Applicant / Sponsor / Application / Dossier

An applicant or sponsor is the person or company who submits an application or dossier for marketing authorization of a new medicine, an update to an existing marketing authorization, or a variation to an existing marketing authorization.

Finished Product

A product that has undergone all stages of manufacture, including packaging in its final container and labelling.

Marketing Authorization and Registration

Marketing authorization is an official document issued by the competent national medicines regulatory authority for the purpose of marketing a product after evaluation for safety, efficacy, and quality. Once a product has been given marketing authorization, it is included in a list of authorized products—the register—and is often said to be “registered” or have a “registration."

The CRS uses the term “registration” instead of “marketing authorization” in that both terms imply the same regulatory review, but only a sovereign country can authorize products for sale in their market.

Medicine

Any substance or pharmaceutical product for human use that is intended to modify or explore physiological systems or pathological states for the benefit of the recipient.

CRS staff obey a code of conduct including observe guidelines on confidentiality and conflict of interest.

Consultants such as expert advisors obey guidelines on confidentiality and conflict of interest and are required to make a confidentiality undertaking and declaration of conflict of interest known as an “Agreement for Performance of Work” or “APW”.

CRS registration recommendations are made public on the CARPHA website.

The CRS publishes other relevant regulatory information on the CARPHA website. Relevant information may include key policies, guidelines, decisions, and performance metrics.

Essential Medicine

Medicines, vaccines and other medical products must be deemed essential as per inclusion in the most recent versions of the WHO Essential Medicines List or PAHO Strategic Fund. Medicines that are not listed as ‘essential’ may be considered based on public health need or value to CARICOM. Applicants are advised to contact the CRS to enquire about the eligibility of unlisted medicines.

WHO Pre-Qualified Medicines, Vaccines and Biotherapeutic Products

The CRS accepts applications for review of finished products prequalified by the World Health Organization (WHO). Applicants are advised to utilize the WHO Collaborative Procedure for the submission of key documents, and expedited review.

Medicines

The CRS currently accepts applications for review of finished pharmaceutical products granted marketing authorization by one of the following Pan American Health Organization (PAHO) designated National Regulatory Authorities of Regional Reference (NRA/RR). These authorities have been assessed by PAHO to meet reference standards in accordance with PAHO Directing Council Resolution CD50.R9. The NRAs/RR provide support for capacity-building to other regulatory authorities in the region. The NRAs/RR of the following countries are eligible:

• Argentina: Argentinian National Institute of Drugs / Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT)
• Brazil: Agencia Nacional de Vigilancia Sanitaria. Ministério da Saúde (ANVISA)
• Canada: Canadian Health Products and Food Branch Inspectorate (HPFBI) – Health Canada / Santé Canada
• Chile: Instituto de Salud Pública (ISP)
• Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA)
• Cuba: Centro para el Control Estatal de la Calidad de los Medicamentos, Ministerio de Salud Pública (CECMED)
• Mexico: Mexican Federal Commission for the Protection Against Sanitary Risks / Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)
• United States Food and Drug Administration (US FDA).

The CRS also accepts applications for non-biologic medicines granted marketing authorization by:

• Australian Therapeutic Goods Administration (TGA)
• Austrian Medicines and Medical Devices Agency / Österreichische Agentur für Gesundheit und Ernährungssicherheit (AGES)
• Belgian Federal Agency for Medicines and Health Products (AFMPS- FAGG)
• Agency for Medicinal Products and Medical Devices of Croatia (HALMED)
• Cypriot Pharmaceutical Services (CyPHS)
• Czech State Institute for Drug Control (SÚKL), Czech Institute for State Control of Veterinary Biologicals and Medicines (ISCVBM)
• Danish Health and Medicines Authority (DKMA)
• Estonian State Agency of Medicines (SAM)
• Finnish Medicines Agency (FIMEA)
• France: French National Agency for Medicines and Health Products Safety (ANSM)
• German Federal Ministry of Health (BMG), Central Authority of the Laender for Health Protection regarding Medicinal Products and Medical Devices (ZLG)
• Greek National Organisation for Medicines (EOF)
• Hungarian National Institute of Pharmacy and Nutrition (NIPN)
• Icelandic Medicines Agency (IMA)
• Irish Health Products Regulatory Authority (HPRA)
• Italian Medicines Agency (AIFA)
• Japanese Ministry of Health, Labour and Welfare (MHLW), Japanese Pharmaceuticals and Medical Devices Agency (PMDA)
• Latvian State Agency of Medicine (ZVA)
• Liechtenstein's Office of Healthcare (AG)
• Lithuanian State Medicines Control Agency (SMCA)
• Maltese Medicines Authority (MAM)
• Norwegian Medicines Agency (NOMA)
• Polish Chief Pharmaceutical Inspectorate (CPI)
• Romanian National Agency for Medicines and Medical Devices (NAMMD)
• Slovak State Institute for Drug Control (SIDC)
• Slovenian Agency for Medicinal Products and Medical Devices (JAZMP)
• Spanish Agency of Medicines and Medical Devices (AEMPS)
• Swedish Medical Products Agency (MPA)
• Swiss Agency for Therapeutic Products (Swissmedic)
• United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA)
• European Directorate for the Quality of Medicines & HealthCare, EMA - European Medicines.

Biotherapeutic Products

The CRS also accepts applications for review of biotherapeutic products and their biosimilars (including insulins). Applicants are advised to review the eligibility criteria outlined here prior to submission: (link to revised eligibility criteria).

Please note that the list of RAs varies for innovative biologics and biosimilars, versus medicines.

The CRS reserves the right to update the list of reference authorities in the future, including for example, factor in new assessment results by PAHO for NRA/RRs.

Medical Products Granted Emergency Authorization for COVID-19

The CRS will accept applications for review of medical products granted emergency use authorization or the equivalent by a regulatory authority of reference: medicines, vaccines, in vitro diagnostics (test kits).

The medical product must meet one of the following criteria:

(I) Be granted Emergency Use Authorization (EUA) for prevention, treatment or in vitro diagnosis of COVID-19, by the WHO Emergency Use Listing for SARS-CoV-2; or

(II) Be granted authorization for emergency use for prevention, treatment or diagnosis of COVID-19 by one of the national regulatory authorities of reference based on type of product shown in Table 1.

Table 1: Regulatory Authorities of Reference (Reference Authorities) by Product Type

The eligibility and technical requirements may be found at CRS Requirements for EU authorized product reviews v2:12.2020.

The CRS reserves the right to update the list of reference authorities in the future, including for example, factor in new assessment results by PAHO for NRA/RRs.

Dossier submissions should be made to CRSRegistration@CARPHA.org.

The documents set forth in the Dossier Submission Requirements must be submitted and sponsors are encouraged to work with CRS staff to ensure files are properly identified and labeled upon submission.

See our Quick Reference Guide for the list of requirements for medicines approved by a reference authority or the WHO

Applicants seeking reviews of innovative biotherapeutic products or similar biotherapeutic products (biosimilars) including insulins should refer to the Guidance for Biotherapeutic Product Applications.

Each product dossier submitted by a sponsor is screened for completeness against the list of required documentation before being assessed.

The CRS conducts two screenings of dossiers. The first is a preliminary or pre-screening of the dossier to check that all required documentation is submitted. This may be done with the sponsor present. If documentation is missing at this stage, the CRS will send a communication to the applicant and request a 10 business day turnaround time. The second is a more in depth screening to check that the submitted material is sufficiently comprehensive and of high quality for the CRS to proceed to assessment.

Dossiers that are considered complete as the result of screening processes are retained for assessment by the CRS.

If the dossier is accepted for assessment, the sponsor is informed of this by written communication. This serves as an agreement between the CRS and the sponsor for the participation in the CRS review and a commitment to comply with the provisions of the CRS review process.

The product information submitted in the dossiers is assessed by a multidisciplinary team of experts.

The assessors must comply with conditions of appointment, as well as confidentiality and conflict of interest rules of the CRS.

The CRS may ask questions of the sponsor during the assessment stage.

The CRS provides an assessment report to the sponsor following the assessment.

The CRS reserves the right to share the assessment report and relevant documentation, including the product summary characteristics, with any interested authorized CARICOM member state.

The CRS expects that sponsors comply with Good Manufacturing Practices (GMP) and this is assessed through correspondence and verification of GMP with RAs. The CRS reserves the right to conduct site inspections.

The CRS reserves the right to request meetings with sponsors at any time.

Meetings requested by sponsors are granted at the discretion of the CRS.

The CRS issues a a recommendation to CARICOM states and the sponsor if the dossier is reviewed favourably.

The conditions of the recommendation include:

• That no changes will be made to pharmaceutical aspects of the product without prior conforming to the CRS policy on variations.
• All information must be consistent with the approved product information.

The CRS publishes recommended products on its website, including, but not limited to, the following information:

• Generic name, dosage form, and strength;
• Brand name, if applicable;
• Registration holder;
• Registration number;

Each sponsor receives a written communication from the CRS informing it of the outcome of the assessment.

If a dossier is recommended, the CRS contacts focal points in each Member State to initiate the marketing authorization process.

It shares relevant dossier documentation, including assessment reports, and if requested, makes the full dossier available.

The intent is for this stage to be accelerated and in general Member States typically request four items: 1) completion of an administrative application form, 2) submission of the CRS assessment report and certificate of recommendation, 3) payment of user fee, and 4) identification of an importer.

The goal is to turn the CRS recommendation into a lawful marketing authorization in CARICOM countries within 60 calendar days.

The CRS uses Memorandums of Understanding between CARPHA and the individual Member States to facilitate this process, however some countries have elected to develop fast track processes that recognize the CRS recommendations independent of the Memorandums of Understanding.

For more information on specific requirements and other related information (such as lists of importers, where available), please contact the CRS. The CRS recommends that applicants submitting dossiers begin the process of identifying an importer as soon as possible so that there is no delay upon any recommendation for marketing authorization.

Note that currently only 6 countries that conduct Marketing Authorization:

• Belize
• Guyana
• Haiti
• Jamaica
• Suriname
• Trinidad and Tobago

Sponsors achieving CRS recommendation for a given product keep that status for 5 years, provided they notify the CRS of any changes or variations in manufacture and control that may have an impact on the safety, efficacy and quality of the product (see “variations” section.

The renewal process will be abbreviated in comparison to the first recommendation but will include showing proof of marketing of products in CARICOM markets.

The CRS requests that sponsors notify the CRS of variations, including provide notifications of variations to dossiers when notifying and receiving decisions from the RA on which the product’s eligibility is based.

The following are examples of significant types of changes that require the sponsor to re-submit the product.

• A change of the API to a different API.
• Inclusion or removal of an API.
• A change in the dose of an API.
• A change in the dosage form.
• A change in the route of administration.
• A change in manufacturing site.

Please consult with the CRS as to the appropriate action regarding a variation if there is any uncertainty about the right path.

The sponsor must notify the CRS of any suspensions, revocations, recalls, and/or withdrawals of the sponsor’s products on the CRS registry—including in markets beyond those of the RA.

The CRS reserves the right to suspend or revoke a product recommendation, including, but not limited to, the following situations:

• The quantitative or qualitative composition is not as agreed in the registration.
• The product is found not to be in compliance with the conditions of the registration.
• The product is a danger to public health.

The CRS reviews each product dossier and issues a decision within 90 calendar days from the date of accepting the dossier for review. This does not include the time taken for sponsors to submit additional information or clarification, if needed after accepting the dossier. The current turn-around time is within 60 calendar days.

The target timeline from the issuance of the CRS’ recommendation to marketing authorization in-country is 120 calendar days.

Applicants are expected to respond to queries sent by the CRS within specific time periods to minimize delays as follows:

• Response to Initial query: The applicant should submit a response to the initial query within 30 calendar days. If no response is received after 30 days, a Follow-up query will be issued.
• Response to Follow-up query: The applicant should submit a response to follow-up queries within 30 calendar days. If no response is received, to satisfy eligibility requirements after 6 months following the initial submission, a Notice of Ineligibility will be issued.  In general, if a dossier fails to meet eligibility within 6 months following initial submission, it will be closed. 
• If a valid dossier fails to progress from ‘Valid’ to ‘Recommended’ after 6 months, the dossier will be closed." 

The CRS accepts any request for appeal or filing of a complaint, provided that the sponsor makes the request or filing in writing.

The CRS addresses appeals and complaints within 30 business days in a written response.

The user fee is outlined below:

Application Fee For manufacturers or market authorization holders: $300 USD per medicine application (due before submission can be considered).

For local importers: $150 USD per medicine application (due before submission can be considered)

Note: The entity that is submitting the application to the CRS (known as the “applicant” (either importer or manufacturer)) is responsible for paying the application fee. This fee is due before the product can be considered, and will be subject to a renewal fee at the time of expiry of the recommendation. Applicants must provide all requested documentation within one year of initial submission, or re-apply by paying the application fee again.

The application fee is independent of the CRS recommendation decision. The lower fee for local importers is designed to encourage manufacturers to submit products through importers when possible, given that in many CARICOM countries, a local importer is a requirement for marketing authorization. Manufacturers/importers will still be responsible for paying all user fees at the local level, independent of the CRS user fees.

The CRS user fees may be reviewed and updated periodically based on the demand for reviews and the resource requirements. Fees may be paid electronically, using the following instructions:

Payment Via PayPal by clicking HERE

Payment to CARPHA’s account at CIBC First Caribbean Bank (we will provide the banking details)