Biosimilars and Biologics
A brief overview of the situation regarding biosimilars and biologics. Prepared in association with SAARPE Association, a leading law firm in Algeria, this is an extract from The Pharma Legal Handbook: Algeria, available to purchase here for USD 99.
1. Are biosimilar medicines considered the same as generic medicines in your country?
The Health Law No 18-11, dated of 2 July 2018 and published in the Official Gazette, has made a clear distinction between similar biotherapeutic products and generic products, and introduced a legal anchorage for biosimilars specific regulations.
A generic product is defined in the Article 210 as any drug having the same qualitative and quantitative composition in active substance, the same pharmaceutical form, and that is interchangeable with the reference product because of its demonstrated bioequivalence by appropriate bioavailability studies, where a drug can only be classified as a reference product if it has been registered in the light of all the data necessary and sufficient on their own for its evaluation.
A similar biotherapeutic product (name used by World Health Organization) has been defined in the same article as any drug in which the active substance is produced from or extracted from a biological source, and that is similar in terms of quality, safety and efficacy to a reference biotherapeutic product. The latter can only be qualified as a reference biotherapeutic product if its registration was carried out in the light of all the data necessary and sufficient in themselves for its evaluation.
2. Are all biologic medicines, including biosimilar medicines, patentable in your country?
Under Patents Ordinance No 03-07, dated of 19 July 2003 and published in the Official Gazette, inventions related to a product or process, which are new, result from an inventive step and which are susceptible of industrial application, can be protected by a patent in Algeria.
An invention is considered as new if it is not included in the state of the art, which consists of everything made accessible to the public by a written or oral description, a use or any other means anywhere in the world before the day of filing the application for protection or the priority date validly claimed for it (for detailed information, refer to Patents and Trademarks).
Thus, all reference biotherapeutic products are patentable in Algeria, at the opposite of similar biotherapeutic products for which the same International Nonproprietary Name (INN) is attributed according to Algerian regulations, and that cannot be patentable, except for a proven new manufacturing process.
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?
There are neither specific regulations for similar biotherapeutic products in Algeria for the moment, nor this term is used in legal provisions prior to Article 210 of the Health Law No 18-11, dated of 2 July 2018 and published in the Official Gazette.
In practice, existing similar biotherapeutic products were approved according to the regulatory framework applicable to other drugs, on the basis of application including manufacturing and quality control data, and where mandatory, non-clinical and clinical comparative data with the reference biotherapeutic product (for detailed information, refer to answer to question 2 of Regulatory, Pricing, and Reimbursement Overview).
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?
The data package to obtain market authorization for a similar biotherapeutic product is not defined since there are not yet specific regulations, but non-clinical and clinical comparative data could be required by the regulatory authorities on case by case basis.
Regulatory authorities with jurisdiction over drugs, biologics and medical devices in Algeria do not confer exclusive right to benefit from the proprietary non clinical and clinical data for a set period of time (also called Regulatory Data Protection) to innovative companies at the moment of granting the market authorization, and similar biotherapeutic products manufacturers are allowed to rely partially upon those data to obtain approval of their abbreviated applications supported by comparative data.
5. What are the requirements for the choice of the reference comparator product?
There are no specific requirements for the choice of the reference biotherapeutic product, whereas according to previous experiences, it was required from the reference biotherapeutic product to be already approved in Algeria.
6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?
This possibility did not occur before (at the opposite of generic products), and there is no specific provision for within the existing regulatory framework.
7. How are the prices of biosimilar medicines regulated? Is this any different from the requirements for the original Biologics drug?
Prices of similar biotherapeutic products are regulated like other drugs by the Pharmaceutical Products Pricing Committee established at Ministry of Health by Ministerial Decree No 66 dated of 11 July 2012 modified and completed, published in the Ministry of Health Official Bulletin (for detailed information, refer to answer to question 12 of Regulatory, Pricing, and Reimbursement Overview).
Price requirement for imported similar biotherapeutic products is the same as for imported generic products (i.e. list price to be lower by 30% compared to the reference product), but it occurred that at the end of list price negotiation the difference was only of 20% between similar and reference biotherapeutic products.
As an incentive given to local production, for a hypothetically first locally-manufactured similar biotherapeutic product of a previously imported reference biotherapeutic product, the ex-factory price could be aligned during the first 5 years of authorization to FOB list price of the reference biotherapeutic product (when the general rule requires a difference of 30% in list price).
After a period of 5 years, locally manufactured similar biotherapeutic products are required to be lower by 10% (if ex-factory price is below 200 DZD), by 15% (if ex-factory price is between 200 and 500 DZD), by 20% (if ex-factory price is between 500 and 1000 DZD), and by 30% (if ex-factory price is above 1.000 DZD) compared to the reference biotherapeutic product.
8. What is the reimbursement policy for biosimilar medicine? Is this any different from the requirements for the original Biologic drug?
National health insurance (social security) is covering the costs of similar biotherapeutic products sold through community pharmacies as for other drugs on the reimbursement positive list fixed and updated by the Reimbursement Committee established at the Ministry of Labor, Employment and Social Security by Interministerial Decree, dated of 16 August 2003 and published in the Official Gazette.
When the reference biotherapeutic product is already on the reimbursement positive list, the similar biotherapeutic product having been attributed the same International Nonproprietary Name (INN) by the regulatory authorities, is automatically admitted to reimbursement without additional assessment (the same rule as for generic products).
Besides that, the Government is fully covering costs for all products dispensed through public hospital pharmacies. These products are purchased by the Hospitals Central Pharmacy (“PCH” – “Pharmacie Centrale des Hôpitaux”) during public tenders and are given free of charge to patients at public hospitals, including all approved similar and reference biotherapeutic products, indistinctively.
9. Does biosimilar competition impact the reimbursement policy of the originator reference products?
The similar biotherapeutic product competition does not impact the reimbursement policy of the reference biotherapeutic product (reimbursed on the basis of the list price), except the case in which the Reimbursement Committee decides to establish a reference tariff for reimbursement on the basis of the cheapest similar biotherapeutic product already on the market.
For hospital products, similar and reference biotherapeutic products enter in competition within the same public tender launched at the PCH. The market could be split between reference/similar or two similar biotherapeutic products to avoid shift of patients already under treatment for non-medical reasons. In this case, transaction price is negotiated with the tender second winner on the basis of the first winner price, and the volumes to be purchased.
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?
There is no legal framework for similar biotherapeutic products prescription (prescribed in trademark at the physician discretion). The only existing two exceptions are:
- With products containing glargine insulin (dispensed through community pharmacies), for which the regulatory authorities have released a position paper, in 2017, requiring from prescribers not to switch patients after initial prescription of the reference or a given similar biotherapeutic product;
- With products containing trastuzumab (dispensed through hospital pharmacies), for which the regulatory authorities have decided, in 2015, in concert with senior physicians to dispense the approved similar biotherapeutic product to all new patients and to continue the treatment with the same product.
As similar biotherapeutic products are not generics, the automatic substitution by the pharmacist (reference/similar, similar/reference, or between two different similar biotherapeutic products) is not allowed within the meaning of Article 145 of the Decree No 92-276, dated of 6 July 1992 and published in the Official Gazette, related to the code of medical ethics. Pharmacists are required only to dispense the reference or the similar biotherapeutic product prescribed in trademark by the physician.
11. Is the system considering physician-led switching and/ or pharmacy-level substitution (without involvement of the clinical decision maker)?
As mentioned in answer to question 10 above, the physician-led switching is at the discretion of the prescriber (except for glargine insulin and trastuzumab containing products), and any pharmacy-level substitution is not allowed.
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 market authorization holder is obliged to notify any identified event related to the product safety that occurred locally or abroad, and must report regularly or upon request to the National Center for Pharmacovigilance and Materiovigilance (“CNPM” – “Centre National de Pharmacovigilance et de Matériovigilance”), created by Decree No 98-192 dated of 3 June 1998 and published in the Official Gazette.
Post-authorization requirements are the same for reference and similar biotherapeutic products in Algeria.
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?
The similar biotherapeutic product labelling materials are expected to clearly identify the product, in apparent font, easily legible, by a unique trade name which does not suggest the name of the reference biotherapeutic product or that of another similar biotherapeutic product.
When an International Non-Proprietary Name (INN) exists (the same attributed to similar and reference biotherapeutic products), it must be put on the internal and external packaging, the Summary of Product Characteristics (RCP) and the package leaflet too.
The mention of the lot number on all packaging elements is essential as it is an important part of the manufacturing information and is critical for traceability in the event of problems with the similar biotherapeutic product.
The information on prescription of the similar biotherapeutic product should be the same as that of the reference biotherapeutic product, with the exception of specific aspects of the product, such as those related to different excipients. This information should be regularly updated, taking into account the most recent information related to the reference biotherapeutic product.
The general labelling rules and requirements are the same as for other drugs (for details information, refer to answers to questions 14, 15 and 16 of Marketing, Manufacturing, Packaging & Labeling, Advertising).
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).
Guidelines on similar biotherapeutic products have been drafted on May 2017 by the General Directorate of Pharmacy and Health Equipment (“DGPES” – “Direction Générale de la Pharmacie et des Equipements de Santé”) at Ministry of Health, mainly to clarify important specific requirements, including without being limited to:
- The choice of the reference biotherapeutic product, with possibility to consider a comparator product sourced from another regulatory jurisdiction (members of International Conference on Harmonization);
- The conditions for Phase III safety and efficacy comparative clinical trials waiver;
- The criteria for safety and efficacy data extrapolation to indications of the reference biotherapeutic product other than those covered in clinical trials;
- The post-authorization requirements for risk management and safety monitoring;
- The labeling and information on prescription, in particular if the prescribing indications are fewer with the similar biotherapeutic product;
- The conditions for pharmacy-level substitution at the initiation of treatment, and for physician-led switch in treated patients.
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?
Legal anchorage for specific regulations related to similar biotherapeutic products has been introduced as part of the Health Law No. 18-11 dated of 2 July 2018 (Article 210).
The Decree No 19-190 dated of 3 July 2019, setting out missions, organization and operating of the National Agency for Pharmaceutical Products (“ANPP” – “Agence Nationale des Produits Pharmaceutiques”, a financially independent institution newly created to replace the former General Directorate of Pharmacy and Health Equipment (“DGPES” – “Direction Générale de la Pharmacie et des Equipements de Santé”), has been published in the Official Gazette No 43 dated of 7 July 2019.
The aforementioned guidelines on similar biotherapeutic products are expected to come into force during 2020 (for detailed information on reform steps and timelines, refer to Regulatory Reforms).