Brazil's regulatory health authority, Anvisa, plans to establish quality requirements for locally produced pharmaceutical
excipients, Anvisa told Pharmaceutical Technology. The organization publicly released a draft proposal on this policy on June 4, 2012 and the public had 60 days to comment.
There is no set timing, however, for the process, according to Anvisa's regulatory and health surveillance specialist Simone
de Oliveira Reis Rodero, as several steps are needed before the actual publication of the new requirements.
Flickr/João Luiz Pacheco Vieira Galvão-Brazil/Goiás/Goiânia/Getty Images
Debate on responsibility
According to information from the Pharmaceutical Trade Union of the State of São Paulo, Sindusfarma, drug manufacturers are
currently responsible for the quality of excipients included in the drugs they produce. Currently, says the Union, the sector
lacks specific rules for such products and the pharmaceutical industry uses only a portion of the overall excipients produced
in Brazil (other sectors such as health and beauty products use them as well). Many producers may not be interested in complying
with all requirements coming from the pharmaceutical industry. The discussion is likely to continue as the industry and regulators
debate competing interests and opinions.
The need for quality requirements
Anvisa is responsible for developing standards, authorizing pharmaceutical company operations, and for supervising the quality
of pharmaceutical excipients used in drug prducts. Anvisa does this through health inspections to ensure compliance with quality
controls in the drug-manufacturing process. Rodero added that Anvisa has started a database of active pharmaceutical excipients
from companies that manufacture, import, export, fractionate, stock, expedite, distribute, and pack such products. "Good manufacturing
practices for pharmaceutical drugs do not include their pharma excipients as criterion for manufacturing differs," says Rodero.
Therefore, a set of clear rules is being suggested to regulate the excipient sector, Rodero says.
"The norms are not being requested by international organizations. The need came up due to the lack of regulation, which makes
the harmonization process difficult during inspections. We requested that health authorities in countries that hold technical
cooperation agreements with Brazil to send information on how excipients are treated regarding local norms and authorizations,"
says Rodero, adding that the responses are now being evaluated and the data consolidated.
The draft proposal, made public on June 4, 2012, was written based on documents from the International Pharmaceutical Excipients
Council–Europe, the World Health Organization, and the US Pharmacopeial Convention, revealed Rodero.
Adverse reactions related to excipients
According to Anvisa, because excipients can affect the final quality of a given drug, the establishment of an "ResoluÇão da
Diretoria Colegiada" (RDC—Anvisa's Collegiate Board of Directors Resolution) is important for minimizing health risks involved
during the manufacturing process. Standardizing GMPs and practices for the Brazilian sector, qualifying suppliers, and strengthening
local producers are part of the goal as well, states the health authority. Excipients used in pharmaceuticals may act as antiadherents,
binders, coatings, disintegrants, fillers, flavours, colors, lubricants, glidants, sorbents, preservatives, and sweeteners,
according to pharmaceutical data from Anvisa.
According to Rodero, the need for local producers of excipients to comply with quality requirements is important to increase
public health safety because excipients can generate side effects or affect the final pharmaceutical product. Excipients in
drugs sold in Brazil were responsible for cases of adverse drug reactions (ADR) in adults and children, according to a study
conducted in 2004 by the Federal University of Ceará.
Brazil's pharmaceutical industry professionals are asking whether a pharmaceutical resolution for excipients would affect
producers. If approved, established companies would have a period of one year to comply with the new rules.
According to Anvisa, changes would facilitate issuance of authorizations and health licenses, because standards would be put
in place and minimum quality requirements needed for guaranteeing the quality of excipients would be absolutely clear. However,
Brazil's National Pharmaceutical Laboratories Association (ALANAC) protests: "ALANAC supports any and all regulation initiatives
as long as they improve the quality of the feedstock used in producing [pharmaceutical] drugs and [only] if it can stimulate
industry competition and the development of local production," said Henrique Uchió Tada, executive technical director for
"Anvisa's public consultation number No. 31/2012 on an RDC resolution for GMPs of pharmaceutical excipients defines that rules
will only be applied to the local production, however, most of the excipients used in the pharma industry are imported," complains
Tada. According to Tada, the association fears that the real objective of having an RDC—achieving quality assurance—will not
be obtained if the rules only apply to excipients produced locally.
Just like the RDC for pharmaceutical drugs, for example, which is valid for local and imported medicaments, "We understand
that this proposal...should also be valid for products manufactured abroad," says Tada.
According to the director of ALANAC, similar rules for excipients are not applied by other countries' health authorities as
the GMP for pharmaceutical drugs already require that industry suppliers be qualified and guarantees quality controls during
all production processes, he adds.
Hellen Berger is a business writer based in São Paulo, Brazil.