[11C]CUMI for Injection: Validation Record PET Radiopharmaceutical Sciences Section, Date of review: 11/27/09 Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bldg. 10, Rm. B3 C338, Bethesda, MD 20892

Document 9: [11C]CUMI for Injection: Validation Record Page 1 of 2

Three batches of [11C]CUMI for Injection were produced and fully analyzed for the purpose of validation of the process. The data are summarized below; refer to the three batch records attached for further detail.

Batch Number Result pH CUMI-09111201 5.5 CUMI-09111202 5.0 Acceptance Criteria:

pH 4.0 to 7.5 CUMI-09111301 5.0

Batch Number Result Membrane filter integrity CUMI-09111201 No bubbles observed at 45 psi CUMI-09111202 No bubbles observed at 45 psi Acceptance Criteria:

No bubbles observed at 45 psi CUMI-09111301 No bubbles observed at 45 psi

Batch Number Result Appearance test CUMI-09111201 Clear, colorless, particulate free CUMI-09111202 Clear, colorless, particulate free Acceptance Criteria:

Clear, colorless, particulate free CUMI-09111301 Clear, colorless, particulate free

Batch Number Result Chemical purity CUMI-09111201 0.51 µg

CUMI-09111202 0.54 µg Acceptance Criteria: Amount of impurity not to exceed 1.0 µg for injected volume. CUMI-09111301 0.37 µg

Batch Number Result

Cold Carrier Limit CUMI-09111201 9.96 µg

CUMI-09111202 10.0 µg Acceptance Criteria: Amount of CUMI carrier not to exceed 10 µg for injected volume. CUMI-09111301 8.09 µg

Batch Number Result Radiochemical purity CUMI-09111201 100 % CUMI-09111202 100 % Acceptance Criteria:

Not less than 95% CUMI-09111301 100 %

Batch Number Result Radiochemical identity CUMI-09111201 Δ tR = 0.52 min CUMI-09111202 Δ tR = 0.52 min Acceptance Criteria:

tR within 1 min of standard (corrected for UV to γ detector delay) CUMI-09111301 Δ tR = 0.48 min

Batch Number Result Specific radioactivity CUMI-09111201 4432 mCi/µmol CUMI-09111202 3632 mCi/µmol Acceptance Criteria:

Not less than 500 mCi/µmol at EOS CUMI-09111301 5828 mCi/µmol

[11C]CUMI for Injection: Validation Record PET Radiopharmaceutical Sciences Section, Date of review: 11/27/09 Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bldg. 10, Rm. B3 C338, Bethesda, MD 20892

Document 9: [11C]CUMI for Injection: Validation Record Page 2 of 2

Batch Number Result Radionuclidic Identity CUMI-09111201 t1/2 = 20.3 CUMI-09111202 t1/2 = 20.0 Acceptance Criteria:

Experimentally determined half life 20.4 ± 2.0 minutes CUMI-09111301 t1/2 = 20.1

Batch Number Result

0.113 mg acetonitrile Residual Solvent CUMI-09111201 3.83 x 104 ng/µL ethanol 0.102 mg acetonitrile CUMI-09111202 4.27 x 104 ng/µL ethanol 0.123 mg acetonitrile

Acceptance Criteria: ≤.4.1 mg acetonitrile in the injectable dose ≤1 x 105 ng/µL ethanol CUMI-09111301

3.74 x 104 ng/µL ethanol

Batch Number Result Bacterial endotoxins CUMI-09111201 < 14.8 EU CUMI-09111202 < 13.8 EU Acceptance Criteria:

No more than 175 EU in the injectable dose CUMI-09111301 < 14.6 EU

Batch Number Result Sterility CUMI-09111201 No growth observed CUMI-09111202 No growth observed Acceptance Criteria:

No aerobic or anaerobic growth observed CUMI-09111301 No growth observed

Batch Number Result 100 % Stability CUMI-09111201

Clear, colorless, particulate free

100 % CUMI-09111202

Clear, colorless, particulate free

100 %

Acceptance Criteria: Product meets radiochemical purity specifications (≥ 95%) and is clear, colorless, particulate free after one hour. CUMI-09111301

Clear, colorless, particulate free

Batch Number Result

Yield CUMI-09111201 145.2 mCi

CUMI-09111202 131.7 mCi Acceptance Criteria: Greater than 20 mCi at EOS CUMI-09111301 133.1 mCi