325 



sibilities in connection with rapid mass application and gradual individual appli- 

 cation of new drugs (preventive or curative) with regard to (a) production and 

 safety; (&) distribution; and (c) application and use?" 



The May 25 hearings were opened with the testimony of Roswell B. 

 Perkins, Assistant Secretary of Health, Education, and Welfare, who 

 spoke for Mrs. Hobby. Mr. Perkins described the activities of DHEW 

 immediately after information had come to the Department that some 

 lots of the vaccine were causing polio in inoculated children. He re- 

 viewed how the Division of Biologies Control had dispatched scien- 

 tists to study the manufacturing process at the Cutter laboratories; 

 these scientists, May 8, had recommended that the vaccination pro- 

 gram be temporarily halted pending revision of standards.^^ Dr. 

 Scheele then told the committee about the destruction of the lots of 

 Cutter vaccine; however, he could only speculate on what had been 

 wrong with them. The infected children might have had lower natural 

 immunity than those who were not infected, or they might already have 

 been infected by polio \drus from a natural source, or there could have 

 been live virus remaining in the vaccine.^^ 



Dr. W. H. Sebrell, Jr., Director of the National Institutes of Health, 

 recounted the development of the vaccine and indicated some of the 

 difficulties that PHS had faced in the safety testing of earlier field 

 trial lots. He reviewed the formation of a vaccine advisory committee 

 to assist PHS in determining minimum safety requirements. He then 

 detailed the complexity of the vaccine manufacturing process and illus- 

 trated the difficulties of arriving at the appropriate margin of safety. 



I may say that the production of Salk vaccine is an intricate manufacturing 

 process. Whenever you move from a laboratory process, you always run into 

 changes for which you have no previous experience. In making the Salk vaccine, 

 if you overtreat it, you have nothing. It has no potency, no ability to immunize. 

 If you do not treat it quite enough, it may have enough live virus in it to cause 

 paralytic polio. Therefore, you have to operate within a range that is safe within 

 these two extremes, one, complete destruction of its ability to confer immunity, 

 and the other, as much safety as you can put around it so that there is not enough 

 live virus in it to cause disease. 



* * * In safety testing you can never be absolutely certain in a biological 

 product that the product in one particular vial is absolutely safe, because the 

 only way you could determine that would be to test every drop of stuff in that 

 vial. Then you would not have anything to use. So you set up the best test you 

 can devise to reduce the chances to as near zero as you possibly can, and then you 

 let the product go on the basis of its probability of complete safety. There is no 

 other way to arrive at that * * *." 



Dr. Sebrell also listed the potential human and mechanical pitfalls 

 in safety testing faced by large-scale vaccine manufacturers. And 

 finally, for the first time. Dr. Sebrell admitted what had been wrong 

 with the Cutter vaccine and administrative flaws of PHS in licensing 

 the vaccine prematurely. In part he said : 



The committee was able to learn from manufacturers that inactivation * * * 

 sometimes fails in the plant for no immediately apparent reason. There was 

 evidence also that the safety tests were perhaps less sensitive than was desired. 

 On some occasions, pools of virus, each containing a single type and each negative 

 after inactivation, were combined into what are called polyvalent pools, which 

 then gave positive tests * * *. 



The supposed margin of safety conferred by inactivation, far beyond the calcu- 

 lated period, appeared no longer to be fully dependable. The sensitivity of the 



^ Ibid., p. 4. . „ 



5= House. Committee on Interstate and Foreign Commerce. Poliomyelitis vaccine. Hear- 

 ings, pt. 1, op. clt., p. 19. 

 ^ Ibid., pp. 26-29. 

 " Ibid., pp. 47-48. 



