A 5 batch analysis report is a requirement for the regulatory approval of a chemical active ingredient with the APVMA and indeed by most global regulatory bodies. However to be acceptable for registration purposes there are a number of areas that require attention during the generation of a 5 batch.
What is a 5 batch study?
It’s the identification and quantification of detectable compounds (at and above 0.1% w/w and all toxicological impurities at any concentration) present in a technical active constituent as manufactured by the process proposed. Representative samples from production relevant batches, or at suitable intervals in a continuous process, are analysed to provide information that is used to generate a specification. That specification or Declaration of Composition is an important part of the regulatory information package.
So what are some of the common deficiencies in a 5 batch analysis report that will result in the report being deemed not suitable for approval purposes?
- Insufficient and unsuitable data to support the elucidation of the chemical structure and other characterisation of structure, e.g. nuclear magnetic resonance (NMR) spectra, mass spectrum (MS) and infrared (IR) spectra. • Insufficient information regarding the description of the manufacturing process (e.g. detailed reaction scheme with conditions) and quality control measures (e.g. specifications for all starting materials, reagents, catalysts, and key intermediate products).
- Batches not representative of the manufacturing process. They should be pilot plant or commercial scale batch size and represent commercial conditions (5kg minimum). Laboratory production runs are not acceptable unless supported by adequate commercial relevant batches.
- Batches not produced in the same physical site proposed for approval.
- Analysis of the batches is older than 5 years.
- Chromatogram peaks not properly identified. All peaks need to be identified and quantified (unless they are less than 0.1% w/w).
- Known relevant and toxicologically significant impurities for that active constituent not analysed. They must be quantified and included in the report.
- Analytical methods not validated or not validated to APVMA requirements. Validation is necessary to demonstrate that all the analytical methods used are fit for purpose.