[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
[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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