文档介绍：SAIC Proprietary 1 Topics ? Brief history of cGMP for biopharmaceuticals ? CMC Issues – Perils of not planning backwards ? Building – Not testing – Quality into the Product ? Product Safety – How soon do I need to start worrying? ? Case Study – – A monoclonal antibody for treatment of late-stage neuroblastoma (or making your own biosimilar without intending to) ? Lessons Learned SAIC Proprietary 2 Foundations of GMP ? All drugs (small molecule and biologic) have to be shown to be safe and effective. ? It was not always so. ? The history of drug law shows us that most of the laws and regulations we have today were in response to tragic events. ? A sampling … SAIC Proprietary 3 It all started with a horse n amed “ Jim ” SAIC Proprietary 4 Diphtheria Antitoxin ? Made in old milk horses – like Jim. In St. Louis, Missouri. The blood of a tetanus-infected retired milk-wagon horse was used for this purpose. Thirteen children who were given the antitoxin died from tetanus. * Led to the Passage of the Biologics Control Act of 1902. SAIC Proprietary 5 Guidance Documents ? Put meaning to the ambiguities in the statutes and regulations. ? Points to consider ? ICH (International Conference on Harmonisation) ? Do not have the force of law but the FDA does expect investigators to adhere to them unless they have an equally sound approach. ? Can be found on FDA web site SAIC Proprietary 6 GMP Rules of Thumb ? If it is not written down – it never happened. ? Until you know it does not matter – it matters. ? GMPs really begin at the bench prior to what would normally be perceived as the true beginning of GMP PD and manufacture. ? Important to keep good records of anything that is needed for inclusion in the Chemistry, Manufacturing, and Control (CTD Module 3). ? What would affect a decision on product safety? Can reach back into the origins of the discovery phase of PD. ? You cannot test quality into the product – it must be built into all as