the identity,purity,and quality of components (including ingredients,reagents,target solutions,and gases);the identity and quality of containers and closures,and other materials (e.g.,transfer lines,purification devices,membrane filters)that come into contact with the final PETradiopharmaceutical;and the identity,purity,and quality of analytical supplies (e.g.,solvents,chromatography columns,and reference materials),sterility test media,endotoxin test reagents,and other supplies intended for use in PETradiopharmaceutical quality control procedures;and

the appropriate storage (i.e.,based on heat,light,and humidity considerations)of components,containers and closures,materials and supplies used for the compounding of PETradiopharmaceuticals.

incorporate,for each PETradiopharmaceutical intended for parenteral administration,sterile membrane filtration (0.22µm);

incorporate,for each PETradiopharmaceutical intended for inhalation,particulate filtration (0.45µm);and

are routinely updated and verified as changes in the compounding procedures are implemented or are reviewed and verified at a minimum of once a year to ensure that they are current.Amaster file of written compounding procedures currently used for each PETradiopharmaceutical is to be maintained within the PETfacility.Copies of outdated compounding procedures shall also be retained,separate from the master file,for review purposes.

include documented evaluations of the radiochemical identity and purity,radionuclidic identity and purity,specific activity,sterility (for parenteral agents),bacterial endotoxins (for parenteral agents),pH,osmolality (for parenteral agents),if appropriate,appearance,stereochemical purity (for applicable compounds),potential organic volatile impurities,other toxic chemicals that may have been used during the synthesis or purification procedure,effective concentration of a stabilizer (if any),chemical purity of the PETradiopharmaceutical [NOTE—Evaluations for chemical purity must include analyses for the presence of starting materials,known intermediates,by-products,and known degradation products],and equivalency of initial and final sub-batches (for PETradiopharmaceuticals with radionuclides having a T½<20.0minutes).For purposes of this chapter,“sub-batch”is defined as a quantity of PETdrug product having uniform character and quality,within specified limits,that is produced during one succession of multiple irradiations,using a given synthesis and/or purification operation;and

be signed,and dated,and retained as an indication that the compounding procedures,equipment,and facilities have resulted in a PETradiopharmaceutical that meets established acceptance criteria.

lot numbers,manufacturer identities,expiration dates,and quantities of all components,containers and closures,and materials used in the compounding procedure;

a description of the individual compounding procedures to be followed;

the initials of the responsible individual indicating that the compounding procedure for the batch is an accurate reproduction of the current,verified compounding procedure;

the initials of the responsible individual indicating that critical steps and processes in the compounding procedure were completed [NOTE—Critical steps in automated compounding processes shall be monitored through direct observation (if possible,considering visual or radiation exposure constraints)or via computer or other feedback mechanisms];

documentation of the investigation of any unplanned deviations in,or unexpected results of,verified compounding procedures or processes,including documentation of the outcome of the investigation;

the percent yield calculated on the basis of the known or expected decay-corrected amount of the starting radionuclide that is synthetically incorporated into the final radiopharmaceutical;

raw analytical data on each batch of compounded PETradiopharmaceutical;and

the date and the signature of the individual assuming overall responsibility for,and adherence to,the verified compounding procedure.

For PETradiopharmaceuticals labeled with a nuclide having a T½³20.0minutes,the following quality control procedures are to be performed on each batch (i.e.,the material produced during a single synthesis and purification operation)prior to release:measurement of the pHof parenteral and oral dosage forms;visual inspection of parenteral and oral dosage forms;determination of the radiochemical purity and identity of all dosage forms;determination of the radionuclidic identity of all dosage forms;and assessment of the specific activity of PETradiopharmaceuticals with mass-dependent localization or toxicity concerns;and evidence of compliance with the established acceptance criteria for residual solvents and other toxic chemicals used during the synthesis or purification procedures.

For PETradiopharmaceuticals labeled with a nuclide having a T½<20.0minutes,a batch is defined as all related sub-batches of the PETradiopharmaceutical compounded during a given day.The following quality control procedures are to be performed on an initial quality control sub-batch of each such PETradiopharmaceutical prior to release for human use of subsequent sub-batches:measurement of the pHof parenteral and oral dosage forms;visual inspection of parenteral and oral dosage forms;determination of the radiochemical purity and identity of all dosage forms;determination of radionuclidic identity of all dosage forms;and assessment of the specific activity of PETradiopharmaceuticals with mass-dependent localization or toxicity concerns;and evidence of compliance with the established acceptance criteria for residual solvents and other toxic chemicals used or produced during the synthesis or purification procedures.

For each batch of PETradiopharmaceutical intended for parenteral administration,perform a membrane filter integrity test immediately after completion of product filtration.This post-filtration integrity test is to be completed prior to release of the batch for human use,except in the case of 15Owater,where it may be necessary to release the batch prior to completion of the post-filtration integrity test.In this case,the test is completed as soon as possible after release of the batch.

For PETradiopharmaceuticals intended for parenteral administration,perform an in-process 20-minute endotoxin “limit test”(i.e.,incorporating positive controls in the range of 5EUper mLto 175EU/V,where Vis the maximum volume of injection)on each batch (T½³20.0minutes)or quality control sub-batch (T½<20.0minutes)of the radiopharmaceutical prior to release,for human use,of the batch or subsequent sub-batches.

For PETradiopharmaceuticals intended for parenteral administration,a standard 60-minute bacterial endotoxin test must be performed on each batch (T½³20.0minutes)or quality control sub-batch (T½<20.0minutes)of the radiopharmaceutical.Endotoxin testing may also be performed using other recognized procedures (see Bacterial Endotoxin Test á85ñ).Regardless of which test is utilized,an assessment of the bacterial endotoxins should be performed prior to release of each batch (T½³20.0minutes)or quality control sub-batch (T½<20.0minutes)of the radiopharmaceutical before release for human use of the batch or subsequent sub-batches.

Sterility tests for each PETradiopharmaceutical intended for parenteral administration are performed on each batch (T½³20.0minutes)or quality control sub-batch (T½<20.0minutes).Sterility tests are also performed following the replacement of system components.Sterility tests are initiated within 24hours of sterile filtration.Product samples are tested individually and are not pooled.