PharmPharmaceutical /Medicine/Drug/OTC registration in Spain

MOH- Ministry of Health

MOH Website- https://www.sanidad.gob.es/en

Regulatory Authority – The Spanish Agency of Medicines and Medical Devices

Regulatory Website- https://www.aemps.gob.es/

Local Authorized Representative Required- Yes

                                                    Drug Approval Process

• Decentralized Process

The Decentralized Procedure (DP) can be used for medications that are not yet approved in the European Union. Manufacturers of these medications may submit simultaneous permission applications to several EU member states. This process is governed by Directive 2004/27/EC. Any state that is only one member of the DP may decide to evaluate the application on its own.

• Mutual Recognition Procedure

  Market authorization issued in one EU member state is recognized in other EU member states under the Mutual Recognition Procedure (MRP). Only in cases where the manufacturer has already received market permission in an EU nation is MRP applicable. The Directive 2001/83/EC establishes the rules for market authorization through MRP. It is necessary to make sure that all MRP applications are comparable if they are sent to multiple EU nations. The nation reviewing the application is referred to as the Reference Member State, and it is its responsibility to inform the other relevant Member States of the application’s status.

• Centralized Procedure

  Manufacturers can submit a single Market Authorization Application (MAA) to the EMA through the consolidated approach. Manufacturers who intend to sell their goods both inside the EU and in Iceland, Liechtenstein, and Norway—members of the European Economic Area (EEA)—will find the CP helpful. Following European Commission (EC) approval, producers can sell their products to healthcare professionals through a centralized mechanism under Regulation (EC) 726/2004.

National Procedure

The national procedure (NP) authorizes medications not covered by the centralized procedure or approved prior to the EMA’s formation. Manufacturers who want market authorization, particularly EU member states, can find it helpful. Applications in this procedure are examined by the relevant EU member state authorities. Every EU member state has its own national protocol.

Regulation

The authorization holder shall clearly notify the Spanish Agency for Medicines and Health Products of the date on which each medicine went into effect for marketing purposes and shall maintain the most recent version of the marketing status of their medications in the Medicines Registry. At least fifteen days prior to the start of marketing, each marketing authorization shall be communicated with.

Without prior marketing authorization from the European Commission or the Spanish Agency for Medicines and Health Products, as well as registration in the medicines register in compliance with the protocols set forth for each case, no industrially manufactured medication may be sold.

Any changes to a medicine’s marketing authorization, whether by notification or request and approval from the Spanish Agency for Medicines and Health Products, are required. These changes must also be documented in the register of authorized medicines, which will be constitutive in the same manner as registration, except medications approved by the European Commission.

Process

After the product’s research phases are successfully finished, a product must apply for authorization to be marketed. To do this, a dossier containing all the findings from the drug’s investigation, information about its manufacturing, a risk management strategy, and other documentation proving the product complies with all authorization requirements must be submitted.

AEMPS examines data from preclinical and clinical trials, as well as information on manufacturing, chemical, and pharmaceutical controls, during the evaluation process. It may also test the drug, its intermediate product, or its raw materials in the agency’s official control laboratories or conduct facility inspections for the drug in question.

Upon a medical product’s evaluation’s positive conclusion, a marketing authorization is granted, along with the AEMPS-established guidelines for appropriate usage (dosage, precautions, and contraindications). These circumstances are covered in the information provided in the package leaflet for each medication and in the data sheet for medical professionals and patients on how to use the medication.

Registration Timeline

• National procedure: 210 days
• Mutual recognition procedure: 90 days + 30 days for the review of translations
• Decentralized procedure: 210 says + 30 days for the review of translations
• Centralized procedure: 210 days + the time required by the decision process of the European Commission.

Generic Approval Process

Article 10(1) of Directive 2001/83/EC states that if the applicant can show that the medicinal product is a generic version of a reference product that is or has been authorised under Article 6 of Directive 2001/83/EC for at least eight years in a Member State or in the Community, he is not required to submit the results of pre-clinical testing or clinical trials.

A generic medication is one that satisfies the following criteria: it has the same active ingredient composition, both qualitatively and quantitatively; it has the same pharmaceutical form as the reference medication; and it has been shown through appropriate bioavailability studies to be bioequivalent to the reference medication.

It should be noted that the eight years following the reference medicinal product’s initial authorization—which offers a period of so-called “data exclusivity”—only apply to reference medicinal products for which the centralized procedure was used to submit the initial authorization application.                                                      

Hybrid Application

In contrast to generic applications, hybrid applications under Article 10(3) of Directive 2001/83/EC need the outcomes of suitable pre-clinical testing and clinical trials in the following three situations:

• When the stringent criteria for what constitutes a “generic medicinal product” are not met;
• When bioavailability studies are insufficient to establish bioequivalence;
• When the active ingredient(s), therapeutic indications, strength, pharmaceutical form, or mode of administration of the generic product differ from those of the reference medicinal product at issue.

As a result, these applications will be based on both fresh data and the outcomes of pre-clinical investigations and clinical trials for a reference product.

                                                   Similar Biologic Application

A biological medicinal product that is similar to a reference biological product must provide the results of appropriate pre-clinical tests or clinical trials related to these conditions if it does not meet the requirements in the definition of generic medicinal products. These requirements include differences in raw material composition or manufacturing processes between the similar biological medicinal product and the reference biological medicinal product. This is stated in Article 10(4) of Directive 2001/83/EC.

                                                                Pharmacovigilance

Spanish Pharmacovigilance Program for Human Medicines: The Spanish Agency for Medicines and Health Products oversees a decentralized structure that unifies the efforts of health administrations to gather, prepare, and handle information on suspected drug side effects when needed. This allows for the identification of new or altered known risks and the execution of any studies deemed essential to validate and/or measure known risks. It consists of the Spanish Agency for Medicines and Health Products, medical professionals, people, and the capable pharmacovigilance bodies of the autonomous communities and the autonomous pharmacovigilance units or centers affiliated with them.

The Spontaneous Notification Program is a pharmacovigilance technique that involves the exchange, gathering, recording, and assessment of reports on possible negative drug effects.

Autonomous Pharmacovigilance Center: Regardless of the title it holds in each autonomous community, this unit is in charge of carrying out the program for spontaneous notification as well as any other pharmacovigilance duties assigned by them.

 Adverse reaction: Any negative, unanticipated side effect of a drug.

License validity – 5 years