Frequently Asked Questions About Medical Device First-in-Human Clinical Trials in Colombia
This is a compilation of the frequently asked questions we receive from medical device clinical trial sponsors when exploring Colombia as their early-stage/first-in-human clinical trial destination.
Why is Colombia a top destination for first-in-human (FIH) clinical trials?
Colombia checks positively on cost, speed, and quality; the three basis requirements for a medical device company to select a destination for its early-stage/feasibility human studies:
Cost: Savings are 30-50 percent over what the same trial would cost in the US or Europe.
Speed: The IRB/EC and MoH (INVIMA) review in Colombia takes 60-90 days.
Quality: Hospitals in Colombia are only allowed to conduct clinical research after they have passed a rigorous ICH/GCP certification process.
Patient recruitment: Colombia's population is 50 million. About 95 percent of the Colombian population is covered by universal health care.
In a nutshell, what's the process to get a clinical trial approved in Colombia?
Select a site from the 110+ GCP-government-certified clinical research centers in Colombia.
Obtain study approval from the site's institutional review board (IRB) (aka ethics committee or EC).
Obtain study approval from Colombia's regulatory agency (INVIMA).
Obtain an import permit at Colombia's Ministry of Industry and Commerce (MinCIT) and ship your investigational devices to Colombia.
What's the scope of your CRO clinical trial services in Colombia?
We can help you operationalize your planned first-in-human medical device clinical trial in Colombia by providing you with the following services:
Study design (i.e., protocol writing, etc.).
Feasibility (i.e., investigator/site selection).
Coordination and attendance of sponsor pre-trial visit in Colombia.
Coordination and execution of the clinical trial agreement (CTA).
Gathering, reviewing study documents: Protocol, investigator's brochure, insurance policy, principal investigator (PI) training certification, and additional supporting documentation as required for approval.
Study submission to the site's ethics committee (EC): Includes gathering of local EC requirement checklist, editing, and assembly of submission package (excludes applicable submission fee).
Study submission to the MoH (INVIMA): Includes completing the application, editing of study documents to comply with INVIMA's guidelines, and final assembly (excludes applicable submission fee).
Submission of one (1) import permit application to Colombia's Ministry of Industry, Commerce, and Tourism (MinCIT).
Coordination and attendance of site initiation visit and training to site's PI, study coordinator, and relevant staff.
Reporting (as mandated by INVIMA and the EC).
We are looking for an investigator and a site to conduct our first-in-human trial, but we are not sure if Colombia is the right place. Can you help us?
Usually medical device companies in need of first-in-human (FIH) clinical trial help approach bioaccess.™ after they have identified a principal investigator (PI) in Colombia at an international conference or through their personal and business connections. This PI is usually someone who has demonstrated expertise in the intended use of the investigational device after presenting at international conferences or after publishing on recognized academic journals.
Only after the medical device company has been in direct contact with the PI and has decided to have him lead and conduct its (FIH/FIM) trial is when we at bioaccess.™ come in and operationalize the trial in Colombia. We contact the PI, gather IRB/EC requirements at the PI's hospital, we assemble the dossier package for IRB/EC submission, and then we apply for MoH (INVIMA) approval. We also help with the importation of the investigational devices and become the project managers and monitors of the study.
So, the choice of conducting a trial in Colombia is first driven by the medical device company's choice of a PI in Colombia. Asides from having the right PI leading your study in Colombia, the country’s advantages are in essence: a) fast MoH review (30-45 days after submission and IRB/EC approval), b) cost savings (~30-50% savings over US hospital fees), and c) large patient pool (50 million people with universal health care).
If your company hasn’t found an investigator in Colombia who has expressed his interest in participating in your FIH trial, then we will have to find it for you —we offer site and PI selection services.
We are planning a trial in Colombia. We already have the site and principal investigator selected. How can you assist us?
If you have a site and principal investigator already selected in Colombia, we can assist you by providing you with our contract research organization (CRO) services in Colombia. We can help you with the trial set-up (e.g., budget and clinical trial agreement approved and executed, ethics committee and Ministry of Health/INVIMA submission, import license, logistics/storage/shipment to site, etc.). We can also help you with post-approval services (e.g., project/study management, site monitoring, medical writing, etc). Read more about our trial-set up services here.
Will our company staff be able to scrub-in with the local investigator at a site in Colombia?
Yes. All of our clients/sponsors want to be able to bring their engineers, physicians and other relevant staff for cases at sites in Colombia. We understand the needs of early-stage medical device companies, and we can accommodate any special request they have to work at a lab in a site in Colombia. We only work with investigators in Colombia at sites that are open to allowing the staff from our clients/sponsors to temporarily “own” the lab or operating room where cases will be done.
Will our company be able to bring any equipment we need to do cases at a site in Colombia?
Yes, you will. We will take care of the proper importation process to get your equipment at the site when you need it for cases. Just tell us what specific equipment you need to bring to Colombia, and at the time of submission of your application for study approval, we will add a clinical supply list with the details of the supporting equipment you need for your study.
How many institutional review boards (IRB) are there in Colombia?
Colombia has about 70 IRBs (also known as “research ethics committees” or ECs) that INVIMA has certified in Good Clinical Practice following ICH/GCP international guidelines. Every site in Colombia can only be associated with one IRB/EC at any point in time.
How many clinical research sites are there in Colombia?
Colombia has about 110+ health institutions (aka IPS' in Colombia) that INVIMA has certified in Good Clinical Practice following ICH/GCP international guidelines.
Will the FDA accept data from a clinical research site in Colombia?
Yes! For international inspections of pharmaceutical trials, the FDA requires conducting the trials according to GCP and under the Ethics Committee approval. For medical devices, the FDA requires the conduct of the trial according to the Declaration of Helsinki (a requirement by Colombian law in Resolution 2378) and to the laws and regulations of the country where the trial is taking place.
If a Colombian research site receives a Good Clinical Practice Certificate from INVIMA, then it is also compliant with FDA requirements for international inspections for studies involving investigational drugs and biologics as well as for studies involving investigational medical devices.
What is the IRB/EC review timeline in Colombia?
Every IRB/EC has its own meeting schedule, however, generally, an IRB/EC in Colombia meets about every 15 or 30 days.
Every hospital in Colombia has its own IRB/EC and their review times depend on their scheduled meeting frequency, and on how efficient and busy they are. Some IRB/ECs meet every week, other ones every two weeks, and other ones meet every 30 days. Top and well known hospitals in Bogota or Medellin usually have longer EC review times. In secondary cities like Cali or Barranquilla, the EC review time at regular hospitals is faster.
You should contact the site that you have in mind for your trial in Colombia, and its staff will tell you the meeting dates for their respective IRB/EC. INVIMA publishes a list of clinical research sites in Colombia and their corresponding IRBs; see the list under the title “Centros de Investigación/Comités de Ética Vinculados a Instituciones Certificadas en Buenas Prácticas Clínicas.
What's the typical competent authority (INVIMA) cycle time for the approval of a medical device clinical trial in Colombia?
INVIMA's medical device committee meets every 30 days (see their meeting schedule here). So, this means that the review takes about 30 days (providing your dossier package/application is reviewed at that meeting). The meeting minutes are published about 7-15 business days after the meeting date. Only then you will know if the committee approved your application or it is requesting additional documentation or clarification before another review (and hopefully approval) at their next meeting.
What has been your typical experience? Does INVIMA's medical device committee typically take the full 40-45 days?
Does this INVIMA timeframe include an opportunity to address and respond to questions or would their questions be issued only at the end of 40-45 days?
Their questions will be issued at the end of the 40-45 days. You will have to submit your answers before the deadline of INVIMA's next meeting.
Does INVIMA have a required time frame to getting back to the sponsor after responses to their questions have been submitted?
No. INVIMA will review your answers and will decide at their next meeting whether to approve your study or not.
How long does it usually takes to get a new pharmaceutical drug developed and approved (from lab to market) in Colombia?
Drug development has two major phases: Pre-clinical and clinical. This phase involves testing the investigational product for safety, toxicity, pharmacokinetics, and metabolism in humans. The information that you gathered from this pre-clinical testing will be submitted to regulatory authorities (in Colombia, to INVIMA), as an Investigational New Drug application or IND. If the IND is approved, development moves to the clinical phase.
The clinical phase (i.e., clinical trials) involves three or four steps:
Phase I trials, usually in healthy volunteers, determine safety and dosing.
Phase II trials are used to get an initial reading of efficacy and further explore safety in small numbers of patients having the disease targeted by the investigational product.
Phase III trials are large, pivotal trials to determine safety and efficacy in sufficiently large numbers of patients with the targeted disease. If safety and efficacy are adequately proved, clinical testing may stop at this step and the investigational product advances to the new drug application (NDA) stage.
Phase IV trials are post-approval trials that are sometimes a condition attached by INVIMA, also called post-market surveillance studies.
It's is very difficult to determine how long this process will take in Colombia. The pre-clinical phase is entirely private and needs no government approval. So, the duration of this phase is entirely depending on your company's cash position, talent pool, and speed to conduct pre-clinical research. The clinical phase may take several years since you will have to conduct at least three clinical trials; each clinical trial may take anywhere from 1 to three years depending on the type of investigational product that you are developing.
Once you gather all the pre-clinical and clinical data, you will need to submit your NDA to INVIMA for approval. INVIMA may take 9-12 months to approve a new drug in the market.
How much does a medical device clinical trial in Colombia cost?
The cost to conduct a medical device clinical trial in Colombia is about 30-50% less than what it would cost to conduct the same trial in the US, Canada or Western Europe.
A medical device clinical trial project has six general cost components (USD):
Study design fees: This includes the costs associated to designing your study and producing its respective documents (i.e., protocol, investigator's brochure, patient informed consent form, case report form). If you decide to outsource this activity to a contract research organization (CRO), then the cost varies depending on the complexity of the study, and it may range anywhere from 25,000 to 60,000 or more.
These fees will depend on the schedule of events in your study protocol. Every trial is different; it is difficult for us as a CRO to give you a ballpark price per patient without fully reviewing your study protocol and creating a proposed budget to present to the site for negotiation and approval. We can help you create a full study budget as part of our CRO services (billable at our standard regulatory consulting hourly rate of $250/hour).
Prices in Colombia are typically 30-50% lower than what the same study would cost at a hospital in North America or in Western Europe. These prices range anywhere between 2,000 per patient for a simple procedure and three follow-up visits to about 10,000 per patient for more complex procedures (e.g., structural heart/cardiovascular implants) and about 12 follow-up visits.
The challenge here is asking sites in Colombia for pricing and waiting for a reply. Most of our clinical trial sponsors already have an idea of the per patient hospital cost they are willing to pay, and they send us a proposed study budget. We then proceed to present the proposed study budget to the site for negotiation.
If you don’t have a proposed study budget we will have to contact several sites to ask them for a per patient ballpark cost and they are usually slow in responding to this type of requests (it is a lot faster if we send them a proposed budget).
Submission fees: About 2,000 (this includes IRB/EC submission of about 1,000 and INVIMA fees of about 1,000).
Translations (from English to Spanish): The average market rate is about 0.25/word (translated to Spanish). The total cost for translating all the documents in a study are generally 5,000 to 15,000 or more depending on the total number of pages and words in Spanish.
Miscellaneous fees: Shipping and importation fees, travel fees, insurance policy, etc.
CRO fees: This includes,
EC/MoH approval: Institutional review board (IRB)/ethics committee (EC) and Ministry of Health (INVIMA) approval.
Trial set-up (i.e., clinical trial agreement (CTA) execution, site visit, import license).
Study monitoring (depending on who you choose to render the study monitoring of your project, expect to pay about 700 per day for a monitoring visit.
Reporting (EC and MoH).
You should budget 40,000-50,000 in total CRO fees depending on the services you choose to contract your CRO for. Click below to see a sample CRO clinical trial services proposal.
How much would you guess clinical trial insurance might be for a small 5-10 patient study in Colombia.
For one of our client/sponsors, on a 10-subject study, Clinical Trial Insurance Services (CTIS) recently quoted them a premium about $7,500 (plus local sales tax) for a $1,000,000 limit for 12 months. This was for a study that required the implantation of a vascular device to treat chronic venous insufficiency.
We don’t get involved in securing insurance for our clients/sponsors. They usually get their insurance policies directly with their own insurance agents. This page has some names of US insurance agencies our sponsors have used in the past.
I am planning to conduct an investigator-initiated trial (IIT) in Canada. I was given a cost of $8,000 to $10,000 per patient. Will this cost be lower in Colombia?
Sponsoring a clinical trial entails numerous regulatory responsibilities, including those set forth in 21 CFR 312 and 812. There is no “lite” version of sponsor responsibilities for sponsor-investigators.
Regardless of who sponsors/funds a trial (for investigator-initiated trials (IIT): a for-profit, non-profit, state, or federal agency; or for industry-sponsored trials (IST): a for-profit entity), you will likely receive from a site a detailed budget. Usually, when a site or an investigator gives you an approximated cost-per patient it only includes actual clinical costs based on the schedule of events on the protocol, and indirect costs (i.e., administrative fees related to start-up costs, an overhead of about 20%, study coordinator time, record storage, etc.).
The costs that an industry-sponsor typically saves on an IIT vs an IST are the following,
Study design (i.e., protocol creation and its accompanying documents including the case report form, the patient informed consent, and the investigator’s brochure)
Study monitoring cost
Data collection and statistical analysis cost
Medical writing and publication of the results
On an IIT, the study design/protocol is a) authored by the investigator within the course and scope of his/her university/hospital employment; or b) an investigator within the course and scope of his/her university employment jointly with an employee of another entity (e.g., an employee of another non-profit institution or an employee of the company funding the study). The same goes for the other costs that I mentioned above.
One of the greatest challenges for IIT is the contract negotiations toward a clinical trial agreement, which averages 70.5 days among the companies surveyed for a recent report by Cutting Edge Information, a Research Triangle Park, N.C.-based business management and consulting firm. The primary reasons for such elongated timelines: complicated contract review processes and complex negotiations and/or disagreements.
If you decide to conduct an IST, then your company will likely assume the cost of designing the study and authoring the protocol and its accompanying documents. This cost may be around $20-60k depending on the complexity of the study. You —the sponsor— will also have to assume the other costs that I mentioned above.
Once a life sciences company agrees to fund an IST, they are essentially spending money on a trial over which they have no control.
IIT clinical trial agreements (CTAs) are different from CTAs for ISTs for three main reasons:
The company does not have the sponsor’s regulatory responsibilities.
The investigator is asking for help from the company, instead of the other way around.
The investigational product is usually a marketed product (as in Phase IV studies).
The main areas of interest in IIT CTAs are the following:
Compliance with laws
Clearly specific who is the “sponsor” from a regulatory perspective.
Sponsor (i.e., PI and/or site, if site is contracting on PI behalf) must comply with applicable laws and regulations.
From industry perspective, helps ensure company can use data in FDA applications, if needed/desired.
Investigator and sponsor duties.
Data ownership rights.
Site/investigator typically owns data, but provides company with periodic and final reports.
Site/iInvestigator may provide a data license to company.
Intellectual Property (PI).
Typically more liberal publication rights for investigator, although company may still review (and perhaps comment) and postpone for certain reasons.
Memorialize that investigator is “responsible party” for clinicaltrials.gov purposes.
Privacy (including HIPAA).
May or may not be mutual – companies often consider their interests in the study, what information they actual provide, and desired use of data and results.
Ex: Does the company want the ability to use the data in marketing submissions or otherwise?
Ex: Is the company supplying proprietary data to help develop study, or was the idea for the study completely the investigator’s?
Investigator is the sponsor and is therefore responsible for monitoring from a regulatory standpoint.
Company may require audit/monitoring rights, depending upon level of company’s involvement.
Serious adverse event (AE) reporting obligations:
Investigator is the sponsor and responsible for regulatory obligations.
Agreement typically requires site/investigator to submit AEs to company.
In post-market context, company may be required to submit AEs if they are involved in the study.
Typically far more limited than in a regular CTA, but depends on company involvement with the study.
Ex: harms directly caused by company product (manufacturing defects/product liability); company use of study data.
Subject injury (it varies): No company reimbursement vs. injuries directly caused by a problem with company product (similar to indemnification) vs. broader, if company is more involved with the study.
Subject injury and indemnification —a major focus in most ISTs with experimental treatments— are typically smaller factors in IIT CTAs because the investigational product is usually a marketed product and the company does not want to accept liability for a study over which it has minimal control. Normally, the company warrants that the investigational product is manufactured per specifications, the investigator indemnifies the company for subject injury, and the company indemnifies the investigator-sponsor for possible commercialization.
If you decide to conduct a trial outside your home country you will have to plan for costs associated with shipping an importation, international travel, etc.
We wrote an article that may give you some idea of the type of savings that you can have by running your trial outside of the US or Canada. The article is titled Did you know 40-65% of all clinical trials involving FDA-regulated products are being conducted overseas?
Every trial is different. It is almost impossible for anybody to give you an approximated cost per patient in Colombia without reading the protocol, identifying the schedule of events on it, putting together a budget grid, and contacting sites in Colombia for pricing.
We have been involved with trials in Colombia that range from $2,000 to $20,000 per patient in different therapeutic areas involving drugs and medical devices. Every trial is totally different from the other. All we can give you (based on our own experience and from gathering international data) is approximated percentages of the savings that you will have when conducting a comparable trial in the US vs in Colombia.
What’s customary in IST is that the sponsor firsts presents a draft/proposed budget to a site (the sponsor sometimes hires the services of the CRO to create this budget), and then waits for the site to respond with a counteroffer. When you present a site a proposed budget, the site will look at it and will determine if it is willing to conduct the trial at your proposed prices or not; here is when the ping-pong game of budget negotiations begin until both parties agree on a final agreed-upon study budget that will be the genesis of a clinical trial agreement between the sponsor and the site.
What are the document requirements for medical device or drug clinical trial approval in Colombia?
Medical devices: See here
Pharmaceutical drugs: See here
All other innovative medical technologies (biotechnology, gene therapy, tissue regenerating) in Colombia are considered "advanced therapies." Colombia's Ministry of Health will evaluate "advanced therapy" study approval applications on a case-by-case basis.
Do a fully executed clinical trial agreement/contract and budget are required for INVIMA clinical trial approval submission?
Yes, but only the study budget (final). You do not have to submit your clinical trial agreement between your company and the site in Colombia. Please see the question and answer above for clinical trial approval requirements at INVIMA in Colombia.
We have a medical device at the R&D (no approval by any regulatory body) stage and we want to know what type of biocompatibility testing would be sufficient for a Colombian IRB to approve a clinical study. Specifically, we would like to know if a systemic toxicity (90 day sub-chronic in rats) or an animal study (dog) would sufficient to show safety prior to proceeding with a clinical study in Colombia.
Every IRB/EC in Colombia has its own set of requirements to approve a clinical study. You should first select the site where you plan to conduct your study, have them tell you the IRB they are associated with, and have a pre-submission meeting with the IRB to let them tell you if the animal data you have is considered sufficient for study approval. IRBs in Colombia generally follow INVIMA's guidelines for the approval of a clinical study.
INVIMA has general requirements for animal data. INVIMA requires that the device’s direct patient risks be mitigated by doing device level tests (i.e., biocompatibility, strength test, corrosion test, traceability, etc.). It's up to the sponsor to prove to INVIMA the device's safety by providing as much documentation as the sponsor deems necessary. You can read INVIMA requirements to approve a medical device clinical study here.
Do I need a Good Laboratory Practices (GLP) certificate to get my drug trial approved in Colombia?
No. You will only need to provide your Good Manufacturing Practices (GMP) certificate. Please see the requirements for trial approval in Colombia here.
What are the reporting requirements for a medical device clinical trial in Colombia?
You must comply with the technovigilance reporting mandated by the IRB/EC at the research site you plan to conduct your trial, and by INVIMA. The report to INVIMA must be sent using this form.
Serious and non serious adverse events (as they occur)
Follow-up (every six months)
Final device usage accountability report (end of the study)
Does Colombia have any clinical trial registry or database where the trials conducted in the country are available for public view?
Colombia's INVIMA has a list (in Spanish) of trials that it has approved. See the list here.
You can also search ClinicalTrials.gov for clinical trials in Colombia.
We are working on a stem cell project, and we are starting to look at sites for our first-in-human trial work. How difficult would it be to bring stem cells from the US into Colombia for the trail?
Easy! All we need is approval from the institutional ethics committee at the site to officially start recruiting patients. We will take care of the importation process. It should be pretty fast and straightforward.
What's the process to import investigational products into Colombia?
In order to legally import the investigational product and additional accessories named on the clinical supply list sent with your INVIMA submission, we must apply on your behalf —for each shipment— for a separate application for an import permit approval at the VUCE office in the Ministry of Commerce, Industry and Tourism (MinCIT). The average processing time is between 5 to 10 business days.
Our product already has CE Marking, it already has marketing authorization from INVIMA, and we are already selling it in Colombia. We would like to conduct a trial on the product (for the same indication of use it is approved for) in Colombia so that we can obtain clinical data for an FDA PMA submission. Does that make our trial easier in Colombia?
Yes! All you have to do is find a clinical research site and get your study approved at its IRB/EC. INVIMA doesn't have to evaluate and approve your study (since you already have INVIMA approval to import your product into Colombia).
We plan to conduct a non-interventional retrospective research study in Colombia. Which agency do we need to apply for ethics or IRB study waiver or exempt status?
You will need to submit your study documents for evaluation and approval at the institutional review board (IRB or also known as institutional ethics committee) that is associated with the site/center where you plan to conduct the study. Every hospital facility in Colombia has its own IRB/ethics committee. If you want to have an official letter from the regulatory agency saying that you are exempt from their jurisdiction, then you have to contact INVIMA and submit a derecho de petición request. You will get an answer from INVIMA within 30 business days.
What should I know about translations?
All documents must be translated to the "Colombian" Spanish dialect. The Spanish spoken in Latin America changes from country-to-country and INVIMA has rejected documents such as an Informed Consent Form that is not easily understood by an average native Colombian citizen.
We recommend that sponsors translate their documents by Colombian Spanish-speaking translators certified by the Colombian Ministry of Foreign Affairs.
A certified translator is a person who has passed the linguistic proficiency test from the relevant agency designated by the Government of Colombia for this purpose. Any translator who passes this test should take office before the Superior Tribunal of the Judiciary District and apply for a certification from the Ministry of Justice and Law, which will accredit him or her as an official certified translator. The certified translator must register his name with the Ministry of Foreign Affairs by submitting a copy of the Oath of Office and a copy of the certification issued by the Ministry of Justice and Law.
We offer our sponsors certified translation services and works with local Colombian certified translators duly endorsed by the Ministry of Foreign Affairs (who therefore, hold the relevant certification issued by the Ministry of Justice and Law) with past experience in the clinical research industry. This will ensure that our sponsor's translations as accurate, faithful and valid to be presented to any government agency such as INVIMA.
Although INVIMA doesn’t specifically require that sponsors submit documents translated to Spanish by official government-certified translators, it’s customary —and expected by the recipient of the document— in Colombia that all translations (both in private business and government dealings) are done by government-certified translators.
Just like there are differences in English expressions, spelling, industry and business terminology among English-speaking countries (USA, UK, Australia, Canada, etc.) Spanish varies throughout Latin America. Colombian Spanish has its own peculiarities just like Mexican or Argentinian Spanish have. For Colombia’s INVIMA purposes, this is important in two ways: a) the evaluation committee members should be able to easily understand the protocol, the investigator's brochure (IB), and all other study-related documents, and b) the patient's informed consent form (ICF) should be written in such a way that an average Colombian native citizen is able to easily understand (there have been cases where the committee has rejected ICFs for being written in non-Colombian Spanish).
A printed document that has been translated by a certified translator in Colombia will have (by law) the following elements:
A "Certified Translation" header.
A consecutive certified translation control number.
The seal of the official translator in which the translator's full name, his or her certification number issued by the Ministry of Justice, the certification issue date, and the languages that the translator is certified to translate.
The signature of the translator in the last page, or at least, the initials of the translator if the document has several pages.
Through a seal and a signature, the translator certifies that the translation is correct and complete and takes responsibility for what is translated. This way, the translator basically acts like a notary authenticating a document. A certified translator is also authorized to be an official interpreter, translating declarations and affidavits before a notary or a judge.