{"id":34215,"date":"2019-04-17T11:00:51","date_gmt":"2019-04-17T10:00:51","guid":{"rendered":"https:\/\/clarivate.com\/?p=34215"},"modified":"2019-04-17T11:00:51","modified_gmt":"2019-04-17T10:00:51","slug":"drug-development-challenge-managing-cmc-submissions","status":"publish","type":"post","link":"https:\/\/clarivate.com\/life-sciences-healthcare\/blog\/drug-development-challenge-managing-cmc-submissions\/","title":{"rendered":"Drug development challenge: Managing CMC submissions"},"content":{"rendered":"

In the era of Breakthrough Therapy and Fast Track drug designations, chemistry, manufacturing and controls (CMC) submissions can cause delays to bring a drug to market, said Drew Barlow,\u00a0vice president, regulatory affairs at\u00a0Syner-G Pharma Consulting.\u00a0<\/span><\/p>\n

Companies need to provide enough information to satisfy the regulatory requirements while recognizing that providing too much information early will result in the need to make changes later, Barlow said, speaking on a panel focused on different approaches to preparing required CMC data<\/a> to the FDA during the early clinical phase of drug development at the Drug, Chemical & Associated Technologies Association\u2019s DCAT Week \u201919, in New York.<\/p>\n

The initial Investigational New Drug submission must be focused on safety and contain information such as drug dose form, investigation population parameters and dosage quantities, Barlow noted.\u00a0 <\/span>Phase 1 reports are still mainly safety-focused, with inclusions of methods of manufacture, toxicology studies and impurity profiles. \u00a0<\/span><\/p>\n

As drug trials progress beyond Phase 1, the agency expects reports to contain preliminary efficacy data, and as manufacture is scaled up companies need to report if new stability or impurity issues occur, Barlow said.<\/p>\n

Abizer Harianawala<\/a>,\u00a0senior director, product development and technical operations at\u00a0TARIS Biomedical, shared insights during the session from his experience in developing compounds with designated Breakthrough Therapy status. Harianawala reminded listeners that a shorter clinical timeline means less CMC time, creating the need to prioritize tasks and focus on important trial aspects such as risk assessment. \u00a0<\/span><\/p>\n

By locking down active pharmaceutical ingredient (API<\/a>) production, formulation and packaging methods early, companies can address these methods in early CMC versions without needing to revise later, he said.<\/p>\n

By locking down API production, formulation and packaging methods early, companies can address these methods in early CMC versions without needing to revise later\u2019
\n\u2013 Abizer Harianawala, TARIS Biomedical<\/span><\/p><\/blockquote>\n

Using cGMP qualified ingredients from the earliest clinical trial<\/a> phases and qualifying secondary contract manufacturing organizations (CMOs) before clinical trials begin are additional ways to prevent unwanted delays, Harianawala said. To avoid delays, stability studies need to be locked down early, he added while other sections such as specifications can be tightened later on.<\/p>\n

Ken Shultis<\/a>,\u00a0managing partner at\u00a0Rondaxe, addressed the different styles of CMC submissions used within the pharmaceutical industry, and discussed which styles were most appropriate for which situations. Researchers using a \u201cminimal style\u201d of CMC preparation include very little information when summarizing early trial phases, he said.\u00a0 <\/span>The advantage of this methodology is that early-phase write-ups move quickly, and there is less need to resubmit information that has changed as the trial has progressed.\u00a0 <\/span>One of the big disadvantages to this method is that there is still a lot of work left to do close to the submission deadline, he added.<\/p>\n

Shultis described the \u201cNDA-ready\u201d style where a company assembles everything as each trial phase is performed as though the FDA will be receiving those summaries as a finished product.\u00a0 <\/span>This method allows the team to use the CMC as a project management tool, and spreads regulatory work out evenly across all trial phases.\u00a0 <\/span>The disadvantage is that any major changes in the project will result in wasted effort as early CMC work needs to be redone. \u00a0<\/span><\/p>\n

Finally, Shultis described a \u201ctransition-style\u201d CMC submission, where the document begins as a \u201cbare-bones\u201d outline which is fleshed out as the trials progress.\u00a0 <\/span>This method provides reviewers with a good baseline, he noted, but still requires a great effort immediately preceding the submission deadline.<\/p>\n

This article is an excerpt from the full DCAT Week \u201919 conference report developed by the team from Newport Premium, a Cortellis solution, from Clarivate Analytics. Additional topics, reported on by analysts Shannon Bennett, Molly Bowman and Emily Kimball, include:\u00a0<\/span><\/p>\n