Institutional clinical records from Norwegian IVF clinics; Carl von Linne Clinic (Sweden) clinical performance data; Human Fertilization and Embryology Authority (HFEA) UK registry data
The sponsor provided retrospective clinical performance data (live birth rates) from various European IVF clinics to demonstrate that the device performs comparably to or better than alternative culture media used in routine clinical practice.
Retrospective analysis of Norwegian IVF clinics; Retrospective observational analysis of clinical outcomes; Follow-up/Duration: 1992-1996; Study Period: 1992-1996
Patients undergoing IVF treatment at Norwegian clinics; Number of Sites: 3
National average
Live birth rates per started cycle
HFEA UK clinic performance data; Retrospective registry data analysis; Follow-up/Duration: April 1, 1996 to March 31, 1997; Study Period: 1996-1997
Patients undergoing IVF treatment at UK clinics using Medi-Cult products; Sample Size: Total cycles across listed clinics; Number of Sites: 10
UK national average
Live birth rate per embryo replacement
Indications for Use
Medi-Cult Universal IVF Medium is used for the fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage (day 2 after insemination). Medi-Cult Universal IVF Medium can also be used as vehicle during embryo transfer.
Device Story
Medi-Cult Universal IVF Medium is a liquid culture medium used in assisted reproduction technology (ART) clinics. It supports fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage; it also serves as a vehicle for embryo transfer. The medium is formulated with Earl's Balanced Salt Solution (EBSS), sodium pyruvate, sodium bicarbonate, and human serum albumin (HSA). Specific variants exclude penicillin/streptomycin or phenol red. The device is used by embryologists and clinicians in laboratory settings to maintain oocyte/embryo viability during in vitro procedures. Clinical performance is monitored via live birth rates per started cycle or embryo replacement. The medium replaces in-house prepared culture media, providing a standardized environment for gamete and embryo development.
Clinical Evidence
Clinical evidence includes retrospective data from multiple European IVF clinics (Norway, Sweden, UK) using Medi-Cult media. Data from 1992-1996 in Norway showed live birth rates per started cycle ranging from 11.4% to 25.35%. 1997 data from a Swedish clinic reported a 34% birth rate per embryo replacement. UK data (1996-1997) across multiple centers showed live birth rates per embryo replacement ranging from 22.3% to 34.5%, generally exceeding the UK national average of 21.8%. No serious adverse events reported in the 1.5 years prior to submission.
Technological Characteristics
Formulated with Earl's Balanced Salt Solution (EBSS), sodium pyruvate, sodium bicarbonate, and human serum albumin (HSA). Variants available without penicillin/streptomycin or phenol red. Quality control testing includes bioburden, filter integrity, sterility, pH, osmolarity, endotoxin levels, and mouse embryo (two-cell) assay (>80% hatched).
Indications for Use
Indicated for fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage (day 2 post-insemination) and as a vehicle during embryo transfer in patients undergoing assisted reproduction procedures.
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.
Submission Summary (Full Text)
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### 510(k) Summary Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination (K991279)
Page 1 of 3
#### The products:
- "Medi-Cult Universal IVF Medium" Cat.No. 1031 -
- "Medi-Cult Universal IVF Medium w/o Phenol" Cat.No. 1030 -
- "Medi-Cult Universal IVF Medium w/o Pen/Strep" Cat.No. 1095 -
#### Indications for use:
"Medi-Cult Universal IVF Medium" is for fertilisation of human oocytes and culture of fertilised oocytes up to the 4-6-cell stage (day 2 after insemination). "Medi-Cult Universal IVF Medium" can also be used as vehicle during embryo transfer.
#### Product formulation:
Earl's Balanced Salt Solution (EBSS) Sodium Pyruvate Assisted Reproduction Technology Supplement (ARTS) Sodium Bicarbonate Human Serum Albumin (HSA) Penicillin (Except product 1095) Streptomycin (Except product 1095) Phenol Red (Except product 1030)
#### Product testing control contents:
- Bioburden, production-test -
- Integrity filter testing, production-test -
- ー Sterility. QC-test
- pH, QC-test
- Osmolarity, QC-test -
- -Endotoxin, QC-test
- Mouse Embryo, (two cells assay; > 80% hatched) QC-test -
The culture media from Medi-Cult have been used by many European IVF-units since the end of 1980. (Produced and distributed by GEA-Biotech 1987 to 1989 and by Medi-Cult a/s from 1989). The Medi-Cult media were at that time introduced as a replacement for in-house prepared culture media.
A number of prospective randomized trials have shown that The Medi-Cult-IVF-medium performs equally well or better than altemative culture media. A number of publications in peerreviewed books or journals have presented data using Medi-Cult media.
The clinical result of a given IVF-clinic will depend on the patient population treated, the clinical procedures, laboratory routines and on the various culture media used. A comparison of the clinical performance of clinics using only Medi-Cult media with other IVF-clinics using similar clinical and laboratory routines will give an indication on the performance of the Medi-Cult culture media. In countries where we have access to both national data from individual clinics, clinics using Medi-Cult media generally perform well.
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K 991279
Page 2 of 3
The IVF-units in the Nordic countries use similar clinical and laboratory protocols and their patient populations are comparable. The clinical data from most Nordic countries are available. In some countries the performance of individual IVF-clinics are available.
The largest IVF clinics in Norway have been using only Medi-Cult media since the end of the 1980's. The data collected in the years from 1992 to 1996 are shown below as live birth rates per started cycle.
| Clinic | 1992 | 1993 | 1994 | 1995 | 1996 |
|-------------------------------------|------|------|------|-------|------|
| Dept of Ob & Gyn, Univ of Trondheim | 22.2 | 22.2 | 19.8 | 25.35 | 18.4 |
| The National Hospital, Oslo | 13.3 | 19.0 | 15.8 | 11.42 | 17.4 |
| National average | 14.6 | 17.5 | 17.9 | 16.84 | 16.3 |
| Table 1. Live birth rates per started cycle obtained in IVF units in Norway | | | |
|-----------------------------------------------------------------------------|--|--|--|
|-----------------------------------------------------------------------------|--|--|--|
In Sweden, the Carl von Linne Clinic uses only products from Medi-Cult for culture of gametes and embryos. For the vear 1997 their birth rate per embryo replacement was 34% their clinical results were the best in Sweden and well above the national average of 25.8%.
The Human Fertilization and Embryology Authority (HFEA) in the UK collects clinical data from all centers licensed to offer treatment for infectility by assisted reproduction. HFEA publishes these data in a booklet and on the web. The clinical data are presented both unadjusted and adjusted for the demographics of the clinics patient population.
In the Table below the clinical data from some UK-clinics that use only Medi-Cult products is shown. These clinics have all given their consent to be presented as clinics using only Medi-Cult products.
Table 2. Live birth rates per embryo replacement obtained in IVF units in the period April 186 1996 to March 31, 1997.
| Name of clinic | Number of | Live birth rate per |
|----------------------------------------------|-------------|----------------------|
| | IVF- cycles | embryo replacement % |
| Northamptonshire Fertility service | 503 | 26.0 |
| The Bridge Centre | 852 | 27.2 |
| Chelsea and Westminster Hospital | 388 | 22.3 |
| CARE at Park Hospital | 650 | 34.5 |
| BMI Ross Hall Hospital | 68 | 27.5 |
| The Woking Nuffield Hospital | 163 | 32.6 |
| Leeds General Infirmary | 1434 | 24.0 |
| Nurture | 1245 | 28.8 |
| Holly House Fertility and IVF | 333 | 30.5 |
| Guy's and St Thomas Assisted Conception Unit | 651 | 27.1 |
| UK national average | 33520 | 21.8 |
There have been some registered complaints on the product but there is no evidence in the last 1.5 years that the product has been the cause of any serious adverse events in connection with its intended use.
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K991279
Page 3 of 3
Thus based on the Federal Register Notice (Final Rule, Vol. 63, No. 175, page 48429, September 10, 1998), "Obstetric and Gynecologic Devices; Reclassification and Classification of Medical Devices Used for In-Vitro Fertilization and Related Assisted Reproduction Procedures" effective on October 13, 1998 and the supportive clinical data we feel that the safety and effectiveness of the product for its intended use is shown in the present submission.
Prepared and Submitted by:
Rune Wilhe-Leonardi 4/21/00
Ronald G. Leonardi, Ph. D. Date
Ronald G. Leonardi, Ph. D. President R & R Registrations P.O. Box 262069 San Diego CA 92196 858-586-0751
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Image /page/3/Picture/1 description: The image shows a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the edge. In the center of the seal is a stylized image of an eagle with its wings spread. The eagle is composed of three curved lines, and there are three wavy lines below the eagle, possibly representing water.
Public Health Service
JUL 2 0 2000
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
Medi-Cult, A/S c/o Ronald G. Leonardi, Ph.D. R & R Registrations P.O. Box 262069 San Diego, California 92196-2069 Re: K991279 Medi-Cult Universal IVF-Medium-Assisted Reproduction Technology Supplement (ARTS) Dated: April 20, 2000 Received: April 21, 2000 Regulatory Class: II 21 CFR 884.6180/Procode: 85 MQL
Dear Dr. Leonardi:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the we have reviewed your Occared or requireditions for use stated in the enclosure) to legally marketed predicate devices device is substantially equivately (10 the moducal of the Medical Device Amendments, or to devices that maneted in interstate conmisions of the Federal Food, Orug, and Cosmetic Act (Act (Act (Act (Act, You may, therefore, nave occh receasured in acorrance that all players of the Act. The general controls provisions of the Act Include mants the october to the goned condevies, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class III (Premarket Approval), it may be subject to il your device (see above) in oknier also title base the pyrum in the Code of Federal Requilations, This 21, Such additions Confiness Existing major regulations and the Current Good Manufacting Practice r ans oo oo oos. A Substantant Squalition (QS) for Medical Devices: General regulation (21 CFR Part 820) and requirements, as sections, 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 the Edefarmediate. Thease note the responses to Joines under the Electionic Product Radiation Control provisions, or other Federal laws or regulations.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of r no to the nequivalence 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.
11 for in esire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for incritor ir you desire specific article for your do hassing of (301) 594-4591. 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" (21CFR 807.97). Other general information on your responsibilities under the million and be obtained to pivision of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmaldsmamain.html".
Sincerely yours,
Daniel C. Schultz, M.D.
Daniel G. Schultz, M.D. Captain, USPHS Director, Division of Reproductive, Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure(s)
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## 510(k) Number (if known): K991279
Device Name: Medi-Cult Universal IVF Medium
Indications for Use:
Medi-Cult Universal IVF Medium is used for the fertilization of human oocytes and culture of fertilized oocytes up to the 4-6-cell stage {day 2 after insemination).
Medi-Cult Universal IVF Medium can also be used as vehicle during embryo transfer.
# (PLEASE DO NO WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (Per 21 CFR 801.109)
OR
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________
David A. Elgerson
(Optional Format 1-2-96)
(Division Sign-Off) Division of Reproductive, Abdominal, ENT, and Radiological Devices 510(k) Number
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.
