GUIDE TO INSPECTIONS OF SOURCE PLASMA ESTABLISHMENTS - Section 2

JUNE 1997
(APRIL 2001 - Editorial Revisions)

NOTE: This document is reference fabric for Investigators and other FDA personnel. The document does not demark FDA, and does not confer any rights, privileges, benefits, or immunities for or on any person(s). An culling approach may exist used if such an approach satisfies the requirements of the applicable statues, regulations, or both.

TABLE OF CONTENTS

Section one
Introduction
General Data
Operations
Standard Operating Procedures
Errors, Accidents and Fatalities
Adverse Reaction
Lookback
Plasmapheresis Facilities
Equipment
Medical Device Reporting
Medical Supervision

Department 2
Donor Identification
Informed Consent
Initial Medical Examination
Immunization
Donor Suitability
Infrequent Donations
Claret Collection
Donor Tape Files
Plasma Separation and Pooling (Manual Only)
Reinfusion of Red Claret Cells (Manual Collection)

Section three
HBsAg, Anti-HCV and Anti-HIV Testing
Handling of HBsAg, Anti-HCV and Anti-HIV Repeatedly Reactive Units
Serum Poly peptide Quantitation
Serologic Test for Syphilis
Storage
Distribution Record
Disposal of Infectious Waste
Computerized Records
Affliction State Donors
"High Risk" Donors
Source Leukocytes
Therapeutic Commutation Plasma

Section 2

DONOR IDENTIFICATION

Adequate identification of a donor is important to forbid cross donation at more than than one plasmapheresis centre, especially in areas where more than one center is located. The SOP should describe a organization to prevent cross donations when applicative. Cross donation occurs when an individual donates at more than 1 plasmapheresis center or blood collection facility.

Acceptable forms of positive identification include a driver's license with photo, a military ID, pupil ID, or whatever other certificate with the donor's signature and either a physical clarification or photo. Some establishments may crave two signed documents. All the same, this is not an FDA requirement.

Plasma centers must have a record against which unsuitable donors may be identified so that unsuitable product from such donors may not be distributed. Plasma centers normally verify the donor'due south deferral condition prior to donation. Computer records, which identify just the donor's proper name and permanent deferral status, are adequate if more detailed information is listed in the donor tape file (DRF). There should be a procedure to keep this data confidential within the center.

INFORMED CONSENT

The potential hazards of the plasmapheresis procedure, both manual and automatic, including possible adverse reactions, must be clearly explained to the donor by a qualified, licensed doc. CBER permits doctor substitutes to obtain the informed consent of donors. Video or audiotapes may exist used to obtain informed consent provided the donor has an opportunity to ask questions and the establishment determines that the donor understands the process.

The importance of the donor's active participation in identification of his/her own ruby-red blood cells (for manual procedure simply) prior to reinfusion should be stressed. For manual procedures, the donor should indicate understanding that two units of whole blood volition exist removed, one at a time, with reinfusion of the first unit of crimson claret cells prior to collection of the 2nd unit of measurement.

The caption of the hazards should be in simple, non-medical terms, and the risks to the donor should non be minimized. Additionally, the potential discomforts and risks of other systemic reactions including hypotension, convulsions, lightheadedness, nausea, vomiting, depletion of proteins (including immunoglobulins), and decrease in hemoglobin, should exist explained to the donor as part of the informed consent. For a farther word of agin reactions, see the department ADVERSE REACTIONS of this document. The physician or approved physician substitute should sign or initial the informed consent form to certify that the hazards take been explained.

The procedure(s) for collection of Source Plasma using automated devices should be explained in lay terms such that the donor understands the process. Donors should be fully informed regarding the possibility of incomplete collections or "cease and restart" situations using automation.

Breakage, leakage, and possible inability to render crimson claret cells should also be addressed. A possible reaction to the anticoagulant, i.east., numbness or "tingling" of the fingers or lips, should also be explained during the informed consent. The hazards of plasmapheresis by manual and automatic procedures are not identical. If the same consent form is used for both manual and automated procedures, it must conspicuously identify the hazards for each procedure.

The hazards of immunization are to be separately discussed. The antigens used have particular risks, and each should exist separately identified. In addition, there are potential general hazards of immunization, such every bit injection site redness and soreness, fever, nausea and vomiting that may accompany the assistants of any antigen. The possibility of anaphylaxis exists with all immunizing agents and should be part of the discussion of hazards. The donor should be informed of the entire schedule of immunizations, the criteria for acceptable response, the procedure to exist followed if no response occurs, and of the institution's obligation to provide evaluation and monitoring for at least one year if cherry-red blood jail cell immunization is done. Donors should be fully informed that they may participate in just one immunization program at a fourth dimension. Participants in crimson blood cell immunization programs should be informed of the following potential hazards of hepatitis and AIDS transmission, the evolution of additional antibodies which may cause the participant'south plasma to be unsuitable for time to come utilize and of possible filibuster in processing of their blood for a transfusion or transplant. In improver, female participants in cherry claret cell programs should be advised of possible risks to a fetus. Currently, CBER does non approve a blood-red blood cell immunization program that permits a female person of childbearing historic period to participate, unless documentation of sterility is obtained from her personal medico. For additional information on obtaining informed consent for participation in immunization programs, run into the Typhoon Reviewers' Guide, Informed Consent for Plasmapheresis/Immunization bachelor through the CBER FAX Data Arrangement.

Each donor should be encouraged to ask questions. All donor questions should be answered fully and completely in a relaxed atmosphere. The interview must be conducted in private and then as to provide an accurate determination of the donor's suitability and in a mode that does not embarrass or disproportionately pressure level the donor to consent. The information on which the donor bases consent should be accurate and understandable to the donor. A donor's decision to turn down consent should be accustomed as a matter of fact with no undue pressure to attempt to alter the decision. The investigator may insist on observing the caption of the informed consent form by the physician without fear that this is an intrusion on the md-patient privacy relationship.

All informed consent forms should be approved past CBER and reverberate currently approved practices. For more information, telephone call the Division of Inspections and Surveillance (HFM-650) at 301-827-6220 or the Partitioning of Blood Applications (HFM-370) at 301-827-3524 . Additional information apropos procedures for obtaining informed consent may be constitute in the DRAFT Reviewer Guidance document, Informed consent for Plasmapheresis/Immunization, dated October i, 1995. See also CPG 250.100, Source Plasma Guidelines for Informed Consent Forms.

INITIAL MEDICAL EXAMINATION

The initial medical examination must [640.63(b)(1)] be performed by a qualified doctor of medicine or osteopathy currently licensed to practice medicine. CBER permits the trained physician substitute, working under the supervision of the md, who must be certified or licensed according to state law, to too perform medical examinations.

AIDS educational materials should be presented to donors at each donation and these materials should conform to the latest FDA recommendations or regulations. After the first donation virtually centers have an abbreviated grade of AIDS materials that donors are asked to read at the time of each donation. Run across CBER memorandum, "Revised Recommendations for the Prevention of HIV Transmission by Blood and Blood Products," dated Apr 23, 1992.

Each donor must exist examined on the solar day of the first donation or no more than than one week earlier the offset donation and at subsequent intervals of no longer than 1 year. See CPG 251.100, Schedule of Concrete Examination for Donors Receiving Immunization Injections. All of the following procedures should be observed with the permission of the donor, preferably a donor of the aforementioned gender equally the investigator. If the donor objects, then an assessment of the exam can be determined by questioning the physician and donors later on the examination and reviewing the records of examinations, or obtaining permission to observe the medical examination from another donor. Observe the caption of the informed consent, including utilise of the AIDS educational materials. While observing the medical examination, privacy should be given to the donor for any questions or concerns of a confidential nature and for the opportunity for the donor to self-exclude in a confidential fashion.

CBER recommends that the following MINIMUM procedures be included in the physical examination, although it may vary from physician to medico:

  1. Middle and lung sounds should be determined on bare skin, both forepart and back, and with several intakes of air during the evaluation.
  2. Abdominal examination is performed at some centers to determine enlargement of the liver, spleen, or lymph nodes. The donor should be relaxed, peradventure with knees bent, and the medico should gently simply firmly press deeply into the abdomen on both right and left upper intestinal areas. Although not required, some centers include palpation of the inguinal (groin) area for lymph node enlargement as part of the examination.
  3. Neurological examination may consist of reflex assessment using a reflex hammer on knees and maybe elbows, ankles, wrists, or other points. Coordination and sensory examinations may also be made, including touch on and balance evaluations.
  4. Examination of the urine for sugar and protein should exist conducted.
  5. The lymph node exam should include the neck from the jaw down towards the shoulders, line-fishing forward from the angle of the jaw and most straight down from backside the ears. Other areas that may be evaluated include under the artillery, at the elbows and the groin region.
  6. The pare should be examined for irregular patches that are reddish to maroon-blue in colour and may be slightly raised. These patches can occur inside the mouth or nose besides as other peel surfaces.
  7. The rima oris should be carefully checked for irregular cottony-appearing white blotches.
  8. It is too important to check nether the natural language, arms, and some centers also check legs for needle tracks.

Demonstrating that the donor has a normal blood pressure level should besides be a role of the physical test. Blood force per unit area (BP) is measured either while the donor is seated or reclining. The gage should be placed on bare peel, i-ii inches above the curve of the elbow. The arm should exist relaxed, supported past the examiner's hand or arm, when the readings are taken. If the BP is elevated beyond acceptable range, it is permissible to have

the donor lie down and relax for five-x minutes and retake the pressure. If however elevated, the donor should be temporarily deferred with advisable medical advice for follow-upwards, and an advisable entry should exist made in the DRF. Still, a donor with a blood pressure outside of normal limits, may be adequate with the examining doc's approval and consistent with a written SOP.

IMMUNIZATION

Report all antigens used and their respective manufacturers. Immunizing agents, such equally tetanus vaccines, rabies vaccines, etc., are licensed products. Cherry-red blood cells for immunization are non licensed products; all the same, they shall be from a source approved by CBER in the Source Plasma license application or supplement.

For each licensed antigen used, there should exist an SOP that complies with the approved package insert. If the antigen is not approved for immunization of donors, CBER should approve the establishment's SOP. Personnel performing immunizations shall be knowledgeable with respect to the SOP. For reddish blood cell immunizations, see CBER memorandum "Revised Recommendations for Carmine Blood Cell Immunization Programs for Source Plasma Donors," dated March fourteen, 1995. If the program does not include utilize of qualified ruddy blood cells for immunization, promptly notify the Division of Inspections and Surveillance (HFM-654) at 301-827-6220 . Reports of these evaluations shall be available for review. CBER requests that Source Plasma establishments seeking blessing for a Red Blood Cell Immunization Program submit records on at least v donors who were successfully immunized and any subsequent agin reactions for review. CBER and/or ORA will conduct an inspection to make up one's mind if the establishment's license awarding or supplement is approvable. The Division of Claret Applications (HFM-370) is responsible for approval these programs.

The institution's physician must evaluate the donor's clinical reaction. For virtually centers, a primal laboratory performs antibody titers. The doctor utilizes the donors' antibiotic titer in determining the schedule of immunizations. Donors should be tested prior to immunization to identify existing antibody titer levels. The facility'due south SOP should indicate the maximum acceptable titer level prior to immunization.

A donor should not participate in more one immunization program concurrently. Donors participating in whatever immunization program may be returned to normal Source Plasma collection if the donor fails to answer to run across the immunization program titer requirements. with the desired titer. If the crimson blood cell recipient should get to another donor center, he/she is excluded from being a Source Plasma donor for twelve months from the date of the last reddish blood cell immunization if the receipt of qualified blood-red claret cells cannot be documented. This procedure should be defined in the SOP.

Singular or unexpected red cell antibodies may develop during the form of immunization. Ruddy blood jail cell immunization recipients should be evaluated for evolution of unexpected antibody responses and reports of these unexpected antibody responses should be kept on file for review during inspections. See CBER memorandum, "Revised Recommendations for Crimson Blood Cell Immunization Programs for Source Plasma Donors," dated March 14, 1995. The doctor should review the development of unexpected antibodies.

Both immediate (due east.yard., hives, localized swelling, etc.) and delayed reactions must be documented, including the firm'due south medical response.

DONOR SUITABILITY

The interview area must offer privacy. This is to make the donor comfy answering questions without fearfulness of existence overheard. Encounter CPG 230.130, Adequate Infinite for Conclusion of Donor Suitability.

If a trainee is determining donor suitability, shut supervision is necessary to assure right performance.

Encounter the following CBER memoranda for additional data:

  1. "Recommendations for the Management of Donors and Units that are Initially reactive for Hepatitis B Surface Antigen (HBsAg)," dated December two, 1987.
  2. "Clarification of FDA Recommendations for Donor Deferral and Product Distribution Based on the Results of Syphilis Testing," dated December 12, 1991.
  3. "FDA Recommendations Apropos Testing for Antibody to Hepatitis B Core Antigen (Anti-HBc)," dated September ten, 1991.
  4. "Revised Recommendations for the Prevention of Human being Immunodeficiency Virus (HIV) Transmission past Claret and Claret Products," dated April 23, 1992.
  5. "Revised Recommendations for Testing Whole Claret, Blood Components, Source Plasma and Source Leukocytes for antibody HCV)," dated April 23, 1992.
  6. "Exemptions to Permit Persons with a History of Viral Hepatitis Before the Historic period of Xi Years to Serve as Donors of Whole Claret and Plasma: Alternative Procedures, 21 CFR 640.120," dated April 23, 1992.
  7. "Deferral of Blood and Plasma Donors based on Medications," dated July 28, 1993.
  8. "Revised Recommendations for Testing Whole Blood, Blood Components, Source Plasma and Source Leukocytes for Antibiotic to Hepatitis C Virus Encoded Antigen (Anti-HCV)," dated August 5, 1993 [this document does not supersede the April 23, 1992, memorandum of the same title].
  9. "Donor Suitability Related to Laboratory Testing for Viral Hepatitis and a History of Viral Hepatitis," dated December 22, 1993.
  10. "Recommendations for Deferral of Donors for Malaria Risk," dated July 26, 1994. [ 1998 revision out for annotate.]
  11. "Recommendations for the Deferral of Current and Recent Inmates of Correctional Institutions as Donors of Whole Blood, Blood Components, Source Leukocytes and Source Plasma," dated June 8, 1995.
  12. "Donor Deferral Due to Ruby-red Blood Jail cell Loss During Collection of Source Plasma by Automated Plasmapheresis," dated December 4, 1995.
  13. "Interim Recommendations for Deferral of Donors at Increased Risk for HIV-one Group O Infection," dated Dec 11, 1996.
  14. "Revised Precautionary Measures to Reduce Possible Chance of Transmission of Creutzfeldt-Jakob Disease (CJD) by Claret and Blood Products," dated December 11, 1996.
  15. "Revised Precautionary Measures to Reduce the Possible Gamble of Manual of Creutzfeldt-Jakob Disease (CJD) and New Variant Cruetzfeldt-Jakob Disease (nvCJD) by claret and Claret Products," November 1999.

In addition to the cocky exclusion provided to the donor in the signed consent argument at each donation, a second self-exclusion opportunity may be offered to the plasma donor during a individual interview conducted by a trained, competent wellness professional person in which the AIDS educational data is presented orally. This 2d self-exclusion may be offered at the initial donation (each fourth dimension for infrequent plasma donors) and yearly as function of the medical test.

Written SOPs should exist available and specify donor suitability criteria. Determination of donor suitability should include:

  1. Temperature - The suggested temperature is 37.5° C [99.6° F] or less. Some plasma centers may take established a low acceptable temperature value, which is unremarkably 97.vi° F (36.5° C). A low temperature is normally of no significance unless the donor has symptoms of viral illness. Mercury-in-glass thermometers, with plastic covers, disposable newspaper thermometers or electronic thermometers with disposable probes are immune.
  2. Blood force per unit area - Donor'south claret pressure must be determined prior to each donation and must be within normal limits. A systolic range of 90-180 mm/Hg and diastolic range of fifty-100 mm/Hg are considered normal limits. Donors with blood pressures outside this range may be acceptable, but but with a physician's approving and consistent with a written SOP.
  3. Hemoglobin or Hematocrit - Hemoglobin must be equal to or greater than 12.5 g/100mL of claret. If the microhematocrit method is used, a value of 38% is equivalent to 12.five m/100 mL.
  4. Pulse charge per unit - Recommended normal pulse rate is 50-100 beats per minute (BPM) with regular rhythm. This is a "normal range"; a physician (dr. substitute) should review results higher or lower or the donor should be deferred. Physicians or physician substitutes may make allowances for a lower pulse rate in an athlete, e.g., joggers, consequent with a written SOP.
  5. Total serum protein (no less than 6.O m/100mL)  - Donors must be deferred for quantitative total poly peptide results of less than vi.0 mg/100mL or for protein composition test results that are outside the limits established by the testing laboratory, until echo testing shows values within acceptable limits, and the donor is reinstated past the physician. A donor who fails to announced in time for a four-month test may be plasmapheresed if no more than six months have elapsed and signed approval of the physician or physician substitute is recorded in the DRF. If donors return after 6 months, or more than, subsequently existence deferred, they shall be treated equally new donors. Also see CPG 255.100, Quantitative Testing for Serum Proteins in Plasmapheresis Donors.
  6. Weight (at least 110 lbs.) – The donor'south weight on the day of donation must exist at to the lowest degree 110 lbs. Personnel should determine the donor's weight to assure the correct volume of claret is drawn. The donor should be weighed each time he/she donates. Personnel should read the weight straight from the scale rather than allow the donor to report his/her weight. Since weight loss or gain may be an indicator of disease or an untoward reaction to plasmapheresis, personnel should monitor a donor'due south weight every bit role of the donor suitability determination. Additionally, the recommendations to decrease the risk of transmitting AIDS from plasma donors country that the existing cumulative records of each Source Plasma donor's weight should be examined to assure that whatever weight loss of 10 pounds or more in less than two months is detected. A donor with an unexplained weight loss should be referred to the physician or physician substitute for complete evaluation prior to whatever further plasma donation. With medical approval that the donor is acceptable, plasma drove may proceed. If the donor is deferred, disposition of plasma from previous units in storage at the plasma center, should exist evaluated.

The donor shall be in adept health on the twenty-four hour period of donation as evidenced by:

  1. Freedom from astute respiratory diseases – Examples of acute respiratory diseases are colds, influenza, persistent cough, sore throat, sinusitis, or other manifestations of upper respiratory infections, and shall exist cause for temporary deferral until active symptoms have subsided. Such symptoms may be early indications of a more serious illness.
  2. Freedom from diseases, other than malaria, transmissible by claret transfusion - The donor must be free of whatever disease that may be transmissible by a blood transfusion. However, persons with a history of malaria are exempt from the foregoing because the organism is transmissible merely by the cellular elements of claret which are not present in the plasma. Some plasma facilities are licensed to collect blood and plasma from donors with circulating hepatitis and HIV antigen and antibiotic for use, e.g., in biological product test kits.
  3. Freedom from infectious pare diseases - A donor with a pare disease shall be deferred if it is manifest at the site of phlebotomy. Balmy skin disorders such as acne, psoriasis, or poison ivy are not cause for deferral unless prevalent at the phlebotomy expanse. Donors with boils or other severe pare infections should be deferred. Blue or imperial spots on the skin (typical of Kaposi's sarcoma) should be referred to the physician.
  4. Freedom of the arms and forearms from scars indicative of narcotic addiction - Before plasma is nerveless from a donor, the arms and forearms must be examined for show of peel puncture or scars which may point abuse/habit to narcotics. Such examination may be fabricated past the person determining donor suitability or past the phlebotomist. This should exist a close, thorough examination and not a brief one. Past or nowadays intravenous drug users must be permanently rejected.
  5. Freedom from a history of or close contact (within 12 months) with individuals having viral hepatitis - Donors with a history of hepatitis must exist permanently deferred. Donors who have had close contact with a person having viral hepatitis other than hepatitis C viral infection are deferred for twelve months after the contact.
  6. Freedom from having received blood or blood products within twelve months - Donors who have received claret or claret products are deferred for twelve months after receipt of the product, unless specifically immunized past with qualified red blood cells in an approved program equally divers in 21 CFR 640.66. See previous section entitled "IMMUNIZATION."

All questions should exist asked slowly and clearly at each donation so that the donor can hear the questions and has time to respond. Since these questions are asked so often by the personnel who are accustomed to receiving a negative reply, they may be asked in a rapid manner and in a monotone phonation, which creates a non-listening environment for the donor. It may exist observed that the donor does non bother to answer the questions; yet the screener automatically checks negative responses. If the procedure is perfunctory, plasma centre direction should be informed.

Screening personnel must defer a donor who is, or who appears to be, nether the influence of booze or drugs, or who does not appear to exist providing reliable answers to medical history questions. The reason for deferral must be permanently recorded in the DRF.

INFREQUENT DONATIONS

Some facilities treat donors as infrequent donors on the initial visit and every bit regular donors on subsequent donations if the donor returns in less than eight weeks. CBER memorandum, "Revision of FDA Memorandum of 8/27/82: Requirements for Exceptional Plasmapheresis Donors," dated March x, 1995, allows infrequent donors to return for plasmapheresis in iv weeks rather than viii. Source Plasma may be collected from infrequent donors without a physical exam, informed consent, or plasma protein tests; however, the establishment should have a supplement to its biologics license for exceptional Source Plasma collection.

Blood COLLECTION

When arm preparation supplies are sterilized past the establishment, SOPs must contain specific information regarding steps to be followed. They should also include directions for acceptable length of fourth dimension such supplies may be used later the sterile packet/container is first opened. If concentrated solutions are used, check that dilutions are properly made and that the proper expiration appointment/time is followed for dilutions. Notation: Quaternary ammonia solutions, e.thou., Pheneen, are easily neutralized and Non Acceptable for utilize in storing forceps.

There are several ways to practice a satisfactory arm grooming. Sufficient duration and vigor of scrubbing are the central factors to removal of superficial microbes. Later on the venipuncture surface area is prepared, the prepared surface area may not exist touched. In club to verify the location of the vein, the area above or below the prepared expanse may be palpated; it is not permissible to put iodine or sterile gauze on the site to locate the vein.

The final collection container shall be marked or identified past number or other symbol, which relates it directly to the donor before filling the container [640.68(b)].

For manual plasmapheresis, the donor's proper name may exist added to the unique donor bleed number on the container to enable both the phlebotomist and the donor or another person to identify the donor's ruby-red blood cells before they are reinfused. The donor'southward name or bed number lone is generally non sufficient identification.

A saline container should be used for simply one donor and no more than four hours afterward entry. If any saline remains in the container after a donor has completed a plasmapheresis procedure, it may be used for laboratory testing but not for another donor. Generally, the volume of saline reinfused should non exceed the corporeality of plasma withdrawn. For automated collections, routine replacement of volume with saline is not necessary, although some centers do use saline for volume replacement.

Neither the needle itself, nor any continuously integral part of the tubing continued with the needle, may be used for more one venipuncture since multiple contacts with skin microbial flora increase the chances of contaminating the blood.

If a needle is added during Source Plasma collection, merely a Sterile Tubing Connecting Device (STCD) approved to weld liquid-filled tubing should be used. See CBER memorandum, "Utilize of an FDA Cleared or Approved Sterile Connecting Device (STCD) in Claret Bank Do," dated August 5, 1994. The source and specifications of added tubing and needles should be addressed in the blood center's SOP and records.

For manual collection : If the first venipuncture fails and the donor consents to a second venipuncture, at a minimum, a new needle and its integral tubing must exist used. If the flow of blood has non reached a connectedness, only the contaminated portion needs to be discarded.

For automated collection there may be times when the disposable fix must be changed subsequently the venipuncture, or there may be times when a new venipuncture must be performed. A new disposable fix may be installed by disconnecting the set from the needle connection in accordance with the manufacturer's instructions. If a new venipuncture is necessary, the dispensable fix can be disconnected from the needle connectedness, the needle changed, the disposable set reconnected, the new venipuncture performed with the new needle, and the procedure continued following the device manufacturer'south directions. When it is necessary to either echo the venipuncture or change the disposable set, this incident, and whatsoever resulting cherry-red blood cell loss, should be recorded.

During manual and automated blood collection or reinfusion of the red blood cells, the phlebotomist should periodically check for slowed or stopped haemorrhage, or the possibility that the needle slipped out of the vein and the blood is infiltrating the surrounding tissues. The automated device is equipped with warning lights and alarms to notify the phlebotomist when the venous pressure level is high.

To clinch donor safety the following should be performed as indicated:

Air removed from arrangement - For manual collection: Earlier the venipuncture is made, saline should be immune to catamenia through the administration set to remove all air from the tubing. This is done by opening the clamps near the saline bag and at the end of the set, allowing the saline to baste into a receptacle until all air is removed from the tubing. The filter chamber should so be half filled with saline. During this procedure, care should be taken not to contaminate the tip of the administration set. For automated collection: Confirm that the beginning-upwards procedures are consistent with instructions in the device operator's transmission.

Anticoagulant mixed with blood - The claret should exist mixed with anticoagulant to prevent formation of clots. Gentle mechanical mixing throughout the collection is platonic; however, if equipment for mixing is non available, periodic manual mixing should exist washed.

Tubing stripped abroad from donor - If the flow rate has slowed or stopped, clots may take formed in the tubing. Therefore, if stripping of the donor tubing is done to remove the clot, it should ever exist in a direction away from the donor to forestall forcing clots into the donor's bloodstream.

Blood bag tubing sealed - Hermetic sealing of the claret bag using a metal clench, white knot, or a dielectric seal must exist done immediately after collection to prevent contagion.

For transmission collection, monitoring to prevent overbleeding can exist done effectively only past weighing each unit of measurement of blood. Each fourth dimension an overbleed is detected, the bedside collection appliance should exist checked and adjusted if necessary before the adjacent unit of blood is nerveless; information technology should exist noted in the records that a check and/or adjustment was made. The whole blood bag weight records would betoken the possibility of overweight collection by transmission methods. Records that show no overweight collections or weights that are identical for all units collected should prompt thorough evaluations of tape keeping practices and the claret collection organization.

Weight of whole blood removed is the total weight less the weight of the blood container and anticoagulant. It is important to know how the weight of the claret container plus anticoagulant is adjusted, i.east., is the scale preset to adjust for this weight or is the subtraction fabricated subsequently?

Determination of whether the proper corporeality has been collected can be calculated as follows:

To collect 500 mL of whole blood, the internet weight of the unit should not exceed 526.v thou (500 mL x 1.053 g/mL = 526.5 g whole claret).

For 600 mL of whole blood nerveless, the net weight should non exceed 631.8 g. (600 mL 10 1.053 one thousand/mL = 631.8 1000 whole blood).

For automatic collections, the internal monitor

weighs the collected plasma more than accurately than an external scale. Overbleeding may occur when a chair or other object interferes with the plasma bag or bottle hanging on the calibration, preventing accurate measurement, or because of operator error in setting up the device for drove. See CPG 252.100, Source Plasma Regulatory Action Based on Overbleeding.

Conversion from manual to automated plasma collection is considered to be a major modify in manufacturing methods and must exist approved in advance by CBER.

Sample dilution : Plasma samples intended for viral mark testing may, nether certain weather condition, get inadvertently diluted with saline in the process of collecting Source Plasma using approved automatic plasmapheresis equipment. Plasma sample dilution may be acquired by human error in the drove process. The almost probable scenario of operator mistake causing saline dilution is at the decision of the collection cycle. If the operator ignores the machine's visual instructions to properly seal/clench the disposable set and pressed the resume (down arrow) key three consecutive times, the machine clamps would open up and saline could enter the plasma line used for viral marker testing. There is likewise the potential for mechanical failures due to changes in tubing specifications or to improper seating of software. Diluted samples could contribute to the possibility of fake-negative viral marking test results.

Firms should have acceptable training programs which:

  1. highlight the need to follow the manufacturer'south instructions when disconnecting the plasmapheresis devices
  2. document bug with automated devices
  3. plant a process for internal investigation and corrective action when saline dilution of samples is suspected or confirmed.

NOTE: The testing laboratory may notify the collecting establishment if diluted samples accept been received or are suspected. Decide if such events accept been documented.

DONOR RECORD FILES (DRF)

DRFs normally include a photograph for donor identification; however, the regulations permit the use of other methods that provide equal or greater

assurance of identifying the donor. Photographs should be clear and current to preclude misidentification.

For all donors, the DRFs should point:

Donors must non be plasmapheresed more frequently than in one case in a 2-day (48 hours) menstruation or twice in a 7-day period.

Collecting from donors in less than 48 hours is acceptable if the donations are two calendar days autonomously. Also acceptable is in one case in four or more weeks for infrequent Source Plasma donors. Donors with rare transitory antibodies may be plasmapheresed inside 8 weeks of Whole Blood donation or afterward an inadvertent loss of a volume of crimson blood cells that would otherwise require an 8 calendar week deferral only if examined and certified by a physician to be adequate for plasmapheresis. The special characteristics of the antibiotic and the demand for plasmapheresing the donor must be documented. See CPG 256.100, Plasmapheresis - 48-hour Period Between Plasmapheresis Procedures.

Medical exams must be performed no more than one calendar week earlier immunization. If the plasma eye has performed a medical exam inside the by 12 months, CBER allows this in place of one performed no more than one week before immunization. If a donor is being immunized earlier the initial plasmapheresis, the medical test may be performed no more than i week before the first injection and need non be repeated, provided that the initial plasmapheresis occurs inside 21 days of the showtime injection. This provision permits the donor to be examined earlier outset the immunization procedure to determine if the donor may have any medical problems with the injection. The boosted 21 days allowed earlier plasmapheresis provides for antibiotic production in the immunized person. If a Source Plasma donor enters the immunization program, an boosted physical examination is unnecessary. See Compliance Policy Guide No. 251.100, Schedule of Physical Exam for Donor Receiving Immunization Injections, for additional information.

Medical exams must exist performed at intervals no longer than one year. The DRF should list the date.

  1. Frequency of donations : Eight weeks must elapse subsequently whole blood donations or later plasma donations when cells are not returned. CBER considers a donor blood loss of more than 200 mL of cherry blood cells during a plasmapheresis procedure (i.e., red blood cell loss incidental to the procedure), to be cause to defer the donor for viii weeks.
  2. Medical examinations performed : Medical (concrete) examinations must exist performed no more one calendar week earlier initial plasmapheresis. This menstruation of one week is allowed to accommodate those centers which take their donors examined in a physician'southward private role. Medical examinations are not necessary for exceptional donors.
  3. Dates when a sample of blood was nerveless for initial testing and at 4 month intervals for :
    1. total plasma or serum protein determination,
    2. plasma or serum protein composition [Serum protein Electropheresis (SPE) or chemical quantitation of components],
    3. serologic test for syphilis (STS).

Either the doc must examine the full protein, protein composition, and STS results besides as the cumulative collection records of the preceding 4 months to determine the donor'southward suitability for connected plasmapheresis. CBER allows this review to be completed past an approved dr. substitute. The review must occur within 21 days after collection of the examination sample and must be signed by the reviewing physician or the md substitute. A physician must evaluate any abnormal findings. Donors with aberrant SPE tests must [640.65(b)(two)(ii)] exist deferred until their results are within normal range. For this reason, SPE results should be reviewed as soon as possible after receipt to preclude donation by unsuitable donors. See Plasma Inspection Guide reference, "Donor Suitability," particular #5. If test results for the 4 month samples are unavailable or the sample is unsuitable, the donor may be plasmapheresed if less than 6 months have passed since the last sample was collected and if approved by the doctor or medico substitute.

The DRFs for donors in an immunization program should indicate: that the donor is only on one immunization program; the type of antigen injected; proper noun and lot number of antigen injected; date of injection; dosage and route of injection; private who gave injection; description of any untoward reaction, if such occurred, and documentation of the effect; tape of pre- and post-immunization titers; and a signed and dated evaluation of the donor's clinical response by a qualified, licensed physician. Often centers include the site of injection in the donor tape. The DRF should besides indicate that only a qualified, licensed physician selects and schedules the immunizing antigen, as well as evaluates the donor's clinical response. CBER has approved alternative procedures under 21 CFR 640.120 to allow the physician substitute to schedule injections and review the donor's clinical response for some immunization programs.

PLASMA SEPARATION AND POOLING IN Manual COLLECTION

Before filling, the plasma pooling container (concluding container) must exist labeled commonly with the donor number and/or the drain number to chronicle it directly to the donor.

Before centrifugation each unit of whole blood should be weighed, and the weight recorded concurrently.

To minimize chances of contamination, careful hygienic techniques must be used during the transfer process. The connection should remain intact and the tubing properly sealed.

Red blood cells should not routinely be permitted to enter the plasma container. Most donors are plasmapheresed regularly, and over a catamenia of time the loss of these red cells may would outcome in anemia.

If an air vent is used for the pooling container when pooling plasma from a donor, it must be sterile and capable of excluding microorganisms, east.grand., a needle filled with sterile cotton, inserted aseptically. Information technology must be kept dry out throughout the pooling procedure. CBER has received reports of contagion of plasma during the pooling process considering of bubbling or leaking of plasma through the vent ports of some pooling bottles.

Pooling bottles should be secured in a way to remain upright during pooling procedures.

The pooling of Source Plasma from two or more donors is permitted provided pooling occurs after the plasma is removed from the blood-red blood cells, and the cerise blood cell containers are sealed. Source Plasma pooled from two or more donors must [640.69(a)(i)] non be used for the manufacture of injectable products. The final product tin only be used for further manufacturing into noninjectable products.

Inadvertent cross pooling of plasma from two donors is a potential problem because of the possibility of cross contamination between the donors' ruddy blood cells. In improver, the likelihood of a wrong red claret cell reinfusion may accompany inadvertent cross pooling.

REINFUSION OF Reddish BLOOD CELLS (MANUAL COLLECTION)

The nigh critical chemical element in manual plasmapheresis is the proper identification of the donor prior to returning the red cells to the donor. The center must have a SOP with clearly defined steps in the proper identification of the donor. Some firms have a ii-person identification and others only 1. Both are acceptable procedures.

Both the donor and the phlebotomist should participate in the identification of the donor'south scarlet blood cells. The regulations do not specifically require that the donor participate in self identification of red claret cells, but CBER has not issued SOP approval unless procedures in the SOP Manual are acceptable to avert infusing the wrong crimson blood cells. Sufficient time and care should be taken for this of import procedure, and it should be performed in accord with the firm'southward SOPs. The regulations do not prohibit or forestall a visually or hearing impaired person from participating in the process of existence a plasma donor every bit long as sufficient safeguards are used to clinch that the donor receives his/her own cells back.

At that place will always exist some blood-red claret cells remaining in the bag, and an endeavor shall be made to render as many of the red cells every bit possible. This is to forestall loss of red cells, which could over fourth dimension crusade a drop in the donor's hemoglobin and hematocrit value. Prior to collection of Source Plasma from a donor, establishments should review the donor record to make up one's mind if any carmine jail cell loss occurred due to technical difficulties during utomated plasmapheresis or if the donor had donated a unit of Whole Blood during the past 8 weeks.

A wrong ruddy blood jail cell infusion is a serious error, which may event in a astringent adverse reaction or fatality if the transfused donor has ABO antibodies to the cerise claret cells transfused by in error. A wrong ruby-red blood cell infusion should be adequately documented. If red blood cells are mistakenly returned to the wrong donor, the recipient of the wrong crimson blood cells should be deferred for 12 months due to this inadvertent transfusion. Medical evaluation of the donor is important to determine if there has been or will be an adverse reaction to the transfusion.

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