GUIDE TO INSPECTIONS OF SOURCE PLASMA ESTABLISHMENTS - SECTION ii

JUNE 1997
(Apr 2001 - Editorial Revisions)

Annotation: This certificate is reference material for Investigators and other FDA personnel. The document does not bind FDA, and does not confer any rights, privileges, benefits, or immunities for or on any person(south). An culling approach may be used if such an approach satisfies the requirements of the applicable statues, regulations, or both.

Tabular array OF CONTENTS

SECTION 1
Introduction
Full general Information
Operations
Standard Operating Procedures
Errors, Accidents and Fatalities
Agin Reaction
Lookback
Plasmapheresis Facilities
Equipment
Medical Device Reporting
Medical Supervision

Section 2
Donor Identification
Informed Consent
Initial Medical Exam
Immunization
Donor Suitability
Exceptional Donations
Claret Collection
Donor Record Files
Plasma Separation and Pooling (Manual Only)
Reinfusion of Carmine Claret Cells (Manual Collection)

Department 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
Illness State Donors
"Loftier Risk" Donors
Source Leukocytes
Therapeutic Exchange Plasma

Section 2

DONOR IDENTIFICATION

Adequate identification of a donor is important to forestall cross donation at more than 1 plasmapheresis center, especially in areas where more than 1 center is located. The SOP should describe a system to prevent cantankerous donations when applicative. Cross donation occurs when an individual donates at more than one plasmapheresis center or claret drove facility.

Acceptable forms of positive identification include a commuter'due south license with photo, a military ID, student ID, or any other document with the donor's signature and either a physical clarification or photograph. Some establishments may crave two signed documents. Notwithstanding, this is not an FDA requirement.

Plasma centers must have a record against which unsuitable donors may be identified and so that unsuitable product from such donors may not exist distributed. Plasma centers unremarkably verify the donor'due south deferral status prior to donation. Computer records, which place only the donor's proper name and permanent deferral status, are adequate if more than detailed information is listed in the donor record file (DRF). There should be a process to keep this information confidential within the heart.

INFORMED CONSENT

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

The importance of the donor'due south active participation in identification of his/her ain red blood cells (for manual procedure only) prior to reinfusion should exist stressed. For transmission procedures, the donor should indicate understanding that 2 units of whole blood will be removed, one at a time, with reinfusion of the first unit of cerise claret cells prior to collection of the second unit.

The explanation of the hazards should be in simple, non-medical terms, and the risks to the donor should not 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 be explained to the donor as role of the informed consent. For a further word of agin reactions, see the department Adverse REACTIONS of this document. The physician or canonical physician substitute should sign or initial the informed consent course to certify that the hazards have been explained.

The process(southward) for drove of Source Plasma using automatic devices should be explained in lay terms such that the donor understands the process. Donors should exist fully informed regarding the possibility of incomplete collections or "stop and restart" situations using automation.

Breakage, leakage, and possible inability to return cerise blood cells should too be addressed. A possible reaction to the anticoagulant, i.e., numbness or "tingling" of the fingers or lips, should also be explained during the informed consent. The hazards of plasmapheresis by manual and automated procedures are non identical. If the same consent course is used for both manual and automatic procedures, it must clearly place the hazards for each procedure.

The hazards of immunization are to exist separately discussed. The antigens used take particular risks, and each should be separately identified. In addition, in that location are potential general hazards of immunization, such as injection site redness and soreness, fever, nausea and vomiting that may accompany the administration 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 unabridged schedule of immunizations, the criteria for acceptable response, the procedure to be followed if no response occurs, and of the establishment's obligation to provide evaluation and monitoring for at least ane year if red claret cell immunization is washed. Donors should exist fully informed that they may participate in only one immunization program at a time. Participants in red claret cell immunization programs should be informed of the post-obit potential hazards of hepatitis and AIDS transmission, the development of additional antibodies which may cause the participant's plasma to be unsuitable for future use and of possible delay in processing of their blood for a transfusion or transplant. In addition, female person participants in red blood cell programs should be advised of possible risks to a fetus. Currently, CBER does not corroborate a red blood cell immunization program that permits a female of childbearing age to participate, unless documentation of sterility is obtained from her personal physician. For additional information on obtaining informed consent for participation in immunization programs, see the Typhoon Reviewers' Guide, Informed Consent for Plasmapheresis/Immunization available through the CBER FAX Information System.

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 individual and so as to provide an accurate decision of the donor'south suitability and in a manner that does non embarrass or disproportionately pressure the donor to consent. The information on which the donor bases consent should be accurate and understandable to the donor. A donor's determination to pass up consent should be accepted as a affair of fact with no undue pressure to endeavor to alter the decision. The investigator may insist on observing the explanation of the informed consent course by the doc without fear that this is an intrusion on the doc-patient privacy human relationship.

All informed consent forms should exist approved by CBER and reflect currently approved practices. For more than information, call the Division of Inspections and Surveillance (HFM-650) at 301-827-6220 or the Division of Blood Applications (HFM-370) at 301-827-3524 . Additional information concerning procedures for obtaining informed consent may be found in the DRAFT Reviewer Guidance document, Informed consent for Plasmapheresis/Immunization, dated October 1, 1995. See besides CPG 250.100, Source Plasma Guidelines for Informed Consent Forms.

INITIAL MEDICAL Test

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

AIDS educational materials should exist presented to donors at each donation and these materials should conform to the latest FDA recommendations or regulations. Afterward the offset donation most centers have an abbreviated course of AIDS materials that donors are asked to read at the time of each donation. Meet CBER memorandum, "Revised Recommendations for the Prevention of HIV Transmission by Claret and Blood Products," dated Apr 23, 1992.

Each donor must be examined on the day of the beginning donation or no more than one week before the beginning donation and at subsequent intervals of no longer than 1 twelvemonth. See CPG 251.100, Schedule of Physical Test for Donors Receiving Immunization Injections. All of the following procedures should exist observed with the permission of the donor, preferably a donor of the same gender as the investigator. If the donor objects, and then an assessment of the test can be determined by questioning the doc and donors after the examination and reviewing the records of examinations, or obtaining permission to observe the medical examination from another donor. Observe the explanation of the informed consent, including use 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 way.

CBER recommends that the post-obit MINIMUM procedures exist included in the concrete test, although it may vary from physician to medico:

  1. Centre and lung sounds should exist determined on bare skin, both front end and back, and with several intakes of air during the evaluation.
  2. Abdominal test is performed at some centers to determine enlargement of the liver, spleen, or lymph nodes. The donor should be relaxed, possibly with knees bent, and the physician should gently just firmly press deeply into the abdomen on both correct and left upper abdominal areas. Although not required, some centers include palpation of the inguinal (groin) area for lymph node enlargement as office of the exam.
  3. Neurological examination may consist of reflex cess using a reflex hammer on knees and possibly elbows, ankles, wrists, or other points. Coordination and sensory examinations may also be made, including touch and balance evaluations.
  4. Exam of the urine for saccharide and protein should be conducted.
  5. The lymph node exam should include the neck from the jaw downward towards the shoulders, line-fishing forward from the angle of the jaw and nearly directly down from backside the ears. Other areas that may be evaluated include under the artillery, at the elbows and the groin region.
  6. The skin should be examined for irregular patches that are crimson to maroon-bluish in color and may be slightly raised. These patches can occur inside the mouth or nose too as other skin surfaces.
  7. The oral cavity should be carefully checked for irregular cottony-appearing white blotches.
  8. It is also of import to check nether the tongue, arms, and some centers as well check legs for needle tracks.

Demonstrating that the donor has a normal blood pressure level should also be a function of the physical test. Blood pressure (BP) is measured either while the donor is seated or reclining. The gage should exist placed on bare skin, 1-ii inches above the bend of the elbow. The arm should be relaxed, supported by the examiner's hand or arm, when the readings are taken. If the BP is elevated beyond adequate range, it is permissible to have

the donor lie downward and relax for v-10 minutes and retake the pressure. If still elevated, the donor should be temporarily deferred with appropriate medical advice for follow-upward, and an appropriate entry should exist made in the DRF. All the same, a donor with a claret pressure outside of normal limits, may be adequate with the examining physician's blessing and consistent with a written SOP.

IMMUNIZATION

Report all antigens used and their respective manufacturers. Immunizing agents, such as tetanus vaccines, rabies vaccines, etc., are licensed products. Carmine blood cells for immunization are not licensed products; however, they shall exist from a source approved by CBER in the Source Plasma license application or supplement.

For each licensed antigen used, at that place should be an SOP that complies with the approved package insert. If the antigen is not approved for immunization of donors, CBER should corroborate the establishment's SOP. Personnel performing immunizations shall be knowledgeable with respect to the SOP. For red blood cell immunizations, see CBER memorandum "Revised Recommendations for Scarlet Blood Cell Immunization Programs for Source Plasma Donors," dated March 14, 1995. If the plan does not include utilise of qualified red 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 approval for a Ruby-red Blood Jail cell Immunization Program submit records on at least five donors who were successfully immunized and whatsoever subsequent adverse reactions for review. CBER and/or ORA will conduct an inspection to determine if the establishment's license awarding or supplement is approvable. The Division of Claret Applications (HFM-370) is responsible for approving these programs.

The establishment'south physician must evaluate the donor'south clinical reaction. For about centers, a central laboratory performs antibody titers. The physician 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'south SOP should indicate the maximum adequate titer level prior to immunization.

A donor should not participate in more than 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 encounter the immunization program titer requirements. with the desired titer. If the cherry-red blood cell recipient should become to some other donor center, he/she is excluded from being a Source Plasma donor for twelve months from the engagement of the last red blood jail cell immunization if the receipt of qualified red blood cells cannot exist documented. This process should be defined in the SOP.

Atypical or unexpected red cell antibodies may develop during the course of immunization. Ruby-red blood cell immunization recipients should exist evaluated for development of unexpected antibody responses and reports of these unexpected antibody responses should be kept on file for review during inspections. Meet CBER memorandum, "Revised Recommendations for Cerise Blood Cell Immunization Programs for Source Plasma Donors," dated March fourteen, 1995. The physician should review the development of unexpected antibodies.

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

DONOR SUITABILITY

The interview area must offering privacy. This is to make the donor comfortable answering questions without fear of beingness overheard. See CPG 230.130, Adequate Space for Determination of Donor Suitability.

If a trainee is determining donor suitability, close supervision is necessary to assure correct functioning.

See the post-obit CBER memoranda for boosted information:

  1. "Recommendations for the Management of Donors and Units that are Initially reactive for Hepatitis B Surface Antigen (HBsAg)," dated Dec 2, 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 10, 1991.
  4. "Revised Recommendations for the Prevention of Human Immunodeficiency Virus (HIV) Transmission past Claret and Claret Products," dated Apr 23, 1992.
  5. "Revised Recommendations for Testing Whole Blood, 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 Age of 11 Years to Serve as Donors of Whole Blood and Plasma: Culling 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 Antibody 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 comment.]
  11. "Recommendations for the Deferral of Electric current and Recent Inmates of Correctional Institutions as Donors of Whole Blood, Blood Components, Source Leukocytes and Source Plasma," dated June eight, 1995.
  12. "Donor Deferral Due to Red Blood 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 Grouping O Infection," dated December 11, 1996.
  14. "Revised Precautionary Measures to Reduce Possible Hazard of Transmission of Creutzfeldt-Jakob Disease (CJD) by Blood and Claret Products," dated Dec xi, 1996.
  15. "Revised Precautionary Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and New Variant Cruetzfeldt-Jakob Disease (nvCJD) by blood and Blood Products," November 1999.

In improver to the self exclusion provided to the donor in the signed consent statement at each donation, a second cocky-exclusion opportunity may be offered to the plasma donor during a private interview conducted past a trained, competent wellness professional in which the AIDS educational information is presented orally. This 2d self-exclusion may be offered at the initial donation (each time for exceptional plasma donors) and yearly equally part of the medical examination.

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.six° F] or less. Some plasma centers may have established a low acceptable temperature value, which is usually 97.six° F (36.v° C). A depression temperature is usually of no significance unless the donor has symptoms of viral illness. Mercury-in-drinking glass thermometers, with plastic covers, dispensable paper thermometers or electronic thermometers with dispensable probes are allowed.
  2. Blood pressure - Donor's claret pressure must be determined prior to each donation and must be within normal limits. A systolic range of ninety-180 mm/Hg and diastolic range of 50-100 mm/Hg are considered normal limits. Donors with blood pressures outside this range may be adequate, but only with a medico'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 blood. If the microhematocrit method is used, a value of 38% is equivalent to 12.5 one thousand/100 mL.
  4. Pulse rate - Recommended normal pulse charge per unit 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.m., joggers, consistent with a written SOP.
  5. Total serum protein (no less than 6.O thou/100mL)  - Donors must be deferred for quantitative total poly peptide results of less than half-dozen.0 mg/100mL or for protein composition examination results that are outside the limits established by the testing laboratory, until repeat testing shows values within acceptable limits, and the donor is reinstated past the physician. A donor who fails to appear in time for a four-month test may be plasmapheresed if no more than six months take elapsed and signed blessing of the doc or medico substitute is recorded in the DRF. If donors return afterwards six months, or more, after being deferred, they shall be treated as new donors. Also run into CPG 255.100, Quantitative Testing for Serum Proteins in Plasmapheresis Donors.
  6. Weight (at least 110 lbs.) – The donor's weight on the solar day of donation must be at least 110 lbs. Personnel should determine the donor'due south weight to assure the right volume of blood is drawn. The donor should be weighed each time he/she donates. Personnel should read the weight directly from the scale rather than allow the donor to report his/her weight. Since weight loss or gain may be an indicator of affliction or an untoward reaction to plasmapheresis, personnel should monitor a donor's weight as part of the donor suitability conclusion. Additionally, the recommendations to subtract the risk of transmitting AIDS from plasma donors state that the existing cumulative records of each Source Plasma donor'due south weight should exist examined to assure that any weight loss of 10 pounds or more in less than 2 months is detected. A donor with an unexplained weight loss should be referred to the physician or physician substitute for consummate evaluation prior to any further plasma donation. With medical approval that the donor is acceptable, plasma collection may go on. 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 skilful health on the day of donation as evidenced by:

  1. Liberty from acute respiratory diseases – Examples of astute respiratory diseases are colds, influenza, persistent cough, sore pharynx, sinusitis, or other manifestations of upper respiratory infections, and shall be cause for temporary deferral until active symptoms take subsided. Such symptoms may exist early indications of a more than serious disease.
  2. Freedom from diseases, other than malaria, transmissible past blood transfusion - The donor must exist free of whatever disease that may exist transmissible by a blood transfusion. Even so, persons with a history of malaria are exempt from the foregoing because the organism is transmissible only by the cellular elements of claret which are non nowadays in the plasma. Some plasma facilities are licensed to collect claret and plasma from donors with circulating hepatitis and HIV antigen and antibiotic for use, due east.g., in biological product test kits.
  3. Freedom from infectious pare diseases - A donor with a skin affliction shall be deferred if it is manifest at the site of phlebotomy. Mild skin disorders such equally acne, psoriasis, or poison ivy are not cause for deferral unless prevalent at the phlebotomy area. Donors with boils or other severe skin infections should be deferred. Blue or royal spots on the skin (typical of Kaposi's sarcoma) should be referred to the doc.
  4. Freedom of the arms and forearms from scars indicative of narcotic addiction - Before plasma is collected from a donor, the arms and forearms must be examined for bear witness of pare puncture or scars which may indicate corruption/addiction to narcotics. Such examination may be made by the person determining donor suitability or by the phlebotomist. This should be a shut, thorough exam and not a cursory 1. Past or nowadays intravenous drug users must be permanently rejected.
  5. Liberty from a history of or close contact (within 12 months) with individuals having viral hepatitis - Donors with a history of hepatitis must be permanently deferred. Donors who have had shut 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 claret or blood products within twelve months - Donors who take received blood or claret products are deferred for twelve months after receipt of the product, unless specifically immunized by with qualified red blood cells in an approved program every bit divers in 21 CFR 640.66. Encounter previous section entitled "IMMUNIZATION."

All questions should be 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 and then ofttimes past the personnel who are accustomed to receiving a negative reply, they may exist asked in a rapid manner and in a monotone voice, which creates a non-listening surround for the donor. Information technology may be observed that the donor does non bother to answer the questions; yet the screener automatically checks negative responses. If the procedure is perfunctory, plasma center management should exist informed.

Screening personnel must defer a donor who is, or who appears to be, under the influence of alcohol or drugs, or who does not appear to be 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 equally 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 10, 1995, allows infrequent donors to render for plasmapheresis in four weeks rather than viii. Source Plasma may be collected from infrequent donors without a concrete test, informed consent, or plasma protein tests; notwithstanding, the establishment should have a supplement to its biologics license for infrequent Source Plasma collection.

Blood Collection

When arm training supplies are sterilized by the establishment, SOPs must contain specific information regarding steps to exist followed. They should also include directions for acceptable length of time such supplies may be used after the sterile package/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. NOTE: Quaternary ammonia solutions, e.1000., Pheneen, are easily neutralized and NOT ACCEPTABLE for apply in storing forceps.

In that location are several ways to exercise a satisfactory arm grooming. Sufficient duration and vigor of scrubbing are the key factors to removal of superficial microbes. After the venipuncture area is prepared, the prepared area may not be touched. In lodge to verify the location of the vein, the area above or beneath the prepared area 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 by number or other symbol, which relates it directly to the donor before filling the container [640.68(b)].

For manual plasmapheresis, the donor'southward name may be 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 carmine blood cells before they are reinfused. The donor'southward proper noun or bed number alone is generally not sufficient identification.

A saline container should exist used for only 1 donor and no more than than four hours after entry. If any saline remains in the container afterwards a donor has completed a plasmapheresis procedure, information technology may exist used for laboratory testing but not for another donor. Generally, the volume of saline reinfused should not exceed the amount of plasma withdrawn. For automated collections, routine replacement of volume with saline is not necessary, although some centers do apply saline for volume replacement.

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

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

For manual drove : If the first venipuncture fails and the donor consents to a second venipuncture, at a minimum, a new needle and its integral tubing must be used. If the flow of blood has not reached a connection, merely the contaminated portion needs to be discarded.

For automated collection there may be times when the dispensable ready must be changed later on the venipuncture, or there may be times when a new venipuncture must be performed. A new dispensable set 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 disposable gear up can exist asunder from the needle connection, the needle changed, the disposable set reconnected, the new venipuncture performed with the new needle, and the procedure connected following the device manufacturer's directions. When it is necessary to either echo the venipuncture or modify the dispensable fix, this incident, and any resulting cherry-red blood cell loss, should be recorded.

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

To assure donor prophylactic the following should be performed as indicated:

Air removed from system - For manual collection: Before the venipuncture is fabricated, saline should be allowed to flow 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 fix, allowing the saline to drip into a receptacle until all air is removed from the tubing. The filter bedroom should then exist half filled with saline. During this procedure, care should exist taken non to contaminate the tip of the administration set. For automated drove: Confirm that the start-upwards procedures are consistent with instructions in the device operator'due south manual.

Anticoagulant mixed with claret - The claret should be mixed with anticoagulant to forbid formation of clots. Gentle mechanical mixing throughout the collection is ideal; however, if equipment for mixing is not bachelor, periodic manual mixing should be done.

Tubing stripped away from donor - If the flow rate has slowed or stopped, clots may have formed in the tubing. Therefore, if stripping of the donor tubing is washed to remove the clot, information technology should always be in a direction away from the donor to prevent forcing clots into the donor's bloodstream.

Blood pocketbook tubing sealed - Hermetic sealing of the blood bag using a metallic clamp, white knot, or a dielectric seal must be done immediately later drove to prevent contagion.

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

Weight of whole claret removed is the full weight less the weight of the blood container and anticoagulant. Information technology is important to know how the weight of the blood container plus anticoagulant is adjusted, i.e., is the scale preset to adjust for this weight or is the subtraction made later?

Determination of whether the proper amount has been collected tin exist calculated as follows:

To collect 500 mL of whole blood, the net weight of the unit of measurement should not exceed 526.5 k (500 mL x 1.053 g/mL = 526.5 g whole blood).

For 600 mL of whole blood collected, the internet weight should not exceed 631.8 g. (600 mL x ane.053 g/mL = 631.8 g whole blood).

For automated collections, the internal monitor

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

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

Sample dilution : Plasma samples intended for viral marker testing may, under sure conditions, become inadvertently diluted with saline in the procedure of collecting Source Plasma using canonical automated plasmapheresis equipment. Plasma sample dilution may be caused by human error in the collection process. The most likely scenario of operator error causing saline dilution is at the determination of the collection wheel. If the operator ignores the machine'south visual instructions to properly seal/clamp the disposable set and pressed the resume (downwards arrow) key 3 sequent times, the car 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 false-negative viral marker exam results.

Firms should have acceptable training programs which:

  1. highlight the need to follow the manufacturer'southward instructions when disconnecting the plasmapheresis devices
  2. document problems with automated devices
  3. establish a process for internal investigation and cosmetic activeness when saline dilution of samples is suspected or confirmed.

NOTE: The testing laboratory may notify the collecting institution if diluted samples take been received or are suspected. Determine if such events have been documented.

DONOR RECORD FILES (DRF)

DRFs unremarkably include a photograph for donor identification; nevertheless, the regulations let the use of other methods that provide equal or greater

balls of identifying the donor. Photographs should be clear and current to forestall misidentification.

For all donors, the DRFs should indicate:

Donors must not exist plasmapheresed more frequently than once in a 2-24-hour interval (48 hours) menstruation or twice in a vii-day menses.

Collecting from donors in less than 48 hours is acceptable if the donations are 2 calendar days apart. Too acceptable is in one case in four or more than weeks for exceptional Source Plasma donors. Donors with rare transitory antibodies may exist plasmapheresed within 8 weeks of Whole Blood donation or after an inadvertent loss of a volume of cherry-red blood cells that would otherwise require an eight week deferral only if examined and certified by a physician to be acceptable for plasmapheresis. The special characteristics of the antibody and the demand for plasmapheresing the donor must exist documented. Run across CPG 256.100, Plasmapheresis - 48-hour Period Between Plasmapheresis Procedures.

Medical exams must be performed no more than than i week before immunization. If the plasma center has performed a medical exam inside the past 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 examination may exist performed no more than 1 week earlier the first injection and need not be repeated, provided that the initial plasmapheresis occurs within 21 days of the first injection. This provision permits the donor to be examined before beginning the immunization procedure to determine if the donor may take whatever medical problems with the injection. The additional 21 days allowed earlier plasmapheresis provides for antibody product in the immunized person. If a Source Plasma donor enters the immunization program, an additional physical examination is unnecessary. Run across Compliance Policy Guide No. 251.100, Schedule of Physical Examination for Donor Receiving Immunization Injections, for additional information.

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

  1. Frequency of donations : 8 weeks must expire after whole blood donations or after plasma donations when cells are not returned. CBER considers a donor blood loss of more than 200 mL of red blood cells during a plasmapheresis procedure (i.e., crimson blood cell loss incidental to the process), to exist cause to defer the donor for 8 weeks.
  2. Medical examinations performed : Medical (physical) examinations must be performed no more than i week before initial plasmapheresis. This period of i week is immune to accommodate those centers which have their donors examined in a physician's private part. Medical examinations are non necessary for infrequent donors.
  3. Dates when a sample of blood was collected for initial testing and at 4 month intervals for :
    1. total plasma or serum protein determination,
    2. plasma or serum poly peptide composition [Serum poly peptide Electropheresis (SPE) or chemical quantitation of components],
    3. serologic test for syphilis (STS).

Either the dr. must examine the total poly peptide, poly peptide composition, and STS results likewise every bit the cumulative drove records of the preceding 4 months to make up one's mind the donor'southward suitability for continued plasmapheresis. CBER allows this review to be completed by an approved physician substitute. The review must occur within 21 days after collection of the test sample and must be signed by the reviewing dr. or the physician substitute. A doctor must evaluate any abnormal findings. Donors with abnormal SPE tests must [640.65(b)(two)(two)] exist deferred until their results are within normal range. For this reason, SPE results should be reviewed equally soon every bit possible later receipt to preclude donation by unsuitable donors. See Plasma Inspection Guide reference, "Donor Suitability," item #5. If test results for the four month samples are unavailable or the sample is unsuitable, the donor may exist plasmapheresed if less than six months have passed since the last sample was collected and if approved by the medico or physician substitute.

The DRFs for donors in an immunization plan should signal: that the donor is only on ane immunization program; the blazon of antigen injected; name and lot number of antigen injected; appointment of injection; dosage and route of injection; individual who gave injection; clarification of any untoward reaction, if such occurred, and documentation of the effect; record of pre- and post-immunization titers; and a signed and dated evaluation of the donor's clinical response past a qualified, licensed doctor. Often centers include the site of injection in the donor record. The DRF should also indicate that only a qualified, licensed physician selects and schedules the immunizing antigen, as well as evaluates the donor'due south clinical response. CBER has approved alternative procedures under 21 CFR 640.120 to allow the md 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 (terminal container) must be labeled usually with the donor number and/or the bleed number to relate information technology directly to the donor.

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

To minimize chances of contagion, careful aseptic techniques must be used during the transfer procedure. The connection should remain intact and the tubing properly sealed.

Scarlet claret cells should non routinely be permitted to enter the plasma container. Virtually donors are plasmapheresed regularly, and over a catamenia of time the loss of these cherry cells may would consequence 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, e.thousand., a needle filled with sterile cotton wool, inserted aseptically. Information technology must exist kept dry out throughout the pooling procedure. CBER has received reports of contamination 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 mode 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 ruby blood cells, and the red blood cell containers are sealed. Source Plasma pooled from two or more donors must [640.69(a)(one)] non be used for the manufacture of injectable products. The final product can only exist used for further manufacturing into noninjectable products.

Inadvertent cross pooling of plasma from two donors is a potential problem because of the possibility of cantankerous contamination between the donors' red claret cells. In addition, the likelihood of a wrong cerise blood cell reinfusion may back-trail inadvertent cross pooling.

REINFUSION OF RED Blood CELLS (MANUAL Collection)

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

Both the donor and the phlebotomist should participate in the identification of the donor's red blood cells. The regulations do not specifically require that the donor participate in self identification of cherry-red blood cells, but CBER has non issued SOP approval unless procedures in the SOP Transmission are acceptable to avoid infusing the wrong ruddy blood cells. Sufficient time and intendance should exist taken for this important process, and it should be performed in accordance with the firm's SOPs. The regulations do non prohibit or forbid a visually or hearing impaired person from participating in the process of being a plasma donor as long every bit sufficient safeguards are used to assure that the donor receives his/her own cells back.

There will ever be some red blood cells remaining in the bag, and an effort shall be made to return every bit many of the red cells as possible. This is to prevent loss of red cells, which could over fourth dimension crusade a driblet in the donor'southward hemoglobin and hematocrit value. Prior to collection of Source Plasma from a donor, establishments should review the donor record to decide if any reddish 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 eight weeks.

A wrong cherry-red blood cell infusion is a serious error, which may result in a severe agin reaction or fatality if the transfused donor has ABO antibodies to the crimson blood cells transfused past in error. A incorrect cherry-red blood cell infusion should be adequately documented. If red blood cells are mistakenly returned to the wrong donor, the recipient of the incorrect crimson claret cells should be deferred for 12 months due to this inadvertent transfusion. Medical evaluation of the donor is important to decide if at that place has been or will be an agin reaction to the transfusion.

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