INTENDED USE: The BBLCRYSTAL™ Neisseria/Haemophilus (N/H) Identification (ID) System is a miniaturized identification method employing modified conventional, fluorogenic, and chromogenic substrates. It is intended for the identification of frequently isolated Nelsseria and Haemophilus as well as several other fastidious bacteria from clinical specimens.

INDICATIONS FOR USE: Use of this product is indicated when Neisseria, Haemophilus and the other fastidious organisms described in Table B-1 have been isolated in pure culture from clinical specimens in a clinical laboratory, and identification of the microorganisms is desired.

Device Description

The main component of the BBLCRYSTAL™ N/H ID System is the base/lid assembly, consisting of the CRYSTAL base and lid. The BBLCRYSTAL lid consists of 29 dehydrated biochemical/chromogenic/fluorogenic substrates and one fluorogenic negative control, on the ends of plastic prongs. The base consists of 30 matching wells; its design allows inoculation of all 30 wells in a single step by pouring the suspension into a target area and tilting the base. The test inoculum rehydrates the dried substrates and initiates test reactions.

The pure culture suspension is prepared by picking several small colonies of the same morphology from non-selective media such as Chocolate Agar, Trypticase® Soy Agar with 5% Sheep Blood, and Columbia Agar with 5% Sheep Blood, and Agar With 5% Horse Blood. Alternatively, selective media such as Martin Lewis Agar, Thayer-Martin Modified Agar, New York City Medium Modified, V Agar, and GC Agar Base with 1% IsoVitaleX® Enrichment may be used. A suspension of this culture is prepared in the BBLCRYSTAL™ ANR, GP, RGP, N/H ID Inoculum Fluid provided. The suspension is added to the target area of the panel base, which the user then rocks back and forth to inoculate all the wells contained in the base.

After the base/lid assembly has been incubated for 4 hours at 35-37°C, the panel is placed on the BBLCRYSTAL Panel Viewer and the color reactions are visually compared to the BBLCRYSTAL N/H Color Chart provided. Each reaction is scored as a positive (+) or negative (-) and recorded on the BBLCRYSTAL N/H Report Form.

After all results are read, a 10-digit numerical profile is calculated by assigning a value of 4, 2, or 1 to each positive reaction. (Negative reactions are assigned a value of "0".) The values for each column are then added together to obtain the 10 digit Profile Number.

The BBLCRYSTAL ID System Electronic Codebook is loaded into the user's PC and the appropriate database is selected. Then the Profile Number and results of any off-line tests are entered, and the Codebook gives one of the following three results:

a definitive ID;
a tie between two or more species; or
no ID possible with data submitted.

In the case of a definitive ID or a tie between two or more potential ID's, the user can access the statistics for that ID as well as background information for the species identified.

In the case where no ID is possible, the Codebook suggests that the user perform a purity check of the test isolate. If culture purity has been established, the Codebook indicates that (i) the test isolate is producing atypical BBLCRYSTAL reactions (which may also be caused by procedural errors), (ii) the test species is not part of the intended taxa, or (iii) the system is unable to identify the test isolate with the required level of confidence. Once again, the Codebook indicates that additional testing must be done to establish an identification.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the BBLCRYSTAL™ Neisseria/Haemophilus (N/H) ID System, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Acceptance Criteria (Implied)	Reported Device Performance
Identification Accuracy	High percentage of correct identifications (specific threshold not explicitly stated but implied by high performance of predicate devices).	93.6% (480 out of 513) of isolates correctly identified (including supplemental testing).
"No Identification" Rate	Low rate of "No Identification" results.	1.4% (7 out of 513) yielded a "No Identification" result.
Reproducibility (Overall)	High overall reproducibility.	95.9%
Reproducibility (Individual Substrate Reactions)	High reproducibility for individual substrate reactions.	Ranged from 87.7% to 99.2%
Reproducibility (Individual QC Organism Reactions)	High reproducibility for individual QC organism reactions.	Ranged from 85.7% to 100%
Reproducibility (Site)	High reproducibility across different sites.	Ranged from 95.2% to 97.2%

Study Details

Sample Size and Data Provenance:
- Test Set Sample Size: 513 isolates.
- Data Provenance: The study was conducted at three clinical laboratories, suggesting isolates were sourced from these clinical settings. The isolates included "Fresh, routine clinical isolates as well as previously identified isolates." This indicates a mix of prospective and retrospective data, with a focus on real-world clinical specimens. The country of origin is not explicitly stated but can be inferred to be the United States, given the context of FDA submission.
Number of Experts and Qualifications for Ground Truth:
- The document does not specify the number of experts used to establish the ground truth for the test set or their specific qualifications. It mentions that the BBLCRYSTAL™ N/H ID System's performance was evaluated against "the RapID™ NH System and other conventional methodologies." It is implicit that the ground truth for these isolates would have been established by trained microbiologists using these conventional and predicate methods.
Adjudication Method for the Test Set:
- The document does not explicitly describe an adjudication method for conflicting results in the test set. The phrase "including supplemental testing" suggests that for cases where the initial identification was unclear or incorrect, additional tests were performed to reach a definitive identification, which could implicitly involve an adjudication-like process by laboratory personnel.
Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, this was not a MRMC comparative effectiveness study. This study focused on the performance of the device (BBLCRYSTAL™ N/H ID System) in identifying microorganisms, not on how human readers' performance improved with or without AI assistance. The device is an automated identification system.
Standalone Performance:
- Yes, a standalone performance study was done. The entire "Performance Data" section describes the performance of the BBLCRYSTAL™ N/H ID System (the algorithm) in identifying isolates. The report describes how the system provides a definitive ID, a tie, or no ID, which are all outputs of the algorithm. Human input is primarily in preparing the inoculum, inoculating the panel, and visually reading color reactions, but the core identification process itself (calculating the 10-digit profile and comparing it to the electronic codebook) is the device's standalone function.
Type of Ground Truth Used:
- The ground truth was established using conventional microbiological methodologies and a predicate device (RapID™ NH System). This implies a combination of phenotypic tests and established identification protocols within clinical microbiology laboratories, rather than pathology (histology), or long-term outcomes data.
Training Set Sample Size:
- The document does not specify the sample size for the training set used to develop the BBLCRYSTAL™ N/H ID System's electronic codebook or database.
How Ground Truth for Training Set was Established:
- The document does not explicitly describe how the ground truth for the training set was established. However, it can be inferred that the database was built upon extensive characterization of known isolates using a comprehensive set of biochemical, fluorogenic, and chromogenic reactions to develop the unique BBLCRYSTAL profiles for each organism. This would have involved expert microbiologists and reference laboratories validating the identity of these isolates and their corresponding reaction patterns over time.

Summary

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K962423
Aug. 2, 1996

June 21, 1996

SUMMARY OF SAFETY AND EFFECTIVENESS

SUBMITTED BY:

Virginia C. Weinknecht Becton Dickinson Microbiology Systems P O Box 243 Cockeysville, MD 21030-0243

NAME OF DEVICE:

Trade Name:	BBLCRYSTAL™ Neisseria/Haemophilus (N/H ID System
Common Name/Description:	Miniaturized Microorganism ID System
Classification Name:	Microbiology - Discs, Strips, and Reagents, Microorganism Differentiation

PREDICATE DEVICES:

Innovative Diagnostic Systems, Inc., RapID™ NH System (K881501)

DEVICE DESCRIPTION:

.......

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Taxa List for BBLCRYSTAL™ Neisseria/Haemophilus (N/H) TABLE B-1: ldentification System

Actinobacillusactinomycetemcomitans	Haemophilus segnis¹	Neisseria gonorrhoeae
	Kingella denitrificans	Neisseria lactamica
Cardiobacterium hominis¹	Kingella kingae	Neisseria meningitidis
Elkenella corrodens	Kingella species (includesK. denitrificans and K. kingae)	Neisseria mucosa
Gardnerella vaginalis		Neisseria sicca
Haemophilusaphrophilus/paraphrophilus	Moraxella atlantae	Neisseria subflava (includes
	Moraxella (Branhamella) catarrhalis	N. subflava biovar flava,N. subflava biovar perflava andN. subflava biovar subflava)
Haemophilus ducreyi	Moraxella lacunata¹	Neisseria weaverii¹
Haemophilus haemoglobinophilus¹	Moraxella nonliquefaciens
Haemophilus haemolyticus	Moraxella osloensis	Oligella species (includesO. urethralis andO. ureolytica)
Haemophilus influenzae (includesH. influenzae biogroup aegyptius,	Moraxella phenylpyruvica¹
H. influenzae biotype I,H. influenzae biotype II,	Moraxella species (includes	Oligella ureolytica¹
H. influenzae biotype III,H. influenzae biotype IV,	M. atlantae,M. lacunata,	Oligella urethralis
H. influenzae biotype V,H. influenzae biotype VI and	M. nonliquefaciens,M. osloensis and	Pasteurella multocida
H. influenzae biotype VIII )	M. phenylpyruvica)	Suttonella indologenes
Haemophilus parahaemolyticus¹	Neisseria cinerea¹
Haemophilus parainfluenzae(includes	Neisseria elongata (includes
H. parainfluenzae biotype I,H. parainfluenzae biotype II,	N. elongata ssp. elongata,N. elongata ssp. glycolytica and
H. parainfluenzae biotype III,and H. parainfluenzae biotype IV)	N. elongata ssp. nitroreducens)
	Neisseria flavescens¹

¹ These taxa have fewer than 10 unique BBLCRYSTAL profiles in the current database.

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PRODUCT DESCRIPTION:

The main component of the BBLCRYSTAL™ N/H ID System is the The Than Componont of the embly, consisting of the CRYSTAL base and lid. The BBLCRYSTAL lid consists of 29 dehydrated biochemical/chromogenic/ The BBCon For AL lies and one fluorogenic negative control, on the ends of noorogenic substrator and the mselving of 30 matching wells; its design plastic promger "The all 30 wells in a single step by pouring the suspension anows inobulation of a target area and tilting the base. The test inoculum of purches the dried substrates and initiates test reactions.

The pure culture suspension is prepared by picking several small colonies of The pare contare coopen media such as Chocolate Agar, Trypticase® Soy the same morphone , Columbia Agar with 5% Sheep Blood, and Agar With o % oncernatively, selective media such as Martin Lewis Agar, Thayer-Martin Modified Agar, New York City Medium Modified, V Agar, and TheyerMarch Moumled Agains of this culture is prepared in the BBLCRYSTAL™ ANR, GP, RGP, N/H ID Inoculum Fluid provided. The Buspension is added to the target area of the panel base, which the use then rocks back and forth to inoculate all the wells contained in the base.

After the base/lid assembly has been incubated for 4 hours at 35-37°C, the Antor the baced on the BBLCRYSTAL Panel Viewer and the color reactions are visually compared to the BBLCRYSTAL N/H Color Chart provided. Each reaction is scored as a positive (+) or negative (-) and recorded on the BBLCRYSTAL N/H Report Form.

After all results are read, a 10-digit numerical profile is calculated by Arter ung a value of 4, 2, or 1 to each positive reaction. (Negative reactions acelginns = "0".) The values for each column are then added together to obtain the 10 digit Profile Number.

a definitive ID; (8)
a tie between two or more species; or (b)
no ID possible with data submitted. (c)

In the case of a definitive ID or a tie between two or more potential ID's, the user can access the statistics for that ID as well as background information for the species identified.

B-3

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In the case where no ID is possible, the Codebook suggests that the user in the case where his is possible. If culture purity has been perform a purity check of the tost isolate is producing atyploal BBLCRYSTAL reactions (which may also be caused by procedurers is unschlo the test species is not part of the intended taxa, or (iii) the system is unable the test species is not part of the required level of confidence. Once user to identify the test labiate with the roquired level that additional testing must be done to establish an identification.

PERFORMANCE DATA:

Clinical Correlation:

In a study conducted at three clinical laboratories, the performance of the In a study conducted at throo billiour leserved was evaluated against
BBLCRYSTAL Neisseria/Heemophilus (N/H) ID System was evely reutine BBCCRYSTAL Nelssena/Asemantional methodologies. Fresh, routine the RapiD " NY System and ochaon as well as previously identified isolates arriving in the clinical laborator you a new utilized in the study. A total of 513 isolates were tested; 93.6% (480) of these isolates were correctly identified (including supplemental testing) using the BBLCRYSTAL" N/H ID identified (including supplemental (octing) and 1.4% (7) yielded a "No ldentification" result.

Reproducibility:

At the same three clinical laboratories, reproducibility of the BBLCRYSTAL" At the same inree clinical laboratories: 10pren (10) Quality Control strains in N/H ID System was established by to vira performed of individual and overall
triplicate on three days. Evaluations were performed of individual and of inter triplicate on three days. Evaluations were ps. of nism reactions, and of interand intra-laboratory reproducibility.

Overall reproducibility was calculated as 95.9%. Reproducibility of individual Overall reproductions ranged from 85.7 to 100%; individual QC organism substrate reactions fanged from 87.7% to 99.2%; and site reproducibility ranged from 95.2% to 97.2%.

167

Regulation Number and Section

§ 866.2660 Microorganism differentiation and identification device.

(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.