GUIDE TO INSPECTIONS OF SOURCE PLASMA ESTABLISHMENTS - Department 2

JUNE 1997
(APRIL 2001 - Editorial Revisions)

Annotation: This document is reference material for Investigators and other FDA personnel. The document does non bind FDA, and does non confer any rights, privileges, benefits, or immunities for or on whatsoever person(s). An culling approach may be used if such an approach satisfies the requirements of the applicable statues, regulations, or both.

TABLE OF CONTENTS

Section 1
Introduction
General Data
Operations
Standard Operating Procedures
Errors, Accidents and Fatalities
Adverse Reaction
Lookback
Plasmapheresis Facilities
Equipment
Medical Device Reporting
Medical Supervision

Department ii
Donor Identification
Informed Consent
Initial Medical Examination
Immunization
Donor Suitability
Infrequent Donations
Blood Collection
Donor Record Files
Plasma Separation and Pooling (Transmission Only)
Reinfusion of Red Blood Cells (Manual Collection)

Section 3
HBsAg, Anti-HCV and Anti-HIV Testing
Handling of HBsAg, Anti-HCV and Anti-HIV Repeatedly Reactive Units
Serum Protein Quantitation
Serologic Test for Syphilis
Storage
Distribution Tape
Disposal of Infectious Waste
Computerized Records
Disease Land Donors
"High Risk" Donors
Source Leukocytes
Therapeutic Exchange Plasma

SECTION 2

DONOR IDENTIFICATION

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

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

Plasma centers must have a record confronting which unsuitable donors may exist identified and then that unsuitable product from such donors may non be distributed. Plasma centers usually verify the donor'southward deferral condition prior to donation. Calculator records, which identify only the donor's proper name and permanent deferral status, are adequate if more detailed data is listed in the donor tape file (DRF). There should be a process to continue this information confidential within the heart.

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 physician. 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 inquire 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 red claret cells (for manual procedure only) prior to reinfusion should be stressed. For manual procedures, the donor should betoken understanding that two units of whole blood will be removed, one at a time, with reinfusion of the kickoff unit of red blood cells prior to collection of the 2d 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 every bit office of the informed consent. For a further discussion of adverse reactions, come across the section Agin REACTIONS of this document. The physician or approved physician substitute should sign or initial the informed consent grade to certify that the hazards have been explained.

The procedure(due south) for collection of Source Plasma using automatic 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 "stop and restart" situations using automation.

Breakage, leakage, and possible inability to return crimson blood cells should also be addressed. A possible reaction to the anticoagulant, i.due east., numbness or "tingling" of the fingers or lips, should also be explained during the informed consent. The hazards of plasmapheresis past manual and automatic procedures are not identical. If the same consent class is used for both transmission and automated procedures, information technology must clearly identify the hazards for each procedure.

The hazards of immunization are to exist separately discussed. The antigens used have particular risks, and each should be separately identified. In addition, there are potential full general hazards of immunization, such as 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 exist part of the discussion of hazards. The donor should be informed of the unabridged schedule of immunizations, the criteria for adequate response, the procedure to exist followed if no response occurs, and of the establishment's obligation to provide evaluation and monitoring for at least ane year if red blood cell immunization is done. Donors should be fully informed that they may participate in only ane immunization programme at a time. Participants in red blood prison 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 exist unsuitable for future use and of possible delay in processing of their blood for a transfusion or transplant. In improver, female participants in scarlet claret cell programs should be advised of possible risks to a fetus. Currently, CBER does non approve a red blood cell immunization plan that permits a female of childbearing age to participate, unless documentation of sterility is obtained from her personal doctor. For additional information on obtaining informed consent for participation in immunization programs, see the Draft Reviewers' Guide, Informed Consent for Plasmapheresis/Immunization available through the CBER FAX Information Organisation.

Each donor should exist encouraged to enquire questions. All donor questions should be answered fully and completely in a relaxed atmosphere. The interview must be conducted in private so equally to provide an accurate decision of the donor's suitability and in a fashion that does not embarrass or unduly force per unit area the donor to consent. The data on which the donor bases consent should be accurate and understandable to the donor. A donor's conclusion to turn down consent should be accustomed as a matter of fact with no undue force per unit area to endeavor to alter the determination. The investigator may insist on observing the explanation of the informed consent form by the physician without fear that this is an intrusion on the md-patient privacy human relationship.

All informed consent forms should be approved by CBER and reverberate currently approved practices. For more information, phone call the Partitioning of Inspections and Surveillance (HFM-650) at 301-827-6220 or the Division of Blood Applications (HFM-370) at 301-827-3524 . Additional information apropos procedures for obtaining informed consent may be institute 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 Test

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 doc substitute, working under the supervision of the dr., who must exist certified or licensed according to state law, to also 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 starting time donation most centers accept an abbreviated form of AIDS materials that donors are asked to read at the time of each donation. See CBER memorandum, "Revised Recommendations for the Prevention of HIV Transmission by Blood and Blood Products," dated April 23, 1992.

Each donor must be examined on the twenty-four hour period of the first donation or no more 1 week before the offset donation and at subsequent intervals of no longer than 1 year. See CPG 251.100, Schedule of Physical Exam for Donors Receiving Immunization Injections. All of the following procedures should be observed with the permission of the donor, preferably a donor of the same gender every bit the investigator. If the donor objects, then an assessment of the exam can be determined by questioning the physician 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 utilize of the AIDS educational materials. While observing the medical exam, privacy should exist 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 manner.

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

  1. Heart and lung sounds should be determined on bare pare, both front 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, possibly with knees bent, and the doc should gently but firmly press deeply into the abdomen on both right and left upper abdominal areas. Although not required, some centers include palpation of the inguinal (groin) area for lymph node enlargement as part 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 fabricated, including touch and residue evaluations.
  4. Test of the urine for saccharide and protein should exist conducted.
  5. The lymph node test should include the neck from the jaw down towards the shoulders, line-fishing forrad from the angle of the jaw and nigh straight downward from behind the ears. Other areas that may be evaluated include under the arms, at the elbows and the groin region.
  6. The skin should be examined for irregular patches that are crimson to maroon-blue in colour and may be slightly raised. These patches can occur inside the oral cavity or nose likewise as other peel surfaces.
  7. The mouth should be carefully checked for irregular cottony-appearing white blotches.
  8. It is too important to cheque under the tongue, arms, and some centers too check legs for needle tracks.

Demonstrating that the donor has a normal blood pressure should also be a part of the physical exam. Blood pressure (BP) is measured either while the donor is seated or reclining. The cuff should be placed on bare skin, 1-2 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 down and relax for five-x minutes and retake the pressure. If still elevated, the donor should exist temporarily deferred with advisable medical communication for follow-up, and an appropriate entry should be made in the DRF. However, a donor with a blood pressure outside of normal limits, may be acceptable with the examining doc's approval and consistent with a written SOP.

IMMUNIZATION

Written report all antigens used and their respective manufacturers. Immunizing agents, such as tetanus vaccines, rabies vaccines, etc., are licensed products. Crimson blood cells for immunization are not licensed products; however, 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 institution'due south SOP. Personnel performing immunizations shall exist knowledgeable with respect to the SOP. For crimson blood cell immunizations, see CBER memorandum "Revised Recommendations for Red Blood Jail cell Immunization Programs for Source Plasma Donors," dated March 14, 1995. If the plan does non include use of qualified red blood cells for immunization, promptly notify the Partition of Inspections and Surveillance (HFM-654) at 301-827-6220 . Reports of these evaluations shall exist available for review. CBER requests that Source Plasma establishments seeking approval for a Red Blood Cell Immunization Program submit records on at least five donors who were successfully immunized and any subsequent adverse reactions for review. CBER and/or ORA volition bear an inspection to determine if the establishment's license awarding or supplement is approvable. The Division of Blood Applications (HFM-370) is responsible for blessing these programs.

The establishment's dr. must evaluate the donor's clinical reaction. For most centers, a central laboratory performs antibody titers. The physician utilizes the donors' antibody titer in determining the schedule of immunizations. Donors should exist tested prior to immunization to identify existing antibiotic titer levels. The facility's SOP should indicate the maximum acceptable 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 come across the immunization program titer requirements. with the desired titer. If the red blood prison cell recipient should go to another donor heart, he/she is excluded from being a Source Plasma donor for twelve months from the date of the concluding blood-red blood jail cell immunization if the receipt of qualified red claret cells cannot be documented. This procedure should be divers in the SOP.

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

Both immediate (e.thou., hives, localized swelling, etc.) and delayed reactions must be documented, including the house's medical response.

DONOR SUITABILITY

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

If a trainee is determining donor suitability, close supervision is necessary to clinch correct performance.

See the following 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 December 2, 1987.
  2. "Clarification of FDA Recommendations for Donor Deferral and Production Distribution Based on the Results of Syphilis Testing," dated Dec 12, 1991.
  3. "FDA Recommendations Concerning Testing for Antibody to Hepatitis B Core Antigen (Anti-HBc)," dated September x, 1991.
  4. "Revised Recommendations for the Prevention of Man Immunodeficiency Virus (HIV) Transmission by Claret and Blood Products," dated April 23, 1992.
  5. "Revised Recommendations for Testing Whole Blood, Blood Components, Source Plasma and Source Leukocytes for antibody HCV)," dated Apr 23, 1992.
  6. "Exemptions to Permit Persons with a History of Viral Hepatitis Before the Historic period of Eleven Years to Serve every bit Donors of Whole Blood 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 Claret, 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 Hazard," dated July 26, 1994. [ 1998 revision out for comment.]
  11. "Recommendations for the Deferral of Current and Recent Inmates of Correctional Institutions equally Donors of Whole Blood, Claret Components, Source Leukocytes and Source Plasma," dated June 8, 1995.
  12. "Donor Deferral Due to Red Blood Jail cell Loss During Collection of Source Plasma by Automated Plasmapheresis," dated December iv, 1995.
  13. "Interim Recommendations for Deferral of Donors at Increased Risk for HIV-ane Grouping O Infection," dated December 11, 1996.
  14. "Revised Precautionary Measures to Reduce Possible Take a chance of Transmission of Creutzfeldt-Jakob Disease (CJD) by Claret and Blood Products," dated Dec xi, 1996.
  15. "Revised Precautionary Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Affliction (CJD) and New Variant Cruetzfeldt-Jakob Affliction (nvCJD) by blood and Blood Products," November 1999.

In addition to the self exclusion provided to the donor in the signed consent statement at each donation, a second cocky-exclusion opportunity may exist offered to the plasma donor during a individual interview conducted by a trained, competent wellness professional in which the AIDS educational information is presented orally. This 2d self-exclusion may exist offered at the initial donation (each time for infrequent plasma donors) and yearly equally part 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.half dozen° F] or less. Some plasma centers may have established a low acceptable temperature value, which is normally 97.6° F (36.5° 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, disposable paper thermometers or electronic thermometers with disposable probes are allowed.
  2. Claret force per unit area - Donor's claret pressure must be determined prior to each donation and must be inside normal limits. A systolic range of 90-180 mm/Hg and diastolic range of 50-100 mm/Hg are considered normal limits. Donors with blood pressures outside this range may be acceptable, just only with a physician's blessing 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 g/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 (physician substitute) should review results higher or lower or the donor should be deferred. Physicians or dr. substitutes may make allowances for a lower pulse rate in an athlete, e.g., joggers, consequent with a written SOP.
  5. Total serum poly peptide (no less than 6.O g/100mL)  - Donors must exist deferred for quantitative total protein results of less than 6.0 mg/100mL or for poly peptide composition test results that are exterior the limits established by the testing laboratory, until echo testing shows values within acceptable limits, and the donor is reinstated past the dr.. A donor who fails to appear in time for a four-month test may be plasmapheresed if no more than six months have elapsed and signed blessing of the doctor or physician substitute is recorded in the DRF. If donors return after half-dozen months, or more, later 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'due south weight on the twenty-four hour period of donation must exist at least 110 lbs. Personnel should determine the donor'southward weight to assure the correct 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 proceeds may be an indicator of disease or an untoward reaction to plasmapheresis, personnel should monitor a donor's weight every bit part of the donor suitability conclusion. Additionally, the recommendations to decrease the take a chance of transmitting AIDS from plasma donors state that the existing cumulative records of each Source Plasma donor's weight should exist examined to assure that any weight loss of 10 pounds or more than in less than two months is detected. A donor with an unexplained weight loss should be referred to the medico or physician substitute for consummate evaluation prior to any farther plasma donation. With medical approval that the donor is acceptable, plasma collection may continue. 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 good health on the solar day of donation every bit evidenced by:

  1. Freedom from astute respiratory diseases – Examples of astute respiratory diseases are colds, influenza, persistent cough, sore throat, sinusitis, or other manifestations of upper respiratory infections, and shall be cause for temporary deferral until active symptoms have subsided. Such symptoms may be early indications of a more serious illness.
  2. Liberty from diseases, other than malaria, transmissible by blood transfusion - The donor must be costless of any illness that may be transmissible by a blood transfusion. Nevertheless, persons with a history of malaria are exempt from the foregoing considering the organism is transmissible only by the cellular elements of blood 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 antibody for utilize, e.g., in biological product test kits.
  3. Freedom from infectious pare diseases - A donor with a skin disease shall be deferred if it is manifest at the site of phlebotomy. Balmy peel disorders such as acne, psoriasis, or toxicant ivy are not cause for deferral unless prevalent at the phlebotomy surface area. Donors with boils or other severe pare infections should be deferred. Blue or purple spots on the pare (typical of Kaposi's sarcoma) should exist referred to the dr..
  4. Liberty 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 testify of skin puncture or scars which may indicate abuse/addiction to narcotics. Such exam may be fabricated by the person determining donor suitability or by the phlebotomist. This should exist a close, thorough exam and not a cursory one. Past or nowadays intravenous drug users must exist permanently rejected.
  5. Freedom from a history of or close contact (inside 12 months) with individuals having viral hepatitis - Donors with a history of hepatitis must be 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 inside twelve months - Donors who have received blood or blood products are deferred for twelve months after receipt of the product, unless specifically immunized by with qualified red blood cells in an canonical program every bit defined in 21 CFR 640.66. See previous department 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 then ofttimes by the personnel who are accustomed to receiving a negative reply, they may be asked in a rapid manner and in a monotone vox, which creates a non-listening environment for the donor. It may be observed that the donor does not carp to respond the questions; yet the screener automatically checks negative responses. If the procedure is perfunctory, plasma heart management should be informed.

Screening personnel must defer a donor who is, or who appears to be, under the influence of booze 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 every bit infrequent donors on the initial visit and as regular donors on subsequent donations if the donor returns in less than 8 weeks. CBER memorandum, "Revision of FDA Memorandum of viii/27/82: Requirements for Infrequent Plasmapheresis Donors," dated March 10, 1995, allows infrequent donors to return for plasmapheresis in 4 weeks rather than eight. Source Plasma may be collected from infrequent donors without a physical examination, informed consent, or plasma protein tests; however, the establishment should have a supplement to its biologics license for infrequent Source Plasma collection.

BLOOD Collection

When arm preparation supplies are sterilized by the establishment, SOPs must contain specific information regarding steps to be followed. They should besides include directions for adequate length of fourth dimension such supplies may be used after the sterile package/container is showtime opened. If concentrated solutions are used, bank check that dilutions are properly made and that the proper expiration engagement/time is followed for dilutions. Note: Quaternary ammonia solutions, e.g., Pheneen, are easily neutralized and NOT Acceptable for use in storing forceps.

There are several means to practise a satisfactory arm preparation. Sufficient duration and vigor of scrubbing are the fundamental factors to removal of superficial microbes. Later on the venipuncture area is prepared, the prepared area may not be touched. In order 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 by number or other symbol, which relates information technology direct to the donor before filling the container [640.68(b)].

For manual plasmapheresis, the donor'southward name may exist added to the unique donor bleed number on the container to enable both the phlebotomist and the donor or some other person to identify the donor'south carmine blood cells earlier they are reinfused. The donor'due south proper name or bed number alone is more often than not non sufficient identification.

A saline container should be used for simply ane donor and no more than iv hours after entry. If any saline remains in the container afterwards 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 amount of plasma withdrawn. For automatic collections, routine replacement of volume with saline is not necessary, although some centers practice utilise saline for book replacement.

Neither the needle itself, nor any continuously integral role of the tubing connected with the needle, may exist used for more than one venipuncture since multiple contacts with pare microbial flora increase the chances of contaminating the claret.

If a needle is added during Source Plasma drove, but a Sterile Tubing Connecting Device (STCD) approved to weld liquid-filled tubing should be used. See CBER memorandum, "Apply of an FDA Cleared or Approved Sterile Connecting Device (STCD) in Blood Banking company Practice," dated August five, 1994. The source and specifications of added tubing and needles should be addressed in the blood center'southward SOP and records.

For transmission 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 be used. If the period of claret has non reached a connection, only the contaminated portion needs to exist discarded.

For automated collection there may exist times when the disposable set must be inverse afterward the venipuncture, or there may be times when a new venipuncture must be performed. A new disposable set may be installed by disconnecting the set from the needle connexion in accordance with the manufacturer's instructions. If a new venipuncture is necessary, the disposable set tin be disconnected from the needle connection, the needle changed, the disposable set reconnected, the new venipuncture performed with the new needle, and the procedure continued following the device manufacturer's directions. When it is necessary to either repeat the venipuncture or change the dispensable set, this incident, and any resulting red blood cell loss, should exist 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 alert lights and alarms to notify the phlebotomist when the venous pressure level is loftier.

To assure donor safe the following should be performed equally indicated:

Air removed from system - For manual collection: Before the venipuncture is made, saline should be allowed to flow through the administration gear up to remove all air from the tubing. This is done past opening the clamps virtually the saline bag and at the terminate of the prepare, allowing the saline to drip into a receptacle until all air is removed from the tubing. The filter chamber should then be half filled with saline. During this process, care should be taken not to contaminate the tip of the administration set. For automatic collection: Confirm that the start-up procedures are consistent with instructions in the device operator'southward manual.

Anticoagulant mixed with blood - The blood should be mixed with anticoagulant to preclude germination of clots. Gentle mechanical mixing throughout the drove is ideal; nevertheless, if equipment for mixing is not available, 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 done to remove the clot, it should always be in a direction abroad from the donor to forestall forcing clots into the donor's bloodstream.

Blood bag tubing sealed - Hermetic sealing of the blood bag using a metallic clench, white knot, or a dielectric seal must be done immediately afterward collection to forestall contamination.

For manual drove, monitoring to foreclose overbleeding can be done effectively merely by weighing each unit of measurement of claret. Each time an overbleed is detected, the bedside collection apparatus should exist checked and adjusted if necessary before the next unit of measurement of claret is nerveless; it should exist noted in the records that a bank check and/or adjustment was fabricated. The whole blood handbag weight records would indicate the possibility of overweight drove by manual methods. Records that show no overweight collections or weights that are identical for all units collected should prompt thorough evaluations of record keeping practices and the blood collection organisation.

Weight of whole blood removed is the full weight less the weight of the blood container and anticoagulant. It is of import to know how the weight of the blood container plus anticoagulant is adapted, i.e., is the calibration preset to adjust for this weight or is the subtraction made afterwards?

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

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

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

For automated collections, the internal monitor

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

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

Sample dilution : Plasma samples intended for viral marker testing may, nether certain weather, become 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 collection process. The almost probable scenario of operator error causing saline dilution is at the conclusion of the collection cycle. If the operator ignores the machine's visual instructions to properly seal/clamp the disposable set and pressed the resume (downwards pointer) central three consecutive times, the machine clamps would open and saline could enter the plasma line used for viral marking testing. There is also 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 adequate training programs which:

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

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

DONOR RECORD FILES (DRF)

DRFs usually include a photograph for donor identification; nonetheless, the regulations permit the utilize of other methods that provide equal or greater

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

For all donors, the DRFs should signal:

Donors must not be plasmapheresed more than frequently than once in a ii-day (48 hours) catamenia or twice in a seven-mean solar day menstruum.

Collecting from donors in less than 48 hours is acceptable if the donations are two calendar days apart. Also acceptable is once in four or more weeks for infrequent Source Plasma donors. Donors with rare transitory antibodies may be plasmapheresed within viii weeks of Whole Claret donation or after an inadvertent loss of a book of red blood cells that would otherwise require an 8 week deferral only if examined and certified past a dr. to be acceptable for plasmapheresis. The special characteristics of the antibody and the need for plasmapheresing the donor must be documented. See CPG 256.100, Plasmapheresis - 48-hour Menstruum Between Plasmapheresis Procedures.

Medical exams must be performed no more one week before immunization. If the plasma heart has performed a medical examination within the past 12 months, CBER allows this in place of one performed no more than than i calendar week earlier immunization. If a donor is beingness immunized earlier the initial plasmapheresis, the medical examination may be performed no more than one week before the first injection and demand not exist repeated, provided that the initial plasmapheresis occurs within 21 days of the start injection. This provision permits the donor to be examined earlier kickoff the immunization procedure to make up one's mind if the donor may have any medical problems with the injection. The additional 21 days allowed before plasmapheresis provides for antibody production in the immunized person. If a Source Plasma donor enters the immunization program, an additional physical examination is unnecessary. Encounter Compliance Policy Guide No. 251.100, Schedule of Physical Examination for Donor Receiving Immunization Injections, for boosted information.

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

  1. Frequency of donations : Eight weeks must elapse later whole blood donations or later on plasma donations when cells are not returned. CBER considers a donor blood loss of more than 200 mL of reddish claret cells during a plasmapheresis procedure (i.eastward., red blood cell loss incidental to the procedure), to exist cause to defer the donor for eight weeks.
  2. Medical examinations performed : Medical (physical) examinations must exist performed no more than one week before initial plasmapheresis. This flow of 1 week is immune to accommodate those centers which have their donors examined in a physician's individual office. Medical examinations are non necessary for exceptional donors.
  3. Dates when a sample of claret was collected for initial testing and at 4 month intervals for :
    1. total plasma or serum poly peptide determination,
    2. plasma or serum protein composition [Serum protein Electropheresis (SPE) or chemic quantitation of components],
    3. serologic test for syphilis (STS).

Either the physician must examine the total protein, protein composition, and STS results also as the cumulative collection records of the preceding 4 months to determine the donor's suitability for continued plasmapheresis. CBER allows this review to be completed by an approved physician substitute. The review must occur within 21 days subsequently collection of the test sample and must be signed past the reviewing doctor or the physician substitute. A physician must evaluate any abnormal findings. Donors with abnormal SPE tests must [640.65(b)(2)(ii)] be deferred until their results are within normal range. For this reason, SPE results should be reviewed as soon as possible subsequently receipt to preclude donation by unsuitable donors. Encounter Plasma Inspection Guide reference, "Donor Suitability," item #5. If examination results for the four calendar month samples are unavailable or the sample is unsuitable, the donor may be plasmapheresed if less than half dozen months take passed since the last sample was collected and if canonical by the physician or doctor substitute.

The DRFs for donors in an immunization program should indicate: that the donor is only on 1 immunization program; the type of antigen injected; proper name and lot number of antigen injected; date of injection; dosage and road of injection; individual who gave injection; clarification of any untoward reaction, if such occurred, and documentation of the upshot; record of pre- and mail-immunization titers; and a signed and dated evaluation of the donor's clinical response past a qualified, licensed physician. Often centers include the site of injection in the donor record. The DRF should also signal that just a qualified, licensed physician selects and schedules the immunizing antigen, equally well every bit evaluates the donor'south clinical response. CBER has approved alternative procedures under 21 CFR 640.120 to allow the medico substitute to schedule injections and review the donor'south clinical response for some immunization programs.

PLASMA SEPARATION AND POOLING IN MANUAL Drove

Before filling, the plasma pooling container (final container) must be labeled usually with the donor number and/or the bleed number to relate it direct to the donor.

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

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

Red claret cells should non routinely exist permitted to enter the plasma container. Most donors are plasmapheresed regularly, and over a menstruation of time the loss of these ruby 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, e.yard., a needle filled with sterile cotton, inserted aseptically. It must be 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 way to remain upright during pooling procedures.

The pooling of Source Plasma from ii or more donors is permitted provided pooling occurs after the plasma is removed from the ruby blood cells, and the red claret cell containers are sealed. Source Plasma pooled from two or more donors must [640.69(a)(1)] not exist used for the manufacture of injectable products. The terminal product can merely exist used for further manufacturing into noninjectable products.

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

REINFUSION OF Red Claret CELLS (Transmission Drove)

The about critical element in transmission plasmapheresis is the proper identification of the donor prior to returning the red cells to the donor. The heart must take a SOP with clearly defined steps in the proper identification of the donor. Some firms accept a two-person identification and others simply one. Both are acceptable procedures.

Both the donor and the phlebotomist should participate in the identification of the donor'south red blood cells. The regulations do not specifically require that the donor participate in self identification of ruddy blood cells, but CBER has not issued SOP approval unless procedures in the SOP Manual are adequate to avoid infusing the incorrect ruby-red blood cells. Sufficient time and care should be taken for this important process, and it should be performed in accordance with the firm's SOPs. The regulations practise not prohibit or prevent a visually or hearing impaired person from participating in the process of being a plasma donor as long equally sufficient safeguards are used to clinch that the donor receives his/her ain cells back.

There will always exist some ruddy blood cells remaining in the bag, and an effort shall be fabricated to return equally many of the red cells as possible. This is to forbid loss of scarlet cells, which could over time cause a drop in the donor'southward hemoglobin and hematocrit value. Prior to collection of Source Plasma from a donor, establishments should review the donor record to determine if any red cell loss occurred due to technical difficulties during utomated plasmapheresis or if the donor had donated a unit of measurement of Whole Blood during the by eight weeks.

A wrong red claret prison cell infusion is a serious mistake, which may issue in a severe adverse reaction or fatality if the transfused donor has ABO antibodies to the red claret cells transfused past in error. A incorrect red blood prison cell infusion should be adequately documented. If red claret cells are mistakenly returned to the wrong donor, the recipient of the incorrect ruby-red blood cells should be deferred for 12 months due to this inadvertent transfusion. Medical evaluation of the donor is of import to determine if there has been or will be an adverse reaction to the transfusion.

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