Source: Quaero, 29/09/2008

With the frequent increase of such establishments in the country, the public health risks caused by the handling of pharmacies in the Brazilian market are discussed. São Paulo, September 2008 - A question that does not leave the minds of Brazilian consumers is the extent to which it is safe to use oral medications manufactured by compounding pharmacies. This questioning affects an increasing number of people, since these pharmacies have multiplied in the national market.

According to Edition nº. 72 of the Revista da Associação Nacional de Farmacêuticos Magistrais (ANFARMAG), of 09/07/2008, “The sector (of magistral pharmacies) integrates a market in dramatic growth (…), it is estimated that pharmacies connected to the sector are responsible for revenue of at least R $ 800 million per year ”. In fact, in 2002 there were about 5.200 manipulation pharmacies. Nowadays, according to data from ANFARMAG, Brazil is already the world's largest market for handling pharmacies, with about 7 thousand such establishments in the country.

According to the Collegiate Board of the National Health Surveillance Agency (ANVISA), there are few handling pharmacies that adequately follow the regulation of Good Handling Practices established by the agency and, given the progressive growth in the number of establishments, their inspection becomes impracticable.

According to a text prepared by the ANVISA Collegiate Board, entitled “Subsidies to the discussion on the proposed regulation for magistral pharmacies”, presented at a Public Hearing at the Chamber of Deputies in June 2005, the full application of the technical regulation on good handling practices "would lead to the banning of most establishments".

Medicines CPI pointed out illegal practices in compounding pharmacies

In 2000, CPI dos Medicamentos' final report had already identified several unethical and illegal practices by handling pharmacies in Brazil, such as (i) products handled and dispensed to the public with the trade name, owned by the industry, which characterizes forgery; (ii) products that require special technology, such as rapid or prolonged disintegration in the body, gastric protection, etc., being handled in gelatin capsules, which do not offer such conditions; (iii) manipulation and production of associations of substances prohibited by health surveillance; (iv) "secret" formulas, without the generic names on the labels, and (v) offering manipulated products as an alternative to commercial products and counterfeit products, in newspaper advertisements.

In the text “subsidies to the discussion on the regulation proposal for magistral pharmacies”, ANVISA asserts that the drugs prepared by the handling pharmacies did not follow the process of adapting the national drug industry to the new level of quality. According to the agency, several manipulation pharmacies have started to copy or modify the formulas of innovative medicines, without subjecting them to the pharmaceutical equivalence and bioequivalence tests, required to prove the safety and efficacy of the medicine.

In several countries, manipulation pharmacies have a complementary role to industries, handling products only when there is no industrialized formulation in concentrations or forms suitable for certain patients who, due to a particular and exceptional clinical condition, require medication that is not standardized.

ANVISA points out that in some provinces of Canada, compounding pharmacy exists only in university hospitals, precisely because it is impossible to guarantee for a medicine produced by hand the same quality control as a modern industry. The agency asserts that "if there is a need for artisanal production of a drug, it must be the exception and this must be very well justified clinically".

From the point of view of public health, the growing concern with the manipulation of medicines in magistral pharmacies is based on reports by ANVISA inspection teams and cases investigated by the agency's pharmacovigilance, including several deaths. In fact, in 2003 the deaths of four children were registered due to the misuse of manipulated drugs that contained a high content of clonidine, a substance used as a growth stimulator. Such an incident led ANVISA to issue a Resolution (RE nº. 1621 of 03/10/2003) prohibiting the manipulation of “low therapeutic index” drugs.

Notwithstanding what happened, at the end of 2003, ANVISA revoked RE 1621, once again allowing the manipulation of “low therapeutic index” drugs despite the recommendation to the contrary by sanitarians, pharmacologists and technicians. Unfortunately, in 2004 more deaths occurred due to manipulated drugs containing the substance clonidine.

According to the final report of the Medicines CPI, of 30/05/2000, corticosteroids (dexamethasone), antibiotics (cephalexin and tetracycline), antiarrhythmics (amiodarone), corticosteroid hormones (prednisone), among others, are quite manipulative and production problematic. However, currently all of these substances are susceptible to manipulation in magistral pharmacies in Brazil.

In the text “subsidies to the discussion on the regulation proposal for magistral pharmacies”, presented in a Public Hearing at the Chamber of Deputies, in June 2005, ANVISA makes it clear that the guarantee of safety is a fundamental item when it comes to public health . To ensure the quality and safety of medicines offered to the public, health surveillance requires industries to carry out validation procedures at the various stages of the production process. According to the agency, the struggle to see the rules that configure good manufacturing practices, as well as all other pertinent to health surveillance, has been constant. In that text, ANVISA points out that when a batch of raw material arrives, in addition to checking the analysis reports sent by the supplier, the industry has to carry out its own tests, keeping the input in quarantine until the completion of these tests. After the beginning of the process, samples are collected in several stages, until each batch of the final product, before being released, undergoes laboratory verification once again.

ANVISA admits that in the case of masterful manipulation, the procedures for quality assurance are practically unviable, as they require specific equipment that most manipulation pharmacies do not have, as well as a quantity of products that allow samples to be taken. representative, which also does not occur in the case of pharmacies of this kind.

When faced with the manipulation of high-power and low-dose drugs, for example, small variations in the production process, including the possibility of unpredictable random errors, can lead to catastrophic results. When looking at the real danger of the situation, ANVISA states that "in the order of magnitude of millionths of a gram, a particle the size of a grain of sand can mean a fatal dose".