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batch processing, the progression through scale-up is dif- ferent. The question often asked is, "At what scale should the DoE be undertaken?" The simple answer is, it depends! It depends on how confident we are that the DoE will continue to be relevant as we scale up to full commercial scale. In fact, the scale for the initial DoE will likely be at either the 1× or 10× scale, depending on the critical scale for the unit operations. However, whatever batch size is selected for the DoE, there should be a written, scientifically sound justification. On completion of the initial DoE, the results will be analyzed to determine the design space and control strat- egy to ensure that the drug product can be manufactured consistently, that it meets specifications, and is fit for its intended purpose. However, for batch processing, at least one further scale-up, i.e., to a full commercial or 100× scale must be performed. If the DoE is undertaken at less than the 10× scale, an initial scale-up to the 10× scale, followed by a scale-up from the 10× to the 100× scale, will be required. As we move up in scale, we need to confirm that the design space and control strategy are still appropriate. That requirement does not mean that the DoE is repeated at the intermediate/pivotal and commercial scale; rather, using scientifically justifiable arguments, the continued relevance of the design space and control strategy at the new scale should be demonstrated. From the DoE, there will be an understanding of the CMAs and CPPs. As more experience is gained with the formulation and process, further understanding will be obtained as to which CMAs and CPPs have the greatest potential to affect the product's CQAs. Finally, the product and process will be transferred to commercial manufacturing. However, there is still further work to be done. Prior to 2011, there would have been a three-batch validation. This has changed and today there would be a process qualification (typically three batches manufactured at commercial scale) followed by continu- ous verification of all further batches. When using continuous processing, scale-up may not apply because larger batch sizes simply require that the process be run for a longer time. The DoE would be undertaken using the same equipment train and scale as would be used for commercial manufacture. However, the DoE may well require less material and time than conventional batch processing would. Often, one of the most critical product attributes of a tablet or capsule will be dissolution. For immediate-release products using water-soluble APIs, the assessment will be relatively straightforward. However, for drug products with very poor water solubility and for modified-release formulations, the assessment may be less straightforward. For poorly water-soluble drug products, a dissolution test method will need to be established that is relevant to the formulation. For modified-release formulations, some form of in vitro/in vivo correlation will be desirable. The stages in a QbD tablet or capsule development project are summarized in Table 1. Summary QbD requires that good decisions are made and justifi- cations provided based on sound scientific principles. It is not just about what must be done to comply with the regulations; it is about providing written justifications and acquiring good supporting data to show that the develop- ment has been undertaken using sound science, and that the regulatory agency can have confidence that product can be manufactured routinely, is stable, will consistently perform as intended, and is fit for its purpose. T&C Chris Moreton is a partner and the vice president of pharma- ceutical sciences at FinnBrit Consulting, Waltham, MA. Tel. 781 894 2572. Website: www.finnbrit.com. He has more than 35 years of international experience in the development of both new drug candidates and generic drug products in many ther- apeutic areas and using different dosage forms and routes of administration. 18 September 2017 Tablets & Capsules A version of this article appeared in "Solid Dose Digest," a twice-monthly e-newsletter for T&C's print and digital subscribers. If you haven't seen the newsletter, contact Kyle Myers to begin receiving it: kmyers@cscpub.com. Allendale, New Jersey Óä£ÈÓnÓääÊUÊÜÜÜ°À>iiÀÕðV `Ài°*iÌÀVJÀ>iiÀÕðV For 35 YEARS the pharmaceutical industry has relied upon ÀBiÀ to de-dust, de-burr and convey tablets with the highest efficiency. To learn more about how to *,"6 the EFFICIENCY of your tableting lines contact Kraemer U.S. Tablet de-dusting solutions from the Global Leader