Therapeutic option
Generic drug registration celebrates 18 years
Data from the Drug Verification Program (Proveme) attest to the quality and safety of evaluated products.
By: Ascom/Anvisa
Published: July 4, 2018, 5:01 p.m.
Last modified: July 4, 2018, 5:45 p.m.
Eighteen years ago, the first generic drug was registered in Brazil. An unprecedented survey by the Brazilian Health Regulatory Agency (Anvisa) reveals that generic drugs on the market have a high approval rate in analyses conducted to certify product quality and safety. Of a total of 284 batches analyzed in 2016 and 2017, 85.9% were in compliance with the manufacturer's information and technical requirements. As they are widely marketed in Brazil, the number of generic drug batches selected for testing during the period represented 61.4% of the total evaluated (462).
The data comes from the Drug Verification Program (Proveme), which evaluates items that are already on the pharmaceutical market and registered with Anvisa. During testing, the physical and chemical aspects of the products are verified. The analyses performed on the drugs may vary according to the pharmaceutical form and characteristics of the product. The most common are: analysis of the active ingredient dosage, weight variation, dose uniformity, analysis of appearance and labeling, as well as its dissolution in the body.
"Periodically, the program conducts a series of new tests on selected products to verify that the items comply with the standards established by the Agency. The results attest to aspects such as safety, quality, and efficacy," explains Anvisa CEO Jarbas Barbosa.
He says that the analyses are carried out by official laboratories belonging to the National Network of Health Surveillance Laboratories (RNLVISA). The results of batches that fail the tests determine various health measures, such as suspension of sale and use, changes in registration, inspection measures, adoption of corrective measures by manufacturers, and initiation of administrative health proceedings.
According to Anvisa, the selection of drugs evaluated is based on the volume of technical complaints and quality deviation reports. Products used by consumers and by Ministry of Health programs, such as Farmácia Popular do Brasil (Brazil's Popular Pharmacy), are also prioritized. The collection of samples for testing is a decentralized action, under the responsibility of state or municipal Health Surveillance coordinators.
Growth in registrations
The number of new generic drug registrations in Brazil rose from 146 in 2014 to 336 in 2017, representing an increase of 130.1% in just four years. In total, there were 1,830 applications for registration of this type of product, of which 1,229 complied with Anvisa requirements. Another 601 applications for registration were rejected for failing to meet health standards for production.
For the agency, the data confirms the growth trend of generics in the market, but also the importance of Anvisa's careful assessment of product quality, efficiency, and efficacy when granting new registrations.
“The domestic market for generic drugs has grown significantly in recent years due to product quality, price, and public confidence in these medicines. Anvisa plays a key role in this scenario, establishing strict standards for product registration and for post-market analysis,” says Jarbas Barbosa.
Some of the main reasons for refusing registration are problems with the quality of the pharmaceutical ingredient, drug stability (assessing whether the drug can withstand Brazilian climatic conditions), and analytical methodology (assessing drug quality parameters, such as product content).
Anvisa requirements
The entry of generic drugs into the Brazilian market has caused drug prices to fall and contributed to expanding the population's access to safe and effective products, which has required improvements in regulation. For this reason, Jarbas Barbosa emphasizes that, in order to obtain registration, manufacturers must prove that generic drugs are of high quality and that they work for their intended purpose, just like the reference product.
The product formulation (recipe) must be based on the Brazilian pharmacopoeia or another pharmacopoeia recognized by Anvisa. Among the necessary and required studies is one on the pharmaceutical bioavailability between the generic and the reference product to verify that the product contains the same drug, the same dosage, and the same pharmaceutical form.
A dissolution profile study is also required, which evaluates the performance of the drug by simulating its behavior in humans. The objective is to verify whether the drug dissolves in the human body in a timely manner to have the expected effect. This test cannot be used in isolation to evaluate a product, but is part of a set of information that is analyzed in the registration process. The dissolution profile is also requested when the manufacturer makes changes after obtaining registration from Anvisa, which must be communicated to the agency.
“It is important to note that the drug must comply with the parameters of the Brazilian pharmacopoeia or another recognized pharmacopoeia, but the dissolution profile must comply with what was used in the registration specification. This is because the pharmacopoeia does not measure the dissolution profile,” says the CEO.
The manufacturer must also include in the dossier on the generic drug guarantees regarding quality, shelf life, and storage conditions. In addition, certification of compliance with good manufacturing practices (GMP) and control of the production site is required. The health authorizations necessary for the proper functioning of the company must also be verified.
In other words, the company and the drug must fully comply with health regulations in order to obtain product registration.
Market dominance
Between 2012 and 2016, the total number of registered products rose from 490 to 882, representing an increase of 80%. This growth is largely due to generics and similar products, which together account for 80% of total registrations between 2012 and 2016, and 82% in the last year of the period.
Currently, Brazilian consumers have access to 6,300 different products in the pharmaceutical market. Considering the volume of synthetic products sold in Brazil, generics and similar products (branded generics) predominate, reaching a percentage of 75.7% in 2016. This figure represents an increase of two percentage points compared to 2012 (73.7%).
According to information from the Organization for Economic Cooperation and Development (OECD) for 2015, Brazil's current index is similar to that of the Netherlands (69.7%) and Canada (70%). The United States and the United Kingdom have percentages of 84% and 83.4%, respectively. For Anvisa, the data is positive because it shows that the drugs have proven quality and acceptance in the global market, as well as among the population.
Of the 20 companies with the highest revenues from sales of this type of product, 16 are Brazilian. Of these, three are public: Oswaldo Cruz Foundation (Fiocruz), Foundation for Popular Medicine, and Vital Brazil Institute. In 2016, the industry's revenues from generics totaled R$ 8.58 billion.