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Resolution RDC nº 53/2015 sets several criteria for reporting, identification and qualification of degradant products in drug products.
The regulation includes standards on forced degradation studies (FDS) to which pharmaceutical companies must comply.
Forced degradation studies are performed:
- To identify degradation products
- To establish degradation pathways and drug molecule stability
- To validate stability-indicating analytical procedures
The RDC 53 guideline stipulates the need to understand the consequences of degradation with a focus on impurities and stability testing to limit the risk of toxic features.
RDC 53 sets out parameters for verifying degradation products in medications, and for preparing the corresponding degradation profile for the reporting of degradation products.
The guideline ensures that:
- Necessary safety studies for degradation products are completed
- Assessment of specific forced degradation conditions is completed and documented
- Consideration is given to degradation resulting from manufacturing and storage
- Stability-related problems are solved by obtaining and explaining mass balance
- Degradation products and potential toxic components are identified
- Identification of toxicity or loss of efficacy of the drugs is identified
RDC 53 stipulates the need to understand the consequences of degradation with a focus on impurities and stability testing.
Lhasa Limited provides an integrated solution to assist in the meeting of the RDC 53 guideline, particularly for the requirements stated under the 'Preparation Phase', which are:
Information on functional groups
Known excipient interactions
Potentially toxic degradants
The decision support that Zeneth offers is invaluable in meeting many of the requirements under RDC 53 and in particular, points 2 and 3, stated under the 'Preparation Phase':
- Zeneth’s comprehensive knowledge of degradation pathways, ensures structure elucidation of experimentally seen degradants.
- Intuitive tools in Zeneth allow filtering of results based on chemical formula, mass and mass difference, allowing experimental data to guide predictions.
- Zeneth swiftly provides predictions for the likely degradation products of query compounds, whilst considering the effect of different excipients and impurities within the final formulated product.
- Structures of common excipients with associated impurities, are provided for easy processing alongside the query compound.
- Predictions are supported by transformation details and degradation pathways, allowing for an understanding of the functional groups involved.
Derek Nexus - expert software for the prediction of toxicity
Once degradants predicted in Zeneth have been easily exported, Lhasa’s toxicity prediction tool, Derek Nexus, enables the analysis of the potential toxicity of those degradants, satisfying step 4 of the ‘Preparation Phase’.
- Derek Nexus predicts potential toxicity for a large number of toxicological endpoints.
- Predictions are clearly represented and contain supporting evidence and patterns associated with the alerts for your compound.
- Used in combination with Sarah Nexus, a combined prediction for mutagenicity can be produced.
Sarah Nexus - statistical software for the prediction of mutagenicity
Sarah Nexus enables the analysis of the potential mutagenicity of degradants, supporting step 4 of the ‘Preparation Phase’.
- Sarah Nexus is the quick, inexpensive way to identify potentially toxic chemicals, aiding experts in rejecting unsuitable drug candidates.
- Predictions are clearly represented and supported by a measure of confidence, the fragments on which the predictions are based and relevant examples from the Sarah training set. This high level of transparency facilitates the expert review process.
- When concerned with mutagenicity, a combined Derek and Sarah Nexus prediction can be provided to increase efficiency.
The rapid access to high quality data from both published and proprietary sources that Vitic provides, offers a distinct solution in satisfying step 1 of the ‘Preparation Phase’ under RDC 53.
- Potential toxicity of existing or prospective chemicals can be evaluated through exploitation of large chemical libraries.
- Internal toxicity data and knowledge can be shared with your colleagues by capturing it within Vitic.
- Carrying out searches across multiple datasets ensures all relevant results are returned within one interactive interface.
Lhasa's solutions are currently used across a range of sectors but most notably pharmaceutical, cosmetic, chemical, regulators, government agencies and academia. A list of members can be viewed here.
When asked why people choose to work with Lhasa Limited, the common responses are:
|Software is easy to use and well supported|
|Transparency of Lhasa systems allows trust and confidence in the science presented|
|All science is developed in-house, providing the opportunity to discuss directly with Lhasa expert scientists|
|Over 35 years of experience in developing state-of-the-art in silico prediction and database systems|
For more information on Lhasa's RDC 53 offering, or to request a demonstration, please contact us.
- Rodrigues, M (2019) RDC 53: Challenges on impurities qualification
- Huynh-Ba, K; Beumer, S. A., (2018) ANVISA: an introduction to a new regulatory agency with many challenges
- Burns, M (2018) How Zeneth Fits into ICH Q3B
- Priscila et al. (2017) Generic Medicines Regulation in Brazil
- Von, V (2017) Forced degradation studies comparison between ICH, EMA, FDA and WHO guidelines and ANVISA s resolution RDC 53/2015
- Presentations from the 2019 Pharmaceutical Industry and Regulators Symposium. Presentations and Recordings