GUIDE TO INSPECTIONS OF SOURCE PLASMA ESTABLISHMENTS - Section two

JUNE 1997
(April 2001 - Editorial Revisions)

Annotation: This document 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(due south). An alternative approach may be used if such an approach satisfies the requirements of the applicable statues, regulations, or both.

TABLE OF CONTENTS

Department ane
Introduction
General Information
Operations
Standard Operating Procedures
Errors, Accidents and Fatalities
Agin Reaction
Lookback
Plasmapheresis Facilities
Equipment
Medical Device Reporting
Medical Supervision

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

Department iii
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 Record
Disposal of Infectious Waste product
Computerized Records
Illness Land Donors
"High Risk" Donors
Source Leukocytes
Therapeutic Substitution Plasma

SECTION 2

DONOR IDENTIFICATION

Adequate identification of a donor is important to foreclose cross donation at more one plasmapheresis middle, especially in areas where more than than ane center is located. The SOP should depict a organization to prevent cross donations when applicable. Cross donation occurs when an individual donates at more than one plasmapheresis heart or claret drove facility.

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

Plasma centers must have a record confronting which unsuitable donors may be identified so that unsuitable product from such donors may not be distributed. Plasma centers usually verify the donor's deferral status prior to donation. Computer records, which place simply the donor's proper noun and permanent deferral status, are acceptable if more detailed data is listed in the donor record file (DRF). There should be a procedure to go along this information 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 dr.. 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 inquire questions and the establishment determines that the donor understands the procedure.

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

The explanation of the hazards should exist in simple, not-medical terms, and the risks to the donor should not exist 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 part of the informed consent. For a further give-and-take of adverse reactions, meet the section Agin REACTIONS of this document. The dr. or approved dr. substitute should sign or initial the informed consent form to certify that the hazards have been explained.

The process(s) for drove 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 "end and restart" situations using automation.

Breakage, leakage, and possible inability to return red claret cells should also exist 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 automatic procedures are non identical. If the same consent class is used for both manual and automated procedures, it 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 exist separately identified. In improver, there are potential general hazards of immunization, such as injection site redness and soreness, fever, nausea and airsickness that may back-trail the administration of any antigen. The possibility of anaphylaxis exists with all immunizing agents and should be role of the discussion of hazards. The donor should be informed of the entire schedule of immunizations, the criteria for acceptable response, the process to be followed if no response occurs, and of the establishment's obligation to provide evaluation and monitoring for at to the lowest degree 1 year if red blood cell immunization is washed. Donors should be fully informed that they may participate in only 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'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 participants in ruby blood cell programs should be brash of possible risks to a fetus. Currently, CBER does not corroborate a cherry-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 Draft 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 private so as to provide an accurate conclusion of the donor'southward suitability and in a style that does not embarrass or unduly force per unit area the donor to consent. The information on which the donor bases consent should be accurate and understandable to the donor. A donor'south decision to refuse consent should be accepted as a thing of fact with no undue pressure level to try to alter the decision. The investigator may insist on observing the explanation of the informed consent class by the physician without fearfulness that this is an intrusion on the physician-patient privacy relationship.

All informed consent forms should exist approved by CBER and reflect currently approved practices. For more than data, 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 constitute in the DRAFT Reviewer Guidance document, Informed consent for Plasmapheresis/Immunization, dated October one, 1995. See also CPG 250.100, Source Plasma Guidelines for Informed Consent Forms.

INITIAL MEDICAL Examination

The initial medical exam 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 physician, who must be certified or licensed according to country constabulary, to as well perform medical examinations.

AIDS educational materials should be presented to donors at each donation and these materials should arrange to the latest FDA recommendations or regulations. Afterwards the beginning donation well-nigh centers accept an abbreviated class 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 Claret Products," dated April 23, 1992.

Each donor must exist examined on the day of the first donation or no more ane week before the commencement donation and at subsequent intervals of no longer than i year. See CPG 251.100, Schedule of Physical 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 same gender as the investigator. If the donor objects, then an cess of the exam can be adamant by questioning the dr. and donors afterwards the examination and reviewing the records of examinations, or obtaining permission to discover the medical examination from another donor. Observe the explanation of the informed consent, including utilize of the AIDS educational materials. While observing the medical test, 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 test, although it may vary from doc to doctor:

  1. Heart and lung sounds should be determined on bare skin, 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 physician should gently merely firmly printing deeply into the abdomen on both right and left upper abdominal areas. Although not required, some centers include palpation of the inguinal (groin) surface area for lymph node enlargement as office of the exam.
  3. Neurological examination may consist of reflex assessment using a reflex hammer on knees and possibly elbows, ankles, wrists, or other points. Coordination and sensory examinations may also be made, including bear on and balance evaluations.
  4. Exam of the urine for saccharide and protein should be conducted.
  5. The lymph node examination should include the neck from the jaw downwardly towards the shoulders, angling forward from the angle of the jaw and nearly straight down from backside 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 reddish to maroon-blue in color and may be slightly raised. These patches tin can occur inside the mouth or nose every bit well as other skin surfaces.
  7. The rima oris should exist carefully checked for irregular cottony-appearing white blotches.
  8. It is likewise important to check under the natural language, arms, and some centers also check legs for needle tracks.

Demonstrating that the donor has a normal blood pressure should also be a part of the concrete examination. Blood pressure (BP) is measured either while the donor is seated or reclining. The cuff should be placed on blank skin, 1-2 inches higher up the bend of the elbow. The arm should be relaxed, supported by the examiner'south hand or arm, when the readings are taken. If the BP is elevated across acceptable range, it is permissible to have

the donor lie down and relax for 5-x minutes and retake the force per unit area. If notwithstanding elevated, the donor should exist temporarily deferred with advisable medical communication for follow-up, and an appropriate entry should exist made in the DRF. Nonetheless, a donor with a blood pressure outside of normal limits, may be adequate with the examining physician's approval and consistent with a written SOP.

IMMUNIZATION

Report all antigens used and their respective manufacturers. Immunizing agents, such every bit tetanus vaccines, rabies vaccines, etc., are licensed products. Red blood cells for immunization are not licensed products; yet, 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 bundle 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 prison cell immunizations, see CBER memorandum "Revised Recommendations for Cherry-red Blood Jail cell Immunization Programs for Source Plasma Donors," dated March 14, 1995. If the program does non include utilize of qualified reddish claret cells for immunization, promptly notify the Partition 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 Carmine Claret Prison 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 volition conduct an inspection to determine if the institution's license application or supplement is approvable. The Sectionalisation of Claret Applications (HFM-370) is responsible for approval these programs.

The establishment'due south physician must evaluate the donor's clinical reaction. For nearly 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 antibiotic titer levels. The facility'due south SOP should indicate the maximum acceptable titer level prior to immunization.

A donor should not participate in more than 1 immunization program concurrently. Donors participating in any immunization programme may be returned to normal Source Plasma collection if the donor fails to respond to encounter the immunization program titer requirements. with the desired titer. If the ruby-red blood jail cell recipient should go to another donor center, he/she is excluded from being a Source Plasma donor for twelve months from the date of the concluding reddish blood cell immunization if the receipt of qualified red blood cells cannot be documented. This procedure should be defined in the SOP.

Atypical or unexpected ruby-red cell antibodies may develop during the class of immunization. Ruddy blood cell immunization recipients should exist evaluated for development of unexpected antibody responses and reports of these unexpected antibiotic responses should be kept on file for review during inspections. See CBER memorandum, "Revised Recommendations for Carmine Claret Cell Immunization Programs for Source Plasma Donors," dated March 14, 1995. The physician should review the development of unexpected antibodies.

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

DONOR SUITABILITY

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

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

See 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 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 Concerning Testing for Antibiotic to Hepatitis B Cadre Antigen (Anti-HBc)," dated September x, 1991.
  4. "Revised Recommendations for the Prevention of Homo Immunodeficiency Virus (HIV) Manual by Blood 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 Earlier the Age of Xi Years to Serve every bit 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 Antibiotic to Hepatitis C Virus Encoded Antigen (Anti-HCV)," dated August 5, 1993 [this certificate does not supersede the Apr 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 Adventure," 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 Automatic Plasmapheresis," dated December 4, 1995.
  13. "Interim Recommendations for Deferral of Donors at Increased Risk for HIV-1 Group O Infection," dated December xi, 1996.
  14. "Revised Precautionary Measures to Reduce Possible Take chances of Manual of Creutzfeldt-Jakob Disease (CJD) by Blood and Blood Products," dated December xi, 1996.
  15. "Revised Precautionary Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and New Variant Cruetzfeldt-Jakob Affliction (nvCJD) past blood and Blood Products," November 1999.

In addition to the cocky exclusion provided to the donor in the signed consent statement at each donation, a second self-exclusion opportunity may be offered to the plasma donor during a private interview conducted by a trained, competent health professional in which the AIDS educational information is presented orally. This second self-exclusion may be offered at the initial donation (each fourth dimension for infrequent plasma donors) and yearly every bit part of the medical exam.

Written SOPs should be bachelor and specify donor suitability criteria. Conclusion of donor suitability should include:

  1. Temperature - The suggested temperature is 37.five° C [99.half-dozen° F] or less. Some plasma centers may have established a depression adequate temperature value, which is normally 97.6° F (36.5° C). A low 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 pressure - Donor's blood pressure must be determined prior to each donation and must exist within 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 exterior this range may be acceptable, but only with a medico'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 claret. If the microhematocrit method is used, a value of 38% is equivalent to 12.5 thousand/100 mL.
  4. Pulse rate - Recommended normal pulse rate is l-100 beats per minute (BPM) with regular rhythm. This is a "normal range"; a doc (dr. substitute) should review results higher or lower or the donor should be deferred. Physicians or md substitutes may make allowances for a lower pulse rate in an athlete, east.g., joggers, consistent with a written SOP.
  5. Total serum protein (no less than 6.O g/100mL)  - Donors must be deferred for quantitative total protein results of less than half-dozen.0 mg/100mL or for poly peptide limerick test results that are outside the limits established by the testing laboratory, until repeat testing shows values within adequate limits, and the donor is reinstated by the md. A donor who fails to appear in time for a four-month examination may be plasmapheresed if no more six months accept elapsed and signed approval of the medico or physician substitute is recorded in the DRF. If donors return after six months, or more, afterwards being deferred, they shall be treated every bit new donors. As well see CPG 255.100, Quantitative Testing for Serum Proteins in Plasmapheresis Donors.
  6. Weight (at least 110 lbs.) – The donor'due south weight on the day of donation must be at to the lowest degree 110 lbs. Personnel should determine the donor's weight to assure the correct volume of blood is fatigued. The donor should be weighed each time he/she donates. Personnel should read the weight directly from the calibration rather than allow the donor to report his/her weight. Since weight loss or gain may exist an indicator of disease or an untoward reaction to plasmapheresis, personnel should monitor a donor'southward weight as part of the donor suitability determination. Additionally, the recommendations to subtract the take chances 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 whatsoever weight loss of ten pounds or more in less than 2 months is detected. A donor with an unexplained weight loss should be referred to the md or physician substitute for consummate evaluation prior to whatever further 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 centre, should be evaluated.

The donor shall exist in good health on the day of donation as evidenced by:

  1. Freedom from astute respiratory diseases – Examples of acute respiratory diseases are colds, influenza, persistent coughing, sore throat, sinusitis, or other manifestations of upper respiratory infections, and shall be cause for temporary deferral until active symptoms accept subsided. Such symptoms may exist early indications of a more serious illness.
  2. Freedom from diseases, other than malaria, transmissible by blood transfusion - The donor must be free of any disease that may exist transmissible by a claret transfusion. Nevertheless, persons with a history of malaria are exempt from the foregoing because the organism is transmissible only by the cellular elements of blood which are not nowadays in the plasma. Some plasma facilities are licensed to collect blood and plasma from donors with circulating hepatitis and HIV antigen and antibody for use, e.grand., in biological production test kits.
  3. Freedom from infectious skin diseases - A donor with a skin disease shall be deferred if it is manifest at the site of phlebotomy. Mild skin disorders such as acne, psoriasis, or poison ivy are not cause for deferral unless prevalent at the phlebotomy area. Donors with boils or other astringent skin infections should be deferred. Bluish or purple spots on the peel (typical of Kaposi'due south sarcoma) should be referred to the physician.
  4. Freedom of the arms and forearms from scars indicative of narcotic addiction - Earlier plasma is collected from a donor, the arms and forearms must be examined for evidence of skin puncture or scars which may indicate corruption/addiction to narcotics. Such test may exist made by the person determining donor suitability or by the phlebotomist. This should be a close, thorough test and non a brief one. Past or present intravenous drug users must exist 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 blood or blood products within twelve months - Donors who have received blood or blood products are deferred for twelve months after receipt of the production, unless specifically immunized by with qualified red blood cells in an approved program as defined in 21 CFR 640.66. Come across previous department entitled "IMMUNIZATION."

All questions should exist asked slowly and clearly at each donation and so that the donor tin hear the questions and has time to respond. Since these questions are asked so often by the personnel who are accepted to receiving a negative reply, they may exist asked in a rapid manner and in a monotone voice, which creates a non-listening environment for the donor. It may be observed that the donor does not carp to answer the questions; however the screener automatically checks negative responses. If the process is perfunctory, plasma heart management should be informed.

Screening personnel must defer a donor who is, or who appears to exist, under the influence of alcohol or drugs, or who does not announced 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 as 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 Infrequent Plasmapheresis Donors," dated March 10, 1995, allows infrequent donors to return for plasmapheresis in iv weeks rather than 8. Source Plasma may be nerveless from infrequent donors without a concrete examination, informed consent, or plasma protein tests; however, the establishment should have a supplement to its biologics license for infrequent Source Plasma collection.

Claret Drove

When arm training supplies are sterilized by the establishment, SOPs must contain specific information regarding steps to be followed. They should too include directions for acceptable length of fourth dimension such supplies may exist used subsequently the sterile package/container is first opened. If full-bodied solutions are used, check that dilutions are properly fabricated and that the proper expiration appointment/time is followed for dilutions. Notation: Fourth ammonia solutions, east.g., Pheneen, are hands neutralized and Not ACCEPTABLE for use in storing forceps.

There are several means to do a satisfactory arm preparation. Sufficient elapsing and vigor of scrubbing are the cardinal factors to removal of superficial microbes. Later the venipuncture area is prepared, the prepared surface area may not exist touched. In society to verify the location of the vein, the area above or below the prepared area may be palpated; information technology is non 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 straight to the donor before filling the container [640.68(b)].

For manual plasmapheresis, the donor'south 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 red blood cells before they are reinfused. The donor's name or bed number lone is by and large non sufficient identification.

A saline container should be used for only one donor and no more than four hours after entry. If whatsoever saline remains in the container subsequently a donor has completed a plasmapheresis process, it may be used for laboratory testing but not for some other 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 use saline for book replacement.

Neither the needle itself, nor whatsoever continuously integral part of the tubing connected with the needle, may exist used for more than 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, only a Sterile Tubing Connecting Device (STCD) approved to weld liquid-filled tubing should be used. See CBER memorandum, "Use of an FDA Cleared or Approved Sterile Connecting Device (STCD) in Blood Banking company Practise," dated August 5, 1994. The source and specifications of added tubing and needles should be addressed in the blood centre'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 be used. If the flow of blood has non reached a connection, simply the contaminated portion needs to exist discarded.

For automated drove there may be times when the disposable set must be changed afterwards the venipuncture, or there may be times when a new venipuncture must exist performed. A new disposable set may exist installed by disconnecting the set from the needle connexion in accordance with the manufacturer's instructions. If a new venipuncture is necessary, the dispensable 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 connected following the device manufacturer'due south directions. When information technology is necessary to either echo the venipuncture or change the disposable set, this incident, and any resulting red claret cell loss, should be recorded.

During manual and automatic claret collection or reinfusion of the 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 automated device is equipped with warning lights and alarms to notify the phlebotomist when the venous pressure is loftier.

To assure donor safety the following should exist performed as indicated:

Air removed from organisation - For manual collection: Before the venipuncture is made, saline should exist immune to flow through the administration set to remove all air from the tubing. This is done by opening the clamps well-nigh the saline bag and at the cease of the set, allowing the saline to baste into a receptacle until all air is removed from the tubing. The filter chamber should then be half filled with saline. During this procedure, care should be taken not to contaminate the tip of the assistants prepare. For automated collection: Confirm that the starting time-up procedures are consequent with instructions in the device operator's manual.

Anticoagulant mixed with blood - The blood should exist mixed with anticoagulant to prevent germination of clots. Gentle mechanical mixing throughout the collection is ideal; however, if equipment for mixing is not available, periodic transmission 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 jell, information technology should always be in a direction away from the donor to prevent forcing clots into the donor's bloodstream.

Blood bag tubing sealed - Hermetic sealing of the claret bag using a metallic clamp, white knot, or a dielectric seal must exist done immediately after drove to prevent contamination.

For transmission collection, monitoring to prevent overbleeding can exist done effectively but by weighing each unit of blood. Each time an overbleed is detected, the bedside collection appliance should be checked and adjusted if necessary earlier the next unit of blood is collected; it should be noted in the records that a check and/or adjustment was made. The whole claret handbag weight records would indicate the possibility of overweight collection 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 claret removed is the total 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 adapted, i.eastward., is the scale preset to adjust for this weight or is the subtraction made later?

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

To collect 500 mL of whole blood, the internet weight of the unit of measurement should not exceed 526.5 chiliad (500 mL ten 1.053 1000/mL = 526.5 chiliad whole claret).

For 600 mL of whole blood nerveless, the net weight should not exceed 631.8 chiliad. (600 mL x one.053 g/mL = 631.8 g whole blood).

For automated collections, the internal monitor

weighs the collected plasma more accurately than an external calibration. Overbleeding may occur when a chair or other object interferes with the plasma purse or bottle hanging on the scale, preventing authentic measurement, or because of operator fault in setting upwards the device for collection. See CPG 252.100, Source Plasma Regulatory Activeness Based on Overbleeding.

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

Sample dilution : Plasma samples intended for viral marker testing may, under certain weather, become inadvertently diluted with saline in the process of collecting Source Plasma using canonical automated plasmapheresis equipment. Plasma sample dilution may exist caused past homo error in the collection procedure. The most probable scenario of operator fault causing saline dilution is at the determination of the drove cycle. If the operator ignores the machine's visual instructions to properly seal/clamp the disposable ready and pressed the resume (downwardly arrow) key 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 simulated-negative viral marker test results.

Firms should have adequate training programs which:

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

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

DONOR Tape FILES (DRF)

DRFs usually include a photograph for donor identification; even so, the regulations permit the use 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 betoken:

Donors must not be plasmapheresed more often than in one case in a ii-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 2 calendar days apart. Too acceptable is once in four or more weeks for infrequent Source Plasma donors. Donors with rare transitory antibodies may exist plasmapheresed within 8 weeks of Whole Blood donation or later on an inadvertent loss of a volume of carmine blood cells that would otherwise require an viii week deferral but if examined and certified past a physician to be acceptable for plasmapheresis. The special characteristics of the antibiotic and the demand for plasmapheresing the donor must exist documented. Encounter CPG 256.100, Plasmapheresis - 48-hr Catamenia Between Plasmapheresis Procedures.

Medical exams must be performed no more than ane week earlier immunization. If the plasma middle has performed a medical exam inside the past 12 months, CBER allows this in place of one performed no more one calendar week before immunization. If a donor is being immunized before the initial plasmapheresis, the medical examination may exist performed no more 1 week before the showtime injection and need not be repeated, provided that the initial plasmapheresis occurs inside 21 days of the first injection. This provision permits the donor to be examined before get-go the immunization process to determine if the donor may have any medical problems with the injection. The boosted 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 test is unnecessary. See Compliance Policy Guide No. 251.100, Schedule of Physical Examination for Donor Receiving Immunization Injections, for additional information.

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

  1. Frequency of donations : 8 weeks must elapse after whole claret donations or later 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 process (i.e., blood-red blood cell loss incidental to the procedure), to exist cause to defer the donor for eight weeks.
  2. Medical examinations performed : Medical (concrete) examinations must be performed no more one week before initial plasmapheresis. This menstruation of 1 week is allowed to adapt those centers which have their donors examined in a physician's private office. Medical examinations are non necessary for exceptional donors.
  3. Dates when a sample of blood was collected for initial testing and at iv month intervals for :
    1. total plasma or serum protein decision,
    2. plasma or serum protein composition [Serum protein Electropheresis (SPE) or chemical quantitation of components],
    3. serologic examination for syphilis (STS).

Either the doctor must examine the full protein, protein composition, and STS results too every bit the cumulative drove records of the preceding 4 months to determine the donor'due south suitability for continued plasmapheresis. CBER allows this review to be completed by an approved physician substitute. The review must occur within 21 days after drove of the exam sample and must be signed by the reviewing physician or the medico substitute. A physician must evaluate any abnormal findings. Donors with abnormal SPE tests must [640.65(b)(2)(2)] be deferred until their results are within normal range. For this reason, SPE results should exist reviewed as soon equally possible afterward receipt to foreclose donation past unsuitable donors. See Plasma Inspection Guide reference, "Donor Suitability," item #v. If test results for the four calendar month samples are unavailable or the sample is unsuitable, the donor may be plasmapheresed if less than vi months have passed since the last sample was collected and if approved by the physician or physician substitute.

The DRFs for donors in an immunization program should indicate: that the donor is simply on ane immunization program; the blazon of antigen injected; proper name and lot number of antigen injected; date of injection; dosage and route of injection; individual who gave injection; clarification of whatsoever untoward reaction, if such occurred, and documentation of the upshot; record of pre- and post-immunization titers; and a signed and dated evaluation of the donor'south clinical response past a qualified, licensed physician. Oft centers include the site of injection in the donor record. The DRF should besides point that only a qualified, licensed physician selects and schedules the immunizing antigen, as well as evaluates the donor'south clinical response. CBER has approved culling procedures under 21 CFR 640.120 to let the dr. 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 (final container) must be labeled usually with the donor number and/or the bleed number to relate it directly to the donor.

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

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

Blood-red claret cells should not routinely be permitted to enter the plasma container. Nearly donors are plasmapheresed regularly, and over a menses of time the loss of these blood-red cells may would result in anemia.

If an air vent is used for the pooling container when pooling plasma from a donor, information technology must be sterile and capable of excluding microorganisms, e.g., a needle filled with sterile cotton, inserted aseptically. It must be kept dry throughout the pooling procedure. CBER has received reports of contamination of plasma during the pooling procedure considering of bubbles 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 2 or more than donors is permitted provided pooling occurs later the plasma is removed from the red claret cells, and the cerise blood cell containers are sealed. Source Plasma pooled from two or more donors must [640.69(a)(1)] not be used for the manufacture of injectable products. The last product can just 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' red claret cells. In addition, the likelihood of a incorrect red blood cell reinfusion may accompany inadvertent cantankerous pooling.

REINFUSION OF Cherry-red BLOOD CELLS (Transmission COLLECTION)

The well-nigh critical chemical element in transmission plasmapheresis is the proper identification of the donor prior to returning the red cells to the donor. The centre must take a SOP with clearly defined steps in the proper identification of the donor. Some firms have a two-person identification and others only one. Both are adequate procedures.

Both the donor and the phlebotomist should participate in the identification of the donor'due south red blood cells. The regulations do not specifically require that the donor participate in self identification of reddish blood cells, just CBER has not issued SOP approving unless procedures in the SOP Transmission are adequate to avoid infusing the wrong red blood cells. Sufficient time and care should exist taken for this of import process, and it should exist performed in accordance with the firm'due south SOPs. The regulations do not prohibit or prevent 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 dorsum.

There will always be some red blood cells remaining in the pocketbook, and an endeavor shall be fabricated to return as many of the red cells equally possible. This is to forbid loss of red cells, which could over fourth dimension cause a drop in the donor's hemoglobin and hematocrit value. Prior to drove of Source Plasma from a donor, establishments should review the donor tape to make up one's mind if whatsoever red cell loss occurred due to technical difficulties during utomated plasmapheresis or if the donor had donated a unit of Whole Blood during the past viii weeks.

A wrong ruddy blood prison cell infusion is a serious mistake, which may consequence in a severe adverse reaction or fatality if the transfused donor has ABO antibodies to the red blood cells transfused by in error. A wrong cherry blood cell infusion should be adequately documented. If blood-red claret cells are mistakenly returned to the wrong donor, the recipient of the wrong red blood cells should exist 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.

Click Here to continue to SECTION 3

Return to: Folio Height | Inspection Starting time