Issue link: https://www.e-digitaleditions.com/i/1420709
20 Pharmaceutical Technology APIs, EXCIPIENTS, AND MANUFACTURING eBOOK 2021 P h a r mTe c h . c o m For Siripragada, quality-by-design technology should be prioritized and implemented during the develop- ment stage, as it provides an indication of the quality of manufactured products prior to testing them. Ac- cording to Siripragada, if a company can adopt all the quality and safety standards at the development stage, it can meet all the requirements of global market. Regulatory hurdles for the registration of APIs The first hurdle, according to Lynn and Schniepp, is knowing the requirements of the country you want to register the API within. After that, they add that the second hurdle is determining what needs to be submitted for the registration. For example, in the United States, there is the US Drug Master File (DMF). In Europe, there is the European DMF. While there are similarities between the two, where and how to file them are different. In the European Union (EU), the DMF is handled by two different agencies, the European Medicines Agency (EMA) and the European Directorate for the Quality of Medicines and Healthcare. In the United States, FDA oversees DMFs. Companies should check DMF requirements for the applicable country. But even when requirements for registering APIs in the different countries are known, there can be room for interpretation—thereby creating differing expecta- tions for each regulatory body. "Despite the increased global harmonization of re- quired information and format for drug substance to support a drug product registration, agencies and as- sessors still have different expectations and interpre- tations," says Bonde. "Some countries like China ex- pect additional details for specific process equipment and material suppliers while other countries' regula- tors mainly refer to a local translated summary of the eCTD [electronic common technical document]." "There are also procedural and interpretation differences between agencies like the FDA and EMA," Bonde continues. "Some regulatory expec- tations—for example, the availability of validation data, the extension of justifications, impurity risk assessments, and process development descrip- tions—might need additional information or need to be modified for a specific regulator. However, we find that to some extent expectations are often up to the individual assessor. The FDA, in our experi- ence, has a more pragmatic or flexible scientific ap- proach to the required manufacturing documenta- tion, especially if the approach has been discussed in a scientific meeting prior to submission, while the EMA is more conservative in nature." Bonde adds that a contract development and manufacturing organization (CDMO) with in-house global regulatory experts can help companies develop a comprehensive plan for global regulatory approvals. "Experience with different regulatory bodies is key to securing useful feedback on filings, includ- ing clarity on risk assessment, de-risking processes, and anticipating potential questions to ensure a molecule reaches the market faster," says Bonde. Preparing documentation Before preparing documentation, it's important for companies to familiarize themselves with the specific APIs Before preparing documentation, companies should familiarize themselves with the specific requirements of the country and regulatory agencies they are submitting the information to.