Volume Limits - Automated Collection of Source Plasma (11/4/92)

Date:     4 November 1992

From:     Director, Center for Biologics Evaluation and
          Research

Subject:  Volume Limits for Automated Collection of Source
          Plasma

To:       All Registered Blood Establishments


The increased number of automated plasma collection devices with
varying capacities for tailoring each collection to the specific
donor has resulted in the existence of multiple Food and Drug
Administration (FDA) approved nomograms which specify, for each
piece of equipment, the maximum volume of plasma to be harvested
from each donor category.  Current considerations in determining
the volume of plasma to be collected include gender, height,
weight, hematocrit, and in some centers, the length of time in
process or the number of cycles.  Because multiple equipment
types commonly coexist in a location, the potential for error  
due to application of an inappropriate nomogram is significantly
increased.  The use of various anticoagulant solutions, differing
concentrations of the anticoagulant, and a range of anticoagulant
to plasma ratios, additionally complicates some schema and
creates additional opportunity for error.

The experience to date with all of the approved equipment
indicates that there is no discernible impact on donor safety or
product quality with the use of any of the current limits in
preference to any other.  Some Source Plasma manufacturers have
requested and received approval for simplified nomograms.  The
FDA supports this type of process change which potentially
improves the consistency of procedures for manufacturing and
minimizes the opportunity for staff error.

To promote rapid implementation of such simplified schema, the
Center for Biologics Evaluation and Research is informing all
manufacturers that the following limits may be adopted without
further notice.  The anticoagulant volume is included in the
third column below.  This volume is based on a 1:16 (0.06) ratio
of anticoagulant to anticoagulated-blood. 

  Donor Weight    Plasma Volume or Weight    Collection Volume


   10-149 lbs          625 mL (640 g)          690 mL (705 g)

   150-174 lbs         750 mL (770 g)          825 mL (845 g) 

   175 lbs & up        800 mL (820 g)          880 mL (900 g)


It has been determined that the use of this simplified nomogram
does not constitute a significant change in manufacturing and,
therefore, does not require advance approval of amendments to
licenses.  However, it should be noted that the nomogram is
intended to be adopted as a complete set of limits.  The
simplified nomogram and the equipment manufacturer's nomogram
should not be used simultaneously in the same center. Portions of
the table should not be selectively applied in combination with
some other system of limits.  Variations will require advance
approval of license amendments based on supporting documentation
including evidence that the chance of error is not increased.

To monitor potential adverse reactions and ensure that no
increased frequency of reactions is observed with this change in
the volume of plasma collected, it is requested that any
reactions observed for the first 1,000 procedures done under your
license be reported to the FDA.  If plasma from 1,000 donors has
not been collected during the first three months after
implementation of the new nomogram, please provide an interim
report of any reactions occurring during the first three months. 
For your convenience we have provided a format for reporting of
the desired information on adverse reactions.  




                                  Kathryn C. Zoon, Ph.D.

     _____________________________________________________

               Addendum to FDA Memorandum
                  Suggested Format for
 Experience Report On Plasma Collection Adverse Events

Automated device used for collection:

Anticoagulant used:

Anticoagulant to anticoagulated-whole blood ratio used during
this collection procedure:

Weight of donor:

Height of donor:

Donor number and gender of donor:

Hematocrit prior to collection:

Total protein prior to collection:

 Amount of plasma collected when reaction occurred:

 Amount of anticoagulant used before reaction occurred:

 Amount of saline administered before reaction (if any):

Type of reaction and severity (mild, moderate, severe, life-
threatening):

Signs/symptoms of reaction:

Blood pressure at time of reaction:

Was physician notified?:

Treatment of donor:

Any operator error detected?

If yes, please provide additional details in accordance with FDA
memorandum, March 20, 1991:  Responsibilities of Blood
Establishments Related to Errors & Accidents in the Manufacture
of Blood and Blood Components.

Other comments:


Submit to: Dr. Kathryn C. Zoon, Director
           Center for Biologics Evaluation and Research
           8800 Rockville Pike HFB-940
           Bethesda, MD 20892