Biosimilars & Biologics
The key facts about biosimilars and biologics in Chile. Prepared in association with Carey, a leading global law firm, this is an extract from The Pharma Legal Handbook: Chile, available to purchase here for USD 99.
1. Are biosimilar medicines considered the same as generic medicines in your country?
No. According to Technical Guideline No. 170, issued by the Ministry of Health on August 21, 2014 and approved by decree No. 945 of 2014 -and its amendments-, which contain the regulations for the sanitary registration of biosimilars (“T.G. No. 170”), a biosimilar is defined as a biotechnological medicine that has proven to be comparable in quality, safety and efficacy to the reference biotechnology product, based on its exhaustive characterization by means of comparability studies under equal conditions, consisting of comparative quality studies and comparative non-clinical and clinical studies.
Therefore, in no case can a biosimilar can be considered a generic product. This is confirmed in Technical Guideline No. 170 as it declares that “the normative framework for the authorization of generic medicines of chemical synthesis is well established as the demonstration of chemical identity and bioequivalence with the reference product, if it were the case, allow inferring the therapeutic equivalence of a product. However, this same criterion, as described, is not applicable to biosimilars, as these products are composed of complex entities, which are difficult to characterize by traditional methods”. In this regard, according to article 53 of Supreme Decree No. 03/2010 (“S.D. 03/10”), which sets forth our pharmaceutical product regulations, biological products cannot be submitted or filed under the simplified or generic pathway.
2. Are all biologic medicines, including biosimilar medicines, patentable in your country?
Biological medicines are patentable in accordance with our local Industrial Property regulations. However, in the case of biosimilars, it would only be possible to obtain patents associated with their manufacturing process, since the molecule itself would not meet the patentability requirements for obtaining a patent.
3. Is there a specific regulatory framework for the marketing authorization of biosimilar medicines in your country? If yes, what is the regulatory framework for the authorization of biosimilar medicines?
Yes, there is a regulatory framework for the approval of biosimilars in Chile.
The general rule is that biological products, including biotechnological products, should undergo a stand-alone procedure, submitting, thus, all full-fledged preclinical and clinical trials to accredit safety and efficacy.
Nevertheless, article 42, letter i) of S.D. No. 3/10, states that a Supreme Decree of the Ministry of Health shall set forth the Technical Guideline for the “abbreviation of clinical studies to evaluate the safety and efficacy of biotechnological products based upon the existence of another registered biotechnological product which utilizes the same active ingredient, unitary dosage, pharmaceutical form and route of administration”. This Technical Norm shall determine the active ingredients and their presentation for which this pathway is enabled (a biosimilar pathway). Our regulations emphasize that the applicant must submit “comparative studies” with the reference product.
In this regard and upon the previously cited provisions, the biosimilar pathway registration is only available for the active ingredients and their respective presentations included in T.G. No. 170 and the list of Reference Biotechnological Product (RBP).
T.G. No. 170 has been amended during the past few years so as to include more RBP (Decree No. 199/2016, Decree No. 50/2018 and Decree No. 30/2019) and it is expected to be further amended for including new RBP.
4. What kind of data package is needed to obtain approval for a biosimilar drug? Is this any different to the requirements for the original Biologics drug?
T.G. No. 170 is based upon the WHO Guidelines for similar biotherapeutic products and structures the biosimilar pathway upon a stepwise comparability process, head to head with the reference product (which is also specifically set within such guidance), for all stages of its development (characterization, non-clinical and clinical studies). It also includes provisions in connection to pharmacovigilance and extrapolation of indications.
Thus, the dossier package of a biosimilar must contain a full characterization dossier of a biological drug, plus comparability studies consisting on the characterization and evaluation of quality aspects, followed by head to head comparative non-clinical and clinical efficacy, safety and immunogenicity evaluation with the RBP.
5. What are the requirements for the choice of the reference comparator product?
T.G. No. 170 does not include a regulated procedure under which new active ingredients and reference biological products will get to be included within the same. Additionally it does not include a term within which new lists of active ingredients or reference biological products should be issued or amended. Therefore, the time and procedure for the inclusion of new products depends entirely on the Ministry of Health’s determination.
Indeed, T.G. No. 170 only states that the list of active ingredients and reference products will be updated in connection with the “state of the art” by resolutions issued by the Ministry of Health upon recommendations of the Public Health Institute (ISP). Based on such faculty, the Ministry decides when and how new products are included in the guideline, notwithstanding the ISP’s recommendations. Therefore, even though T.G. No. 170 entered into force at the beginning of the year 2014, only three updating resolutions have been issued (in 2016 through exempt decree No. 199, in 2018 through exempt decree No. 50 and in 2019, through exempt decree No. 30).
6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?
As already explained, the biosimilar pathway is only available for the active ingredients and their respective presentations included in T.G. No. 170 and its amendments. Upon S.D. 03/10 (article 42, letter i) the reference product must be registered, but it does not make specific reference as if it is required to be registered in Chile.
Additionally, under T.G. No. 170 the reference biotechnological product must be (i) recognized as such by the national medicines sanitary authority; (ii) must have its own quality, safety and efficacy studies; (iii) the same RBP must be used throughout the comparability exercise; (iv) the RBP cannot be a biosimilar; and (v) the biosimilar candidate must have the same dosage form, active ingredient, unitary dose, indication(s), concentration and administration route as the RBP. Again, it does not state that it is required to be registered in Chile.
Indeed, upon the latest modification of T.N. No. 170 of April of 2018, the list includes a reference product which is not registered in Chile. Nevertheless, please consider that this is a very novel case, since it has only been included in April of 2018 and there has been no prior experience with these cases in Chile.
Finally, as mentioned in question 5 and according to T.G. No. 170, there is no official procedure for the inclusion of reference products in the list.
7. How are the prices of biosimilar medicines regulated? Is this any different from the requirements for the original Biologics drug?
Up-to-date, there is no price regulation for medicines in Chile.
8. What is the reimbursement policy for biosimilar medicine? Is this any different from the requirements for the original Biologic drug?
In Chile, there is no general reimbursement system or process. The owner of the product can determinate the sale price of a medicine, such as biologicals and biosimilars. The Chilean healthcare system is primarily structured by a mandatory medical coverage which is required by law. This coverage is financed by health insurance contributions paid to the providers of healthcare insurance (FONASA or the ISAPREs) on a monthly basis by certain persons such as employees (in which case the relevant employers are legally bound to withhold the relevant amounts from employees’ monthly wages), independent workers, pensioners, etc. The law provides for a minimum medical coverage and the additional features depend on the health institution and the health plan chosen by each individual.
Additionally, there are two universal coverage programs, which are Explicit Guarantees in Health (GES plan) and the High Cost Treatment Financial Protection System (Ley Ricarte Soto), which cover specific treatments and medicines, some of which are, indeed, biotechnological products.
Isolated coverage has also been provided under the Extraordinary Auxiliary Fund administered of the MoH.
For further information, please see answers to queries No. 10 and 11 of Exhibit A.
9. Does biosimilar competition impact the reimbursement policy of the originator reference products?
No, please refer to question no. 8 above.
10. What is the legal framework for biosimilar medicines prescribing (clinical decision maker) and dispensing (pharmacy level, hospital or retail)? Is this any different to the requirements for the original Biologics drug?
The applicable legal framework is the same for any other pharmaceutical product.
Regarding prescription of medicines, this can be only performed by physicians (also dentists and midwives in their respective fields of competence and allowed medicines) based on the agreed decision of the attending physician.
On the other hand, the dispensing of medicines must be carried out by an establishment that must comply with all regulations applying to reception, storage, transport, distribution and dispensing of pharmaceutical products. Additionally, the professional who dispense the medicine must be in possession of the title of Pharmacist and be registered at the National Registry of Individual Health Providers. Products authorized for sale under prescription (Rx conditions) can only be sold in pharmacies and chemist’s stores (“Almacenes Farmacéuticos”). The professional must request the prescription before dispensing the medicine and should verify the compliance with prescription requirements.
11. Is the system considering physician-led switching and/ or pharmacy-level substitution (without involvement of the clinical decision maker)?
Please consider that T.G. N° 170 expressly states that “interchangeability or substitution” of biosimilars must be performed only under the decision of the treating physician, who will evaluate the risks and benefits, duly inform the patient and under a stepwise and controlled proceeding with strict medical supervision.
In this regard, our regulations do not permit the automatic substitution of a biosimilar product at the pharmacy level. This is a special provision for biosimilars, as under the Sanitary Code substitution by pharmacists of pharmaceutical bioequivalent products is permitted under the request of the patient, which is a provision applicable only to chemically synthesized products.
12. What are the post-authorisation requirements (including pharmacovigilance, risk management plans, post-approval studies) for biosimilar medicines? Is this any different to the requirements for the original Biologics drug?
The post-authorisation requirements for biosimilars are no different than biological and/or biotechnological drugs requirements.
Regarding the Pharmacovigilance of biotechnology and biosimilar products, the requirement of having Risk Management Plans (PMRs) is indicated and it is also indicated that said guideline indicates that it will be based according to what is stated in Title X of the Supreme Decree. No. 3/10 (S.D. No. 3/10) and Technical Guideline No. 140/12 (T.G. No. 140), identifying the biotechnological drug, its manufacturer, country of origin, INN, trademark and lot number.
13. Are there specific policies and requirements for labelling biosimilar medicines in the event of second medical use patents? Is this any different from the requirements for the original Biologic drug?
No, in Chile there are no specific policies for biosimilar labelling in the event of second medical use patents (e.g. carve outs or skinny labels).
14. Have there been any significant legal/judicial developments in relation to biosimilars in your country? (Including but not limited to IP, procurement, competition, misleading information campaign, access to reference comparator product)
Please take into account that, in Chile, there has been significant discussion in connection with the possibility of direct purchases for public procurement of products under which patients have initiated treatment, as such products could not be automatically substituted at the pharmacy level. The Chilean MoH, in consultation with the ISP, have indicated a treatment continuity policy for patients who have initiated treatment with a biotechnological product or a biosimilar enabling direct purchase for such products and not within a public bid. Such policy has been already implemented for several products within the High Cost Treatment Financial Protection System (Ley Ricarte Soto).
15. Are there proposals for reform or significant change to the legal, regulatory, procurement of biosimilars? If yes, when are they likely to come into force?
Please be aware that there is a bill of law currently in Congress (Bill of Law No. 9914-11) that contemplates interchangeability (in general) as one of its main topics.
In particular, this bill of law states that the Ministry of Health must incorporate in the National Drug Policy, an Interchangeability Strategy for Pharmaceutical Products and establish an Implementation Plan for it, which must be approved by resolution of the Minister of Health.
Also, it states that the Ministry of Health, by decree, must dictate, within six months following the date of publication of the resolution indicated in the preceding paragraph, a new Technical Guideline, at the proposal of the ISP, that determines the evidence to which must be submitted to pharmaceutical products to demonstrate their interchangeability. Said norm will determine the interchangeability tests according to the nature of the pharmaceutical products, among which will consider bioequivalence, good manufacturing practices, particle size and pharmacovigilance, among others.
In addition to the above, this bill of law also states that the ISP will determine the pharmaceutical products that are not interchangeable, which will be established in the sanitary registration (MA) of said products.
Thus, it may be possible that, in the future, the rule on interchangeability for biosimilars be modified as per the entering into effect of the provisions included in this bill of law.