- Regulatory Information
Posted 22 June 2022 | By
DIA: World initiative to standardize CMC high quality knowledge gaining steam
CHICAGO – A number of initiatives within the works amongst regulators and the pharmaceutical trade are gaining momentum to harmonize chemistry, manufacturing, and controls (CMC) info submitted within the Widespread Technical Doc (CTD). One such effort is the formation of an trade consortium that’s in search of to develop a structured content material cloud-based CMC Module 3 template with enter from regulators.
These plans had been mentioned on 20 June 2022 through the Drug Data Affiliation’s annual assembly in Chicago, throughout which officers mentioned a few of the present challenges associated to the submission of Module 3 CMC knowledge.
“The issue assertion is that although many corporations are world and have a standard product … the truth that there are differing regulatory necessities means that there’s not a single world file. Moreover, as soon as a file is submitted, the variety of info requests that are available that necessitate modifications in one in every of extra of the CTD parts, imply there are plenty of upkeep actions that need to be carried out by the advertising authorization holders within the totally different markets,” stated Nina Cauchon, director of regulatory affairs CMC at Amgen, who moderated the session.
Greg Rullo, senior director of regulatory affairs CMC at AstraZeneca, concurred. “You might be all most likely conscious that many drug merchandise come out of some manufacturing websites,” but these merchandise have to fulfill totally different CMC necessities. “We’ve got regulators who’ve totally different interpretations of what these requirements is likely to be and this results in a really troublesome postapproval surroundings,” he added.
To deal with a few of these challenges, a consortium of pharmaceutical corporations was lately established to standardize the CMC info submitted in Module 3.
Sheetal Gaiki, a senior scientist with Janssen, known as the initiative “a novel CMC content material mannequin to supply structured and standardization for CMC knowledge necessities.” Known as Accumulus, this initiative is being developed with enter from world commerce associations and well being authorities.
Pharmaceutical trade members embrace Amgen, Astellas, AstraZeneca, GSK, Johnson & Johnson and Roche. Trade members have already met with well being authorities and world commerce associations to hammer out a structured content material mannequin.
World commerce affiliation members embrace the European Federation of Pharmaceutical Industries and Affiliation (EFPIA), the Worldwide Federation of Pharmaceutical Producers & Associations (IFPMA), the Pharmaceutical Analysis and Producers of America (PhRMA), the Biotechnology Innovation Group (BIO), the Product High quality Analysis Institute (PQRI), DIA Europe and the Parenteral Drug Affiliation (PDA).
The hassle is being launched underneath the umbrella of Accumulus Synergy, a worldwide, non-profit group established in 2020 that develops knowledge trade platforms and works to enhance collaborations between biopharmaceuticals corporations and world well being authorities.
The initiative goals to standardize the knowledge in Module 3 of the CTD equivalent to a standard PQ/CMC knowledge info format protecting batch or lot info, manufacturing course of info, and pharmaceutical high quality specs.
The top consequence shall be a product that “will assist current content material in a structured format consistent with the eCTD or future pathways,” stated Gaiki.
“Accumulus will create reference maps to hyperlink the narrative and uncooked knowledge whereas permitting every to move independently, structuring the content material, when essential,” she stated.
The template would come with a core content material block, with sub-content blocks for the sponsors, with regulators having an identical core content material and sub-content blocks. The knowledge shall be saved within the cloud and might be accessed in real-time.
FDA making inroads in CMC standardization
Complementary efforts are additionally being undertaken on the US Meals and Drug Administration (FDA) to standardize knowledge opinions for CMC info underneath the company’s PC/CMC initiative.
FDA’s Geoffrey Wu stated that this standardization will make sure that trade and FDA are utilizing the identical knowledge. “For trade, the profit offers a constant format for inside and exterior knowledge administration. For FDA, this initiative ensures the company receives constant high-quality knowledge that may be consumed by pc techniques with out knowledge entry and interpretations.”
At present, all Module 3 info is submitted in a PDF format with unstructured high quality info, inflicting reviewers to hunt and peck by means of functions for the standard info they want. This format “considerably hinders the effectivity of knowledge trade, knowledge assessments, high quality assessments and lifecycle data administration,” Wu stated.
The final word objective is for this knowledge to feed into FDA’s inside assessment template KASA, Wu stated, including that “This initiative is a big enabler for KASA.” (RELATED: FDA taking incremental strategy to launching KASA opinions, Regulatory Focus 5 November 2021)
Section 1 of the PC/CMC initiative was accomplished on the finish of 2020. On this part, FDA standardized about 33% of Module 3 knowledge. Beneath Goal 2, which started in January 2022, FDA is growing a knowledge trade commonplace for submission of PQ and CMC knowledge.
DIA annual assembly
© 2022 Regulatory Affairs Professionals Society.
Research led by a Wayne State University Department of Mathematics professor is aiding researchers in Wayne State’s Department of Psychiatry and Behavioral Neurosciences in analyzing fMRI data. fMRI is the preeminent class of signals collected from the brain in vivo and is irreplaceable in the study of brain dysfunction in many medical fields, including psychiatry, neurology and pediatrics.
Andrew Salch, Ph.D., associate professor of mathematics in Wayne State’s College of Liberal Arts and Sciences, is leading the multidisciplinary team that is investigating how concepts of topological data analysis, a subfield of mathematics, can be applied to recovering “hidden” structure in fMRI data.
“We hypothesized that aspects of the fMRI signal are not easily discoverable using many of the standard tools used for fMRI data analysis, which strategically reduce the number of dimensions in the data to be considered. Consequently, these aspects might be uncovered using concepts from the mathematical field of topological data analysis, also called TDA, which is intended for use on high-dimensional data sets,” said Salch. “The high dimensionality that characterizes fMRI data includes the three dimensions of space — that is, where in the brain the signal is being acquired — time — or how the signal varies as brain states change in time — and signal intensity — or how the strength of the fMRI signal changes in response to the task. When related to task-induced changes, the results reflect biologically meaningful aspects of brain function and dysfunction. This is a unique collaborative work focused on the complexities of both TDA and fMRI respectively, show how TDA can be applied to real fMRI data collected, and provide open access computational software we have developed for implementing the analyses.”
The research article, “From mathematics to medicine: A practical primer on topological data analysis and the development of related analytic tools for the functional discovery of latent structure in fMRI data,” appears in the Aug. 12 issue of PLOS ONE.
In it, the team used TDA to discover data structures in the anterior cingulate cortex, a critical control region in the brain. These structures — called non-contractible loops in TDA — appeared in specific conditions of the experiment, and were not identified using conventional techniques for fMRI analyses.
“We expect this work to become a citation classic,” said Vaibhav Diwadkar, Ph.D., professor of psychiatry and behavioral neurosciences and research collaborator. “Instead of merely applying TDA to fMRI, we provide a lucid argument for why medical researchers who use fMRI should consider using TDA, and why topologists should turn their attention to the study of complex fMRI data. Moreover, this important work provides readers with empirical demonstrations of such applications, and we provide potential users with the tools we used so they can in turn apply it to their own data.”
“Our ongoing research utilizing TDA with fMRI will provide a unique and complementary method for assessing brain function, and will give medical researchers greater flexibility in tackling complex properties in their data,” said Salch. “In particular, our work will help fMRI researchers become aware of the significant power of TDA that is designed to address complexity in data, and will enhance the value of using fMRI in neuroscience and medicine.”
In addition to Salch and Diwadkar, co-authors on the paper include Adam Regalski, Wayne State mathematics graduate student; Hassan Abdallah, Wayne State mathematics department alumni and current graduate student at the University of Michigan; and Michael Catanzaro, assistant professor of mathematics at Iowa State University and Wayne State mathematics department alumni.
This work is supported by the National Institutes of Health (MH111177 and MH059299), the Jack Dorsey Endowment, the Cohen Neuroscience Endowment, and the Lycaki-Young Funds from the State of Michigan.