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Turkey-TITCK (Türkiye İlaçveTıbbiCihazKurumu)-Approval Processes for Biological Products

Regulatory Authority:

Turkish Medicines and Medical Devices Agency (TMMDA)

Link for Regulatory Authority:

https://www.titck.gov.tr/iletisim

Local Authorised:

Yes

Classification:

Novelty, Therapeutic Category, and Risk.

Registration Timeline:

30 to 60 months

Registration Fee:

  • Full MMA: TRY 100,000 – TRY 500,000 (approx. USD 5,000 – USD 25,000)
  • Conditional MMA: TRY 50,000 – TRY 250,000 (approx. USD 2,500 – USD 12,500)
  • Import Permit for Clinical Trials: TRY 10,000 – TRY 50,000 (approx. USD 500 – USD 2,500)

License Validity:

5 Years

These are the different types of documents required for the marketing authorization application of a biological drug in Turkey:

1. Administrative Documents:

  • Marketing Authorization Application Form: Provides basic information about the applicant, the biological drug, and the intended marketing authorization.
  • Cover Letter: A formal letter introducing the application and highlighting key points.
  • Payment Receipt: Proof of payment of the application fee.
  • Letter of Authorization/Authorized Representative Certificate (ARC): Needed for non-Turkish manufacturers, appointing a local authorized representative in Turkey.
  • Manufacturing Authorization: Confirms the manufacturing site complies with Good Manufacturing Practices (GMP) for biological products.

2. Quality Documents:

  • Drug Substance (DS) and Drug Product (DP) Specifications: Detailed descriptions of the characteristics of the drug substance and product.
  • Manufacturing and Packaging Process Descriptions: Documentation outlining the manufacturing and packaging processes.
  • Quality Control Data: Analyses conducted on the drug substance and product to ensure their quality and consistency.
  • Stability Data: Demonstrates the stability of the drug substance and product under various storage conditions.

3. Non-clinical and Clinical Data:

  • Non-clinical Study Reports: Studies conducted on animals to assess the safety and efficacy of the biological drug.
  • Clinical Study Reports: Trials conducted on human subjects to evaluate the safety, efficacy, and dosage of the biological drug.
  • Bioequivalence Data (if applicable): Demonstrates that the generic biological drug is comparable to the reference product.

4. Additional Documents:

  • Environmental Risk Assessment: Evaluation of the potential environmental impact of the biological drug and its manufacturing process.
  • Labelling and Package Information: Proposed labelling and packaging materials for the biological drug, complying with Turkish regulations.
  • Pharmacovigilance Plan: Outlines procedures for monitoring and reporting adverse events associated with the use of the biological drug.

Biological and Biotechnological Products Unit

  1. Correct Product Name and License Information:
    • Ensure that the product name in the cover letter, application form, and related documents matches the information stated in the license.
  2. Consistent Variation Application Type:
    • The variation application type must be consistent and mentioned both in the cover letter and the application form.
  3. Verification of Attachments:
    • Confirm that all attachments mentioned in the cover letter are uploaded to the Electronic Document Management System (EBYS).
  4. Response to Deficiency Letter:
    • Respond to deficiency letters issued by the institution via EBYS using the same tracking number.
  5. Same Date for Different Products:
    • Applications for different products with the same variation subject must be submitted on the same date.
  6. Focused Variation Information:
    • Submit only information and documents directly related to the variation as attachments in variation applications.
  7. Separate Fee for Group Variation:
    • For group variation, pay a separate accrual fee for each application, and clearly state each application separately in the cover letter.
  8. Adherence to Variation Guide:
    • Ensure compliance with the conditions outlined in the Guide on Variations in Licensed Medicinal Products for Human Use, especially regarding the “test method.”
  9. Product-Specific Information:
    • Include only information and findings related to the product in question, avoiding data from different products in the application file.
  10. Batch Size Information:
    • Submit batch size information for all batches produced since pharmaceutical development.
  11. Stability Studies for Special Conditions:
    • Provide stability studies for products with special storage conditions, including shelf life after reconstitution/dilution, alternative shelf life, and shelf life after opening.
  12. Submission of Stress Stability Studies:
    • Submit stress stability studies for products, such as photostability studies for light-sensitive products. Include results with acceptance criterion ranges for the relevant analysis.
  13. Quantitative Data Presentation:
    • Present results of studies in the file with specific quantitative data rather than using the generic term “appropriate.”
  14. Legible Presentation of Data:
    • Ensure that presented chromatograms, gel images, etc., are clear, legible, and selectable.
  15. Caution Regarding Biosimilar Comparison Studies:
    • Avoid using a reference standard instead of a reference medicinal product in biosimilar comparison studies.
  16. Extractable and Leachable Studies:
    • Conduct necessary studies on extractable and leachable substances and present the results.
  17. In Vitro Activity and Binding Studies:
    • In preclinical investigations, compare products in a sufficient number of series to demonstrate similarity in in vitro activity and binding studies.
  18. Detailed Patient Information in Clinical Studies:
    • Provide detailed information about the number of patients and patient exclusion criteria in clinical studies.
  19. Detailed Information on Batches Used in Clinical Studies:
    • Offer comprehensive information about the batches used in clinical studies, including serial numbers, production location, and the source of the active substance.
  20. Correct Animal Model in In Vivo Studies:
    • Ensure the correct choice of the animal model in in vivo studies.
  21. Summary Tables for Studies:
    • Include summary tables containing all preclinical and clinical studies at the beginning of the relevant module.
  22. Avoiding Use of Clinical Data to Justify Quality Differences:

Do not use clinical data to justify significant differences in quality characteristics. Provide independent justifications for quality differences.