The ANMAT regulations for registration of biological drug products are relatively new (October 2011) and are established in the Disposition 7075.
This regulation comprises the following drug products for human use, when industrially manufactured, or when some steps in their elaboration are industrial processes:
- Products obtained with recombinant DNA techniques
- Monoclonal antibodies
- Biological drugs produced from biologic fluids or animal tissues
- Other biologic products
The following products are excluded:
- Vaccines regulated by Disposición ANMAT 705/05, modifications y/o complementary regulations
- Products that don’t require registration, such as drugs for advanced therapies fully elaborated by an authorized specialized center, to be used in that center under authorized conditions
- Individualized alergenic vaccines
- Whole blood, plasma and human blood cells and its components.
To request marketing authorization for a biologic product, the information required has to be presented in a dossier with the information and format specified below, consisting of a general index, the registration form and five chapters: Administrative Information and Indications, Summary of Technical Chapters, Pharmaceutical and Biologic Information, Preclinical Information and Clinical Information. Note the high level of similarity with the CTD format.
For the case of biosimilar/biocomparable biologic drug products (generic) only the physicochemical, pharmaceutic and biologic information has to be provided, together with evidence supporting the biosimilarity, in terms of identity, strength and purity profile, and regarding the safety and efficacy. The product of reference has to be authorized and widely marketed in Argentina or in other country with similar regulatory and controlling functions. This case is regulated by Disposition 7729. (November 2011)
For the case of biological drug products obtained through processes of recombinant DNA, and for monoclonal antibodies, the complementary Disposition 3379 (June 2012) specifies additional information to include in the dossier, (in addition to the applicable to all biologic products) with focus on more detailed process description, process control, origin and production of raw materials, immunological processes and other relevant aspects.
For all biologic drug products
Fee: 10.000 ARS (Argentine pesos)
(Official) Timeline for approval: 180 working days
Content and format of information dossier:
A. GENERAL INDEX
A.1- CHAPTER l. ADMINISTRATIVE INFORMATION AND INDICATIONS
1. Solicitor information
1.3. Record number
1.4. Legal address
1.5. Technical responsible
1.6. Legal representative
2. Marketing authorization holder information
2.2. Legal address
3.Summary of product features and labeling information
3.1. Commercial name
3.2. List of APIs
3.3. Dosage form/s
3.4. Route of administration
3.5. Pharmacological classification
3.6. ATC code
3.7. Proposed indications
3.8. Strength, concentration or doses per unit.
3.9. Complete unitary formula (per dose, dosage unit or percentual) including excipients.
3.10. Origin of API/s
3.11. Summarized description of API source/s.
3.12. Presentations including primary and secondary packaging, both for final-user distribution and for hospital use.
3.13. Content per marketed unit.
3.14. Shelf life and storing conditions, for the original and the reconstituted product, when applicable. (temperature, humidity and light sensitivity)
3.15. Proposed marketing condition
3.17. Therapeutic action
3.18. Pharmacodynamic, pharmacokinetic and toxicologic properties.
3.21. Warnings and precautions
3.22. Use during pregnancy and lactation
3.23. Interactions and incompatibilities
3.24. Secondary effects
3.25. Intoxication: symptoms, urgency treatment and antidotes.
3.26. Preparation instructions
3.28. Primary packaging labeling
3.29. Secondary packaging labeling
3.30. Patient/doctor information leaflet
4. Manufacturer/s information
4.1. API manufacturer/s
4.2. Finished product manufacturer/s
4.3. Outsourced sites and activities in which they are involved
4.4. Other manufacturing sites
CHAPTER II. SUMMARY OF TECHNICAL CHAPTERS
1. Index of chapter
3. Quality summary
3.2. API summary
3.3. Finished product summary
4. Preclinical summary
5. Clinical summary
6.1. Description of installments and equipment involved in product manufacturing.
6.2 Safety assessment regarding external agents. Products containing human/animal material, or when human/animal material has been used during the manufacturing process: Transmisible Spongiform Encephalopathy risk assessment.
A.3. CHAPTER III. PHARMACEUTICAL AND BIOLOGIC INFORMATION
1. Index of chapter
2. Pharmaceutical development
4. Active Pharmaceutical Excipient (API)
4.1. General information
4.2. Description of manufacturing and packaging process
4.2.1. Manufacturing flux diagram indicating control process parameters, specifications and reference to analytical methods.
126.96.36.199. Raw materials
188.8.131.52. Proof of absence of external agents or ability to eliminate them during the manufacturing process
184.108.40.206. Reprocessing: acceptance and rejection criteria
220.127.116.11. Filling and closure process description for API
18.104.22.168. Filling and closure process description for intermediate products
22.214.171.124. Packaging processes
126.96.36.199. Processes for maintenance of cold chain
188.8.131.52. Proof of consistency in production
4.3. Quality specifications
4.3.1. Quality specifications for API
4.3.2. Characterization, physicochemistry, biochemistry and immunology of API.
4.3.3. Purity and impurities profile
4.3.4. Analytical methods: description, limits, acceptance rejection criteria, standards used and corresponding validation
4.3.5. Primary packaging quality specifications
4.3.6. Raw materials/excipients quality specifications
4.4. Stability studies
5. Finished product
5.1.1. Batch formula, including batch size
184.108.40.206. Manufacturing flux diagram
5. 1.2.2. Decription of the whole process, manufacturing methods and controls
220.127.116.11. Description of equipment, spaces and installations
18.104.22.168. For product in process: specifications, limits and description of analytical methods for each step of the manufacturing process
22.214.171.124. Filling and closure procedure for intermediate or finished product/s
126.96.36.199. Packaging procedure
188.8.131.52. Cold-chain-maintenance procedure
5. 1.2.8. Proof of absence of external agents or ability to eliminate them during the manufacturing process
184.108.40.206. Proof of production consistency
5.2. Control methods
5.2.1. Quality specifications for finished product
5.2.2. Quality specifications for excipients
5.2.3. Quality specifications for primary packaging
5.2.4. Reference materials
5.2.5. Stability studies
6. Reference materials
7. Stability studies
8. Validation of processes, reprocesses and non-codified
9.1. Descriptions of installations and equipment involved in manufacturing
9.2. Safety assessment regarding external agents. Products containing human/animal material, or when human/animal material has been used during the manufacturing process: Transmisible Spongiform Encephalopathy risk assessment.
9.3. Bibliographic references
A.4. CHAPTER IV. PRECLINICAL INFORMATION
1. Chapter index
2. Preclinical studies
3. Bibliographic references
A5. CHAPTER V- CLINICAL INFORMATION
l. Chapter index
2. Clinical studies
3. Post-marketing information
4. Published and unpublished studies
5. Bibliographic references
A.6. DOCUMENTS TO ATTACH
l. Receipt for fee payment
2. Copy of ANMAT authorization certificate/s for declared manufacturing and quality control site/s located in Argentina, of ownership of the solicitor
3. Copy of ANMAT authorization certificate/s for declared contract manufacturing and quality control site/s located in Argentina.
4. Copy of document enabling solicitor to representan of foreign company, if applicable.
5. Copy of contract manufacturing/quality control contracts, in agreement with GMP
6. GMP certificate issued by health authority of origin country for all manufacturing sites, own and contracted.
7. GMP certificate issued by ANMAT and corresponding supporting disposition.
8. Origin CPP, if the final product is already authorized for marketing.
9. List of countries where the finished product is registered and/or marketed.
10. Information on countries where the drug product is undergoing sanitary registration process, and on countries which have rejected the application for registration.
11. Proposed labeling texts
12 Proposed patient/doctor information leaflet texts
Last update: October 2013