[Federal Register Volume 60, Number 38 (Monday, February 27, 1995)]
[Notices]
[Pages 10593-10594]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-4689]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Docket No. 94D-0422]


Draft Guideline on the Manufacture of Positron Emission 
Tomography Radiopharmaceutical Drug Products; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guideline entitled ``Draft Guideline on the 
Manufacture of Positron Emission Tomographic (PET) Drug Products'' 
prepared by FDA's Center for Drug Evaluation and Research (CDER). The 
draft guideline is intended to assist persons in determining whether 
certain manufacturing practices, procedures, and facilities used in the 
small-scale production of liquid injectable radiopharmaceutical drug 
products used for positron emission tomography (PET 
radiopharmaceuticals) are in compliance with FDA's current good 
manufacturing practice (CGMP) regulations for finished pharmaceuticals.

DATES: Written comments by May 30, 1995.

ADDRESSES: Submit written requests for single copies of the draft 
guideline entitled ``Draft Guideline on the Manufacture of Positron 
Emission Tomographic (PET) Drug Products'' to the CDER Executive 
Secretariat Staff (HFD-8), Center for Drug Evaluation and Research, 
Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855. 
Send two self-addressed adhesive labels to assist that office in 
processing your requests. Submit written comments on the draft 
guideline to the Dockets Management Branch (HFA-305), Food and Drug 
Administration, rm. 1-23, 12420 Parklawn Dr., Rockville, MD 20857. 
Requests and comments should be identified with the docket number found 
in brackets in the heading of this document. A copy of the draft 
guideline and received comments are available for public examination in 
the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through 
Friday.

FOR FURTHER INFORMATION CONTACT: John W. Levchuk, Center for Drug 
Evaluation and Research (HFD-322), Food and [[Page 10594]] Drug 
Administration, 7500 Standish Pl., Rockville, MD 20855, 301-594-0095.

SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a 
draft guideline entitled ``Draft Guideline on the Manufacture of 
Positron Emission Tomographic (PET) Drug Products.'' PET is a 
diagnostic imaging modality consisting of onsite production of 
radionuclides that are intravenously injected into patients for 
diagnostic purposes. The potential usefulness of a PET 
radiopharmaceutical is based upon the product's interaction with a 
biochemical process in the body. For example, the product may be 
substituted for glucose in anaerobic glycolysis, theoretically 
localizing in ischemic tissues where glucose metabolism is the 
predominant energy source (epileptic foci, acute vascular insufficiency 
states).
    The manufacture of PET radiopharmaceuticals consists of a process 
that takes place within a few hours. A target material is irradiated by 
a cyclotron; chemical synthesis takes place in a programmed, automated 
apparatus; and the final solution is compounded and filled. The 
biological distribution of a PET radiopharmaceutical in the body is 
monitored by a positron tomograph, or PET scanner, which detects the 
photons emitted as a result of the radioactive decay of the PET 
radiopharmaceutical. Because of their short half-lives, PET 
radiopharmaceuticals are characteristically manufactured in PET centers 
in response to daily demand for relatively few patients. PET centers 
are usually located in medical centers.
    PET manufacturing procedures differ in a number of important ways 
from those associated with the manufacture of conventional drug 
products, mainly due to the short half-lives involved:
    1. A maximum of only a few lots are manufactured per day, with one 
lot equaling one multiple-dose vial. This is administered to the 
patient usually within a matter of hours. Prolonged manufacturing time 
significantly erodes the useful clinical life of PET 
radiopharmaceuticals.
    2. The quantities of radioactive active ingredients contained in 
each lot of a PET radiopharmaceutical generally vary from nanogram to 
milligram amounts, depending upon various product parameters.
    3. Because one lot equals one multiple-dose vial containing a 
homogeneous solution of a PET product (e.g., 2-deoxy-2 
[<SUP>18F]fluoro-D-glucose), results from end-product testing of 
samples drawn from the single vial have the maximum possible 
probability of being representative of all the doses administered to 
patients from that vial, barring sampling or testing error.
    4. An entire lot may be administered to one or several patients, 
depending upon the activity remaining in the container at the time of 
administration. Consequently, the administration of the entire quantity 
of a lot to a single patient should be anticipated for every lot 
manufactured. This is an important consideration when establishing the 
testing limits for certain attributes such as endotoxins and 
impurities.
    5. PET radiopharmaceuticals usually do not enter a general drug 
distribution chain. Rather, the entire lot (one vial) is usually 
distributed directly from the PET center either to a single medical 
department or physician for administration to patients or to a 
radiopharmacy for dispensing. Distribution may occur to other centers 
when the geographic proximity will allow for distribution and use 
within the drug product's half-life parameters.
    Conventional compliance with CGMP regulations would be expected 
where special characteristics such as those listed above do not exist; 
for example, in large-scale PET operations. Elsewhere in this issue of 
the Federal Register, FDA is publishing (1) A proposed rule that would 
authorize the Director, CDER, or the Director, Office of Compliance, 
CDER, to approve exceptions or alternatives to the application of the 
provisions of 21 CFR part 211 to the manufacture of PET 
radiopharmaceuticals, and (2) a notice of a public workshop and FDA 
guidance on the regulation of PET radiopharmaceuticals.
    The guideline entitled ``Draft Guideline on the Manufacture of 
Positron Emission Tomographic (PET) Drug Products'' discusses, 
generally, quality control units, personnel qualifications, staffing, 
buildings and facilities, equipment, components, containers, closures, 
production and process controls, packaging and labeling control, 
holding and distribution, testing and release for distribution, 
stability testing and expiration dating, reserve samples, yields, 
second-person checks, and reports and records.
    FDA is making this draft guideline available for public comment 
before issuing a final guideline. If, following the receipt of 
comments, the agency concludes that the draft guideline will assist 
persons in determining whether manufacturing practices used in the 
small-scale production of liquid injectable PET radiopharmaceuticals 
are in compliance with FDA's CGMP regulations for finished 
pharmaceuticals, then the agency will prepare a final guideline and 
will announce its availability in the Federal Register.
    Guidelines are generally issued under Sec. 10.90(b) (21 CFR 
10.90(b)), which provides for the use of guidelines to state procedures 
or standards of general applicability that are not legal requirements 
but are acceptable to FDA. The agency is now in the process of revising 
Sec. 10.90(b). Therefore, if the agency makes the guideline final, the 
guideline would not be issued under the authority of current 
Sec. 10.90(b), and would not create or confer any rights, privileges, 
or benefits for or on any person, nor would it operate to bind FDA in 
any way.
    Interested persons may, on or before May 30, 1995, submit to the 
Dockets Management Branch (address above) written comments on the draft 
guideline. Two copies of any comments are to be submitted, except that 
individuals may submit one copy. Comments are to be identified with the 
docket number found in brackets in the heading of this document. The 
draft guideline and received comments may be seen in the office above 
between 9 a.m. and 4 p.m., Monday through Friday.

    Dated: February 17, 1995.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 95-4689 Filed 2-24-95; 8:45 am]
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