Three formats cover almost every market a generic exporter from India will meet. The ICH CTD, in five modules, is the default \u2014 Nigeria\u2019s NAFDAC has adopted it, and so have India, the EU, the US, Japan, Canada and most WHO-aligned regulators. The ASEAN ACTD reorganises the same evidence into four parts. A smaller group of regulators still runs a format of its own. The evidence barely changes between them. Where it sits changes completely, and that is where dossiers lose months.<\/p>\n\n\n\n
The\u00a0ICH CTD<\/strong>\u00a0has five modules. Module 1 is regional administrative information \u2014 application forms, labelling, product information, local fees \u2014 and is deliberately\u00a0not<\/em>\u00a0part of the harmonised CTD, which is why it differs in every country. Module 2 holds the summaries and overviews. Module 3 is quality. Module 4 is nonclinical study reports. Module 5 is clinical study reports. ICH M4Q is the guideline that governs Module 2.3 (the Quality Overall Summary) and the whole of Module 3.<\/p>\n\n\n\n The\u00a0ASEAN ACTD<\/strong>\u00a0(Revision 1) has four parts: Part I administrative and product information, Part II quality, Part III nonclinical, Part IV clinical. These map to CTD Modules 1, 3, 4 and 5. There is no ACTD part corresponding to Module 2 \u2014 the summaries sit inside their own parts instead. Part II opens with Section A (table of contents), Section B (the Quality Overall Summary) and Section C (Body of Data: drug substance first, then drug product), closing with Section D for key literature references.<\/p>\n\n\n\n For a generic application the ACTD is explicit that \u201cthe documentation of this part is not required for Generic Products, Minor Variation Products and some Major Variation Products\u201d \u2014 that applies to Parts III and IV.<\/p>\n\n\n\n One conversion trap is worth naming, because it catches people who assume the two formats are a relabelling exercise. The ACTD\u2019s drug product section runs to\u00a0P9, Product Interchangeability<\/strong>\u00a0\u2014 bioequivalence data sits\u00a0inside<\/em>\u00a0the quality part. In the CTD, bioequivalence goes to Module 5. Convert an ACTD to a CTD by renaming folders and the BE study ends up in the wrong module.<\/p>\n\n\n\n Regulatory affairs can write the overviews. Module 3 has to come out of the plant, and the list is fairly fixed:<\/p>\n\n\n\n \u2022\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0The batch formula, and the manufacturing site name, address and licence number exactly as they appear on the manufacturing licence<\/p>\n\n\n\n \u2022\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0A process flow chart plus a narrative description with equipment class, batch size range and critical process parameters \u2014 not equipment brand names, but not \u201cas per SOP\u201d either<\/p>\n\n\n\n \u2022\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0In-process control tests with numerical limits and the stage at which each is applied<\/p>\n\n\n\n \u2022\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Batch analysis data on production-scale batches, with the analytical procedures and their validation<\/p>\n\n\n\n \u2022\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Excipient specifications, supplier certificates of analysis and the source declaration for anything of animal origin<\/p>\n\n\n\n \u2022\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Container-closure system specification, including foil and film grades and dimensional drawings<\/p>\n\n\n\n \u2022\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0Stability data on the exact pack offered<\/p>\n\n\n\n On stability, the WHO conditions are the ones to work to. Accelerated testing runs at 40 \u00b0C \u00b1 2 \u00b0C \/ 75% RH \u00b1 5% RH for at least six months. Long-term testing for hot climates is at 30 \u00b0C \/ 65% RH (Zone IVa) or 30 \u00b0C \/ 75% RH (Zone IVb) \u2014 Nigeria is Zone IVB. A minimum of 12 months of long-term data is expected at submission where the proposed shelf life is 12 months or more. Confirm which Zone IV condition your destination regulator wants before you put a chamber on it; the two are not interchangeable.<\/p>\n\n\n\n This is not a matter of opinion. WHO Prequalification published a list of common deficiencies found in finished pharmaceutical product dossiers (WHO\/PQT: medicines, 27 February 2018), with figures drawn from its own assessment record. Two clusters dominate.<\/p>\n\n\n\n 3.2.S \u2014 the drug substance section.<\/strong>\u00a0\u201cIn 35% of the reviewed dossiers missing or inadequate control of polymorph identity and\/or PSD were noted.\u201d The other recurring findings are an API specification that does not match the API manufacturer\u2019s own approved specification, and limits for unspecified impurities set wider than the ICH Q3A\/Q3B identification threshold. Almost all of this depends on what the API supplier will actually put in writing, which is why it stalls.<\/p>\n\n\n\n 3.2.P.2 and 3.2.P.3 \u2014 pharmaceutical development and the process description.<\/strong>\u00a0\u201cInadequate or poorly defined end point for wet granulation process affected about 50% of the reviewed dossiers.\u201d WHO is direct about the language: \u201cstatements such as \u2018stop granulation when required consistency is achieved\u2019 are not acceptable.\u201d Missing hold-time justification and missing multimedia dissolution profiles on the biobatch appear repeatedly. Related, and larger still: \u201cabout 60% of the reviewed applications had protocols deficient\u201d on process validation, including failure to validate a compression machine speed range.<\/p>\n\n\n\n The uncomfortable part is that both clusters are things the factory already knows and the file simply does not say. They are documentation failures, not manufacturing failures \u2014 which is why they are cheap to prevent and expensive to answer.<\/p>\n\n\n\nWhat Module 3 actually needs from the manufacturing site<\/strong><\/a><\/h2>\n\n\n\n
The two sections that generate the most rework<\/a><\/strong><\/h2>\n\n\n\n
Which market wants which<\/a><\/h2>\n\n\n\n