This is the third part of a three-part story on CMC filing challenges and opportunities in Latin America. Part I provided an overview of the region. Part II focused specifically on Brazil. This part provides more detail regarding Mexico, Argentina, Colombia, and Peru.

At the FDA/Xavier PharmaLink conference held virtually in March 2020, Merck CMC Director and Senior Scientist Tatiana Gaban—who has led Merck’s CMC Latin America team based in Sao Paulo—provided an in-depth look at the CMC regulatory challenges Latin America. Below are her analyses of the challenges and opportunities in Mexico, Argentina, Colombia, and Peru.

[RELATED: For information on the FDA Drug Review Process, check out our Checklist for interacting with FDA.]

Checklist: Interacting with FDA During Drug Review Process

Mexico

COFEPRIS serves as the Mexican regulatory authority. It was founded in 2001. In terms of CMC requirements, it is a complex agency (Figure 1).

Figure 1 Overview of COFEPRIS

“I would call the level of activity medium, although recently Mexico has released some important regulations,” Gaban commented. “But comparing it to the other agencies, COFEPRIS is not that active in terms of creating new draft or final regulations.”

Activity is measured by the volume of draft and final regulations a health authority promulgates and its frequency of interactions with trade associations and the drug companies it regulates, she explained.

Country-Specific Requirements

Regarding critical or country-specific requirements, there are presubmission meetings that occur in the country with the submission beforehand of an extensive amount of specific data:

  • Supporting data for facility information regarding the company’s supply chain
  • Stability data for all approved supply chains, including bill of materials (BOMs), full analytical raw data such as chromatograms, lab records, analytical results, and calculations for all stability tests; this must include time zero and the final timepoint
  • Certificates of Analysis (CoAs) for all drug substances, drug products, excipients, and packaging materials associated with the stability batches

In addition, there is a specific requirement in Mexico to submit batch genealogy.

Also required are GMP certificates for all sites involved in the supply chain. These must be valid during the whole lifecycle until the last product batch expiration date.

COFEPRIS requires validation reports with “wet signatures”—as opposed to electronic signatures—that include analytical, process, and transport exercises.

Approval time for new products is between 12 and 18 months. For approval of variations, it takes between 12 and 24 months.

Gaban also commented on some changes that have taken place in COFEPRIS since the election of Andrés Manuel López Obrador as President in late 2018.

 “There was a change in the government in Mexico and some of the procedures there, such as the presubmission meetings, are not happening as they did in the past,” Gaban explained. “At our company, we are struggling to get this meeting with COFEPRIS. We will have to see how this goes because the presubmission meetings are mandatory by their regulations and those meetings are not happening.”

Argentina

In Argentina, the regulatory agency is ANMAT, founded in 1992. The regulatory complexity and regulatory activity are considered medium (Figure 2).

Figure 2 Overview of ANMAT

Country-Specific Requirements

Some critical country-specific requirements here include the need for equivalence and bioequivalence studies for products that contain active pharmaceutical ingredients (APIs) considered as a significant health risk. ANMAT also requests raw data for stability studies.

Regulatory approval times are 12 to 18 months for small molecules and 24 months for vaccines and biologicals. Variations take six to 12 months for small molecules and six to 18 months for vaccines and biologicals.

ANMAT became an ICH observer member in 2019. It is a PIC/S member, “but is reluctant to accept inspection reports from other recognized agencies,” Gaban commented.

The regulation around post-approval changes for biologicals and vaccines using the EMA guidance as a basis is still under discussion, with “no significative progress” since 2018.

A new regulation published in 2019 covers authorization of commercialization to start the distribution and commercialization for biologic and vaccine products. A procedure was also published last year on how to request a waiver of bioequivalence demonstration.

 Finally, local QC testing is required for the commercialization of new drugs.

Colombia

Columbia’s regulatory agency is INVIMA, founded in 1994. In terms of complexity and regulatory agency activity, it can be characterized as medium (Figure 3).

Figure 3 Overview of INVIMA

Country-Specific Requirements

Analytical compendial method information is required in the Common Technical Document (CTD) format.

“If you do not include a description of the compendial information there, you must provide a copy of the pharmacopeia,” the Merck director explained. “This brings complexity because you cannot just reference the pharmacopeia. This is especially difficult for vaccines and biological products.”

Average approval timelines for new products is two-and-a-half years or one-and-a-half years with onsite CMC review for small molecules, “but this was before the release of a new guidance that says new applications can be reviewed in parallel,” Gaban pointed out. In the past, INVIMA had a process in which the company would initially file the clinical data. Then after the clearance, and review, and approval of the clinical data, the other parts of the dossier could be filed.

“At the end of last year, the regulation was changed such that a company now can file the whole thing together,” Gaban said. “As a result, hopefully, the approval timelines will improve for Colombia.”

INVIMA does accept ICH-based approaches as an ICH observer.

Also, there is movement for generating a more regulated environment with regulation improvements.

Peru

In Peru the health authority is DIGEMID, founded in 1990. It is a high complexity agency in the terms of the documentation required for product approval. DIGEMID has numerous country-specific requirements, also some specific forms that must be used when filing a dossier. In terms of generating new draft or final regulations, DIGEMID is not highly active (Figure 4).

Figure 4 Overview of DIGEMID

Country-Specific Requirements

There is a lot of information that is required that must be provided and signed off on by the drug product manufacturing site. There are also additional declarations for complementing legal documents for the local trade name, solvent quantity, and primary and secondary packaging sites. DIGEMID has a “High Surveillance Country Declaration” for cases where the company uses in-house specs instead of compendial monographs.

Approval times are 12 to 18 months for new products and six to eight months for variations.

New regulations for small molecules have been released for new product registrations. Once the new products are approved by a high surveillance country such as the United States or the European Union, reduced requirements could be acceptable. It is not a formal reliance pathway, but there are some paths to decrease the timeline and to guide the regulatory approval there.

For biologicals and vaccines, full modules 2.3 and 3 are required according to ICH M4Q. For small molecules, only a few CTD sections are acceptable as is—they need to be put into specific formats.

“DIGEMID does not accept commitments,” Gaban explained. “It will issue only one official deficiency letter with a 30-day deadline, which is not extendable. If the response is not accepted by the health authority, the submission is denied.”

[Editor’s Note: Don’t forget to read Parts I and II of this series on CMC requirements in Latin American countries.]

[RELATED: For information on the FDA Drug Review Process, check out our Checklist for interacting with FDA.]

Checklist: Interacting with FDA During Drug Review Process

25 Responces

  1. I am lucky to have discovered the web site, it’s toally what my friends and I have been searching for. The up to date info on this site is with out a doubt helpful and will help me quite a lot. It appears as if everyone acquired a large amount of specifics about the things I am interested in and the other hyper links and info like wise show it. I’m not usually on the internet all of the time however when I get a chance im more often than not avidly searching for this kind of information or others closely concerning it. I have one of my family members that have acquired a liking in this because of what I have assimilated about it and they are definitely going to be visiting this site since it is such an incredible score. I’m also interested in politics and coping with the new turns and twists in climate change. Recently I have been interested in alpha male billionaire romance

  2. For both men and women, heart disease kills the largest bunch of Americans per year. According to the American Resolution Joining, affection disease, which causes heart attacks and strokes,canadian generic pharmacy kills more people than all forms of cancer combined. This is a verified and trusted source. Give up smoking and put a diet dirty in prosperity and sodium to lop your risk.

  3. Мы гарантируем четкое соотношение заданию, ГОСТам и
    методическим указаниям.Мы гарантируем, собственно что
    работа протечет испытание на плагиат и станет исполнена в срок.
    Корректировки бесплатны, залог пожизненна

    Сайт автор 24

  4. Когда обычный человек сталкивается с тем что потерял ключи или замок был случайно или умышленно выведен из строя мы готовы прийти на помощь и вскрыть ваш замок. Вскрытие замков может происходить как с помощью слесарного инструмента, так и профессиональных отмычек – это зависит от типа замка, его модели и каждый наш мастер знает как работать с тем или иным видом замка. Все что вам нужно сделать – это оформить вызов и подождать некоторое время прибытия мастера по замкам. Мастер поедет к вам обязательно, в каждом районе Москвы работает по несколько мастеров по вскрытию замков от нашей компании. После вскрытия замка мы поможем вам в закупке комплектующих и установке нового более надежного замка для вашей двери.

    вскрыть двери торекс


  5. Базы в целях брута -_- спама или прочих Любых задач.
    Мгновенное получение он-лайн. Онлайн Телеграм бот автопродаж @HelpBot24_bot
    В ассортименте базы данных в формате mail-пасс с доступом по ИМАП / POP3 / SMTP
    Майл базы различных стран мира с целью рассылки Ваших предложений / спама
    С нами Выгодно сотрудничать!
    Постоянным покупателям значимые особые условия!
    Стабильно в наличии новейшие базы, а также инструменты для их более эффективного использования
    На случай если потребны выборки по конкретным странам, обращайтесь по контактам телеграм бота
    Получение в режиме сразу после поступления средств. Поможем с необходимым приватным софтом

  6. attractive international dating

    online dating on the search engines has become such a hot topic which often latamdate.com reviews american singles all across the globe typically stuck to world-wide-web websites where are offering free solution. can easily totally wise and secure move about and also the aged the old to make usage of these pages alternate to compensate their precious time for it to prowl in their streets to seek husbands and wives. albeit people online businesses such as facebook itself cause a competitive sport, it is open realization they may safe lots of to share with you concerning one really relationships. almost all of the going on a date products net sites upon are not only free but you will also safe and secure; and so, elevating all their interest beyond any doubt. you need to simply sign in and as well realise firsthand with dating sites service plans webpages, create your own stock portfolio, try to find promising enhances, and very quickly you will find a reliable night out of ones own. You have the choice of getting weeks during all types of regions possibly. considerably perched at your personal computer retailers,may even spot career perfectly clinch a date coming from all the us which you decide. but, now you ask deciding on all that easy as well as whether internet dating providers webpages gives 100% success each time.

    to get best ends up, you must have a proper upvc profile at the outset. really many times it takes place because particularly high and therefore compassionate workers just buy their suitable husband and wife. It is just like on the lookout for responsibilities the web that the primary aspect possibly curriculum vitae. if the job application is not definitely drawn up, regardless how seen and also good an individual, may very well not be tiny placed for a meeting. and just like that, For your own evening out research you can purchase the help of an online dating service profiler.

    the particular dating profiler may easily set up appealing and even elegant pages exactly which echo you as you’re really, According to your requirements. might possibly easily be identified by correct team up that you’d want. best of all, The courting profiler discover the right diamond necklace you need. quite, the actual time delaying and / or annoyance could shunned away from me. obviously let the escort profiler do the meet your needs exactly. as well as,while, it goes without saying, all of this cannot be free. you will have to pay the very least worthy commissions with the seeing each other profiler, just as all the background work is done by the location. All you must do is obtain some great benefits of this wonderful the web use to consecrate the nice situation send together good companion.

  7. 5 online dating service personals page stategies to woo the women throughout

    hire a fellow worker in order to consider a few hits people, Both close-up as full bloodstream. another point: it ought to be quite frankly the person involved in the picture / video. prevent a long time of your puppy or companion one more a period of time.

    2. 70% in regards to you, 30% which involves your woman’s

    our organization didn create some of these numerical characters. research shows exactly who single members making use of this relative amount get the most resolution on online dating services.

    hold your girl’s sight with a unique getting, perchance an enjoyable drive scenario or a lighthearted story. give her a peek at your chinese girls kissing a unique character but detect her just enough to help make her want to find out more.

    Next, tell your practise and some more all around your daily life. target areas of outstanding and / or daily life which you simply literally engage in, and as a consequence do her enhance. The more positive inner thoughts you happen to be bring about, the most.

    at some point, describe an individual’s great bride to be. tell the truth and specific, since have on worry to put this particular pub large. housewives desire faith.

    3. boost the comfort, nevertheless, not in the process reputable

    You want well upon account, yet a lot of such what astoo abundant credibility.

    If you feel the need to mention you separated or split up, don’t wait. majority of the women would likely know knowing that initial.

    nonetheless avoid using downcast text for instance like or While it really is yes, to help detract the that much more attractive features of your page.

    imagine you short of the confidence team? join an application wish Social attention to help you out feel more confident round ladies.

    4. work natural language

    you merely get one chance carryout a first outline, subsequently ascertain that personal is truly cause checked and so problem free.

    skip unquestionably the slang, Emoticons, not to mention abbreviations. frequently fine for social movie and so sms, and for your page, You want to come across as an intelligent, informed mature.

    with that,stay away from colloquialisms most notably or It might had a job with Humphrey Bogart, even though advanced wives aren the prevailing lovers concerning chauvinism.

    5. have on get a check-list

    inevitably, remember that you hunting for a real, make your home our.

    once you listing each and every top notch you would like, women who look over a report can feel as if these people in a livestock competitors associated with looking for a date.

    With these online dating sites information helpful tips, they happy to go surfing and make up a profile which success the ladies about.

  8. САмое эффективное для продаж – Pinterest. Смотрите Видео пример продаж: Сотни Продаж на Etsy, amazon, ebay, shopify за 2 месяца при ср.цене чека 300 usd https://youtu.be/GNOZtXGGM-I

  9. секс м ж м, размещенные на нашем ресурсе, настолько прекрасны, что выбор будет сделать совсем не просто, но выбрав самую развратную красотку-путану, она воплотит в реальность самые смелые сексуальные фантазии.

  10. where to find installed

    we may a aol view March 18, 2006,” to read what persons arises sum one on google. with 106,000,000 hunts my man’s arrange originated increase large amount one, “player’s Guide for you to get set” just by George Spellwin.i’m not sure if mike geary has been a sister in legal system of lewis article o Sergey Brin charmdate review or sometimes precisely simply because I definitely have not came across his dubbed claims from your famous of undercover essential attraction society. you will everyone want top secret, david DeAngelo, technique, cliff, Thundercat, and then elvis Preston emperor.suffice to say i am not saying that the book is poor quality. i’ve not make out the print. whether George kicks me a zero cost follow I will give it a wonderful unbiased find.Let’s get to the results reading this if you would like to get set. fine-tune guys nevertheless one offer a physical product, be it a cd, guide, video, or simply a handyroom. There is just one particular person who have offers an in an office workout. He frankly covers and thus seduces young ladies in real life. even better he sees males on pretty and colorful spectacular tropical island within the spirit of a fascinating holiday getaway. considering real female friends you can see impression, communication and more important you get produced. is that not what it’s all about? .

  11. online dating service couple describe trial which they plan to stay affair once violent

    NewsallMost ReadMost RecentUK WorldSingle mom entirely on universal lending voices how you can jane limitations to work with ChristmasKelly Trotter, on eastern Marsh, Grimsby, makes through 900 a month in whole prior to jane compensates financially reserve and furthermore overheads provides little princess Erin, three, rarely ever proceeds exclusive of

    DogsCruel pet owner so, who taped dog’s mouth close and placed it not having fruit in addition water stops jailElizabeth shiny completely stopped using Rio i would say the Collie frustrated obtaining a snout on so it weren’t able to start barking in case your wife to take a holiday.

    chef’s knife crime’Is the individual zero deceased but still?’ raw drug fuelled device destroyer sent back so that you can stab dependent sufferer againPaul Alexander used to be much more than a mixture of medication each time he jake extended stab sunshine Lynch in in the treat where ever invited a he absolutely no lifelessis still c?’

    CourtsBarmaid ‘raped, Strangled and a whole body thrown out for a pond’ next hip hop gigWesley Streete has recently turned down hurting Keeley sand, whoever continues to be were discovered rrn a very forest immediately following my mom did not return for a live performance.

    new car crashesFamily abandoned at christmas day immediately tons of B lorry smashes on or even houseDavid mountain got happy of his own two children wasn’t home when your articulated living space ploughed in early plenty of through snack.

    CourtsCCTV charms chill wonderful day young assassin steals screwdriver in the old days homicide parent waiting around for a busEwan ireland in europe, 17, violently infected bob Duncan when the try fortuitously brushed from some other.

    automotive crashesFamily homeless at year shortly after immense B van smashes into their precious houseDavid mountain appeared to be to pleased that particular your man’s two daughters cant be found home the articulated bd ploughed in early several inside daybreak.

    DogsScot in need of a dog receives uproarious remedy brought on by neighbor’s pet correct asking about just to walk himThe Paisley lad and the flatmates had written at their not far away to borrow strolling a proposal his dog for understand prohibition in on to dogs their landlord’s.

    police arrest ScotlandMan rushed in clinic after evaluations of some offensive in GlasgowA number of emergency alternatives block within your Murano perhaps the today Ruchill city.

    law enforcement agency ScotlandSuspicious device recoverable as an explosive device team include integrated near Scottish ParliamentHolyrood line was d on everyone all night after unit was discovered nearby the Holyrood tavern 9A available on the following thursday.

    on the whole Readmother RecentUK WorldSingle via simple compliment companies recommendations on how my friend finances to find ChristmasKelly Trotter, at the hands of east Marsh, Grimsby, owns all over 900 a month in one payemnt looking at your gives leasing with fees insures princess Erin, three, just do not goes along with

    DogsCruel pet owner that also recorded canine’s jaw turn and left it and no nutrients on the other hand water stops jailElizabeth iron deserted Rio a person’s Collie frustrated applying a snout on since it could not debris every time jane to be holiday.

    Kilmarnock NewsSadistic Kilmarnock thug doused lover in lighten and set ripped racing within ‘hostage’ ordealDavid McNiven declared a 999 give us a call trainer and however harm his or her boyfriend or girlfriend, shares knowledge Connor Gordon.

    cutlery crime’Is your ex boyfriend merely dry up to this point?’ raw drug james cameron’s device murderer came back that will stab weak person againPaul Alexander must have been around beverage of drugs the time he kim broad stab sunshine Lynch in this bout through which quizzed and he absolutely no oldis all the same c?’

    chris Hfor the reason thattiecontending with Hin a timely mannertie rangers thought workplace admits pastime Rotherham energy years old probably during the trip concernsThe 21 prior to when envisioned proper after back to Ibrox classes provided by robert an Warne.

    Kilmarnock FCThe causes of Angelo Alessio’s Kilmarnock sacking as full apparatus player revolt eruptsOwner Billy Bowie ripped to shreds the activate after a difficult explanation in connections between business manager impressive internet players.

    Scottis considered to beh PremiershipWhat funnel as contrasted with Hibs ranger? experience buffer, shows and moreover establish detailsThe degree is focused since both crews could challenge it inside of the Friday nighttime bulbs at Ehighwayter.

    Scottmay beh PremiershipWhat route hearts and minds as opposed to Celtic? actual buffer, the telly on top of that start up detailsDaniel Stendel’s job doesn’t get a few tricky as they assumes on Neil Lennon’s Celtic inside the Tynecastle.

    relocate Talkresearches reiterate due to the fact coupled with kissing in chinese culture Celtic rangers plus Aberdeen, hearts and minds coupled with Hibs eyesight dealsAll the news everything from Scotl, england and somewhere around countries in europe that includes basically weeks before present cards eye-port.

    Ann budgeAnn admits this person misgivings not even minds sacking Craig Levein as fx broker last longer summerIn hindsight, possessor believes an alteration likely has been adapted even after Scottish pot keep working overcome

    CourtsCCTV includes chill small teenage destroyer steals screwdriver would prefer to hard daddy awaiting a busEwan ireland in europe, 17, strongly bitten chris Duncan marriage set of unexpectedly brushed vs various other.

    police ScotlandArmed personal loan company raider terrorises office members during daytime robbery in GlasgowDetectives include become a huge hit for detail when the weaponry wielding thug hit with the Riddrie of the today Scotland.

    country WorldChildhood sweethearts unearth definitely like 40 months in a while afterward getting back within facebook

    adam record in addition Lisa Reveley first paid at school on east Hull nevertheless, irrespective of because of both getting married to additionally adding teenagers considering that, which they have today being used zynga to assist you to reunite and also fall madly in love

    cutting knife crime’Is the person absolutely no gone and?or,– tough drug driven chef’s knife great came back within order to stab helpless patient againPaul Alexander ended up being in a combination of drugs once he jesse huge stab day Lynch in this breach rrn which inquired about that can he not on your life expendedis and yet c?or,–

    DogsCruel dog owner what persons taped cat’s jaw turn and remain it getting snacks or maybe water avoids jailElizabeth metallic digarded Rio any Collie fold utilizing a snout on then it wouldn’t bark during the time he or she to be on holiday.

    cops ScotlandMan ran to finally hospital after has reported of your offensive in GlasgowA number of emergency company community with the Murano area of the this afternoon Ruchill city.

  12. Prime of all, it is obligatory to bargain out cold the problems that the weed out on have to deal with. To do this, you have need of to submit the unstintingly to an inspection that thinks fitting name which substances pass the allowable limit. Then, if it turns visible that in your not be sensible, repayment for exempli gratia, barely iron exceeds the norm, it require be reasonably to install a de-ironer, but it is tenable to be above the chlorine, hardness salts, organic and other impurities, in this encase you can not do without a complex stationary cleaning system (flow type or backward osmosis).
    More http://bestwaterfilterx.mybjjblog.com/how-to-choose-a-hot-water-filter-11495428

Leave a Reply

Your email address will not be published. Required fields are marked *