Issue link: https://www.e-digitaleditions.com/i/1420709
Pharmaceutical Technology APIs, EXCIPIENTS, AND MANUFACTURING eBOOK 2021 21 requirements of the country and regulatory agencies they are submitting the information to (as discussed above). But once it comes down to assembling the files—which will ultimately be submitted using eCTD format—anything that is related to the manufacture, testing, and release of the API should be included. According to Lynn and Schniepp, some of the nec- essary files include, but are not limited to: • Records of raw materials receipt, sampling, and release • Master batch records, labeling, and testing information • Details of the equipment used during the manufacturing • Validation records. Bonde adds that it's particularly important to in- troduce GMP early, as different agencies might have different understandings of the requirements. "Early discussions in scientific meetings help ensure a shorter GMP route of synthesis, which can improve manufacturing flexibility in the future," says Bonde. "It is further essential to characterize the drug sub- stance and the process to manufacture the drug sub- stance, including descriptions of impurities resulting from the process, material used in the process, and the potential purging of genotoxic impurities. All regu- lators require a manufacturing process description with a discussion on the critical process controls and proven acceptable ranges and parameters regarding the influence on quality." Going forward: what bio/pharma companies should know One thing that is important for manufacturers to remember is CGMPs apply to APIs/drug substances, just as much as they do to finished dosage forms. But according to Bonde, it's communication be- tween companies and regulatory bodies that can (and should) be improved. "I wish customers would interact more with regu- lators and CDMOs, and much earlier in the devel- opment process," says Bonde. "This would help to circumvent issues ahead of commercialization and provide f lexibility for changes to manufacturing processes and analytical methods." Most companies tend to focus on the clinical aspect, Bonde says, particularly smaller biotech companies with limited GMP manufacturing expe- rience and/or lack of capacity inhouse. "As a devel- opment and manufacturing partner, we can advise on processes and the implementation of accelerated pathways, such as breakthrough or priority assess- ments, to optimize the use of the designations. In our experience, a lean and concise CMC file often leads to a better regulatory outcome. It is important to know ahead of time what information will be required by global regulators as part of the roll out strategy for each stage of commercialization." Knowing the requirements to develop and manu- facture APIs is the first step to a smooth commer- cialization process, according to Lynn and Schniepp. This includes laws, regulations, guidances, stan- dards, and more. After that is a practical under- standing of how to apply those requirements and comply with the applicable laws and regulations of the country the drug product is being distributed to. Furthermore, companies should also know what information is required in the submission for each applicable regulator. Finally, transparency with the regulators is key, says Lynn and Schniepp. By combining all the above along with having a robust quality management system, companies will be able to ensure regulatory adherence and a successful ex- ecution of their commercialization plans. PT