In this article, Senior Drug Substance Consultant James Mencel from DS InPharmatics offers information on his experience with CMC management and how the pharmaceutical industry has been impacted by expedited drug development programs.
The article will describe breakthrough designations, best practices and the regulations required regarding these programs.
Usually, a minimum of eight years is required for a novel drug to finish the journey to the marketplace from first discovery. It can take an average of five to seven years for Phase 3 trials alone. The expense of drug development is made greater as the process becomes longer.
There has recently been much-expedited activity, particularly in the smaller biopharma fields.
This delivers some novel difficulties for CMC that are on the border between phase two and phase three programs, despite the possibility of improving life-threatening conditions. By nature, fast-tracked CMC development programs vary from regular programs.
CMC and expedited development
The FDA’s primary aim is to offer lifesaving products to patients. The organization fully supports expedited drug development where there is a strong cause for it. The interest in this from the market is both business and scientific.
Aside from the breakthrough alone, accelerated strategies make getting to the initial in-human investigations and proof-of-concept to direct decisions on developability more efficient, and the development strategies later can attain faster commercialization and approval.
The advantages of accelerated CMC development should be balanced against the danger of insufficiently understanding the process and product. An aim of any CMC development program must be to guarantee the continual manufacture of an effective and safe commercial product.
The development speed does not change or minimize the content of the latest Drug Application (NDA/BLA) CMC Quality Modules. The extent and type of the CMC information anticipated at the time of NDA/BLA submission may be flexible in contrast to what can be submitted after approval or during BLA/NDA review.
The majority of this is dependent on process knowledge, the robustness of the control strategy, and product knowledge, along with the danger of negligible CMC data versus the advantages for the patient.
CMC development must be aligned with clinical development from the start. The existing process should be continually dependable and viable if the program is expedited and commercialized. A process must be able to provide all the required information for CMC submission.
Frequent meetings during the development can be used to schedule inspections, streamline paths for qualifying expression systems, and determine comparability across sites.
Better communication at the BLA review cycle can allow challenges to be solved faster and reach a consensus on what must be submitted after approval.
Expedition support
There are a number of techniques to accelerate drug development, but the majority of them result in restricted CMC timeframes. The FDA will not compromise in quality, although it understands that there is stress on CMC.
Instead, the FDA meets with sponsors more often than normal to assist them in moving through expedited development for the efficiency, suitability and quality of the drug product and substance.
Regulatory support is received by the expedition for development. The stress for CMC is continual, and eventually, the filing must be submitted, and the FDA has to approve.
Expedition procedures
Plenty of negotiation should be expected in the process. ICH determines processes for the testing, marketing and expedited development of novel treatments designed to help people with conditions that are life-threatening where there are no effective alternative treatments. There is no flexibility on accurate scientific techniques.
For example, a smaller degree of stability may be allowed by the FDA, but trustworthy data from earlier stages of development and the same chemical process on the equivalent site will be required.
For example, if the FDA was approached with a request to change locations, the agency will listen to the justification for the request to change from where the pivotal registration or clinical trial batches were made to the place where process validation will be performed.
A strategy must be in place that demonstrates consistency in the material produced in both locations. The FDA will predominantly only approve this in expedited development as they will appreciate a three or four-year window is not available.
In Phase Three, a one-year window is available to achieve everything that would be achieved in three years.
When to seek expedition
There is both scientific and business interest in expedition, as outlined before. One example is where an anti-cancer agent program is being developed, established on a model that has been proven to be essentially authenticated.
The majority of sponsors will contact the FDA for expedition prior to reaching phase one when a validated model, a molecule that targets it and a receptor site are in place. This usually occurs for discoveries that involve conditions that are challenging to treat.
A different acceleration journey can arise in the course of clinical development. If impressive data is received that demonstrates a therapeutic potential of substances for conditions that have no cure, the FDA would be keen to listen to the case.
Corporate organizations included in this must determine whether all the processes are ready because the data is made public at this phase. Success and traction will be expected. It will not be good for optics if the required infrastructure for the development is not in place.
In summary
The chemistry must be focused on in every stage of the journey. If expedition is being discussed, development personnel should be included, and all aspects must be perfected from the chemical process to data and testing because the existing process may be the commercial route.
Imperfections must be anticipated ahead of time as factors like particle size and polymorph cannot be altered after a certain stage. Prepare for all factors to perform as expected when the phase three trials occur.
Acknowledgments
Produced from materials originally authored by Meranda Parascandola from Design Space InPharmatics.
About DS InPharmatics 
DS InPharmatics (DSI) provides regulatory, technical, and project management consulting services to healthcare product companies that manufacture and/or market pharmaceuticals, biopharmaceuticals, and cellular and gene therapy products.
Since 2007 we have provided our clients with innovative strategies and exceptional quality work products intended to enhance product development, approval, and marketing presence. Whether advocating CMC strategy, directing CMC operations or developing CMC submission content that represent the best interests of emerging biotech, we focus on the critical CMC issues and build programs that enhance development.
In April 2021 we were thrilled to announce that DSI has just become part of ProductLife Group.
French-headquartered ProductLife Group (PLG) is well-known in the Life Sciences market. It has a track record of successfully managing global outsourcing programs and insourcing services for its international client base. The company is on a mission to help transform human health outcomes by optimizing regulatory affairs, safety & vigilance, and quality compliance for life sciences organizations worldwide.
The fit between our two organizations could not be more perfect. We will complement PLG's growing biotech services portfolio. US biotech sponsors recognize DSI as a leader in consulting for go-to-market strategies and RA pre-market consulting. At the same time, PLG has a strong reputation for managing end-to-end outsourcing of regulatory affairs and pharmacovigilance activities worldwide.
Our merger with PLG will harness our combined strengths, offering our clients on both sides of the Atlantic support with their developed drugs approvals and post-approvals compliance, plus advisory services on the best market strategies to deliver a rapid ROI on their development. Together we will offer our clients increased pharmacovigilance capabilities - including a QPPV; pharmacovigilance consulting; and a fully validated safety database - as well as complementary toxicology-related services; RIM/electronic document management services; and support for medical device regulatory requirements.
We see enormous potential in this new chapter for DSI and you, our clients. As a PLG company, we have the opportunity to become part of a global force in life sciences regulatory and compliance solutions and services, and we're incredibly excited to add our momentum to that effort.
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