Summary Basis of Decision for Galli Eo

Review decision

The Summary Basis of Decision explains why the product was approved for sale in Canada. The document includes regulatory, safety, effectiveness and quality (in terms of chemistry and manufacturing) considerations.

Product type:

Drug

Contact: Office of Regulatory Affairs, Biologic and Radiopharmaceutical Drugs Directorate (ORA-BRDD)

Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product. The SBD for Galli Eo is located below.

Recent Activity for Galli Eo

SBDs written for eligible drugs approved after September 1, 2012 will be updated to include post-authorization information. This information will be compiled in a Post-Authorization Activity Table (PAAT). The PAAT will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decisions were negative or positive. PAATs will be updated regularly with post-authorization activity throughout the product's life cycle.

Post-Authorization Activity Table (PAAT) for Galli Eo

Updated:

2022-11-04

The following table describes post-authorization activity for Galli Eo, a product which contains the medicinal ingredient gallium ⁶⁸Ga chloride. For more information on the type of information found in PAATs, please refer to the Frequently Asked Questions: Summary Basis of Decision (SBD) Project: Phase II and to the list of abbreviations that are found in PAATs.

For additional information about the drug submission process, refer to the Management of Drug Submissions and Applications Guidance.

Drug Identification Number (DIN):

DIN 02492806 – 1.85 GBq, gallium ⁶⁸Ga chloride, solution

Post-Authorization Activity Table (PAAT)

Activity/submission type, control number	Date submitted	Decision and date	Summary of activities
Drug product (DIN 02492806) market notification	Not applicable	Date of first sale: 2020-07-29	The manufacturer notified Health Canada of the date of first sale pursuant to C.01.014.3 of the Food and Drug Regulations.
NDS # 221824	2018-12-05	Issued NOC 2019-11-13	NOC issued for New Drug Submission.

Summary Basis of Decision (SBD) for Galli Eo

Date SBD issued: 2020-03-09

The following information relates to the new drug submission for Galli Eo.

Gallium ⁶⁸Ga chloride generator

Drug Identification Number (DIN):

DIN 02492806 - 1.85 GBq, solution

IRE ELiT S.A.

New Drug Submission Control Number: 221824

On November 13, 2019, Health Canada issued a Notice of Compliance to IRE ELiT S.A. for the diagnostic radiopharmaceutical Galli Eo.

The market authorization was based on quality (chemistry and manufacturing) information submitted. Based on Health Canada's review, the gallium (⁶⁸Ga) chloride eluate produced by the Galli Eo generator is considered to be acceptable for use in the in vitro radiolabelling of radiopharmaceutical ligands for diagnostic procedures using positron emission tomography (PET). The gallium (⁶⁸Ga) chloride eluate is not intended for direct administration to patients.

1 What was approved?

Galli Eo, a radionuclide generator, produces gallium (⁶⁸Ga) chloride eluate which is authorized for the in vitro radiolabelling of radiopharmaceutical ligands for diagnostic procedures using positron emission tomography (PET). The gallium (⁶⁸Ga) chloride eluate is not intended for direct administration to patients.

There are no known contraindications for Galli Eo.

Galli Eo was approved for use under the conditions stated in its Product Monograph taking into consideration the potential risks associated with the use of this product.

Galli Eo (available in activities of 0.74 GBq, 1.11 GBq, 1.48 GBq, and 1.85 GBq gallium [⁶⁸Ga] chloride, drug not to be administered directly) is a generator which produces a gallium (⁶⁸Ga) chloride eluate. The Galli Eo generator features a titanium dioxide column and an integrated 0.1M hydrochloric acid eluent. The column is enclosed in a tungsten radiation shield, which is covered by a lead radiation shield. The shielded column and the eluent bag are contained in a plastic case. A set of five sterile evacuated vials, five needles, and five Luer-lock tubings and connectors is also supplied with the Galli Eo generator.

For more information, refer to the Quality (Chemistry and Manufacturing), Non-clinical, and Clinical Basis for Decision sections.

Additional information may be found in the Galli Eo Product Monograph, approved by Health Canada and available through the Drug Product Database.

2 Why was Galli Eo approved?

Health Canada considers that the gallium (⁶⁸Ga) chloride eluate produced by the Galli Eo generator is acceptable for use in the in vitro radiolabelling of radiopharmaceutical ligands for diagnostic procedures using positron emission tomography (PET).

Positron emission tomography is a nuclear imaging tool used to observe the metabolic function of various organs and tissues, enabling the diagnosis and evaluation of a wide range of diseases. Imaging is possible through the detection of signals emitted by a radiopharmaceutical introduced into the patient's body, which consists of a ligand labelled with a radioactive isotope. Radiopharmaceutical development often exploits the tendency of a particular element or its ligand to accumulate in regions with high metabolic or chemical activity, which often correspond to diseased areas of the body.

Galli Eo is a radionuclide generator in which the radioactive gallium 68 isotope (⁶⁸Ga) is generated from the decaying radioactive germanium 68 (⁶⁸Ge) isotope. The gallium (⁶⁸Ga) chloride eluate produced in the generator may be used for in vitro radiolabelling. The resulting ⁶⁸Ga labelled ligand is a radiopharmaceutical, and may be used for diagnostic imaging in a PET scan.

The gallium (⁶⁸Ga) chloride eluate produced in the Galli Eo generator is not intended for direct administration to patients. Due to the nature of the product, the gallium (⁶⁸Ga) chloride eluate does not have a stand alone clinical indication. Therefore, clinical and non clinical data were not expected. Only quality data were submitted and reviewed.

The risk of chemical toxicity is considered negligible. The dose of ⁶⁸Ga that would be administered as a ⁶⁸Ga labelled ligand is in the nanogram range and would be devoid of any pharmacological or toxicological activity. However, the use of any radiopharmaceutical carries the inherent risk of exposure to radiation. The Serious Warnings and Precautions box in the Galli Eo Product Monograph therefore includes an instruction that radiopharmaceuticals should only be handled by healthcare professionals with the appropriate training.

A Risk Management Plan (RMP) was not required or provided for this submission, as Galli Eo does not have a clinical indication. Additionally, the gallium (⁶⁸Ga) chloride eluate produced by the generator is not intended for direct administration to patients.

The submitted labels meet the necessary regulatory labelling, plain language and design element requirements.

Galli Eo is considered acceptable for its intended use based on the quality data reviewed. Appropriate warnings and precautions are in place in the Galli Eo Product Monograph to ensure safe use of the product.

This New Drug Submission complies with the requirements of section C.08.002 and therefore Health Canada has granted the Notice of Compliance pursuant to section C.08.004 of the Food and Drug Regulations. For more information, refer to the Quality (Chemistry and Manufacturing), Non-clinical, and Clinical Basis for Decision sections.

3 What steps led to the approval of Galli Eo?

Submission Milestones: Galli Eo

Submission Milestone	Date
Submission filed:	2018-11-12
Screening
Screening Deficiency Notice issued:	2019-02-07
Response filed:	2019-03-19
Screening Acceptance Letter issued:	2019-04-15
Review
Labelling Review complete:	2019-09-16
Quality Evaluation complete:	2019-09-19
Clinical/Medical Evaluation complete:	2019-10-07
Notice of Compliance issued by Director General, Biologics and Genetic Therapies Directorate:	2019-11-13

For additional information about the drug submission process, refer to the Management of Drug Submissions Guidance.

4 What follow-up measures will the company take?

Requirements for post-market commitments are outlined in the Food and Drugs Act and Regulations.

5 What post-authorization activity has taken place for Galli Eo?

Summary Basis of Decision documents (SBDs) for eligible drugs authorized after September 1, 2012 will include post-authorization information in a table format. The Post-Authorization Activity Table (PAAT) will include brief summaries of activities such as submissions for new uses of the product, and whether Health Canada's decisions were negative or positive. The PAAT will continue to be updated during the product's life cycle.

The PAAT for Galli Eo is found above.

For the latest advisories, warnings and recalls for marketed products, see MedEffect Canada.

6 What other information is available about drugs?

Up to date information on drug products can be found at the following links:

See MedEffect Canada for the latest advisories, warnings and recalls for marketed products.
See the Notice of Compliance (NOC) Database for a listing of the authorization dates for all drugs that have been issued an NOC since 1994.
See the Drug Product Database (DPD) for the most recent Product Monograph. The DPD contains product-specific information on drugs that have been approved for use in Canada.
See the Notice of Compliance with Conditions (NOC/c)-related documents for the latest fact sheets and notices for products which were issued an NOC under the Notice of Compliance with Conditions (NOC/c) Guidance Document, if applicable. Clicking on a product name links to (as applicable) the Fact Sheet, Qualifying Notice, and Dear Health Care Professional Letter.
See the Patent Register for patents associated with medicinal ingredients, if applicable.
See the Register of Innovative Drugs for a list of drugs that are eligible for data protection under C.08.004.1 of the Food and Drug Regulations, if applicable.

7 What was the scientific rationale for Health Canada's decision?

7.1 Quality Basis for Decision

Characterization of the Drug Substance

The germanium 68 (⁶⁸Ge) active pharmaceutical ingredient (API) is considered to be the drug substance, as it decays in the generator to produce the gallium 68 (⁶⁸Ga) radioisotope. Analytical methods used to evaluate the specific activity, identity, radionuclidic purity and chemical purity of the ⁶⁸Ge API were all validated. The batch analysis data reflected consistency in the manufacturing process, and demonstrated that the ⁶⁸Ge API met pre established specifications listed in a European Pharmacopeia monograph.

Manufacturing Process and Process Controls of the Drug Substance and Drug Product

Drug Substance: ⁶⁸Ge active pharmaceutical ingredient

The ⁶⁸Ge API is considered to be the drug substance. In the Galli Eo generator, it decays and becomes the ⁶⁸Ga radioisotope, which is found in the eluate.

Manufacturing of the ⁶⁸Ge API begins with the production of a ⁶⁸Ge solution intermediate using a cyclotron, in which the target consists of a gallium/nickel alloy. The target body of the cyclotron is irradiated through proton bombardment, and then left to rest for a period of time to allow unwanted, short lived isotopes to decay. The target body is then stripped using an acidic mixture, and the ⁶⁸Ge intermediate is extracted from the stripped solution.

To produce the ⁶⁸Ge API, the ⁶⁸Ge solution intermediate is diluted and then purified to eliminate various metallic and radioactive impurities.

Drug Product: Galli Eo generator

The radionuclide generator, Galli Eo, is considered to be the drug product. It consists of a titanium dioxide column and an integrated 0.1M hydrochloric acid eluent.

The titanium dioxide column is prepared, sealed, and sterilized. It is then placed into a tungsten radiation shield and packed in an additional lead radiation shield in an aseptic production cell. Other components of the container closure system are also assembled in the aseptic production shell. The generator is then packed in a resin shell and labelled.

To prepare the hydrochloric acid eluent (0.1M), hydrochloric acid is combined with water for injection to reach the targeted concentration. The solution then undergoes sterile filtration and is transferred aseptically into polyethylene bags to be included in the generator.

The stability data provided were acceptable.

Control of the Drug Substance and Drug Product

The control strategies for the ⁶⁸Ge intermediate, the ⁶⁸Ge API, the Galli Eo generator, and the hydrochloric acid eluent component of the generator were all reviewed and validated. Each of these met the relevant acceptance criteria for in process controls and release testing. Batch analysis data were reviewed, and demonstrated consistency and reproducibility with respect to the established manufacturing processes and controls.

Stability of the Drug Substance and Drug Product

Stability testing of the ⁶⁸Ge intermediate included assessments of radionuclidic purity, metallic impurities, radiochemical concentration, and specific activity. Stability data indicate that the intermediate solution is stable for 12 months. The ⁶⁸Ge API, which is produced from the intermediate, must be used within three days of manufacturing.

Stability testing of the Galli Eo generator included assessments of chemical and radionuclidic purity, elution yield, and sterility of the eluate. A shelf life of 53 weeks from the calibration date was determined to be acceptable based on the stability data reviewed.

The generator must be stored upright, at a temperature at or below 25°C. The eluate produced from the generator should be used immediately after elution. Once expired, the residual activity of the generator must be estimated and the generator must be returned to the sponsor.

Facilities and Equipment

A Good Manufacturing Practices (GMP) certificate was granted by the European Medicines Agency (EMA) to the facility responsible for manufacturing and testing of the ⁶⁸Ge API and the assembly of the generator.

Adventitious Agents Safety Evaluation

The Galli Eo generator met specifications for sterility and bacterial endotoxin levels defined in a European Pharmacopeia monograph. The antimicrobial activity of the titanium dioxide column and the ability of the container closure system to maintain sterility of the eluate were also confirmed.

None of the components of the drug substance or drug product are of human or animal origin.

7.2 Non-Clinical Basis for Decision

The gallium (⁶⁸Ga) chloride eluate produced in the Galli Eo generator is not intended for direct administration to patients, and the generator does not have a clinical indication. Non clinical data were therefore not expected or submitted.

For more information, refer to the Galli Eo Product Monograph, approved by Health Canada and available through the Drug Product Database.

7.3 Clinical basis for decision

The gallium (⁶⁸Ga) chloride eluate produced in the Galli Eo generator is intended for use in the preparation of kit-based radiopharmaceuticals for diagnostic imaging using positron emission tomography (PET), and is not for direct administration to patients. Therefore, clinical data were not expected or submitted. The Galli Eo Product Monograph contains sufficient information to ensure proper preparation of a ⁶⁸Ga labelled radiopharmaceutical and to mitigate any risk of unintentional direct exposure to gallium (⁶⁸Ga) chloride eluate to patients. The safety and efficacy of ⁶⁸Ga labelled radiopharmaceuticals are to be established under separate market authorization applications.

Clinical Safety

The risk of chemical toxicity is considered negligible. The dose of ⁶⁸Ga that would be administered as a ⁶⁸Ga labelled ligand is in the nanogram range and would be devoid of any pharmacological or toxicological activity. Additionally, the lower radiation risk of ⁶⁸Ga relative to gallium (67Ga) citrate, an approved radiopharmaceutical, is well documented.

However, the use of any radiopharmaceutical carries the inherent risk of exposure to radiation. The Serious Warnings and Precautions box in the Galli Eo Product Monograph therefore includes an instruction that radiopharmaceuticals should only be handled by healthcare professionals with the appropriate training.