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RDC 53/2015: Brazilian Pharmaceutical Company Turns to Zeneth to Meet New Regulations

Date: 04 April 2018


In the development of a new Drug Substance (DS) or product, forced degradation studies (FDS) are essential to gain understanding of the stress characteristics. They also provide insight into degradation pathways and degradation products of the DS, and, in turn, aid the development of the formulation and packaging of the end product.

Aché Laboratórios Farmacêuticos S.A, is a Brazilian company which manufactures, markets and distributes a huge range of pharmaceutical products including prescription, generic and Over-The-Counter drugs to treat respiratory, musculoskeletal, women's health, central nervous system, cardiology, dermatology, and oncology related diseases; plus vitamins and cosmetics. Founded in São Paulo in 1966, Aché employs more than 4,600 people across three sites and is one of the largest companies in the Brazilian pharmaceutical industry.

Prior to the 2015 introduction of the RDC53 regulatory guidelines by Anvisa, the Brazilian National Health Surveillance Agency, Aché was following the RDC58 regulations which required either FDS or alternative studies to be carried out. Aché was therefore carrying out forced degradation studies on a case-by-case basis. The introduction of RDC53, and the guideline Nº4/2015, defined how the forced degradation studies needed to be conducted, which criteria should be followed, and how to assess the toxicity of a degradation product. The RDC53 and guideline Nº4/2015, require a single report covering a suitability assessment of the proposed stability indicating method; molecular structure review and its connection to the degradation profile; FDS; interpretation of data; toxicological assessment; and application of informed decisions/controls leading to the final formulation design, packaging selection and recommendation on storage condition. The report should include conclusions on the degradation profile and a safety profile assessment and include assurances on degradation mitigation through production conditions and formulation storage controls.1

As a result of these new guidelines, Aché needed to implement a structured approach to their FDS and therefore required software to help with the process.

Aché was already working with Lhasa Limited and had sponsored both its Derek Nexus and Zeneth software. Degradation Product Specialist at Aché, Dr Mariah Ultramari, had learned about Zeneth during her PhD and so turned to the Lhasa team to draw on their expertise and understand how Zeneth could help the business to meet the more stringent RDC53 requirements.

Zeneth is an expert, knowledge-based software that gives accurate forced degradation predictions quickly and it is the only commercially available, actively maintained software of its kind. Based on data implemented by scientists at Lhasa Limited, Zeneth can give predictions for a variety of degradation conditions whilst also taking into account the effect of excipients and impurities. It is used across a range of industry sectors but most notably within pharmaceutical departments.

Most importantly for Aché, Zeneth follows the guidelines established by Anvisa in the RDC53. It helps by predicting possible degradation pathways in the Active Pharmaceutical Ingredient (API), as well as its interactions with the excipients. It also provides references which help to elaborate the final report.

Aché now implements Zeneth across a number of stages of drug and product development: prior to the experiments to help guide the experimental design; at later stages to help elucidate the structure of the degradants and their formation pathways; and also at the very beginning of projects, in the compatibility studies stage, to help in identifying excipients and APIs that pair well with minimal cross-reactivity. These early compatibility studies normally precede an FDS.

Aché has also recorded significant time savings through use of Zeneth. In addition to streamlining and speeding up the FDS process itself, Aché has reduced the amount of time spent analysing FDS results by its in-house organic chemists.

Dr Mariah Ultramari, Degradation Product Specialist at Aché, said: “Zeneth is a true help on forced degradation studies. Beyond that it also really helps designing the formulation, as it mitigates the risk of possible API/excipient interactions”.

Dr Carlos Eduardo da Cunha, Account Manager at Lhasa Limited, said “Zeneth offers an easy and straightforward way to look at chemical degradation under a series of possible conditions. The RDC58 regulations primed the industry and RDC53 created a consensus across the board – it was a game changer in the Brazilian pharmaceutical market, requiring a standardised approach on forced degradation studies. Fortunately for Aché and our other Brazilian members, Zeneth was already a mature software and ready for use. Once RDC53 came into effect, Zeneth was no longer an alternative tool to be used in some cases, it became the central strategic tool to design the stability studies and to analyse the FDS ones. Its usage has increased thousands of times over in the last two years and the current feedback from our Brazilian members has also really helped us to shape and develop the next iterations of the software and its knowledge base.”


1) http://www.americanpharmaceuticalreview.com/Featured-Articles/184364-Impact-from-the-Recent-Issuance-of-ANVISA-Resolution-RDC-53-2015-on-Pharmaceutical-Small-Molecule-Forced-Degradation-Study-Requirements/

  • Summary:

    As a result of new RDC53 guidelines, Aché needed to implement a structured approach to their FDS and therefore required Zeneth to help with the process.

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