Regulatory Schema for Blood Transfusion Microbiotal transplant conference Baltimore, 3-4 December 2015 John R. Hess, MD, MPH, FACP, FAAAS Professor of Laboratory Medicine Medical Director, Transfusion Service Harborview Medical Center U. of Washington School of Medicine, Seattle Special Advisor to Director General, Blood Safety, 2003 WHO Expert Panel, Blood Transfusion Medicine, 2006-2012
The safest blood is Collected from the safest members of the population Tested for infectious diseases of risk Stored and transported in a safe manner Given to the right patient For the right reason WHO Global Program for Blood Safety
Biologics Control Act of 1902 Followed St. Louis disaster (diphtheria antitoxin contaminated with tetanus killed 13 children) Pre-market approval (license) to manufacture a product to be shipped in interstate commerce Registration of a manufacturer Naming of a responsible head (authorized official)
Pure Food and Drug Act of 1906 Progressive era, Sinclair Louis & The Jungle For preventing the manufacture, sale, or transportation of adulterated or misbranded or poisonous or deleterious foods, drugs, medicines, and liquors,. Purity and potency required (but not safety or efficacy). False claims illegal, but anything in the US Formulary or US Pharmacopea was legal if correctly labeled. Subsequent deaths from dinitrophenol, cincophen, radium, iodine, etc.
Food, Drug, and Cosmetics Act of 1938 Followed Elixor of Sulfanilamide disaster (sulfa in diethylene glycol labeled as elixor killed >100 people) Drugs sold in interstate commerce must be safe. Blood for transfusion is a drug. Authority with FDA
Drug Amendments of 1962 Followed thalidomide disaster in Germany and England (phocomelia in infants) Drugs must be safe and effective.
Where are we? Blood is a drug Unit of manufacture is the single donation Must be safe and effective, but that cannot be measured on every unit prospectively So we enforce purity and potency
The regulatory divide Blood Well understood process and highly reproducible product Minimal manipulation of the product Human cells and tissues Poorly understood processes. Highly variable products Highly manipulated product
Source Plasma Collection Commercial plasma collection centers using paid donors for manufactured plasma products Albumin, IVIg, RhoGam, RabiesIg, Vig All of these products undergo 4-10 log of pathogen reduction by Solvent/detergent treatment Nanofiltration Other methods
The safest blood comes from altruistic voluntary nonremunerated donors. WHO Global Program for Blood Safety
Give Blood The national blood policy established in the late 1970s requires that blood for transfusion be donated by voluntary donors. It s not a monumental effort
Making a blood product Define a product (like a unit of RBCs) Describe a process to make it Prove it works (under an IND) Get a license to make the product by following procedures that define the process.
Modern integral blood bag system
Making Blood Products Recruiting donors Qualifying donors Collecting whole blood Testing blood collected Making components Labeling Storage Shipment
Donor Suitability Blood components for transfusion Serum eye drops Plasma for fractionation Human milk Human sperm or ova Human fecal microbiota Human vaginal microbiota Human oral microbiota
21 CFR 640.3 Suitability of donor (a) Method of determining. The suitability of a donor as a source of Whole Blood shall be determined by a qualified physician or by persons under his supervision and trained in determining suitability. a thru f: (covering or referencing just about everything)
cgmp Current good manufacturing practice, the model is ISO-9001 Have a quality program Have written procedures for each process Measure deviation from the process Perform root-cause evaluations into sources of deviations Minimize deviation from the process by enforcing or changing procedure
Blood Safety in US is a matter of FDA regulation and industry standards FDA regulations in 21 CFR 200, 600, 800, & 1270 series, 42 CFR 493w Blood collection and product manufacturing facilities are licensed and distributing facilities are registered. FDA inspections biannually Hospitals, laboratories, and blood banks are accredited by TJC, CAP, and AABB State health department license
CFR Title 21- Food & Drugs Chapter 1 FDA in DHHS Subchapter C Drugs: general Part 210 cgmp in manufacture, processing, packing or holding of drugs: general Sect 210.1 Status of cgmp regulations Sec 210.1(b) The failure to comply with any regulation set forth in this part and in parts 211, 225, and 226 of this chapter in the manufacture, processing, packing or holding of a drug shall render such a drug to be adulterated...
21 CFR Quality Regulations 211.22 QC/QA 211.25 Personnel qualifications 211.28 Personnel responsibilities 211.192 Production records review 211.194 Laboratory records & review 606.20 Personnel 606.40 Facilities 606.60 Equipment 606.65 Supplies, reagents 606.100 SOPs 606.160 Records 606.170 Adverse reactions 606.171 BPDs
21 CFR 610.53 Dating periods for licensed biological products The minimum dating periods in paragraph (c) of this section are based on data related to usage, clinical experience, or laboratory tests that establish the reasonable period beyond which the product cannot be expected to yield its specific results and retain its safety, purity, and potency, provided the product is maintained at the recommended temperatures
Labeling Labeling of a blood product is highly regulated and all such products in the US use a schema called ISBT 128. Label can only be applied when all conditions are met.
Labeling Human fecal slurry for microbiotal transplant Brand name Source & address FDA Registration # Unique ID # Outdate Volume Storage instructions Reference to use instructions For administration only under the direction of a licensed physician
Apheresis Platelet Components Single donor platelets by apheresis must contain > 3 x 10 11 per unit, but some donors can give > 600 or 900 billion at a setting, enough for 2 or 3 doses. Huge advantage because of cost of collection and testing is spread over more units single donor platelets by apheresis
Size of donation matters because the cost of testing is spread over the number of products produced from each donation.
21 CFR 640.5 Testing the blood All laboratory tests shall be made on a specimen of blood taken from the donor at the time of collecting the unit of blood, and these tests shall include the following: a thru f: (covering or referencing just about everything)
42 CFR 493.857 Condition: Immunohematology The speciality of immunohematology includes four subspecialties for the purposes of proficiency testing: ABO group and D (Rho) typing, unexpected antibody detection, compatibility testing, and antibody identification. Three times yearly proficiency testing with external quality standards CAP surveys
42 CFR 493.859 Standard: ABO & RhD typing (a)failure to attain a score of at least 100 percent of acceptable responses for each analyte or test in each testing event is unsatisfactory analyte performance for the testing event. Failures are reported to your state health department, who visits you.
42 CFR 493.1834 Civil money penalty (a) Statutory basis. Sections 1846 of the Act and 353(h)(B) of the PHS Act authorize the Secretary to impose civil money penalties on laboratories. Section 1846(b)(3) of the Act specifically provides thea incrementally more severe fines may be imposed for repeated or incorrected deficiencies.
Washington Post, 9 Sept 2006 Regulation is designed to ensure that blood collection and product manufacturing are in compliance with laws and regulations.
Increased personal choice and market forces in blood collection and donation may not be useful answers.
Fecal donor for microbial tranplant guidelines suggested by the Infectious Disease Society and 4 US GI Societies in 2013
Welcome to AdvancingBio: offering treatment to those suffering with C. diff through Fecal Microbiotal Transplant See website of AdvancingBio Subsidiary of BloodSource, the Sacramento area blood collector
Thank you for all your efforts to encourage blood donation.