thousand inspections within a twoyear period naturally has placed a big burden on the manpower and administrative

resources of the

Bureau, which heretofore has had a staff of 20 qualified people to inspect the facilities and operations of the 165 interstate blood banks and their multiple locations. To accomplish the task of inspecting the intrastate banks, FDA has made available a number of senior food and drug inspectors from the Office of the Executive Director of Regional Operations (EDRO).

These top-level inspectors are scattered in FDA's 19 Districts or in resident posts. All have undergone orientation courses conducted by Bureau of Biologics personnel, and continue to work closely with that Bureau.

The Bureau hopes to use these experienced EDRO inspectors to complete inspections of several hundred of the intrastate banks by June 30. At that time, planners in the Bureau's Office of Compliance will determine if the manpower allocated is adequate to complete the work in two years before continuing with the remaining visits.

Inspection of a blood bank takes one to six hours on the premises, depending on the size of the operation and the volume of blood handled, the variety of blood products processed, the numbers and kinds of violations or improper practices noted, and a number of other factors. When the inspection is completed, the inspector reports adverse findings and the problems that require correction to the person in charge of the blood bank.

During the inspection the inspector carries a checklist of the most common blood bank practices to check out. This includes the kinds of products processed; the thoroughness with which the health and other fitness qualifications of the blood donors are investigated; the presence of a physician on the premises; collection techniques; suitability of containers, equipment, and facilities; preparation of the donor; collection of pilot samples; sealing of contain

ers; collection records; grouping and typing of blood; tests of blood for certain diseases that can be transmitted to a recipient; labeling of containers; sterile techniques; care of stored blood and blood products; and refrigeration and shipping practices. Other checks involve methods of processing and handling blood component products.

Today there are few American families in which one or more members will not at some time be involved either in giving or receiving blood. But barely a century ago the medical practice of using one human's blood to preserve the life of another existed only as a daring, dangerous, and desperate experiment—almost always a last resort. Physicians who performed transfusions, even though they were among the most advanced of their times, were coping against odds that were impossible to assess from the medical knowledge then available.

Experiments with transfusions date back into ancient history but exact methods and results have been uncertainly or tenuously documented for us. Early experiments involved the transfusion of animal blood to man. Successes obviously were rare, and failures, in the light of today's knowledge, almost a foregone conclusion.

Even after the English physician, William Harvey, published his discovery of the circulatory system in 1628, thus generating new interest in the possibilities of blood transfusions, the high rate of fatalities sometimes led to legal sanctions against the practice. Physicians had to struggle against ignorance and superstition inherited from the Dark Ages, including a rather widespread belief that the recipient of blood might take on the physical or other characteristics of the donor, animal or human.

But the more realistic difficulties concerned medicine's lack of knowledge about sterile techniques, incompatibility of blood groups and types, transmission of infections in blood, and coagulation or clotting. The Dark Ages closed in for another 150 years.

In the early 19th century, interest revived and mechanical syringing was developed. In 1818 the first successful transfusion of human blood was documented. A little later, transfusions were made with blood from which clotting agents had been mechanically removed.

Refinements continued, some beneficial and some not, and the number of transfusions, successful and unsuccessful, gradually increased. By the end of the century, physicians generally were aware of many of the problems. In 1900 a researcher was able to classify the blood of different people into three groups based on cross-reaction of blood samples. Other researchers classified a fourth group two years later. These nonchanging, inherited characteristics are now known as the ABO system and consist of groups A, B, AB, and O.

These immensely important discoveries made it possible to match a donor's blood with the recipient's before a transfusion was made and thus to avoid serious reactions in a patient from receiving incompatible blood. This major step set the stage for the greatly increased use of blood in human therapy.

Physicians experimented with the various mechanical means of overcoming coagulation and later tried adding chemical agents to transfused blood to act as anticoagulants and preservatives. A big advance was made in this area in 1914 with the use of sodium citrate. When the amount was reduced to a level nontoxic to the recipient, this method proved to be simple and practical and reasonably successful. The technique was available to all physicians and became standard for blood transfusions in World War I.

Most transfusions through the 1920's and 1930's were not made with blood previously collected, but directly from donor to recipient. The first blood bank in the country was set up at the Cook County Hospital in Chicago in 1938. By this time, blood could be held for three or four days before deterioration set inmainly hemolysis, or separation of

the hemoglobin from the corpuscles -and it was no longer suitable for

use.

An improved method was discovered in 1942 consisting of the use of acid-citrate-dextrose (ACD) as an anticoagulant. This made it possible to hold blood for about 21 days before it deteriorated to the point of unsuitability.

The last major obstacle to making the transfusion of blood the commonly accepted therapeutic method it is today was surmounted in 1940 with the announcement of the discovery of the "Rh" factor. Researchers found that occasional adverse reactions, sometimes resulting in fatality, were caused by certain incompatibilities between the blood of a donor and that of a recipient, even though they were of the same group. These findings demonstrated that adverse reactions occurred usually in a recipient whose blood contained no Rh factor (that is, was Rh negative), from a donor whose blood was Rh positive. Furthermore, it was shown that the reaction tended to occur in a recipient only at the time he received a second transfusion of blood from an Rh-positive donor.

The researchers showed that when an Rh-negative person first received blood containing the Rh factor, antibodies were formed in his blood to combat this alien factor, or Rh antigen occurring on the transfused red blood cells. With formation of the antibodies, he became permanently sensitized, and when he received blood containing the Rh factor a second time, a severe reaction occurred, caused by the interaction between the antibodies and the invading Rh-positive cells. A similar kind of adverse reaction was shown in the case of some newborn infants, usually not first children, caused by sensitization of an Rhnegative mother's blood by a preceding fetus which had inherited its father's Rh-positive blood. Since then a treatment has been developed that can prevent the mother from becoming thus sensitized.

With this discovery and the development of typing by Rh factor,

named for rhesus monkeys used in tests that led to discovery of this factor, there followed an expanding use of blood and its components, reaching large-scale use during World War II.

After World War II, blood banking expanded rapidly along with blood-collecting activities by the American Red Cross and others. The Philadelphia Blood Center became the first licensed interstate blood bank in 1946. An improved anticoagulant-preservative, citratephosphate-dextrose (CPD), also came into general use in the 1950's and 1960's.

Accompanying the expanding use of blood in therapy has been a trend away from whole blood to the use of blood components that serve specific needs.

The major blood component products in use today include red blood cells and several fractions of blood plasma for specific therapeutic use. Red blood cells, a solid component of blood which can be separated from the plasma or liquid part through sedimentation, is used in transfusions when the oxygencarrying ability of the red cells is needed more than blood volume expanding properties.

Plasma, the fluid part of the blood, is the source of antihemophilic factor, used to treat the disease hemophilia in which the victim bleeds excessively; factor IX complex, to treat another bleeding disorder; fibrinolysin, to dissolve blood clots; fibrinogen, to control hemorrhage in childbirth; albumin and plasma protein fraction, to treat shock or protein deficiency; and globulins, which provide antibodies, to protect against specific diseases, such as tetanus, measles, whooping cough, and mumps. Whole blood and red cells can be held only 21 days, but plasma and its fractions can be held for considerably longer periods.

Although use of blood and its components in treating our injuries and diseases has become commonplace, many important problems remain to challenge us in this field of

medicine. We need to find ways to store blood longer so that stockpiles can be accumulated to meet emergencies and waste can be kept to a minimum. Although basic discoveries have been made in blood typing, every person's blood is different in some ways from every other person's. The ideal blood for treating any person is his own, a compelling reason for seeking new ways to store a person's blood for his own use in some later emergency.

Today, although most hazards involving transmission of infection through blood have been eliminated through laboratory testing and careful selection of donors, one major problem remains: the transmission of a viral disease, serum hepatitis or jaundice. Post-transfusion hepatitis in the past has been responsible for 1,500 to 3,000 deaths a year. Two developments in the past year offer promise in substantially reducing this hazard.

The first is an FDA regulation, effective July 1, 1972, which requires that all federally licensed (interstate) blood banks test the blood of each donor to determine if it gives a negative reaction to Hepatitis Associated Antibody (AntiAustralia Antigen) as a condition of accepting the blood for transfusion. Present methods for detecting the hepatitis-associated antigen have been developed only in recent years and are capable of detecting about 20-25 percent of the bloods implicated in post-transfusion hepatitis.

The second is the Bureau of Biologics action on July 28, 1972, in licensing a new hepatitis-associated antigen detection method that it believes will detect two to five times the number of units of blood, plasma, or serum that harbor hepatitis virus as are now being identified. Extensive laboratory testing by both the manufacturer and the Bureau indicates the new method is much more sensitive than the previous procedures.

Harold C. Hopkins is editorial director of FDA CONSUMER