Guidance for Industry 

and FDA Staff 

Class II Special Controls Guidance 

Document: Automated Blood Cell 

Separator Device Operating by 

Centrifugal or Filtration 

Separation Principle 

DRAFT GUIDANCE 

This guidance document is being distributed for comment purposes only. 

Submit comments on this draft document by the date provided in the Federal Register

notice announcing the availability of the draft guidance. Submit comments to the Division 

of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 

rm. 1061, Rockville, MD 20852. You should identify all comments with the docket number 

listed in the notice of availability that publishes in the Federal Register. 

Additional copies of this draft guidance are available from the Office of Communication, 

Training and Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Rockville, MD 

20852-1448, or by calling 1-800-835-4709 or 301-827-1800, or from the Internet at 

http://www.fda.gov/cber/guidelines.htm. 

For questions on the content of this draft guidance contact the Office of Blood Research and 

Review at 301-827-6178. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Biologics Evaluation and Research 

January 2005
Guidance for Industry 

and FDA Staff 

Class II Special Controls Guidance 

Document: Automated Blood Cell 

Separator Device Operating by 

Centrifugal or Filtration 

Separation Principle 

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i 

Table of Contents 

I. PURPOSE................................................................................................................. 1

II. BACKGROUND ...................................................................................................... 2

III. THE LEAST BURDENSOME APPROACH........................................................ 2

IV. DEVICE DESCRIPTION ....................................................................................... 3

V. RISKS TO HEALTH............................................................................................... 3

VI. SPECIAL CONTROLS........................................................................................... 4

VII. CONCLUSION ........................................................................................................ 5

REFERENCES.................................................................................................................. 5
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1 

Guidance for Industry and FDA Staff 

Class II Special Controls Guidance Document: Automated 

Blood Cell Separator Device Operating by Centrifugal or 

Filtration Separation Principle 

This draft guidance, when finalized, will represent the Food and Drug Administration’s 

(FDA’s) current thinking on this topic. It does not create or confer any rights for or on 

any person and does not operate to bind FDA or the public. You can use an alternative 

approach if the approach satisfies the requirements of the applicable statutes and 

regulations. If you want to discuss an alternative approach, contact the appropriate 

FDA staff. If you cannot identify the appropriate FDA staff, call the appropriate number 

listed on the title page of this guidance. 

I. PURPOSE 

We, FDA, are issuing this draft guidance document in conjunction with a Federal 

Register proposed rule proposing to reclassify from class III to class II the automated 

blood cell separator device operating on a centrifugal separation principle intended for 

the routine collection of blood and blood components. This guidance is issued for 

comment purposes only. If the final rule does not reclassify this device type, this 

guidance document will be revised. This document serves as the special control to 

support the reclassification. Also, this document, when final, will serve as the special 

control for the automated blood cell separator device operating on a filtration principle 

intended for the routine collection of blood and blood components reclassified as class II 

on February 28, 2003 (68 FR 9530). Special controls, when combined with general 

controls, ordinarily address the risks associated with use of the device. 

FDA’s guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe FDA’s current thinking on a topic and 

should be viewed only as recommendations, unless specific regulatory or statutory 

requirements are cited. The use of the word should in FDA’s guidances means that 

something is suggested or recommended, but not required. 

Following the effective date of a final rule reclassifying the device, any firm submitting a 

510(k) premarket notification for an automated blood cell separator device operating by 

centrifugal or filtration separation principle intended for the routine collection of blood 

and blood components will need to address the issues covered in this special control 

guidance. However, the firm need only show that its device meets the recommendations 

of this guidance or in some other way provides equivalent assurances of safety and 

effectiveness. 
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II. BACKGROUND 

FDA believes that special controls, when combined with general controls, will be 

sufficient to provide reasonable assurance of the safety and effectiveness of the 

automated blood cell separator device operating on a centrifugal or filtration separation 

principle and intended for the routine collection of blood and blood components. Thus, a 

manufacturer that intends to market a device of this generic type should (1) conform to 

the general controls of the Federal Food, Drug, and Cosmetic Act (the Act), including the 

premarket notification requirements described in 21 Code of Federal Regulations (CFR), 

Part 807, Subpart E, (2) address the specific risks to health associated with the automated 

blood cell separator device identified in this guidance, and (3) obtain a substantial 

equivalence determination from FDA prior to marketing the device (see also § 807.85 (21 

CFR 807.85)). 

This special control guidance identifies the relevant classification regulation, which 

provides a description of the applicable automated blood cell separator device (refer to 

section IV. – Device Description, below). In addition, other sections of this special 

control guidance list the risks to health identified by FDA and describe measures that, if 

followed by manufacturers and combined with general controls, will ordinarily address 

the risks associated with these automated blood cell separator devices. 

This document supplements the specific content requirements of a premarket notification 

submission under § 807.87 and other FDA documents on this topic (e.g., 510(k) Manual 

– Premarket Notification 510(k): Regulatory Requirements for Medical Devices, 

August 1995; and, The New 510(k) Paradigm – Alternate Approaches to Demonstrating 

Substantial Equivalence in Premarket Notifications; Final Guidance, March 20, 1998. 

(See references 1 and 2)). A manufacturer may submit a Traditional 510(k) premarket 

notification or has the option of submitting either an Abbreviated 510(k) or a Special 

510(k) (See The New 510(k) Paradigm). We believe an Abbreviated 510(k) provides the 

least burdensome means of demonstrating substantial equivalence for a new device, 

particularly once we have issued a special control guidance. Manufacturers considering 

modifications to their own cleared devices may lessen the regulatory burden by 

submitting a Special 510(k) (See The New 510(k) Paradigm at page 3). 

III. THE LEAST BURDENSOME APPROACH

We recommend that you address the following issues identified in this guidance before 

your device can be marketed. In developing this guidance, we carefully considered the 

relevant statutory criteria for FDA decision-making. We also considered the burden that 

may be incurred in your attempt to comply with the statutory and regulatory criteria in a 

manner suggested by this guidance and in your attempt to address the issues we have 

identified. We think that we have provided the least burdensome approach to resolving 
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these issues. If, however, you believe there is a less burdensome way to address the 

issues, please follow the procedures outlined in the document, The Least Burdensome 

Provisions - Activities Related to Implementation (See reference 3). 

 

IV. DEVICE DESCRIPTION 

Title 21, Code of Federal Regulations, § 864.9245 provides the classification for 

automated blood cell separators. The automated blood cell separator is a device that 

operates on a centrifugal or a filtration separation principle intended for the routine 

collection of blood and blood components. The device automatically withdraws whole 

blood from a donor, separates the whole blood into blood components, collects one or 

more of the blood components, and returns to the donor the remainder of the whole blood 

and blood components (apheresis donation). The blood components collected are 

transfused or used for further manufacture. 

This draft guidance applies to automated blood cell separator devices that operate by 

either centrifugal or filtration separation principles and where the intended use is for the 

routine collection of blood and blood components. FDA has proposed that these 

automated blood cell separator devices be classified as class II (special controls). 

V. RISKS TO HEALTH 

In order to provide assurances for the safe and effective use of the device, we first 

identify risks to health associated with the device’s intended use. Then, we determine if 

the general and special controls will sufficiently address the identified risks. Presently, 

we have identified the following risks associated with apheresis blood donation and 

processing: 

 

• potential loss of blood due to leaks, 

• thrombosis due to activation of factors by foreign surfaces, 

• moderate-severe toxic reaction to citrate anticoagulant (e.g., tetany, seizures, 

cardiac arrhythmias), 

• damage to red blood cells, activation of complement, and denaturation of 

proteins, 

• potential for sepsis and fever due to bacterial contamination of the donor’s blood 

returned to the donor, 

• infectious disease risk to the donor or to the operator due to leaks, 

• electrical shock hazard, 

• donor stress reaction due to removal or loss of blood, 

• air embolism, 

• hemolysis, and 

• reservoir rupture. 
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VI. SPECIAL CONTROLS 

For currently marketed products not approved under the premarket approval (PMA) 

process, the manufacturer should file with FDA for three consecutive years an annual 

report on the anniversary date of the device reclassification from class III to class II, or, 

on the anniversary date of 510(k) clearance. Any subsequent change to the device 

requiring the submission of a premarket notification in accordance with section 510(k) of 

the Act should be included in the annual report. Also, a manufacturer of a device 

determined to be substantially equivalent to the automated blood cell separator device 

operating by centrifugal or filtration separation principle intended for the routine 

collection of blood and blood components, should comply with the same general and 

special controls. 

This draft guidance (special control) recommends that each annual report include, at a 

minimum, the following information: 

1. A summary of anticipated and unanticipated donor adverse device events that 

have occurred and that are not required to be reported by manufacturers under 

Medical Device Reporting (MDR).1

 We recommend summarizing and 

reporting donor adverse device events such as those required under 

§ 606.160(b)(1)(iii)2, 3 to be recorded and maintained by the facility4 using the 

device to collect blood and blood components. Under § 803.50(b)(2), 

manufacturers are responsible for conducting an investigation of each event 

and evaluating the cause of the event. Therefore, this information should be 

available to the manufacturer to summarize and provide to FDA in the annual 

report. We emphasize that safety information submitted to FDA is not to be 

considered an admission of causation or liability (October 27, 1994, 59 FR 

54046 at 54051). 

 

1

 21 CFR § 803.1(a) – “device user facilities, importers, and manufacturers, as defined in § 803.3, must 

report deaths and serious injuries to which a device has or may have caused or contributed . . . 

manufacturers and importers are also required to report certain device malfunctions . . . .” 

2

 21 CFR § 606.160(b) – “Records shall be maintained that include, but are not limited to, the following 

when applicable: . . . (1)(iii) Donor adverse reaction complaints and reports, including results of all 

investigations and followup.” 

3

 In separate proposed rulemaking (Safety Reporting Requirements for Human Drug and Biological 

Products; Proposed Rule (68 FR 12405, March 14, 2003), FDA has proposed amending 21 CFR § 606.170 

to require the investigation and recording by blood establishments of any complaint of a serious adverse 

reaction related to the collection or transfusion of blood or blood components. 

4

 “Facility” means any area used for the collection, processing, compatibility testing, storage or distribution 

of blood and blood components (21 CFR § 606.3(h)). Also, applicable is “device user facility” under § 

803.3(f), meaning “a hospital, ambulatory surgical facility, nursing home, outpatient diagnostic facility, or 

outpatient treatment facility . . . .” (Note: The donor becomes a patient when he or she experiences and is 

treated for an adverse event contributed to or caused by the medical device.) 
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2. Any subsequent change to the device requiring the submission of a premarket 

notification in accordance with section 510(k) of the Act (Ref. 4). 

3. Any subsequent change to the preamendments class III device requiring a 30-

day notice in accordance with § 814.39(f). 

MDR reportable events may include operator infection or injury; equipment failures, 

including software, hardware, and disposable item failures; thrombosis; sepsis; and shock 

resulting from blood loss. You do not have to include the MDR reports in the annual 

report. If not reportable under MDR, please refer to 1. above, under this section. 

VII. CONCLUSION 

This guidance contains recommendations with regard to the reporting of adverse device 

events that typically are not reported under the MDR regulation. The reporting of 

adverse device events summarized in an annual report will alert FDA to trends or clusters 

of events that might be a safety issue otherwise unreported under the MDR regulation. 

These special controls along with the general controls should provide reasonable 

assurance of the safety and effectiveness of the device. 

REFERENCES 

1. 510(k) Manual – Premarket Notification 510(k): Regulatory Requirements for 

Medical Devices, August 1995; http://www.fda.gov/cdrh/manual/510kprt1.html. 

2. The New 510(k) Paradigm – Alternate Approaches to Demonstrating Substantial 

Equivalence in Premarket Notifications; Final Guidance, March 20, 1998; 

http://www.fda.gov/cdrh/ode/parad510.html. 

3. The Least Burdensome Provisions - Activities Related to Implementation; 

http://www.fda.gov/cdrh/modact/leastburdensome.html. 

4. Guidance - Deciding When to Submit a 510(k) for a Change to an Existing 

Device, January 10, 1997; http://www.fda.gov/cdrh/ode/510kmod.html. 

5. Guidance for Industry, Recommendations for Collecting Red Blood Cells by 

Automated Apheresis Methods, January 2001; Technical Correction February 

2001; http://www.fda.gov/cber/gdlns/rbcautoph2.htm. 

6. Medical Device Reporting Guidance, Medical Device Reporting for 

Manufacturers, March 1997; http://www.fda.gov/cdrh/manual/mdrman.pdf.