Medical products for animal use - Swedish Medical Products Agency

Chemical medicinal products

Even though drugs are based on originally natural products, today they are often produced synthetically and can be described most simply as chemical substances.

Non-clinical testing

For veterinary medical products, non-clinical assessment comprises user safety, consumer safety, and environmental risk assessment.

User safety

An assessment must be undertaken of the risks to the user, who in this case is the veterinarian, the animal owner, or others in the surroundings who may come into contact with the medicinal product, or the animal being treated. Any risks are to be addressed with advice for handling, protective measures, and warnings in product information.

Consumer safety

Treating food-producing animals with medicinal products can leave residue in various tissues. Therefore, to protect the consumer, waiting periods are calculated for all products approved for food-producing animals. The waiting period represents the minimum amount of time that must pass between the last treatment and slaughter or exploitation of e.g. milk for human consumption, and calculation of the waiting period is based on studies of residue and the MRL value (see that heading).

Read guidelines on consumer safety

Environmental risk assessment

An environmental risk assessment must be carried out for all veterinary medicinal products. This entails calculating how much residue there is in the soil following treatment of animals. Diffusion in soil occurs via manure from grazing animals or spreading of farmyard manure. If the levels exceed a certain limit, it must be assessed how the substance affects various organisms in nature and how it behaves in nature in terms of diffusion, accumulation, and the like. The results of the environmental risk assessment are then factored into the risk/benefit assessment.

Ecotoxicity Phase I CVMP/VISH/592/98

Ecotoxicity Phase II CVMP/VISH/790/03

Production of an investigational medicinal product

Pharmaceutical quality comprises how a medicinal product is constructed/manufactured from the synthesis of its active substance, the formulation of the intended form of preparation, and through the manufacture of the finished product. An application also documents what the medicinal product contains, how the active substance, the auxiliary compounds included, and the finished medicinal product are monitored, and how long the useful life of the medicinal product is.

Documentation of the product

Pharmaceutical quality must be documented by describing how the medicinal product is produced and what controls are carried out during and after its manufacture. The complete composition of the medicinal product must be stated, with reference given to a pharmacopoeial monograph or own specification of each ingredient. Information about the useful life of the substance and the product must also be included.

Read about the European Pharmacopeia at EDQM

Permission for production - IMP

A production permit is required for the manufacture of an investigational medicinal product (IMP).

Inspection

Guideline

Information about what pharmaceutical quality documentation must be included in the application for an investigational medicinal product for animals in clinical trials can be found in Annex 1 in LVFS 1996:17. The guideline for pharmaceutical quality documentation for investigational medicinal products for human use may also be used as guidance for veterinary investigational medicinal products .

Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials

Clinical trials of a medicinal products

A clinical trial of a medicinal product is a study that aims to discover or verify the clinical, pharmacological, or pharmacodynamics effects of a pharmaceutical that is administered to animals. The goal of the trial may also be to identify any side effects and to study the absorption, distribution, metabolism, or secretion of a medicinal product for the purpose of guaranteeing its safety and effect. Scientific investigations that do not include animal patients in clinical animal health care are not covered by the requirement of a permit for clinical trials of pharmaceuticals.

LVFS 1996:17

The trial requires an advance permit from the Medical Products Agency.

Clinical trial application form - veterinary medicinal products (in Swedish)

The trial must also be approved by the Regional Ethical Review Board.

the Regional Ethical Review Board

Commercial production

All manufacture of medicinal products requires a production permit issued by the Medical Products Agency and must be done in compliance with Good Manufacturing Practice, GMP.

For production of medicinal substances (API) the Medical Products Agency grants permits following inspection.

To the application form for a production permit (in Swedish)

Medicinal products occur in various preparations with specific requirements. In EudraLex, Volume 4 (Good manufacturing practice (GMP) Guidelines), the basic chapters deal with quality assurance, which applies to the manufacture of medicinal products in general. Specific forms of preparation are treated in Annexes.

Eudralex Vol 4 GMP Guidelines

Approval of medicinal products

When a company wishes to place on the market a medicinal product it must be approved before sale, i.e. the company must apply for marketing authorisation of the medicinal product. There are different procedures to choose from for chemical pharmaceuticals: a centralised procedure, a mutual recognition procedure, and a decentralised procedure, as well as a national procedure.

Immunological medicinal products

An immunological veterinary medicinal product (IVMP) is a veterinary medicinal product that is administered to animals to invoke active or passive immunity or to diagnose the immune status of animals.

Non-clinical testing

For veterinary medical products, non-clinical assessment comprises user safety, consumer safety, and environmental risk assessment.

User safety

An assessment must be undertaken of the risks to the user, who in this case is the veterinarian, the animal owner, or others in the surroundings who may come into contact with the medicinal product, or the animal being treated. Any risks are to be addressed with advice for handling, protective measures, and warnings in product information.

Guideline on user safety for immunological medicinal products(EMEA/CVMP/IWP/54533/2006)

Consumer safety

Treating food-producing animals with medicinal products can leave residues in various tissues. For immunological medicinal products, no residue studies are generally required, but if adjuvants and/or preservatives are used, the possibility of residue in food must be considered. If necessary, a waiting period must be calculated. However, a waiting period must always be stated, even if it is 0 days, which is often the case for immunological medicinal products. There are no specific guidelines

Environmental risk assessment

An environmental risk assessment must be carried out for all veterinary medicinal products. The environmental exposure is estimated and the risk entailed by this exposure is assessed.

Guideline for environmental risk assessment for immunological medicinal products(EMEA/CVMP/074/95)

Production of an investigational medicinal product

Pharmaceutical quality comprises how a medicinal product is constructed/manufactured from the synthesis of its active substance, the formulation of the intended form of preparation, and through the manufacture of the finished product. An application also documents what the medicinal product contains, how the active substance, the auxiliary compounds included, and the finished medicinal product are monitored, and how long the useful life of the medicinal product is.

Documentation of the product

Pharmaceutical quality must be documented by describing how the medicinal product is produced and what controls are carried out during and after its manufacture. The complete composition of the medicinal product must be stated, with reference given to a pharmacopoeial monograph or own specification of each ingredient. Information about the useful life of the substance and the product must also be included.

Read about the European Pharmacopeia at EDQM

Pemission for production - IMP

A production permit is required for the manufacture of an investigational medicinal product (IMP).

Inspection

Guideline

Information about what pharmaceutical quality documentation must be included in the application for an investigational medicinal product for animals in clinical trials can be found in Annex 1 in LVFS 1996:17. The guideline for pharmaceutical quality documentation for biological investigational medicinal products for human use may also be used as guidance for veterinary investigational medicinal products:

Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials

Clinical trials of a medicinal products

A clinical trial of a medicinal product is a study that aims to discover or verify the clinical, pharmacological, or pharmacodynamics effects of a pharmaceutical that is administered to animals. The goal of the trial may also be to identify any side effects and to study the absorption, distribution, metabolism, or secretion of a medicinal product for the purpose of guaranteeing its safety and effect. Scientific investigations that do not include animal patients in clinical animal health care are not covered by the requirement of a permit for clinical trials of pharmaceuticals.

LVFS 1996:17

A clinical trial requires an advance permit from the Medical Products Agency.

Clinical trial application form - veterinary medicinal products (in Swedish)

The trial must also be approved by the Regional Ethical Review Board.

the Regional Ethical Review Board

Commercial production

Like other medicinal products,Investigational veterinary medicinal products (IVMPs) must be produced in compliance with Good Manufacturing Practice (GMP) for medicinal products. A delineation of what requirements apply to commercial production of immunological medicinal products can be found in Annex 1 to Directive 2001/82, amended by Directive 2009/9/EC, in the guidelines issued by the Committee for Veterinary Medicinal Products within the European Medicines Agency (EMA) and in the European Pharmacopoeia.

Annex 1 to directive 2001/82

All manufacture of medicinal products requires a production permit issued by the Medical Products Agency and must be done in compliance with Good Manufacturing Practice, GMP. For production of medicinal substances (API) the Medical Products Agency grants permits following inspection.

To the application form for a production permit (in Swedish)

Approval of medicinal products

When a company wishes to place on the market a medicinal product it must be approved before sale, i.e. the company must apply for marketing authorisation of the medicinal product. There are different procedures to choose from for immunological medicinal products: a centralised procedure, a mutual recognition procedure, and a decentralised procedure, as well as a national procedure.

For further questions, please contact the Innovation Office by sending an email to innovation@mpa.se

Herbal medicinal products and natural remedies

For both herbal medicinal products and natural remedies it is possible to apply for approval for use in animals. However, this is not possible for traditional herbal medicinal products that are exclusively for human use. Herbal medicinal products for veterinary use are covered by Directive 2001/82/EC which has been implemented in Swedish legislation through the Medicinal Products Act (1992:859) and regulations issued by the Medical Products Agency.

For further questions, please contact the Innovation Office by sending an email to innovation@mpa.se

Homeopathic medicinal products

Homeopathic medicinal products must be produced in compliance with established homeopathic methods and contain raw materials with documented homeopathic use. Registration in Sweden is done in accordance with articles 17 and 18 in the Directive on Veterinary Medical Products Directive 2001/82/EC.

Safety documentation

The safety of homeopathic medicinal products must be demonstrated through reference to the scientific literature or product-specific data.

Effect documentation

There are no requirements to show via clinical studies or literature references that homeopathic medicinal products have an effect. Nor may any effect and/or indication be stated for a homeopathic medicinal product.

Quality and manufacture of the product

All manufacture of medicinal products requires a production permit from the Medical Products Agency and must be done in compliance with Good Manufacturing Practice (GMP).

To the application form for a production permit (in Swedish)

Raw materials and mother tincture preparations

Read more about quality requirements for raw materials and homeopathic mother tincture preparations in Medical Product Agency regulations and general advice about registering certain homeopathic products (LVFS 1997:9 consolidated version).

LVFS 1997:9 (consolidated version) (in Swedish)

Finished products

Read more about quality requirements for finished products in Medical Product Agency regulations and general advice about registering certain homeopathic products (LVFS 1997:9 consolidated version).

LVFS 1997:9 (consolidated version) in (Swedish)

Quality documentation

The part of application documents that describes production and various controls of raw materials and the finished product is called quality documentation. The same requirements apply to homeopathic medicinal products as to conventional medicinal products.

LVFS 1997:9 (consolidated version) (in Swedish)

Registration procedure

Homeopathic products must be registered with the Medical Products Agency before sale in Sweden.

Applications

Applications must be in the CTD-format (Common Technical Document)

Fees

Read more about application fees and annual fees for application and registration of homeopathic medicinal products

Procedures

Application to register a homeopathic medicinal product may involve national registration in Sweden or, under certain conditions, registration in several EU countries simultaneously.

National procedure

An application in the national procedure applies only to the Member State to which the application is submitted. Following approval, registration applies only to the Member State in question.

Decentralised and mutual recognition procedures

Decentralised procedure (DCP)
Mutual recognition procedure (MRP)

Decentralised procedure is obligatory for homeopathic medicinal products for animals. Mutual recognition is possible but not obligatory for homeopathic medicinal products for animals.

Regulatory advice

Advanced therapy medicinal products

There is no specific legislation for medicinal products for advanced therapies in which gene- or cell-therapy products are included in veterinary medicine. Companies or researchers developing advanced therapy products for use in animals should seek advice either from the Medical Products Agency or the European Medicines Agency, EMA. It is possible to submit a special application to have certain scientific questions and developmental plans reviewed by an expert panel under the CVMP, Committee for Veterinary Medicinal Products at the EMA, via a scientific consultation procedure.

Read about scientific advice on veterinary products at EMA

Regarding vaccines, there are guidelines for, among other things, virus vectors and living vaccines that can provide support for developmental work, even though they do not include any specific requirements for medicinal products for advanced therapies. Requirements for quality control of cells used in vaccine production can also provide support for developmental efforts. Both the EMA and the European Pharmacopoeia have monographs and guidelines in the field of vaccines that set up specific requirements for cell substrates and virus grafts in vaccine production. Of special importance is microbiological monitoring regarding the absence of alien agents such as viruses and bacteria as well as the purity of the virus and virus vectors used.

Even though there is no specific legislation for medicinal products for advanced therapy in the veterinary field, the product may nevertheless come to be classed as a medicinal product for veterinary medical use (see under 'Approval' tab below).

For more information about the quality and manufacture of a product, please see under the 'Immunological medicinal products' tab above.

Read about the European Pharmacopeia at EDQM

Is the product an ATMP?

Thus far only a few medicinal products have been classified or approved as medicinal products for advanced therapy (so-called Advanced Therapy Medicinal Product, ATMP). Questions regarding whether a certain gene therapy, cell therapy, or tissue technology therapy is a pharmaceutical may be directed to the Medical Products Agency expert group for AT by sending a mail to registrator@mpa.se. Write “Advanced therapy” in the subject field.

Questions may also be put to the European Medicines Agency (EMA) by mail to advancedtherapies@ema.europa.eu.

Approval of ATMPs

Advanced therapy medicinal products must be approved via the central procedure in the EU. The European Medicines Agency (EMA) is responsible for investigation of applications for approval together with national experts. The final decision is made by the European Commission.

Read about regulation for advanced therapy at EMA

Medicinal products in food (MRL)

MRL stands for Maximum Residue Level and involves the highest permissible concentration of a substance that may occur in foods, such as meat, milk, and eggs. The MRL must have been assessed for all substances used in food-producing animals and must thereby be included in the European Commission regulations (EC)470/2009 and (EC)37/2010. Application to determine an MRL status is done for each substance via the central application procedure.

Waiting periods for a medicinal product are based on MRLs

Read about Maximum Residue Limits at EMA

Swedish National Food Agency

Minor uses minor species (MUMS)

The European Medicines Agency, EMA, has developed guidelines that delineate what documentation is needed regarding preclinical and clinical effect and safety in order to assess an application for central approval for sale of products that are judged to have small market owing an unusual disease or a minor type of animal (Minor Uses Minor Species – MUMS).

MUMS guideline Pharmaceuticals EMEA/CVMP/EWP/117899/2004

MUMS guideline Immunologicals EMA/CVMP/IWP/123243/2006-Rev.2

MUMS guideline för safety and residues data requirement EMEA/CVMP/SWP/66781/2005