Source: https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&mc=true&n=pt21.7.640&r=PART&ty=HTML
Timestamp: 2020-01-21 18:40:47
Document Index: 665027785

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Title 21 → Chapter I → Subchapter F → Part 640
Subpart A—Whole Blood
§640.1 Whole Blood.
§640.2 General requirements.
§640.4 Collection of the blood.
§640.5 Testing the blood.
§640.6 Modifications of Whole Blood.
Subpart B—Red Blood Cells
§640.10 Red Blood Cells.
§640.11 General requirements.
§640.12 Eligibility of donor.
§640.13 Collection of the blood.
§640.14 Testing the blood.
§640.15 Segments for testing.
§640.16 Processing.
§640.17 Modifications for specific products.
§640.20 Platelets.
§640.22 Collection of source material.
§640.23 Testing the blood.
§640.24 Processing.
Subpart D—Plasma
§640.30 Plasma.
§640.31 Eligibility of donors.
§640.32 Collection of source material.
§640.33 Testing the blood.
§640.34 Processing.
Subpart I—Plasma Protein Fraction (Human)
§640.90 Plasma Protein Fraction (Human).
§640.91 Processing.
§640.92 Tests on final product.
§640.93 General requirements.
§640.94 Labeling.
§640.101 General requirements.
§640.104 Potency.
Subpart M—Definitions and Medical Supervision
§640.125 Definitions.
§640.130 Medical supervision.
(3) The blood has been stored continuously at 1 to 6 °C and shipped between 1 and 10 °C;
(4) The blood is held for observation until a significant inspection consistent with the requirements of §640.5(e) can be made.
(b) The donor center. The pertinent requirements of §§600.10 and 600.11 of this chapter shall apply at both the blood establishment and at any other place where the bleeding is performed.
(e) Donor identification. Each unit of blood shall be so marked or identified by number or other symbol as to relate it to the individual donor whose identity shall be established to the extent necessary for compliance with §630.10 of this chapter.
(1) One or more segments shall be provided with each unit of blood when issued or reissued except as provided in §640.2(c)(2) and all segments shall be from the donor who is the source of the unit of blood.
(f) Test for relevant transfusion-transmitted infections. Whole Blood shall be tested for evidence of infection due to relevant transfusion-transmitted infections as required under §610.40 of this chapter.
(a) The antihemophilic factor shall be removed in accordance with paragraphs (a), (b), and (c) of §640.52.
(b) Although the closed system between the red blood cells and plasma shall be maintained, the red blood cells shall be maintained between 1 and 6 °C at all times, including that time when the plasma is being frozen for removal of the antihemophilic factor.
(a) Storage. Immediately after processing, the Red Blood Cells shall be placed in storage and maintained at a temperature between 1 and 6 °C.
Establishments must determine the eligibility of donors of the source blood for Red Blood Cells in accordance with §§630.10 and 630.15 of this chapter.
(a) The source blood shall be collected as prescribed in §640.4.
Blood from which Red Blood Cells are prepared shall be tested as prescribed in §610.40 of this chapter and §640.5 (b) and (c).
(c) Final containers. Final containers used for Red Blood Cells shall be the original blood containers unless the method of processing requires a different container. The final container shall meet the requirements for blood containers prescribed in §640.2(c). At the time of filing, if a different container is used, it shall be marked or identified by number or other symbol so as to relate it to the donor of that unit of red cells.
(a) Proper name and definition. The proper name of this product shall be Platelets. The product is defined as platelets collected from one unit of blood and resuspended in an appropriate volume of original plasma, as prescribed in §640.24(d).
(a) Whole blood used as the source of Platelets shall be collected as prescribed in §640.4.
(c) If plateletpheresis is used, the procedure for collection must be as prescribed in §§640.21, 640.64 (except paragraph (c)), and 640.65, or as described in an approved biologics license application (BLA) or an approved supplement to a BLA.
(a) Blood from which plasma is separated for the preparation of Platelets shall be tested as prescribed in §610.40 of this chapter and §640.5 (b) and (c).
(c) The time and speed of centrifugation must have been demonstrated to produce an unclumped product, without visible hemolysis, that yields a count of not less than 5.5 × 1010 platelets per unit in at least 75 percent of the units tested.
(1) 20 to 24 °C.
(2) 1 to 6 °C.
(a) Whole Blood donors must meet the criteria for donor eligibility prescribed in §§630.10 and 630.15 of this chapter.
(a) Whole Blood must be collected, transported, and stored as prescribed in §640.4. When whole blood is intended for Plasma, Fresh Frozen Plasma, and Liquid Plasma, until the plasma is removed, the whole blood must be maintained at a temperature between 1 and 6 °C or as specified in the directions for use for the blood collecting, processing, and storage system approved for such use by the Director, Center for Biologics Evaluations and Research. Whole blood intended for Platelet Rich Plasma must be maintained as prescribed in §640.24 until the plasma is removed. The red blood cells must be placed in storage at a temperature between 1 and 6 °C immediately after the plasma is separated.
(b) Plasma obtained by plasmapheresis shall be collected as prescribed in §640.64 (except that paragraph (c)(3) of §640.64 shall not apply), and §640.65.
(a) Blood from which plasma is separated shall be tested as prescribed in §610.40 of this chapter and §640.5 (b) and (c).
(b) Manufacturers of Plasma collected by plasmapheresis shall have testing and recordkeeping responsibilities equivalent to those prescribed in §§640.71 and 640.72.
(a) Plasma. Plasma shall be separated from the red blood cells and shall be stored at −18 °C or colder within 6 hours after transfer to the final container or within the timeframe specified in the directions for use for the blood collecting, processing, and storage system unless the product is to be stored as Liquid Plasma.
(b) Fresh Frozen Plasma. Fresh frozen plasma shall be prepared from blood collected by a single uninterrupted venipuncture with minimal damage to and minimal manipulation of the donor's tissue. The plasma must be separated from the red blood cells or collected by an apheresis procedure, and placed in a freezer within 8 hours or within the timeframe specified in the directions for use for the blood collecting, processing, and storage system, and stored at −18 °C or colder.
(d) Platelet Rich Plasma. Platelet rich plasma shall be prepared from blood collected by a single uninterrupted venipuncture with minimal damage to and manipulation of the donor's tissue. The plasma shall be separated from the red blood cells by centrifugation within 4 hours after completion of the phlebotomy or within the timeframe specified in the directions for use for the blood collecting, processing, and storage system. The time and speed of the centrifugation shall have been shown to produce a product with at least 250,000 platelets per microliter. The plasma shall be stored at a temperature between 20 and 24 °C immediately after filling the final container. A gentle and continuous agitation of the product shall be maintained throughout the storage period, if stored at a temperature of 20 to 24 °C.
(e) Modifications of Plasma. It is possible to separate Platelets and/or Cryoprecipitated AHF from Plasma. When these components are to be separated, the plasma shall be collected as described in §640.32 for Plasma.
(2) Cryoprecipitated AHF shall be removed as prescribed in subpart F of part 640. The remaining plasma shall be labeled “Plasma, Cryoprecipitate Reduced.”
(3) Plasma remaining after both Platelets and Cryoprecipitated AHF have been removed may be labeled “Plasma, Cryoprecipitate Reduced.”
(2) With the exception of Platelet Rich Plasma and Liquid Plasma the final product shall be inspected for evidence of thawing or breakage at the time of issuance, however, the containers need not be stored in a manner that shows evidence of thawing if records of continuous monitoring of the storage temperature establish that the temperature remained at −18 °C or colder. If continuous monitoring of the product is not available, the final product shall be stored in a manner that will show evidence of thawing and shall not be issued if there is any evidence of thawing.
Source: 42 FR 27583, May 31, 1977, unless otherwise noted.
(b) Source material. The source material of Plasma Protein Fraction (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§640.1 through 640.5, or Source Plasma prepared as prescribed in §§640.60 through 640.76.
(d) Storage of bulk fraction. Bulk concentrate to be held more than 1 week prior to further processing shall be stored in clearly identified closed vessels at a temperature of −5 °C or colder. Any other bulk form of the product (exclusive of the sterile bulk solution) to be held more than 1 week prior to further processing, shall be stored in clearly identified closed vessels at a temperature of 5 °C or colder. Any bulk fraction to be held one week or less prior to further processing shall be stored in clearly identified closed vessels at a temperature of 5 °C or colder.
(e) Heat treatment. Heating of the final containers of Plasma Protein Fraction (Human) shall begin within 24 hours after completion of filling. Heat treatment shall be conducted so that the solution is heated continuously for not less than 10 or more than 11 hours at an attained temperature of 60±0.5 °C.
(f) Stabilizer. Either 0.08±0.016 millimole sodium caprylate, or 0.08±0.016 millimole sodium acetyltryptophanate and 0.08±0.016 millimole sodium caprylate per gram of protein shall be present as a stabilizer(s). Calculations of the stabilizer concentration may employ the labeled value 5 percent for the protein concentration of the product.
(g) Incubation. All final containers of Plasma Protein Fraction (Human) shall be incubated at 20 to 35 °C for at least 14 days following the heat treatment prescribed in paragraph (e) of this section. At the end of this incubation period, each final container shall be examined and all containers showing any indication of turbidity or microbial contamination shall not be issued. The contents of turbid final containers shall be examined microscopically and tested for sterility. If growth occurs, the types of organisms shall be identified as to genus and the material from such containers shall not be used for further manufacturing.
(a) Protein concentration. The final product shall be a 5.0 ±0.30 percent solution of protein.
(c) pH. The pH shall be 7.0 ±0.3 when measured in a solution of the final product diluted to a concentration of 1 percent protein with 0.15 molar sodium chloride.
(f) Heat stability. A final container sample of Plasma Protein Fraction (Human) shall remain unchanged, as determined by visual inspection, after heating at 57 °C for 50 hours, when compared to its control consisting of a sample, from the same lot, which has not undergone this heating.
(b) The cautionary statement placed in a prominent position on the label, “Do Not Use if Turbid. Do Not Begin Administration More than 4 Hours After the Container Has Been Entered.”
(a) Heat stability test. Approximately 2 ml. of completely processed material of each lot shall not show any visible sign of gelation after heating in a 12 × 75 mm. stoppered glass tube at 57 °C for 4 hours.
(b) pH. The pH of final container material shall be 6.8 ±0.4 when measured in a solution diluted to 1 percent protein with 0.15 molar sodium chloride.
(d) Date of manufacture. The date of manufacture is the date of initiating the last valid measles or poliomyelitis antibody test (§640.104(b) (2) and (3)) whichever date is earlier.
(a) Antibody levels and tests. Each lot of final product shall contain at least the minimum levels of antibodies for diphtheria, measles, and for at least one type of poliomyelitis. In the event the final bulk solution is stored at a temperature above 5 °C the antibody level tests shall be performed after such storage with a sample of the stored material.
Source: 80 FR 29906, May 22, 2015, unless otherwise noted.
The definitions set out in §630.3 of this chapter apply to the use of those defined terms in this part.
The requirements for medical supervision established in §630.5 of this chapter supplement the regulations in this part.