For evaluation of colonic transit in adult and pediatic patients (at least 2 years old) with chronic constipation and used to aid in differentiating slow and normal transit constipation.

Device Description

The device is intended to be used for evaluation of colonic transit time in patients with chronic constipation and used to aid in differentiating slow and normal transit constipation in adults and pediatric patients (at least 2 years old). Ten (10) radiopaque markers per day are swallowed for six consecutive days. On day seven an abdominal radiograph is taken. Based on the number of retained markers and the position in colonic transit time is calculated and compared to reference values. Both total transit and segmental transit dysfunction in the colon can be evaluated with the device. By dividing the particle dose on day six by taking five (5) markers in the morning and five (5) markers in the evening, the whole range of transit times (slow, normal, rapid) transit can be measured from the radiograph.

The device is a convenience package of radiopaque markers (22% Barium Sulphate, 78% Elastosil® R 401/60 Silicone rubber) placed in vegetarian capsules from cellulose (HPMC, Hydroxypropylmethylcellulose), intended for single patient use. The dimension of the markers is 2x4.5mm (ring-formed markers) and 6x2mm (tube-formed markers). The capsules are packed in a blister pack is placed inside a folding box.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for Transit-Pellets:

It's important to note that this document is a 510(k) clearance, which determines substantial equivalence to a predicate device, rather than a full pre-market approval (PMA) that requires extensive clinical trials to establish de novo safety and effectiveness. Therefore, the "studies" mentioned often refer to comparisons with predicate devices, existing literature, or post-market follow-up, rather than new, large-scale randomized controlled trials.

Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in a quantitative, measurable format with target performance values (e.g., "sensitivity must be >X%", "specificity must be >Y%"). Instead, the performance is demonstrated by showing substantial equivalence to a legally marketed predicate device (Sitzmarks) and by leveraging existing clinical literature and post-market data.

The key performance aspect for Transit-Pellets is its ability to accurately measure colonic transit time (CTT) and thereby aid in differentiating slow and normal transit constipation. The acceptance is implicitly based on the predicate device's established performance and the demonstration that the subject device performs equivalently and safely, especially for the expanded pediatric population.

Table of Performance Comparison (based on equivalence to predicate):

Performance Characteristic/Acceptance Criteria	Reported Device Performance (Transit-Pellets) - based on equivalence and PMCF
Ability to Measure Colonic Transit Time	Equivalent to K181760 (Primary Predicate) and K181750 (Reference Predicate, Sitzmarks). Capable of calculating CTT/OATT numerical values in days.
Aid in Differentiating Constipation Types	Equivalent to K181760 and K181750. Used to differentiate slow and normal transit constipation.
Safety in Adult Population	Established by K181760 clearance.
Safety in Pediatric Population (≥ 2 years)	Supported by PMCF study literature review (1054 children/young adults across 18 studies). No device-related adverse events reported. Confirmed by user survey.
Biocompatibility	Confirmed non-cytotoxic, non-irritant, non-sensitizing per ISO 10993-5, -10. No systemic toxicity or pyrogenic response per ISO 10993-11.
Radiopacity	Confirmed visible for intended use duration/environment per ASTM F640-12.
Mechanical Strength (Bite Force)	Can withstand similar forces as the reference predicate Sitzmarks, for accidental biting of markers without capsules in pediatric use.

Study Details:

The document primarily refers to a Post-Market Clinical Follow-Up (PMCF) study as the clinical evidence for the expanded pediatric population. This PMCF study appears to be a literature review combined with a user survey.

Sample Size Used for the Test Set and Data Provenance:
- Literature Review: The PMCF study identified 18 clinical investigations involving similar devices. These studies collectively involved 1054 children and young adults.
- Data Provenance: The document does not specify the country of origin for these 18 studies. The nature of these studies (retrospective/prospective) is also not explicitly stated, but common for such literature reviews, they could include both types.
- User Survey (part of PMCF): No specific sample size for the user survey is provided, only that it involved "professional users." Data provenance is implied to be from current users of Transit-Pellets or similar devices, likely international given the company's location (Sweden).
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
- Ground Truth for Literature Review: The "ground truth" in the 18 studies would have been established by the methods and clinicians within those individual studies, which are not detailed here. For colonic transit time, the ground truth is typically the radiological assessment of marker distribution and retention by medical professionals (e.g., radiologists, gastroenterologists).
- Experts for PMCF Literature Review: The document does not explicitly state how many experts reviewed the identified 18 clinical investigations or their specific qualifications for the PMCF literature review itself. It implies a "literature review carried out during the PMCF study," suggesting a regulatory or scientific team conducted the review.
- Experts for User Survey: "Professional users" were surveyed, but their number and specific qualifications (e.g., pediatric gastroenterologists, radiologists) are not provided.
Adjudication Method:
- Not explicitly described. For the PMCF literature review, it's unlikely a formal adjudication method (like 2+1 or 3+1 for individual case review) was applied since it was a review of aggregate published data, not individual case interpretations.
- For the original 18 studies, the adjudication methods would vary per study; this document does not provide such detail.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, an MRMC study was not done in the context of this 510(k) submission. This is not typically required for a Class II diagnostic device seeking substantial equivalence, especially when expanding an indication based on existing technology and literature. The focus is on the device's inherent ability to measure CTT, not on reader performance improvement with AI assistance.
Standalone Performance (Algorithm Only without Human-in-the-Loop Performance):
- Yes, in essence, the "device" is standalone. Transit-Pellets are passive markers. The "performance" being evaluated is their physical and chemical properties (biocompatibility, radiopacity, mechanical strength) and their ability to be visualized and used by a clinician to manually calculate colonic transit time from an X-ray image. There is no AI component or algorithm-only performance to assess in the typical sense of software as a medical device. The physician interprets the X-ray/fluoroscopy image and calculates CTT based on the marker count and position.
Type of Ground Truth Used:
- The ground truth for measuring colonic transit time is based on radiological imaging (abdominal radiograph or fluoroscopy) and the subsequent manual counting and positional analysis of the radiopaque markers by a clinician. This is a well-established method in gastroenterology.
- For the safety and effectiveness in the pediatric population, the PMCF study relied on published clinical investigation results (which would have used radiological ground truth) and user feedback.
Sample Size for the Training Set:
- Not applicable in the typical sense of AI/ML training. There is no "training set" for an algorithm, as this device consists of physical markers interpreted by human readers.
- If viewed in a broad sense, the "training" for the device's design (marker size, material, dosing regimen) comes from decades of clinical practice and research using radiopaque markers for colonic transit studies, which predates this specific device.
How the Ground Truth for the Training Set Was Established:
- Not applicable as there is no specific training set for an algorithm. The principle of "ground truth" in this context refers to the accuracy of colonic transit time measurements derived from the markers. This has been established through clinical consensus and research over time, validating the correlation between marker distribution on X-rays and actual colonic transit physiology.

Summary

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January 18, 2023

Medifactia AB % Cherita James Regulatory Consultant M Squared Associates Inc. 127 West 30th Street 9th Floor New York, NY 10001

Re: K222000

Trade/Device Name: Transit-Pellets Regulation Number: 21 CFR 876.1725 Regulation Name: Gastrointestinal motility monitoring system Regulatory Class: Class II Product Code: FFX Dated: December 16, 2022 Received: December 16, 2022

Dear Cherita James:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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 Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdri/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-devices/medical-device-safety/medicaldevice-reporting-mdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-devices/device-advicecomprehensive-regulatory-assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerelv.

Sivakami Venkatachalam -S

for

Shanil P. Haugen, Ph.D. Assistant Director DHT3A: Division of Renal, Gastrointestinal, Obesity and Transplant Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K222000

Device Name

Transit-Pellets

Indications for Use (Describe)

For evaluation of colonic transit in adult and pediatic patients (at least 2 years old) with chronic constipation and used to aid in differentiating slow and normal transit constipation.

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)	□ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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In accordance with 21 CFR 807.92, the following information constitutes the Medifactia AB summary for the Transit-Pellets.

l. Submission Date

January 11, 2023

II. Submitter

Medifactia AB

C/O IOffice Business Center

Kungsgatan 60

Stockholm

Sweden 11122

Contact person: Diana Nyström

Phone number: +46 (0) 31-787 70 77

E-mail: diana.nystrom@medifactia.com

Official Correspondent: Cherita James Regulatory Consultant M Squared Associates, Inc. 127 West 30th St, Floor 9 New York, New York 10001 Ph: 347-954-0624 E-mail: Cjames@Msquaredassociates.com

III. Device

Name of device: Transit-Pellets Common or usual name: System, Gastrointestinal Motility Regulatory class: Class II according to 876.1725

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Classification code: FFX

Panel: Gastroenterology/Urology

IV. Predicate device

510(k)	Company	Device
Primary: K181760	Medifactia	Transit-Pellets
Reference: K181750	Konsyl Pharmaceuticals	Sitzmarks

V. Device Description

There is no change to the Transit-Pellets previously cleared in K181760 for this expanded patient population.

VI. Intended use

For evaluation of colonic transit in adult and pediatric patients (at least 2 years old) with chronic constipation and used to aid in differentiating slow and normal transit constipation.

VII. Comparison of the technology characteristics with the predicate devices

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	Subject device	Primary Predicate	Reference Predicate	SE
	Medifactia ABTransit-Pellets	Medifactia ABTransit-Pellets	KonsylPharmaceuticalsSitzmarks
K#	K222000	K181760	K181750
Indication foruse/Intended use	For evaluation ofcolonic transit in adultand pediatric patients(at least 2 years old)with chronicconstipation and usedto aid indifferentiating slowand normal transitconstipation.	For evaluation ofcolonic transit inadult patients withchronicconstipation andused to aid indifferentiating slowand normalconstipation.	SITZMARKS capsuleis a diagnostic testindicated for aidingin the evaluation ofcolonic motility inpatients with severeconstipation, asdiagnosed by yourhealthcareprofessional, butotherwise negativeGI evaluations.SITZMARKS capsule,for use in adult andpediatric patients(at least 2 yearsold), is to bedispensed only byphysicians topatients for oralintake.	X
Application	Measuring and usingcolonic transit time toevaluate patients withchronic (severe)constipation.	Measuring and usingcolonic transit time toevaluate patientswith chronic(severe)constipation.	Measuring andusing colonic transittime to evaluatepatients withchronic (severe)constipation.	X
Targetpopulation	Adult and pediatricpatients (at least 2years old) patientswith chronic (severe)constipation.	Adult patients withchronic (severe)constipation.	Adult and pediatricpatients (at least 2years old) patientswith chronic(severe)constipation.	X
	Subject device	Primary Predicate	Reference Predicate	SE
	Medifactia ABTransit-Pellets	Medifactia ABTransit-Pellets	KonsylPharmaceuticals
			Sitzmarks

Anatomical site	Gastrointestinaltract/colon	Gastrointestinaltract/colon	Gastrointestinaltract/colon	X
Where used	Hospitals, clinics	Hospitals, clinics	Hospitals, clinics	X
Design	Ring-formed andtube-formed markers.	Ring-formed andtube-formedmarkers.	Three differentshapes of markers:O Rings, Double Dand Tri-Chamber.	X
Dimensions/Capsule size	2 x 4.5mm, 6 x 2mmSize -00-	2 x 4.5mm, 6 x2mmSize -00-	1mm x 4.5mmSize -00-	X
Materials	Markers: Bariumsulphate, Elastosil® R401/60 SiliconerubberCapsules: HPMC,Hydroxypropyl-methylcellulose	Markers: Bariumsulphate, Elastosil®R 401/60 SiliconerubberCapsules: HPMC,Hydroxypropyl-methylcellulose	Radiopaque Marker• Polyvinyl ChlorideResin (PVC)• Bis(2-ethylhexyl)Phthalate (DEHP)• Epoxides Soya Oil• Calcium/ZincStabilizers• PhosphateStabilizer• Fatty Ester &PolyamideLubricants• UltramarineTinting Agents• Barium Sulfate• Dioctyl Phthalate	X
	Subject device	Primary Predicate	Reference Predicate	SE
	Medifactia ABTransit-Pellets	Medifactia ABTransit-Pellets	KonsylPharmaceuticalsSitzmarks
			• Mono &DiglyceridesCapsules:Hypromellosa
Principle ofoperation	Patient swallows afixed dose radiopaquemarker for a numberof days. On day 7 asingle abdominalradiograph orfluoroscopy is taken.Based on the numberof retained markerson abdominal film andtheir position in colona colonic transit timeis calculated andcompared toreference value.	Patient swallows afixed doseradiopaque markerfor a number ofdays. On day 7 asingle abdominalradiograph orfluoroscopy istaken. Based on thenumber of retainedmarkers onabdominal film andtheir position incolon a colonictransit time iscalculated andcompared toreference value.	Patient swallows afixed doseradiopaque markerfor a number ofdays. Severalabdominalradiographs may benecessary. Based onthe number ofretained markers onabdominal film(s)and their position incolon a colonictransit time iscalculated andcompared toreference value.	x
Performance	Colonic Transit Time(CTT/OATT) numericalvalues reported indays.	Colonic TransitTime (CTT/OATT)numerical valuesreported in days.	Colonic Transit Time(CTT/OATT)numerical valuesreported in hours.	x
Biocompatibility	Yes, safe for intendeduseISO 10993-5, -10, and-11	Yes, safe forintended useISO 10993-5, -10,and -11	No information	x
Packaging	Blister and folding box	Blister and foldingbox	Folder combo/singlepack	x
Sterile	No	No	No	x
	Subject device	Primary Predicate	Reference Predicate	SE
	Medifactia ABTransit-Pellets	Medifactia ABTransit-Pellets	KonsylPharmaceuticalsSitzmarks
Shelf life	2.5 years	2.5 years	Unknown
Rx Only	Yes	Yes	Yes	×

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VIII. Performance testing

Transit-Pellets have a size <8mm and are made tube-formed and ring-formed. To test transit characteristics of various types of markers, five types of distinguishable markers in the specific gravity range 1.2-1.6 were examined. The size of the particles was chosen in the range 2-7 mm so that emptying from stomach was likely to occur also with a meal. Transit-Pellets were designed for their size and configurations and are safe and effective for their intended use when compared to the predicate device. Simulated capsule digestion testing in a simulated gastric fluid, dimensional analysis, as well as the clinical literature provided in the predicate 510k submission (K181760), confirms the device performs as intended for the proposed indication for use, i.e., is safe and effective for evaluation of colonic transit in patients with chronic constipation and used to aid in differentiating slow and normal constipation. The Transit-Pellets is substantially equivalent to Sitzmarks regarding material, technological characteristics, and indications for use.

Biocompatibility testing to ISO 10993-5 and -10 of the Transit-Pellets confirm the device is noncytotoxic, non- irritant, and non-sensitizing. Testing to ISO 10993-11 confirmed that the Transit-Pellet extracts did not induce a significantly greater biologic reaction than the control following systemic injection and produced a non-pyrogenic response. Additionally, 14 Day Repeat IV and Intraperitoneal Toxicity in Rats did not demonstrate systemic signs of toxicity over 14 days.

Radiopacity Testing in accordance with ASTM F640-12 confirms visibility of the Transit-Pellets for the duration and environment of their intended use during colonic transit.

Medifactia conducted Bite Force testing with both the Transit-Pellets and the reference predicate device to confirm the safe use of the subject device consumed without a capsule in the proposed pediatric population in the event of accidental biting of the markers. The testing concluded that the Transit-Pellets can withstand similar forces as the reference device, when subjected to simulated bite force testing.

IX. Clinical Evidence

A Post-Market Clinical Follow-Up (PMCF) study provided supports the safe and effective use of barium sulphate impregnated particles to measure colonic transit time in pediatric patients at least 2 years old. The literature review carried out during the PMCF study identified 18 clinical investigations performed on similar devices to be of satisfactory quality. In summary, the device performance and safety were successfully measured colonic transit time on 1054 children and young adults. In 12 of the 18 clinical

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investigations, the principle of taking markers for six days were applied. No device related adverse event reported in any of the clinical investigations.

Further, a user survey, also part of the PMCF study, confirmed that the Transit-Pellets and the Transit-Pellets principle are used to measure colonic transit time in children and young adults with no adverse events or side-effects identified. The survey also confirmed that some professional users inform patients that they can open the capsules and only swallow the markers. The Transit-Pellets meets of the professional users.

X. Conclusion

The subject and primary predicate device are identical. The subject device includes a patient population of both adults and pediatric patients (at least 2 years old) patients with chronic (severe) constipation which is the same as the reference predicate. All devices share the indication for use of measuring and using colonic transit time to evaluate patients with chronic constipation. The original Transit-Pellets submission (K181760) established substantial equivalence to the reference device for use in adults.

The information provided in this 510(k) support that the Transit-Pellets is substantially equivalent in function, composition, and intended use in a pediatric population to the predicate devices. The proposed device raises no new issues of safety and effectiveness.

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Regulation Number and Section

§ 876.1725 Gastrointestinal motility monitoring system.

(a)
Identification. A gastrointestinal motility monitoring system is a device used to measure peristalic activity or pressure in the stomach or esophagus by means of a probe with transducers that is introduced through the mouth into the gastrointestinal tract. The device may include signal conditioning, amplifying, and recording equipment. This generic type of device includes the esophageal motility monitor and tube, the gastrointestinal motility (electrical) system, and certain accessories, such as a pressure transducer, amplifier, and external recorder.(b)
Classification. Class II (performance standards).