High Pressure Liquid IAEA Specification

Chromatography System
Project: BUL6013 Dated 8 Dec 2016

TECHNICAL SPECIFICATIONS

High Pressure Liquid Chromatography (HPLC) System

1. Scope
This specification describes the requirements for a High Pressure Liquid
Chromatography System - HPLC system (hereinafter referred to as the “System”) for
Quality Control (QC) of radiolabelled compounds, to be installed at the Department of
Nuclear Medicine, University Hospital Alexandrovska; Medical University, ul.Zdrave 2,
Sofia 1431, Bulgaria (hereinafter referred to as the “End-User”).
68 177
The System shall be used for: QC procedures of labelled Ga and Lu imaging
molecules, including:

i. Validation upon acceptance of new Ge68/Ga68 generator

ii. Validation of Ga-labelled radiopharmaceuticals – radiochemical purity
iii. Validation of modified synthesis and QC procedures

Additional purposes include:

i. Prompt analysis of F-18-FDG
ii. Validation of research and development labelling and QC procedures

2. References, Definitions, Acronyms, and Abbreviations

The following References, Definitions, Acronyms, and Abbreviations shall apply

throughout this Specification.

i. Monographs of the European Pharmacopeia (Current version)

ii. OECD Good Laboratory Practice (GLP) compliance manual
iii. F-18-FDG: fluoro-2-deoxy-d-glucose labelled with F-18

In the event of conflict between the documents listed above and the content of this
specification, the contents of the specification shall prevail.

3. Requirements.
The System shall meet following functional and performance specifications:
i. High speed injection for large number of samples;
ii. Full automation;
iii. Self-diagnostics;
iv. EU Good Manufacturing Practices (GMP) compliant.

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 High Pressure Liquid IAEA Specification
Chromatography System
Project: BUL6013 Dated 8 Dec 2016

4. Technical Requirements:

4.1. Quaternary pump

i. Maximum pressure 600 bar;
ii. Flow range 0.2 – 10 ml/min;
iii. Adjustable flow range with 0.001ml increment.

4.2. Degassing unit:

i. 3 or 4 channel built-in unit;
ii. Shall include connecting capillaries, solvent mounting cabinet, CAN cable.

4.3. Starter kit:

The System shall include a starter kit with solvent bottles, Rheotool, tubing
cutter, cybertool for adjustment and use of 3-4.6mm columns.

4.4. Manual injector:

The System shall include manual injector (600bar valve, 10 or 20 μL sample
loop).

4.5. HPLC Column switch:

The System shall include HPLC column switch for up to 6 columns.

4.6. Detector(s) specifications:

i. Variable Wavelength Detector with fast and programmable single wavelength
analysis up to 80Hz data rate;
ii. Wavelength range: 190 – 600 nm;
iii. Must include RFID tracking technology for UV lamp and flow cells.

4.7. Flow cells:

i. Must include flow cell(s) for 68Ga and 177Lu – at least 10mm path length;
ii. 14 μL volume;
iii. pressure tight to 40bar.

4.8. Gama flow-monitor and associated software requirements:

i. 2x2’’ NaI (Tl) pin hole detector;
ii. 50mm shielding for the scintillation detector included;
iii. Suitable flow cell for NaI(Tl) detector with 5 and 250 μL volumes;
iv. Single event counting (SEC) strategy with at least 2 UV and 2 Radioactivity
channels;
v. Automatic data recording storage;
vi. Automatic and manual range selection;
vii. Selectable smoothing;
viii. On-line (and off-line) half-time correction;
ix. External standardization / internal standardization;
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 High Pressure Liquid IAEA Specification
Chromatography System
Project: BUL6013 Dated 8 Dec 2016

x. Peak detection and manipulation:

xi. Automatic peak and baseline detection;
xii. Automatic report generation and printing;
xiii. Method file ‘wizard’ or development tool;
xiv. USB and RS232 connecting ports.

4.9. PC and software controls:

i. PC (desktop or laptop) with RS 232 connecting port and Windows 7 (at least)
professional with monitor, printer and HPLC software pre-installed;
ii. Software control for:
- HPLC pump and gradient control;
- Binary or quaternary gradient control;
- Flow gradient programmable;
- Non-linear gradients supported;
- Compressibility correction of mobile phase(s);
- UV detector control.

4.10. The HPLC kit shall include:

i. At least four (4) C18 columns (for example Gemini 5µ C18, 50/100 × 21 mm);
ii. RHM column: 50/100 × 46mm;
iii. Luer adapters and locks included;

5. Consumables

The Contractor shall provide also:

5.1. Two (2) complete sets of PEEK (due to rad. stability) vials, sample loops, fittings,
nuts, waste and lab bottles/ vials;
5.2. Three (3) sets of 5, 10, 20, and 25 ml PEEK volumetric flasks;
5.3. TFA (trifluoroacetic acid) – HPLC grade solution, 2,5 L for two (2) consecutive years;
5.4. Acetonitrile and Water –HPLC grade solutions, 10 L each, for two (2) consecutive
years.
5.5. Two (2) sets of standards (freeze) for QC validation of Ga-DOTA-TOC and Ga -
PMSA, according Eu.Ph. monographs.

6. Marking:
The System shall have all safety markings in English language.

7. Packing.
The System shall be packed in accordance with international standards that are
applicable for the shipment by air for this kind of equipment.

8. Quality requirements:
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 High Pressure Liquid IAEA Specification
Chromatography System
Project: BUL6013 Dated 8 Dec 2016

8.1. The System shall be manufactured, shipped and installed in accordance with the ISO
quality assurance system or an equivalent quality assurance system;
8.2. The Contractor shall document the compliance with the quality assurance system.

9. Testing and Acceptance.

9.1. The System, prior to shipment, shall be tested for conformance of the System with
manufacturer’s performance specifications and the minimum requirements specified
herein. Conformance certificate or statement shall be supplied prior to on site
validation.
9.2. The System, after installation, shall be tested by the Contractor together with the End-
User representatives (on site) to demonstrate that the performance meets the
manufacturer’s performance specifications and the minimum requirements specified
herein as determined by the IAEA and the End-User.
9.3. The results of the testing of the System shall be documented by the Contractor in an
acceptance protocol that shall be signed by the End-User representative.

10. Installation and Training.

10.1. The Contractor shall install the System at the End-User facility;
10.2. The Contractor shall provide minimum five (5) days operation and safety training to
up to three (3) End-User staff members.

11. Documentation:
11.1 The Contractor shall provide two (2) complete sets of operation and servicing
manuals and technical drawings in English.
11.2 Certificate or statement of conformance (ref. section 9.1 above);
11.3 A Final Acceptance Protocol (ref. section 9.3 above).