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Biologics and Biosimilars Regulations and Registration in Australia (TGA)

The landscape of the Australian healthcare system has changed as a result of the availability of biologic and biosimilar medications.

The market for Australian biosimilars, which was anticipated to be worth $230 million in 2022, is expected to increase at a compound annual growth rate (CAGR) of 23.7% from 2022 to 2030 and will total $1263 million in 2030.

Human growth hormones, granulocyte colony-stimulating factors, insulins, erythropoietin, monoclonal antibodies, and tumor necrosis factor inhibitors are only a few of the biosimilars that have received TGA approval for usage in Australia.


This article outlines the Biologics and Biosimilars Regulations and Registration process in Australia (TGA)


In Australia, biologics and biosimilars are regulated by the Therapeutic Goods Administration (TGA), which is part of the Australian Government Department of Health. The TGA is responsible for assessing and regulating the safety, quality, and efficacy of therapeutic products, including biologics and biosimilars.

  1. Biologics Regulation: Biologics are complex medical products derived from living organisms, such as proteins, nucleic acids, and cells. They are used to treat various diseases and conditions, including cancer, autoimmune disorders, and genetic diseases. Biologics go through a rigorous regulatory process in Australia before they are approved for use.

  2. Biosimilars Regulation: Biosimilars are products that are highly similar to an already approved reference biologic product (originator) but are not identical due to the inherent variability of biological systems. The development of biosimilars involves demonstrating similarity in terms of quality, safety, and efficacy to the reference product.

Clinical Trial Requirements

  1. Clinical Trial Notification (CTN) Scheme: Under the CTN scheme, clinical trials involving biologics and biosimilars must be notified to the TGA before they commence. This involves submitting a Clinical Trial Notification Form to the TGA detailing information about the trial, including the investigational product, trial protocol, and ethics committee approval.

  2. Clinical Trial Exemption (CTX) Scheme: For some low-risk clinical trials, including early-phase trials, a Clinical Trial Exemption may be obtained. This allows trials to be conducted without prior TGA approval, but they must still adhere to certain regulatory requirements and ethical considerations.

  3. Ethics Committee Approval: Before commencing a clinical trial, researchers must obtain ethics committee approval from an accredited Human Research Ethics Committee (HREC). This approval ensures that the trial is conducted ethically and in compliance with relevant guidelines.

  4. Clinical Trial Conduct: Clinical trials for biologics and biosimilars must adhere to Good Clinical Practice (GCP) guidelines, which provide standards for the design, conduct, monitoring, and reporting of clinical trials. These guidelines ensure the safety, rights, and well-being of trial participants.

  5. Informed Consent: Participants in clinical trials must provide informed consent after receiving detailed information about the trial, its purpose, procedures, potential risks, and benefits. Informed consent is a crucial ethical requirement in clinical research.

  6. Quality and Safety: Trials involving biologics and biosimilars must demonstrate the quality, safety, and efficacy of the investigational product. This includes providing information about the manufacturing process, quality control, and stability of the product.

  7. Comparability Studies for Biosimilars: Trials for biosimilars often involve comparability studies to establish the similarity of the biosimilar to the reference product. These studies assess various aspects, including physicochemical characteristics, biological activity, and clinical performance.

  8. Safety Reporting: During the trial, adverse events and safety concerns must be promptly reported to both the ethics committee and the TGA, as per regulatory requirements.

  9. Post-Trial Responsibilities: After the trial is completed, researchers must provide a summary of the trial results to the ethics committee and, in some cases, to the TGA. This contributes to the transparency and dissemination of clinical trial data.

Important Documents

Quality Information:

  • Chemistry, Manufacturing, and Controls (CMC) Data: Detailed information about the manufacturing processes, analytical methods, and quality control procedures for the biologic or biosimilar.

  • Specifications: Specifications for the product's identity, strength, purity, and quality.

  • Stability Data: Data demonstrating the stability of the product under various conditions over its shelf life.

  • Comparability Studies: For biosimilars, data comparing the quality attributes and characteristics of the biosimilar to the reference product.

Non-Clinical Data:

  • Pharmacology and Toxicology Studies: Data from non-clinical studies that demonstrate the pharmacological activity and safety profile of the product.

Clinical Data:

  • Clinical Trial Protocols: Detailed protocols outlining the design, objectives, methodology, and endpoints of the clinical trials.

  • Clinical Study Reports: Comprehensive reports summarizing the results of clinical trials, including safety and efficacy data.

  • Immunogenicity Assessment: Information about the potential immunogenicity of the biologic or biosimilar, including data on anti-drug antibodies and their impact.

Comparability Studies (for Biosimilars):

  • Comparative Analytical Data: Detailed data comparing the biosimilar to the reference product in terms of physicochemical characteristics, biological activity, and other relevant attributes.

  • Immunogenicity Data: Data on the potential to induce an immune response and its clinical implications.

Risk Management Plan:

  • Risk Evaluation and Mitigation Strategy (REMS): A plan outlining how risks associated with the biologic or biosimilar will be managed during its use in clinical practice, including strategies for minimizing potential safety concerns.

Labeling and Product Information:

  • Product Information (PI): Comprehensive information about the product's indications, dosing, administration, contraindications, warnings, and precautions.

  • Package Insert: The package insert that accompanies the product, providing essential information for healthcare professionals and patients.

Summary of Product Characteristics (SmPC):

  • SmPC: A document that provides concise and standardized information about the product's characteristics, indications, dosage, administration, contraindications, warnings, and other key details.

Post-Marketing Data and Commitments:

  • Post-Marketing Surveillance Plan: Plans for monitoring the product's safety and efficacy in real-world use.

  • Post-Marketing Commitments: Any commitments made by the manufacturer to conduct additional studies or provide further data after the product is approved.

Approval Process

Pre-submission Activities:

  • Preparation: Manufacturers gather all necessary data, documents, and evidence related to the quality, safety, and efficacy of the biologic or biosimilar.

  • Regulatory Strategy: Develop a regulatory strategy that outlines the approach for seeking approval and addresses potential challenges or questions.

Submission to the TGA:

  • Application: Manufacturers submit a comprehensive application package to the TGA, including data on quality, non-clinical studies, clinical trial results, risk management plans, labeling, and more.

  • Validation: TGA reviews the submitted package for completeness and validity. If the application is deemed valid, the evaluation process begins.

TGA Review and Assessment:

  • Quality Review: TGA assesses the manufacturing processes, quality control, and analytical methods used for the biologic or biosimilar.

  • Non-Clinical and Clinical Review: TGA reviews the non-clinical data (pharmacology and toxicology) and clinical trial data to evaluate the safety, efficacy, and potential benefits and risks of the product.

  • Comparability (for Biosimilars): For biosimilars, TGA assesses comparative analytical data and other relevant data to establish similarity to the reference product.

Advisory Committees (if applicable):

  • ACBS or PBAC Review (For Reimbursement): If the product will be covered by government reimbursement schemes, such as the Pharmaceutical Benefits Scheme (PBS), it may undergo review by the Australian Community Pharmacy Authority (ACBS) or the Pharmaceutical Benefits Advisory Committee (PBAC) for pricing and reimbursement decisions.

Decision and Approval:

  • Recommendation: Based on the review and assessment, the TGA makes a recommendation on whether the product should be approved.

  • Delegate's Decision: The TGA delegate reviews the recommendation and makes a final decision on the approval of the biologic or biosimilar.

Applicable charges:

Application and evaluation fees for the biologics and biosimilars are approximately $20,939 and $83,110 respectively.

Timelines: After an application is accepted, the TGA expects to finish the application examination in 255 working days.


Post Marketing Surveillance

Monitoring Adverse Events:

  • Healthcare professionals, patients, and consumers report adverse events, side effects, and unexpected reactions related to biologics and biosimilars to regulatory authorities, such as the Therapeutic Goods Administration (TGA) in Australia.

  • Manufacturers are also required to report any adverse events they become aware of to the regulatory authority.

Signal Detection:

  • Regulatory authorities analyze the collected data to identify potential safety signals. A signal is an indication of a potential safety issue that may require further investigation.

Assessment and Investigation:

  • If a safety signal is identified, regulatory authorities conduct thorough assessments to understand the nature and significance of the signal.

  • This may involve reviewing available data, conducting epidemiological studies, and collaborating with healthcare professionals, manufacturers, and other stakeholders.

Risk Assessment and Management:

  • The regulatory authority assesses the risk-benefit profile of the product in light of the new information.

  • If necessary, regulatory actions may be taken, such as updating product labels with new safety information, issuing warnings, requiring additional studies, or even removing the product from the market if the risks outweigh the benefits.

Communication:

  • Regulatory authorities communicate safety findings and recommendations to healthcare professionals, patients, and the public through official announcements, safety alerts, and other communication channels.

  • Manufacturers may also communicate updates and safety information to healthcare professionals and patients.

Ongoing Monitoring:

  • Post-marketing surveillance is an ongoing process that continues throughout the product's lifecycle.

  • Long-term monitoring helps ensure that any emerging safety concerns are promptly identified and managed.

Collaboration:

  • Regulatory authorities collaborate with international partners and regulatory agencies to share safety information and benefit from global pharmacovigilance efforts.

Reporting and Transparency:

  • Regulatory authorities maintain transparency by making safety information available to the public and healthcare professionals through public databases and reports.

References:


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