for use in assisted reproductive technology procedures that involve the manipulation of gametes or embryos. Specifically, HTF is intended for use as a culture medium for the embryo after fertilization, when used with an incubator, and as a medium to support in vitro fertilization. Modified HTF is intended for use as a sperm-processing medium in washing procedures, as an oocyte retrieval medium, for transport of the embryo, and as a support medium for implantation of the embryo. Both HTF and Modified HTF are intended to simulate the substances found in the human, female reproductive system.
## (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
ustive. Abdominal, ENT,
Human Tubal Fluid (HTF) Modified Human Tubal Fluid (mHTF)
Two short videos show you everything — or skip straight to the written tutorial if you'd rather read. You can reopen this any time from the Tutorial button in the top bar.
Part 1 — Search, results, and everyday workflows 16 min
Part 2 — Embeddings: the galaxy map 3 min
1. Search: exact and fuzzy
Type a phrase like "coronary artery calcification" into the search box. You get two kinds of results. Exact results match the literal phrase — prefix searches work ("coronary artery calcificati") but suffix searches do not. Fuzzy results match on the meaning and intent of your phrase rather than the exact words, and are sorted by relevance score. Hover over the Exact or Fuzzy badge on any row to see exactly why it matched.
Use the checkboxes above the results to narrow: SaMD keeps only software-only devices, AI / ML keeps only devices with AI.
Exact vs. fuzzy search: what's the difference?
Exact matches on the literal phrase (prefix search works, suffix does not). Fuzzy matches on the meaning and intent of the phrase rather than the exact words. Hover over the badge on any row to see why it matched.
You search "coronary artery calcification" and want only software devices with AI. What two filters do you apply?
Narrow by SaMD (software-only devices), then narrow by AI/ML (devices with AI).
2. The results table
Scroll right in the results table. The intended use is extracted for you — no need to open the PDF. The device story gives a high-level snapshot of what the device does and how it's used. The AI Performance sub-table shows each output name, acceptance criteria, observed values, and development/test dataset descriptions — the same format Innolitics uses for regulatory strategy outputs, and the fastest high-level fingerprint of an AI device. It is AI-generated but has been very reliable in practice.
Where do you find a device's intended use without opening the PDF?
Scroll right in the search results table. The intended use column is extracted for you; no need to dig into the 510(k) summary PDF.
What does the AI Performance sub-table show, and why is it useful?
Output name, acceptance criteria, observed values, development dataset description, and test dataset description. It's the same format we use for regulatory strategy output and Fast 510(k) input, and the fastest high-level fingerprint of an AI device. AI-generated but reliable in practice.
3. Judging fuzzy relevance
Fuzzy results trail off in relevance as you scroll. Use three signals to decide how far down to go: the fuzzy badge explanations, the intended use column, and whether your target output (e.g., Cobb angle) still appears in the AI Performance sub-table. Once it stops appearing, you're past the relevant zone. A top hit with a low score (~0.4) and a stretched explanation is a hint the closest predicates are far away — the project may be headed for De Novo. Note the fuzzy search is a pattern match: it doesn't handle negation ("not") well, and hardware devices can appear — filter by SaMD/AI ML to cut them.
How do you judge how far down fuzzy search results to go?
Use the relevancy signals: the fuzzy badge explanations, the intended use column, and whether the target output (e.g., Cobb angle) still appears in the AI Performance sub-table. Once it stops appearing, results are trailing off in relevancy.
4. Device detail page: chat and citations
Click a device name to open its detail page: device facts on the left, a chat window on the right. Ask something like "Describe the training data". The answer carries little citation bubbles — click one to jump to the highlighted passage in the source PDF, so you can verify every AI answer against the document. There's also a Download PDF button for sharing.
How do you verify an AI chat answer on the device detail page?
Click the citation bubbles to jump to the relevant highlight in the source document.
Reading rule for every project: how many summaries do you read in full?
At least the three most relevant 510(k) or De Novo summaries, in full. After that, use targeted chat questions to confirm your memory quickly. The tool supports this professional habit — it doesn't replace it.
5. Side-by-side comparison
Select multiple rows in the results table (aim for under ~10), then open the PDF Viewer tab. Ask one question — it goes to all selected devices in parallel, each with citations. This is the fastest way to compare and contrast devices: training data, PCCP scope, how they handled adding new scanners, and so on.
What does the side-by-side PDF viewer mode do?
Select multiple devices, open the PDF viewer tab, and ask one question (e.g., "Describe the training data"). It queries all selected devices simultaneously with citations, so you can compare and contrast quickly.
6. Collections
With rows selected, go to the Collections tab and create a labeled collection (e.g., "Cobb Angle Project"). Reload that selection any time — before a client call, pull up the collection and ask questions across all of its devices at once.
How do you save a set of selected devices for later use?
Select the rows, go to the Collections tab, and create a labeled collection (e.g., "Cobb Angle Project"). You can reload the selection anytime and carry it into the PDF viewer and other tabs that support selections.
7. Product codes and the regulations tree
Click a product code in the results to jump to it in the regulations tree — identification text, sibling product codes, and devices you can open in a PDF viewer on the right. Click a regulation number to see its identification, special controls, and related product codes. You can also search by product code or regulation number at the top of the tree. Always read the special controls if any exist for your device — it broadens your search and sharpens pre-kickoff research.
What can you do from the regulations tree view?
Browse product codes and regulation numbers, read the identification text and special controls, browse sibling product codes, open device PDFs on the right, and search by product code or regulation number at the top of the tree.
8. Chart view
Click Show Chart and segment by regulation number (or product code) to see which regulations dominate your result set. Clicking a regulation takes you into the regulations tree. Great for spotting that most matches are, say, hardware laparoscopic devices — a cue to go back and filter.
How do you see which regulations dominate a search result set?
Click "Show Chart" and segment by Regulation Number. Clicking a regulation takes you to the regulations tree.
9. The predicate graph
Open the Predicates tab for a family-tree view of predicate relationships. Click a node to trace its parents and children; selections from search carry over pre-selected. Commonly predicated devices are worth reading — a lot of people predicated them for a reason. The visual lineage is also handy on client calls, e.g. to show how a predicate family evolved and justify why your predicate still holds.
In the predicate graph, why are commonly predicated devices worth reading?
A lot of people predicated them for a reason. Clicking a node traces parents and children, and selections from search carry over pre-selected.
10. Embeddings: the galaxy map
The Embeddings tab plots every matching document in a 2-D "galaxy map" where semantically similar devices cluster together. Hover or click clusters to explore, and let AI label the clusters for you. Embeddings beat product codes for grouping: two devices can carry different product codes (LLZ vs. QIH) yet do the same thing — the embedding captures the meaning of the intended use and device story. This is also exactly how retrieval-augmented generation (RAG) works under the hood, and it makes a great visual on client calls.
Try it yourself
Head to the search page and work through a few of these AI/ML fuzzy searches to build intuition: perivascular fat on CT · aortic valve calcification opportunistic screening on noncontrast CT · breast cancer prediction on digital pathology slides · autism detection · gestational age prediction · a hearing aid that can also detect a pulse · foundation model based analysis of ECG · large language models · penetration test. Watch how the relevance scores, intended use, and AI Performance tables tell you when results stop being meaningful.
