Art. 8 Principle

Art. Preparations of animal origin

Art. 10 Organ-based preparations

Art. 11 Nosodes

Art. 12

Art. 13 Principle

Art. 14 Manufacturing processes

Art. 15 Manufacturing processes

Art. 16 Drugs with Indication

Art. 17 Medications without indication

Art. 18 Drug labelling and information

Art. 19 Conditions for Homeopathic Medicines and Anthroposophic Drugs

Art. Conditions for the salt of Schüssler

Art. Announcement content

Art. Base Folder

Art. Individual Announcements

Art. 24 Drug labelling and information

¹ The documentation to be submitted in connection with an application for authorization should be as follows:

-

Part I: General documentation and recapitulations;

-

Part II: Documentation on quality;

-

Part III: Toxicological Documentation;

-

Part IV: Clinical Documentation.

² The different parts will be presented separately from each other. They may also be presented in the CTD format.

The application for authorisation of homeopathic and anthroposophical medicinal products filed with the Institute must be accompanied by parts I-IV of the documentation. For Part I, the number of copies of originals and copies fixed by the Institute shall be respected. In addition, the documentation of Parts II, III and IV must be provided in two separate, clearly separated copies (folders or A4 workbooks), including a table of contents and a critical recapitulation.

¹ The following documents must be correctly and fully completed, with a valid and dated signature:

A.

Accompanying letter;

B.

"Request for Authorization/Amendment" form with the required appendices;

C.

"Manufacturers information" form; and

D.

GMP certificate in case of manufacture abroad.

² The Institute shall publish the list of certificates it accepts as evidence of GMP compliance of the manufacturer of the medicinal product concerned.

¹ The container (box, vial, ampoule, pommade tube, etc.) as well as the outer packaging (cartonnage) must be equipped with the information required by art. 12, para. 1, in relation to Annex 1, c. 1, para. 1, let. A to h, OEMed. ¹ , which will be supplemented by the following indications:

A.

The supplement "homeopathic medicine", "homeopathic medicine-spagyric", "spagyric drug" or "anthroposophical drug"/"medicinal product based on anthroposophical knowledge", in a printing character of at least half the Size of the name used;

B.

The declaration of excipients in accordance with Annex 3 EMEds or in the form of a complete declaration of all excipients, taking into account the provisions of Annex 3 OEMEds.

² In addition, for all drugs containing alcohol, which are administered orally, the instructions set out in Annex 2 must be complied with.

¹ Information requirements for patients are derived from s. 14 in relation to Annex 5.2 OEMed.

² The requirements for information on a veterinary drug are derived from s. 15 in relation to Annex 6 OEMed.

This part shall contain copies of the consolidated summaries of the three parts (II, III and IV). The name and curriculum vitae of the author, his signature and the date must be attached at the end of each recapitulation.

The complete (qualitative and quantitative) composition of the finished product should be indicated. To the extent possible, the active principles should be identified on the basis of HAB, Ph.F., B.Hom.P. or Pharmacopoeia. With regard to galenical forms whose composition (including the choice of excipients) is not defined in HAB, in Ph.F., in the recognized manufacturing requirements of B. Hom.P or Pharmacopoeia, the choice of excipients Must be justified.

¹ The manufacturing requirements, as well as the manufacturing formulae for the intended batch sizes, must be provided. The manufacture of drugs from raw materials to mothers, solutions or first triturations must be accurately described (manufacturing process). In addition, the controls in process must indicate the tolerance limits and the frequency of the controls.

² The documents submitted must show how the recognized homeopathic and anthroposophical processes as well as the monographs of the Pharmacopoeia concerning galenical forms are applied. The equipment of the company must allow the fulfilment of the conditions under which these manufacturing processes must take place. Finally, the parameters of the processes as well as the machinery and apparatus used must be described in detail.

³ The current Pharmacopoeia requirements must be met for galenical forms (p. Ex. Pommades, suppositories or sterile products such as collyres or parenteral preparations). In addition, sterilization processes should be described in detail.

⁴ Process validation documents and manufacturing processes critical to the quality of the product must be submitted.

⁵ A complete manufacturing protocol should be submitted for at least one lot.

It is essential to submit documents on the quality and quality control of all the raw materials and all the active ingredients and excipients, as well as, for examinations not carried out by the laboratory The company, the corresponding certificates of the supplier.

¹ The documents submitted must show that the raw materials meet the monographs for the homeopathic preparations of the current Pharmacopoeia and the general requirements defined for the raw materials in the Pharmacopoeia, HAB, Ph.F and B.Hom.P.

² It must be demonstrated that all the requirements of the recognized monographs on substances are met. In the absence of an official monograph, the monograph shall be established by the manufacturer. Depending on the raw materials used, it is necessary to present quality documents (identity, purity and, where appropriate, other criteria) which guarantee their quality, as in a pharmacopoeial monograph. The controls chosen must be justified and the methods validated.

³ Additional testing, including microbiological testing, is required for some raw materials. With regard to raw materials of plant origin, precise data on the parts of the plant used are required. Dried plant parts generally need microscopic analysis. In addition, residue analyses (phytosanitary products, heavy metals, etc.) may be required, depending on the contamination situation.

¹ For active principles, documentation should be provided on the quality not only of their raw materials, which complies with the requirements of point 2 above, but also mothers, solutions or first triturations Which result.

² In the case of dynamisation of the preparations, it is also necessary to indicate how this operation is carried out and how the recognised manufacturing processes are applied. Finally, the documents on the dynamisation process, the quality and the quality controls of the dynamizations must be submitted.

¹ For mother-dyes, solutions and first triturations, analytical requirements (specifications and analytical methods) should be presented which take into account the following parameters:

A.

General parameters (p. Ex. Organoleptic aspects, density, pH);

B.

Qualitative parameters (identification reactions, purity controls, chromatographic characterization, etc.); and

C.

Quantitative parameters (desiccation residue, limits and determination of the content of defined constituents such as inorganic substances or potent active substances such as alkaloids, cardiotonic glycosides, etc.).

² It is appropriate to indicate how the mother-dyes (if any, solutions or first crush) are made from the raw materials (whether the manufacturing is done by the company itself or by a supplier) and How recognized manufacturing processes are applied.

³ For each motherboard, solution or first crush used as an active principle as is or after dynamization, batch protocols must be submitted to the institute. Traceability to the raw material must be ensured in all cases.

⁴ Mothers, solutions and first triturations must be studied for stability. If stored before being processed, the storage conditions and shelf life must be defined.

⁵ Similar documents must be presented for anthroposophical drugs manufactured using a specific anthroposophical manufacturing process.

In addition to the documents listed in Part II C, c. 1 to 3, documents showing how the requirements for organ-based preparations (chap. 2, section 1, s. 10) are completed.

In addition to the documents listed in Part II C, c. 1 to 3, parts showing how the requirements for nosodes (chap. 2, section 1, s. 11) are fulfilled.

In the specifications and analytical requirements for the excipients used, it is possible to refer to monographs of the Pharmacopoeia, HAB, Ph.F. or the Swiss Food Manual.

A description of the container and data on the vessel's materials and specifications should be provided. If they appear in a pharmacopoeial monograph, a simple reference to the relevant text is sufficient. However, where appropriate, the Institute may require the presentation of analytical methods for the materials of the container and of documents certifying that they are appropriate.

As quality assurance, it may be useful to carry out certain checks on intermediate products (cf. Part II E) which can no longer be performed on the finished product.

¹ Depending on the galenic form and the dilution or concentration of the active ingredients in the finished product, the specifications and analytical methods (y c. Validation documents) should be presented for the following parameters:

A.

Organoleptic aspects (p. Ex. Appearance, smell, possibly taste);

B.

Physical parameters (p. Ex. Density, pH, viscosity, refractive index)

C.

Identifications (mainly by chromatographic processes for the low dilutions and the parent teintumers contained in the finished product);

D.

Determination of the content of inorganic substances and plant components with strong action (p. Ex. Alkaloid drugs) or limit values analysis;

E.

Dry residue or desiccation loss;

F.

Alcohol content;

G.

Content of conservative agents;

H.

Specific pharmaceutical technology controls for the pharmaceutical form (p. Ex. Uniformity of mass, homogeneity and precision of dosing (dropper bottles), tonicity, filling volume or extraction volume, disaggregation time); and

I.

Sterility testing.

² The documents must prove that the general requirements for the defined pharmaceutical (galenical) forms of the Pharmacopoeia are met, in particular those concerning microbiological purity.

³ An analytical protocol should be submitted for at least one lot.

¹ Documents on the stability of each galenical shape should be presented in its original container, providing the following information:

A.

Batch numbers, batch dates and batch sizes, general testing methodology (containers, storage conditions [defined air temperature and humidity]), analytical methods, etc.;

B.

Specifications for the shelf-life specifications and the results of analyses;

C.

Evaluation of the results and proposal for shelf life and storage conditions to be mentioned on the packaging;

D.

For galenical forms whose retention period after opening is relatively short, results of the stability control after opening evaluation of the results and proposal concerning the time limit for use after opening.

² The conservation specifications must be completed throughout the shelf life. To the extent that only the general parameters and the specific parameters of the galenic form are decisive for the conservation, the stability of the preparation is considered proven when the stability of the galenic form is And that any interaction with the active principles may be excluded. If the parameters specific to the active principles are also decisive for conservation, they must be proved in turn.

³ The tests must cover at least two lots and cover the entire shelf life. At least one of the two lots must be a production lot.

⁴ The application for authorisation must be accompanied by results relating to at least 6 months of the duration of the long-term study as well as a binding schedule of analyses. If, at the time of application, no production batches have been manufactured, the results of two pilot batches and the detailed stability testing schedule for the first batch of production can be submitted. These results can be supplemented by accelerated test results. Finally, the long-term results of the long-term study should be presented periodically and spontaneously.

This section should summarize from a critical point of view the quality documents in the order of the original documentation. It must be limited to the essential and allow its reader to make a full assessment of the quality of the preparation. It should be written by an expert.

The nature and extent of the documentation required depends primarily on the composition of the drug, its safety and safety, its therapeutic range, its mode of administration, and similar factors.

¹ Is known as known (in relation to the mode of administration, e.g. Oral or topical) the toxicological profile of the raw materials and active ingredients which enter into the composition of authorised medicinal products or which are admitted as foods within the meaning of the foodstuffs legislation, As well as that of the excipients described in the Pharmacopoeia, in HAB or Ph.F. For the raw materials known in homeopathy or anthroposophical medicine which are included in the SHA list, it is possible to refer to them, even if Certain additional documents or evidence may be required depending on the degree of Dilution of the drug and its mode of administration.

² In the presence of active ingredients and excipients to the toxicological profile considered safe, and in particular of substances listed in the SHA list in dilutions under the heading "Announcement procedure from" or above, it is in principle May waive the submission of toxicological documentation. However, toxicological safety must be justified.

¹ In the presence of raw materials, active ingredients and excipients not known to the toxicological profile, documentation should be submitted on acute and chronic toxicity, embryotoxic or teratogenic effects As well as the risks of allergenic, carcinogenic and mutagenic effects. Local medicines on the skin or mucous membranes and those administered parenterally, which contain new active ingredients or excipients, also require an examination of local tolerance and sensitizing properties After single application and after repeated applications.

² Further tests on the animal or, where possible and judicious, tests carried out using validated methods of substitution shall be undertaken only where sufficient documentation has not been obtained from the published literature or Other sources. In summary, the waiver of toxicological testing should be justified, with a clear reference to the literature on which this decision is based. The scientific articles concerned must in all cases be presented.

³ In the presence of raw materials and new active ingredients in a dilution or concentration that excludes any potential allergenic or toxicity risk, there is no need for toxicological testing in animals.

⁴ Documents and studies on the allergenic potential of new raw materials and active ingredients are required, in particular when these substances are contained in the drug concerned with dilutions up to and including D7. Any renunciation of the presentation of these documents must be justified.

⁵ Documents on the potential for interactions of new raw materials and active new principles are required, in particular where these substances are contained in the medicinal product concerned as active ingredients in final dilutions Less than 10 ^-4 . Any waiver of the presentation of these documents must be justified.

¹ Wherever possible and judicious, the preferred alternative methods for animal testing should be preferred.

² The acute toxicity study (single administration) should provide information on the clinical presentation of intoxication in the case of overdose and, if necessary, approximate the lethal dose.

³ Data on chronic (repeat) toxicity of active ingredients and excipients include observations on sequelae in prolonged administration, as well as the definition of target organs for toxicity. The mode of administration chosen in the trial should, if possible, correspond to the intended therapeutic use.

⁴ Drugs intended for local application should be subject to a review of local tolerance (irritating and sensitizing properties) after single or repeated application.

⁵ Documentation of embryotoxic and teratogenic effects (fetotoxicity) and mutagenic effects (mutation of hereditary traits) should be presented.

⁶ In the case of allergenic potential, it is appropriate to include in the 28-day study in rats immunotoxicological endpoints or to undertake new immunotoxicological studies.

⁷ For the study of the potential for interactions, the in vitro studies that measure the influence on cytochrome isoenzymes in hepatic microsomes are recognized.

⁸ For each new active or excipient principle, it is necessary to analyse possible carcinogenic effects (causing or promoting cancer). The results of appropriate animal experiments should be presented if they are necessary to prove safety.

This part should summarize in a clear, accurate and critical manner the tests performed and the toxicological data according to their order of presentation in the original documentation. The implementation phases and the results of the various studies should be clearly presented, in the form of tables if this proves to be appropriate. Finally, a summary should be prepared by an expert.

General Requirements

¹ Clinical document requirements (scientific documentation on case reports, application data, controlled clinical studies, etc.) depend on the composition of the drug, the mode of administration, The claimed indication, dosage and duration of treatment, safety, and other similar factors.

² Proof of tolerance for the advertised product for authorization should be provided.

¹ The therapeutic use and benefit of a unit or combination of known dilutions in homeopathy, in particular, depends on the pathogenicity of this drug. It should also be demonstrated that:

A.

The homeopathic rules governing the choice and manufacture of a drug are met; and

B.

The unit is sufficiently tested and known for the area of application claimed, particularly given the current therapeutic use of the unit.

² It is appropriate to justify the choice of the degree of dilution, the expected dosage, the galenic form, the mode of administration and, if this is important for the treatment, its duration.

¹ The choice of each unit and its contribution to the overall claimed effect should be motivated for the complexes. This includes demonstrating:

A.

That the homeopathic rules for composition and manufacturing are respected;

B.

The main symptoms with respect to the unit cover the area of application claimed; and

C.

There is no confusion with herbal medicine or allopathy.

² The choice of the degree of dilution of the units, of the expected dosage, of the pharmaceutical form, of the mode of administration and, as far as this is important for the treatment, of its duration, must be justified. If the units are present in different quantities, the reasons should be given.

³ For homeopathic complexes that do not meet or partially meet the requirements set out in s. 1 and 2, it is necessary to provide additional documents which demonstrate the therapeutic benefit of the association for the area of application claimed.

For anthroposophical medicinal products, it is necessary to demonstrate that the composition, manufacture and therapeutic benefit are in conformity with the anthroposophic knowledge of human beings, animals, substances and nature.

It can be demonstrated that the requirements set out in c. 1 and 2 are completed by the following documents:

A.

Review of scientific articles recognized in homeopathy and anthroposophical medicine, the contents of which may apply to the claimed indication;

B.

Results of analyses of scientifically based homeopathic medicines;

C.

Clinical trials (i.e., application data);

D.

Systematic review of clinical trials; where it can be demonstrated that they have been conducted in accordance with the recognized Good Clinical Trial Practice rules, it is possible to provide only the results of these trials;

E.

Monographs of the BfArM Special Commission for Homeopathic Medicines (Commission D);

F.

Monographs of the BfArM Special Commission for Medicinal Products (Commission C);

G.

Established scientific documentation of case study reports, which will indicate not only the therapeutic benefit of the drug, but also any adverse reactions that may have been attributed to it;

H.

Other data based on scientific methods;

I.

Medical investigations based on various parameters and aimed at improving the quality of life; they are particularly important in chronic diseases and must be validated and relate to the claimed indication.

¹ The scope of the documents proving the therapeutic benefit depends, in particular, on the claimed indication, the need to make a medical diagnosis or to monitor the treatment, the obligation to associate the delivery of the medicinal product with advice Provided by a person exercising a medical profession, the degree of awareness of the drug in the traditional use, the safety of the drug, and the manner in which it is administered.

² Bibliographic documentation is sufficient if:

A.

The composition may be validly justified by traditional use; for this purpose, it is necessary to prove the reputation of the medicinal product in homeopathy and anthroposophical medicine in the field of application claimed;

B.

There is sufficient knowledge of possible adverse effects;

C.

The claims claimed are conditions whose symptoms may be identified by lay persons and do not require immediate diagnosis or treatment by a physician or. A veterinarian, or conditions that rarely require a diagnosis or medical follow-up of treatment.

³ In addition, clinical trial results should be provided if:

A.

Indications refer to diseases which require in principle a diagnosis or medical follow-up;

B.

New indications are claimed which are not sufficiently documented in the specialized literature.

⁴ If the advertised drug is directly comparable to an already authorized drug, it is possible to refer to existing studies.

⁵ In justified cases, the Institute may require other documents.

¹ The clinical tolerance of the drug should be documented in general on the basis of clinical studies or, in justified cases, in the form of scientifically established application data.

² Any waiver of documentation must be justified.

³ If adverse reactions occur in trials to demonstrate therapeutic benefit, or if they are associated in the literature with the drug or one of its components, they should be identified and evaluated. Qualitatively and quantitatively. Isolated cases of particularly severe or hypersensitive reactions should be described accurately.

⁴ If the drug is already marketed in another country, the information that has been collected should be collected and taken into account in the safety assessment of the drug.

For oral preparations which contain only active ingredients known and tested in homeopathy or anthroposophy in sufficient dilution, in particular the substances mentioned in the SHA list in Of dilutions in the "Advertised at" or above column, as well as known excipients, or even conventional vehicles in homeopathy or anthroposophy, it is not necessary to present a literature on tolerance.

Local tolerance, as well as single application sensitizing properties and repeated applications, should be studied for locally applied drugs on the skin or mucous membranes. To demonstrate this clinical tolerance, at least 50 application data collected by several medical investigators should be submitted. A bibliography may be sufficient for preparations containing known active principles of homeopathy or anthroposophy and present in a dilution that excludes any reaction of clinical intolerance and excipients whose good tolerance Is demonstrated (composition according to HAB, Ph.F., B.Hom.P. or Pharmacopoeia).

For drugs intended for parenteral administration, clinical safety data should be submitted in the form of clinical studies, such as clinical studies. Evidence of tolerance in humans or in the claimed animal species. Clinical trials may be waived in the case of drugs containing known active principles of homeopathy or anthroposophy and present in a dilution that excludes any reaction of clinical intolerance and that they are Manufactured (including excipients) according to a manufacturing process for parenteral preparations described in HAB, Ph.F. or Pharmacopoeia.

In addition to the evidence of topical tolerance in animals (for preparations for local or parenteral administration), there is also a need to examine the tolerance of nosodes and organ-based preparations in humans or in humans. The claimed animal species. Clinical documents may be waived if these preparations contain active ingredients present in a dilution that excludes any reaction of clinical intolerance and known excipients, or even conventional vehicles Homeopathy or anthroposophy.

¹ The recapitulation must clearly reflect the therapeutic benefit and the clinical tolerance. The name of the preparation, the galenic form, the mode of administration, the dosage and the therapeutic use should be indicated in the introduction. The summary should also summarize from a critical view the clinical documents with reference to all the applications claimed. Finally, in all cases, a benefit/risk ratio must be established, which must present and evaluate the relevant positive and negative results obtained in the clinical studies as well as the literature.

² If several clinical studies, application data, etc., are presented, each must be evaluated separately. In view of its importance, this part must be drafted by a specialist. All the facts and data mentioned in the recapitulation must be provided with a clear and precise reference to the documentation, which will continue to be paging. Finally, all important data must be presented in tabular or schematic form.

¹ The simplified application filed with the Institute with a restricted file must be accompanied by the following documents:

A.

Administrative documents:

1.

Cover letters,

2.

"Request for Authorization/Amendment" form,

3.

"Manufacturer Information" form, and

4.

GMP certificate in the case of manufacture abroad; the Institute shall publish the list of certificates it accepts as evidence of GMP compliance of the manufacturer of the medicinal product;

B.

Data on manufacturing processes used for raw material processing;

C.

Indication of the source of the monograph on the quality of the raw material (compendial monograph or product monograph) and the precise definition of raw materials that are not subject to a monograph in the Pharmacopoeia, HAB or Ph.F.;

D.

Certification that the requirements set out in s. 17, para. 1, and 18, para. 2, are fulfilled, that the medicinal product is manufactured from the defined raw material (s) and according to the manufacturing processes recognised and specified in the application and that the quality is controlled according to methods according to the current state of the Knowledge;

E.

Certification that the labelling complies with the requirements of Schedule 1 A OEMEd ¹ ;

F.

Certificate certifying that the medicinal product contains only active ingredients derived from the raw materials listed in the SHA list, in the dilutions indicated therein;

G.

For substances and dilutions not included in the SHA list:

1.

Evidence of sufficient knowledge of homeopathy or anthroposophical medicine and, if necessary, evidence of traditional use in these therapies, as per c. 2 of this Annex,

2.

Documents relating to the safety and safety of the drug, as per c. 3 of this Annex, and

3.

Documents relating to tolerance, in accordance with c. 4 of this annex;

H.

For the active principles of dilutions or concentrations subject to an order (provided that no announcement procedure is provided for them):

1.

Documents on tolerance, as per c. 4 of this Annex, and

2.

If the raw materials are not subject to any monograph in the Pharmacopoeia, HAB or Ph.F., a monograph that, in the image of homeopathic pharmacopoeias, demonstrates the quality of the active ingredient;

I.

For all active ingredients and excipients manufactured from or using products of animal or human origin:

1.

"Animal or human products" form, if applicable with the documents required to reduce the risk of TSE transmission, and

2.

Documents proving that the substances meet the general requirements for raw materials of animal or human origin. Where the substances are subject to the announcement procedure within the meaning of Art. 19, these documents should only be submitted in the cases mentioned in the SHA list in the form of a master file;

J.

For drugs administered parenterally and those applied to or on the eye, as well as for veterinary drugs used intramammary or intrauterine:

1.

Master file on the manufacture of the galenic form, in accordance with the c. 5 of this Annex, and

2.

Documents on tolerance, as per c. 4 of this annex. It is generally possible to provide independent evidence of the active ingredient for dilutions from D12/C6 as well as for substances that may be subject to a drug announcement procedure. Administered parenterally within the meaning of s. 19, provided that the manufacturing complies with the process described in the master file. Any renunciation of the presentation of documents must be justified;

K.

For drugs containing substances regulated by the OStup ² And whose dilutions are less than or equal to D8/C4, it is necessary to prove that an authorization as required by the OStup has been issued.

² If the data required under para. 1 is valid for several products, the documents required by the let. G to k can be submitted once, in the form of a master folder.

³ In the event of an announcement procedure, it is sufficient to submit the documents cited in para. 1, let. B, c and i to k.

⁴ For units which, from the point of view of the qualitative composition and the galenic form, are identical but are present in the medicinal product at different concentrations or dilutions, it is possible to file only one application. The requirements to be met are those applicable to the lowest dilution.

¹ A raw material or an active ingredient is deemed to be sufficiently known:

A.

If there is evidence that the raw material or the active ingredient is in the official homeopathic pharmacopoeia of a country that has instituted drug control equivalent to the Swiss system;

B.

If there is a monograph of commissions C or D of BfArM; on an exceptional basis, it is possible to refer to a negative monograph, if the negative assessment results from the fact that the use of a substance is known to be in homeopathy or Anthroposophy, but its field of application is not sufficiently proven;

C.

Whether the substance is sufficiently described in recognized homeopathic or anthroposophical scientific publications; or

D.

Evidence of continued use and sufficient knowledge of the substance in HM or anthroposophical medicine for at least 30 years.

² A fixed drug association is considered to be sufficiently known or used in a traditional manner where it is possible to provide for each of its components one of the evidence cited in para. 1.

¹ To prove safety and safety, it is possible to refer to the following sources:

A.

The official pharmacopoeial monographs of a country that has instituted drug control equivalent to the Swiss system;

B.

Monographs of commissions C or D of the BfArM and other publications and results arising from the work of these commissions;

C.

Scientifically proven results from the use of these substances in other areas (p. Ex. Allopathy, herbal medicine or food); lists of substances in the Institute may serve as a basis;

D.

Scientific literature on toxicology;

E.

Examinations of the dosages of the toxicological components and documents attesting to the determination of the threshold values;

F.

Results of procedures to ensure drug safety (revision procedure).

² Safety and safety documents are not required for a degree of dilution as of D12/C6. In justified cases, this rule may be restricted.

¹ To prove the tolerance, the following documents may be presented:

A.

The evidence of the tolerance set out in Schedule 1, Part IV B; or

B.

The indication:

1.

Annual sales figures (packaging or units sold) in Switzerland and abroad,

2.

The date from which the preparation is on the market and possible changes in quality, and

3.

Adverse reactions, contraindications, and discovered interactions.

² The Institute shall check whether the documents provided are sufficient and, if not, require further evidence in accordance with Annex 1, Part IV B.

A master file relating to the manufacture of the galenic form shall contain the following documents:

A.

Description of the process used to ensure sterility (p. Ex. Final sterilization, aseptic manufacturing);

B.

Detailed description of the manufacturing process (y c. Specifying standard batch sizes), data on the preparation of the filling solution (y c. Isotonisation) and on the packaging in the primary receptacle; the following information shall also be given:

1.

Identification of the process steps that are critical to quality and therefore critical and those that are not. These assessments must be justified,

2.

Specifying critical (critical) parameters for the process (p. Ex. Temperature and duration of sterilization with acceptance criteria,

3.

Description of apparatus and types of facilities used in manufacturing (p. Ex. Type of autoclave with indication of load capacity) and specification of filters for sterile filtration of solution, and

4.

Indications on cleaning and sterilization (p. Ex. Temperature, duration, and value F ₀ ) Of all the elements that come into contact with the product, in particular:

-

Filtration devices and filter membranes upstream of sterile filtration,

-

The container that collects the sterile filtered solution,

-

The primary container of the drug and

-

Filling and closing machines;

C.

Process and end of process controls, y c. Specification of acceptance limits and results of microbiological contamination analyses (bioburden) of the bulk solution before sterile filtration, indication of method Applied analysis to control the integrity of the sterile filters used and an indication of the leak analysis of the filled primary receptacles; and

D.

Validation documents for manipulations that are not performed under the standard conditions defined in the Pharmacopoeia.

As part of an application for the authorization of Asian medical fixed drug associations without any indication, reference may be made to the following reference works in accordance with s. 27:

A.

Chinesische Arzneimittelrezepte und Behandlungsstrategic: Bensky und Barolet, 1996;

B.

Chinese Herbal Medicine: Formulas & Strategies by Bensky and Barolet, 2009;

C.

Large Chinese Pharmacopoeia Form, E. Marié, 1991;

D.

Complete External Therapies of Chinese Drugs, Xu Xiangcai, Foreign Language Press, Beijing, 1998;

E.

Manual of Dermatology in Chinese Medicine, Shen Dehui, Wu Xiufen, Nissi Wang, Eastland Press, 1996;

F.

Chinese Herbal Formulas and Applications: Chen, John K., Chen, Tina T., 2009.

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