The Caribbean Regulatory System (CRS)

The Caribbean Regulatory System (CRS) is an initiative of the Caribbean Community and Common Market (CARICOM) and is managed as a regulatory unit within CARICOM’s regional public health body, the Caribbean Public Health Agency (CARPHA). It is supported by a number of partners, including the Pan American Health Organization/World Health Organization (PAHO/WHO), PAHO designated National Regulatory Authorities of Regional Reference (NRA/RR) (Argentina, Brazil, Canada, Chile, Colombia, Cuba, Mexico, United States), and the Bill and Melinda Gates Foundation (BMGF).

 

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LEGAL AUTHORITY:  

The CRS derives its legal authority from CARPHA’s public health mandate , the Caribbean Pharmaceutical Policy , and various other Ministerial health frameworks  and decisions.

CARICOM’s Technical Advisory Committee on Pharmaceutical Policy (TECHPHARM), made up of representatives from CARICOM Member States and institutions, advises the CRS on policy and technical matters.
 
The CARPHA Drug Testing plays an integral role, including thorough post market surveillance.

PURPOSE: 

The CRS helps states perform key regulatory functions. The CRS does this using efficiencies, such as reliance on reference authorities and a focus on essential medicines, to enable a sustainable enterprise in the resource-constrained environment of small states. This contributes to CARPHA’s mandate to prevent diseases, promote health and respond to public health emergencies.

FOCUS ACTIVITIES:  

Very broadly, the CRS carries out the following regulatory focus activities: 

  • *Conducts abbreviated reviews of product dossiers for safety, quality, and efficacy of medicines and vaccines that meet the following CRS eligibility criteria, including:
    • 1) the product has a current approval/registration/marketing authorization from a CRS-designated “reference authority” (national regulatory authority of Argentina, Brazil, Canada, Chile, Colombia, Cuba, European Union, Mexico, United States or WHO prequalification); and
    • 2) the product is is named on the most recent version of the WHO Essential Medicine List (here) or PAHO Strategic Fund (here) - this includes innovative and generic medicines, and vaccines;"
  • *Recommends all favourably reviewed products to CARICOM Member States, and requests completion of in-country processes to grant approval/registration/marketing authorization/import permit within 60 calendar days,
  • *Carries out pharmacovigilance and post market surveillance of medicines and vaccines in the region.

BENEFITS TO INDUSTRY: 

The CRS benefits industry in a variety of ways. It offers a central portal for access to CARICOM’s markets of over 17 million people.

  • *These Member States are:
    • Antigua and Barbuda, Bahamas, Barbados, Belize, Dominica, Grenada, Guyana, Haiti, Jamaica, Montserrat, Saint Lucia, St. Kitts and Nevis, St. Vincent and the Grenadines, Suriname, and Trinidad and Tobago
  • *Associate Member States are:
    • Anguilla, Bermuda, British Virgin Islands, Cayman Islands, and Turks and Caicos Islands
  • *Because these countries are diverse and have different regulatory requirements and timelines for processing, the CRS benefits companies by giving them one streamlined set of requirements and a known and accelerated timeline for processing compared to what currently exists.
  • *The requirements are based on an abbreviated and accelerated procedure WHO uses for Prequalification when a product has already been registered by a reference authority.
  • *The CRS also participates in the WHO Collaborative Procedure, whereby sponsors that hold a prequalified product can authorize the release of corresponding assessments and inspectional information, to the CRS for review.

MORE INFORMATION

For more background and context, please see the recent article “Regionalization as an approach to regulatory systems strengthening: a case study in CARICOM Member States” published in the Pan American Journal of Public Health. 

CONTACT

For more information or submission inquiries, please contact: CRSRegistration@carpha.org

CARICOM Member state engagement

CARICOM Ministers of Health issued a decision to implement the CRS in 2014 and have reaffirmed that decision in subsequent years

The CRS has also begun to pursue Memorandums of Understanding with individual states to further cement engagement. The below graphic shows the present state of this engagement

Note that the OECS Pharmaceutical Procurement Service signed an MOU so those participating countries are coloured in.

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CARPHA/CRS recommended medicines

CARPHA/CRS recommends the medicines listed in this document to CARICOM member states for granting marketing authorization/import permit.

Latest News

    Laboratory Technician

    CARPHA/CRS Participates in Access to Medicines Meeting

    The CARPHA/CRS participated in a regional PAHO- sponsored meeting on Access to Medicines in Port of Spain, Trinidad and Tobago October 11-12, 2017. Delegations of government health and procurement officials from Bahamas, Belize, Guyana, Jamaica, the Organization of Eastern Caribbean States, Suriname, and Trinidad and Tobago attended, and discussed a variety of pressing issues including quality, price, procurement, and other supply chain challenges. The group will continue to meet and work on common challenges, including related to improving access to strategic and high cost medicines through a variety of mechanisms, including use of the PAHO Strategic Fund, and the CARPHA CRS.

     

    National Regulatory Authority of Guyana Grants Marketing Authorization  for a CARPHA CRS Recommended Medicine
    A CARPHA/CRS recommended medicine was recently granted marketing authorization by the National Regulatory Authority of Guyana, signifying the first time ever a CARICOM Member State has done this in the history of the newly created mechanism. The product, a 1st line triple-fixed dose combination therapy for HIV, manufactured by Mylan, was fast-tracked for marketing authorization through a voluntary agreement between Guyana and CARPHA. The total time from receipt of the application by the CRS to marketing authorization by Guyana was 3 months or 90 calendar days. This is a much improved timeline over what currently exists in many Caribbean countries, where limited resources hamper regulatory activities, sometimes taking years for products to gain the legal approval needed for access by patients. The CARPHA/CRS recommends only essential medicines that have already been approved by a reference regulatory authority, such as WHO or the US Food and Drug Administration, and encourages Member States to grant marketing authorization to these  products within 60 calendar days. It is part of a broader effort by partners, including PAHO/WHO, and the Bill and Melinda Gates Foundation, to strengthen regulatory capacity in the region, and improve timely access to strategic and high cost medicines for patients.

Operational Policy

Glossary of Key Terms 
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.
Accountability, Confidentiality, Conflict of Interest, and Transparency 
  • 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.
Eligibility Criteria 

The CRS currently accepts dossiers for finished products already given at least one marketing authorization by 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; NRAs/RR provide capacity building support to other regulatory authorities in the region. NRAs/RR include the countries:    

    • Argentina,  Brazil, Canada, Chile, Colombia, Cuba, Mexico, and United States of Americia
    • The CRS also accepts dossiers for products already given marketing authorization in the European Union. This is because of the close historical and cultural ties to countries in the Caribbean.
  • Together, these authorities are referred to as “Reference Authorities” or “RAs”.
    • The CRS reserves the right to modify the list of RAs in the future, including for example, factor in new assessment results by PAHO for NRA/RR.
    • The CRS also accepts dossiers for finished products prequalified by the World Health Organization (WHO).
    • All products must be listed on the most recent versions of the WHO Essential Medicines List (here) or PAHO Strategic Fund (here).
Submitting a Dossier 

 

Screening of Dossiers Submitted 
  • 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.

 

Dossier Assessment 
  • 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.
    Site Inspection 
    • 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.

     

    Meeting with Sponsors 
    • 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.
    Issuance of Recommendations for Marketing Authorization/lmport Permit 
    • 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.

     

    Marketing authorization in CARICOM Member States 
    • 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 5 countries that conduct Marketing Authorization:
           Guyana
           Haiti
           Jamaica
           Suriname
           Trinidad and Tobago

    Maintenance of Recommendation Status 
    • 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.

     

    Variations 
    • 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.
    • Some types of changes are so significant that the sponsor must re-submit the product. These include:
    • 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.

     

    Suspension, Revocation, Recall, Withdrawal 
    • 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.

     

    Timelines 
    • The reviews sponsor dossiers and issues a decision within 180 calendar days (though typically within 60 calendar days) from the date of accepting the dossier for review, not including time that additional information or clarification is needed from the sponsor after accepting the dossier.
    • The The target timeline from CRS recommendation to marketing authorization in-country is 60 calendar days.
    Appeals and Complaints 
    • 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.
    User Fees 
    • The CRS will charge user fees for the regulatory work it conducts in the future, which will enable a sustainable system.
    • The project is currently in the pilot phase and all user fees have been waived
    • Note that the Member States may charge their own fees in the marketing authorization phase.  It is important to keep these fees in place as they are a meaningful source of revenue for local authorities.

    Stakeholder Information

    FOR INDUSTRY
    Question: Can I submit the dossier and/or packaging/labelling in another language besides English?

    Answer: No, at this time, all dossier/packaging/labelling materials must be submitted in English.

    Question: What climate zone do I need to submit stability data for? And if this differs from the Reference Authority zone, what do I do?

    Answer: WHO’s prequalification program has guidance on this (http://apps.who.int/prequal/info_general/documents/guidelines/Storage_June2015.pdf) and the CRS follows this approach. Generally, zone IVb stability data (data generated at 302C/75 5%RH) on the primary or production batches of the product in the same packaging as approved for marketing of the finished product in the Reference Authority (RA) country, should be provided.

    If these zone IVb data are not available at the time of submission, applicants should initiate as soon as possible long-term stability testing at these conditions in the same packaging as approved by the RA. When complete, the full long term data (at minimum 12 months) should be submitted to the CRS team. Questions regarding this matter can be directed to CRSregistration@CARPHA.org 

    The CRS team has compiled procurement data for select priority medicines from sample Member States and procurers in the region. It can be downloaded here
    Question: What happens if my product is recommended by the CRS?

    Answer: A positive CRS review is posted on the CARPHA/CRS website, and triggers a process whereby the CRS notifies CARICOM Member States and Associate Member States, as well as regional and national procurers, of the recommendation. Pertinent dossier information, such as the assessment report compiled by the CRS, is then shared with focal points in each of these entities, and the clock begins to tick for sovereign countries to turn the recommendation into a marketing authorization. The goal is 90 calendar days.

     

    Trinidad and Tobago’s 2016 procurement list can be found under “New pharmaceutical pricelist booklet”.  Click here 
    The CRS team has compiled procurement data for select priority medicines from sample Member States and procurers in the region. It can be downloaded here.

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    FOR GOVERNMENTS AND CRS FOCAL POINTS

    The CRS has requested countries/territories to provide officially nominated government focal points to engage with the CRS. The following are terms of reference for focal point responsibilities. Click here to read terms of reference.