Attachment IV - Page 20 
- 2 - 
FDA's Comments on NIH's Proposed "Points to Consider i'n the Design 
and Submission of Human Somatic-Cell Gene Therapy Protocols." 
1. In the Introduction on p. 2942, middle column, third complete paragraph: 
following reference to the DHHS regulations (45 CFR, Part 461, add "and 
FDA regulations (21 CFR, Parts 50 and 561." The next sentence would then 
need to be modified to clarify that "these regulations" refer to the DHHS 
regulations. 
2. In the discussion of the unlikelihood of proprietary information in gene 
therapy proposals, it should be noted that where proprietary information 
is included, those portions of proposals would be discussed during closed 
sessions. While this may not happen frequently, the option for closed 
sessions should be available. 
3. In section I.B.l.b. on p. 2943, we suggest that the wording would be 
clearer in the first sentence if it were, "What is the composition of the 
material ..." 
4. In section I.B.l.b on p. 2943, we suggest the addition of two new sections: 
a. Cine would request the investigator to, "Describe in detail the 
methods for harvesting, extraction, and purification, and for the 
removal of any toxic chemicals introduced by these procedures." 
b. The second would contain a warning that penicillin and other 
beta-lactam-containing antibiotics should not be used in the 
production of materials administered to patients. 
5. In Section I.B.l.b. (11 on p. 2943, we suggest the addition of questions 
about: (11 the methods for assaying potency of the product used to treat 
ceils or administered to a patient: and (2) the consistency of the product 
lot-by-lot, if different lots will be used on the same patient or on 
different patients: and (31 the stability of the product under the 
projected conditions of storage. 
6. In section I. R. 2. a. (21 on p. 2943, because it will be difficult to predict 
the frequency of insertion of the desired DNA sequences into the patient's 
cells prior to performance of the experiment ( parti cul arl y if in vivo 
selection is crucial 1 and "adequate" is vague and left undefined, this 
section should be revised. 
7. In section I.B.2.C. on p. 2943, we suggest the addition of a section which 
would request a description of previously-reported similar human studies 
and their resui ts (including foreign studies 1. 
8. In section I.B.2.C. (1 1 ( c 1 on p. 2943, in the first sentence, "malignancy" 
should read "tumors." Moreover, because this section is relevant to gene 
therapy whether or not a retroviral vector is employed, it should be 
relocated to above I.B.2.C. (1 1. 
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