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REGISTRATION FORM FOR SUBUNIT IMMUNOGENS OBTAINED THROUGH BIOTECHNOLOGICAL PROCESSES

CAMEVET

Code: 

PROCEDURE

Effective date

REGISTRATIONOF VETERINARY PRODUCTS

 REGISTRATIONFORM FOR SUBUNIT IMMUNOGENS OBTAINED THROUGH BIOTECHNOLOGICAL PROCESSES

 

INTRODUCTION:

Subunit vaccines composed of semi-pure or purified proteins have been commercially available since the early1980s, with subunit components produced by recombinant DNA technology available since the 1990s (Cohen,1993; Rhodes et al., 1994; Ulmer et al., 1993; 1995). The latter have attracted growing interest and activity since that time. Subunit vaccines do not include live recombinant vector technologies, which provide the delivery ofrecombinant proteins in vivo. The field of genomics and related areas has revolutionized the manner in whichmicrobial antigens are identified. Since the first bacterial genome was sequenced in 1995, there has been a hugeincrease in the number of bacterial, viral, and parasite genomes for which genome sequences are available.

Indeed, virtually all pathogens of animals are represented and those pathogens that are not can readily beobtained in less than a day. More importantly, the development of the bioinformatics resources and tools that arerequired to analyze these genomes has proceeded in parallel and it is now relatively easy to identify surfaceexposedantigens, specific B- and T-cell epitopes, etc. There is no requirement to have the ability to grow theorganism in culture.

The production of subunit antigens can be achieved by both conventional biochemical or recombinant DNAtechnologies. The latter involves a range of prokaryotic and eukaryotic expression systems including yeast, insectcell and plants (Chichester&Yusibov, 2007) by means of a variety of integrated or transient expressionstrategies. Biochemical techniques remain useful in some cases where recombinant expression is not appropriate,such as antigens requiring complex assembly (e.g. fimbriae), or when post-translational modification is necessary.

Subunit vaccines could have some advantages over live attenuated and inactivated vaccines, including the abilityto induce strong humoral and cell-mediated immune response. The vaccines furthermore have an excellent safetyprofile, and can be used in combination with other subunit vaccines.One of the biggest advantages of subunit vaccines is that they are generally compatible with DIVA(Differentiating Infected from Vaccinated Animals) strategies aslong as the antigen is not being used as a marker.

The current guideline aims at enabling the registration process of subunit immunogens, obtained through biotechnological processes, for CAMEVET countries.

 

REGISTRATION FORM FOR SUBUNIT IMMUNOGENS OBTAINED THROUGHBIOTECHNOLOGICAL PROCESSES

DATE:

1. - PRODUCT COMMERCIAL NAME  

2. – CLASSIFICATION - GENERIC NAME(Exclusive official use)

3.-APPLICANT BUSINESS ESTABLISHMENT: PROPRIETOR/ LEGAL REPRESENTATIVE

3.1.Name: 

3.2. Commercial domicile(Street – City– Country): 

3.3. Official filling out authorization Nº:

3.4. Technical person in charge: 

3.4.1 Profession: 

3.4.2 Professional identification Nº (Registration number or Record):

4. – MANUFACTURING ESTABLISHMENT(for products processed in the country)

4.1 Name: 

4.2 Commercial domicile(Street – City – Country):

4.3 Officialfilling out authorizationNº:

4.4 Technical person in charge: 

4.4.1 Profession: 

4.4.2 Professional identification Nº (Registration number or Record):

In case several manufacturers are involved in the manufacture of the immunogen, all of themshall be listedwith the same piece of information and the main manufacturer shall be declared.(defined by the contract between the manufacturers or the holder who submit the product for registration).     

5. - ORIGINMANUFACTURING ESTABLISHMENT (for importedproducts)

5.1 Name:

5.2 Commercial domicile(Street – City – Country):  

5.3 Official filling out authorization Nº:

5.4 Technical person in charge: 

5.4.1 Profession: 

5.4.2 Professional identification Nº (Registration number or Record):

In case several manufacturers are involved in the manufacture of the immunogen, all of themshall be listedwith the same piece of information and the main manufacturer shall be declared.(defined by the contract between the manufacturers or the holder who submit the product for registration).   

6.-LEGAL DOCUMENTS

6.1 Manufacture Agreement/s.

6.2 Manufacturer Representation Agreement in origin.

6.3 Certificate of Authorization of the Manufacturing Establishment.

6.3.1. Habilitation Certificates from other manufacturers of the product (where applicable). 

6.4  For imported products: Certificate of Registration and Free Sale (CAMEVET form) or equivalent documentation, sent by the authorities in the country of origin or in their default Manufacture Authorization (Export Certificate)and explanation of the reasons why it is not commercialized in that country.

6.5 Trademark Registration Certificate in the country of origin for products that are not generic or common international denomination. (In accordance to the regulations established in each country)

7. - BIOLOGICAL LINE DEFINITION

7.1 Chemical and/or biological designationof the active principles.

8. –PHARMACEUTICAL FORM

9.-QUALITATIVE-QUANTITATIVE FORMULA - BIOLOGICAL AND CHEMICAL CONSTITUTION

9.1 Formula of representative batch by dose: Active Pharmaceutical Ingredient (s), adjuvants,excipients, diluents, others.

10. –SPECIFICATIONS AND CONTROL METHODS OF THE COMPONENTS OF THE FORMULA

10.1Active principle.

10.1.1 General information.

10.1.1.1 Physical form.

10.1.1.2 Structural formula. (Sequence)

Inclusion in the case of proteins theconformationalstructure data.

10.1.1. 3Relative molecular mass.

10.1.1.4 pH.

10.1.1.5Structural evidences of the active ingredient.

Include comparison data with the natural or reference form whenever possible.

10.1.1.6Biological, immunologic, and physical - chemical characterization.

10.1.1.7Expression of the potency or Biological Activity.

In case the potency is shown in units, the unit shall be defined.

10.1.2 Genetic development.

10.1.2.1 Gene of interest: Name, origin, strategy of isolation, construction, sequence,rationality for the selection of the gene.

10.1.2.2 Description of the origin strain or cellular line: Name, origin, history,

Identification characteristics andextraneous agents testing

10.1.2.2.1Preparation of the production strain (or cellular line).

10.1.2.2.2Construction of the expression vector: Name and origin.

10.1.2.2.3Description of the production strain and/or cellular line.

Biological properties of the elements found in the final formulation.

10.1.2.2.4 Genetic stability during the storage and conservation and during production.

10.1.3Cell Bank Systems.

10.1.3.1Preparation and description of the Master Cell Bank (MCB).

Identification of the MCB. Indicate details of the number of vials, volume and estimated duration of the MCB, as well as storage conditions.

10.1.3.2 Preparation of the subsequent Work Cell Bank (WCB) from the MCB (Acceptance criteria).

Identification of the WCB. Indicate details of the number of vials, volume and estimated duration of the WCB, as well as storage conditions.

10.1.3.3 Routine control methods of the MCB and of the WCB.

Tests carried out for the quality control of the cell banks. Expected results. Frequencyof testing.Justification of the quality control methods in the case of mammalian cells.

11.  METHODS OF PRODUCT MANUFACTURE

11.1 Active principle(s).

11.1.1 Description of the process of obtaining of the active principle(s), Fermentation and harvest (expression in bacteria, yeasts) culture cells, animals or plants asbioreactors.

11.1.1.1 Name of the production site(s). Refer to all the sites where all active ingredients are produced. 

11.1.1.2Definition of the production batch. (Include details of the production scale: minimum volume, maximum volume, average volume)

11.1.1.3 Flowchart. (Process description)

11.1.1.4 Storage and conservation of the intermediate harvests.

11.1.1.5 Process controls including the acceptance criteria of every harvest.

11.1.2 Purification.

11.1.2.1 Name of the site(s) of purification.

11.1.2.2 Definition of a batch (Include details of the production scale: minimum volume, maximum volume, average volume).

11.1.2.3 Flowchart.

11.1.2.4 Storage of the intermediate products.

Conditions and duration.

11.1.2.5 Process controls. 

11.1.2.6 Reprocessing criteria.

 (Reprocessing criteria of every purification step)

11.1.2.7Control of the materials used in the process.

11.1.2.8 Control of the critical points and intermediate products.

11.1.3 Impurities and/or contaminants.

11.1.3.1 Detection andidentificationof impurities (Quality control methods, quantification and specification limit).

11.1.3.2 Other considerations (Inactivation methods and determination ofnonviability).

11.1.4 Quality Controlsof the Active Principle.

11.1.4.1 Specification.

11.1.4.2 Analytical procedures.

11.1.4.2.1 Validation of the analytical procedures.

11.1.4 3 Analyses of the batches. Production consistency.

11.1.4.4 Reference Materials.

11.1.4.4.1 Primary Reference Material.

11.1.4.4.2 Working Reference Materials.

11.1.5 Characteristics of thepacking materials.

11.1.6 Stability.

11.1.6.1 Accelerated stability studies.

11.1.6.2 Real-time stability studies.

11.1.7 Proposal of storage conditions and retest periods.

11.2 Final Product.

11.2.1 Name of the site(s) of production(includes all the manufacturers of the Final Product).

11.2.2 Productive process. Description.

11.2.2.1 Preparation of the formulation system.

11.2.2.2Formulation. Composition by size of the formulation batch. (Maximum batch size, minimum batch size, average batch size)

11.2.2.3 Filling.

11.2.2.4 Labeling and packaging.

11.2.2.5 Process description. Flowchart.

11.2.2.6 Controls during the process.

11.2.2.7 Quality Control of Excipients.

11.2.2.7.1 Specifications.

11.2.2.7.2 Analytical procedures and their validation.

11.3    Risks in product manufacturing process.

11.3.1 Describe the procedures used to eliminate possible risk factors for human/animal health and the environment during the product manufacturing process.

12. - CONTROL METHODS OF THE FINISHED PRODUCT

12.1Specifications.

12.2 Analytical procedures.

12.2.1 General physical-chemical and microbiological requirements.

12.2.2 Safety. Innocuousness control.

12.2.2.1 Type of test and species.

12.2.3 Control of immunologicaleffectiveness and potency.

12.2.3.1 Type of method and species.

12.2.4 Validation.

12.2.5 Analysis of the batches. Production consistency.

13- WAY OF PRESENTATION AND CONTENT

(General descriptions of multi-pack boxes, clamshell packaging, etcetera)

14. - SPECIFICATION AND CONTROL OF PACKAGES

14.1 Characteristics of the package.

14.2 Packaging security. Tamper-proof features.

14.3 Quality control of packages.

14.4 Description of the batch key.

15.- STABILITY STUDIES 

Enclose the stability and galenicdevelopment studies of the product that justify the declared period of validity.

16.-PERIOD OF VALIDITY (Expiration)

16.1 Period of validity of the final product.

16.2 In case ofmultidoseproducts, period of validity once the package has been opened.

16.3 For products administered in drinking water, stability, compatibility and the period of time of its effectiveness in the solution shall be indicated.

16.4The maximum use timeshall be indicated after their preparation or reconstitution.Attach the stability and clinical studies of product development to support the stated expiration date.  

17. –SAFETY AND EFFICACY TESTS

17.1 Animal safety studies in the target species.

17.2 Efficacy studies.

17.2.1 Efficacy in the animal model.

17.2.2 Studies for determination of the doses.

17.2.3 Optimum dose studies.

17.2.4 Challenge studies.

17.3 Clinical field studies (Phase III) 

17.3.1 Clinical Studies Reports.

17.4 Additional studies to establish the efficacy.

17.5 Pharmacovigilance data (Reportsonphases I, II and III).

18. - INDICATIONS FOR USAGEAND COMMERCIALIZATION CATEGORY 

18.1. Main and/or complementary indications(if applicable).

18.2. Target animal species.

19. - ROUTE OF ADMINISTRATION andUSE OF THE PRODUCT

Parenteral, oral, dermal, pulverization, scarification, ocular, nasal or others.

20. - DOSAGE

20.1 Dose of the product in preventive or curative application bybody weight according to species and age. 

20.2 Recommended application schedule.

20.3 Necessary time to onset of immunity and its duration.

21.- POSSIBLE ADVERSEEFFECTS (Local and/or general), INCOMPATIBILITIES AND ANTAGONISMS

21.1 Contraindications and use limitations (cases in which its administration could give place to harmful effects).

21.2 Precautions that must be adopted before, during or after its administration.

21.3 Warnings.

22. –WITHDRAWAL PERIOD

Provide details in case of meat, milk, and eggs, when appropriate.

23. - GENERAL PRECAUTIONS

23.1 Maximum and minimum temperature limit for its correct conservation.

23.2 Describe the suitable way of storage, transportation and destruction of the product, as well as the method of elimination of the packages that constitute a risk factor for the public health, animal health and the environment.

23.3 Precautions for technicians, trained personnel, and veterinarians when administering theimmunogen.

24. – LABELSAND LEAFLETS - GRAPHICLETTERING PROJECT

25. - SCIENTIFIC WORKS AND/OR MONOGRAPHS

The scientific works and/or monographs related to the product should be enclosed.

The translation of the abstract and the conclusions of the above-mentioned works in the corresponding official language should be included.

26. - OBSERVATIONS

27. - AUTHORIZED SIGNATURESAND DATE