Pharmaceutical manufacturers have been submitting applications electronically to FDA for years. So the agency’s announcement that it intends to switch its current paper system for accepting Drug Master File (DMF) information to an electronic one may not cause immediate surprise or alarm. However, packaging material suppliers that hold Type III DMFs haven’t typically used the electronic Common Technical Document (eCTD) system that FDA will require as of May 2017 for new DMFs, annual reports, and amendments, reports Frank Bieganousky, managing director and cofounder of Montesino Associates. “Packaging suppliers are now part of this world,” he says.
FDA’s CDER Small Business and Industry Assistance (CDER SBIA) will be holding the Webinar, “New Requirement for Electronic Submission of Drug Master Files (DMFs): What You Need to Know,” on February 4, 2016. For details on the Webcast click here. And for more details on DMFs, click here.
“The binding guidance, published on May 5, 2015, requires electronic (rather than paper) submission of NDAs, BLAs, ANDAs, INDs, and DMFs. It clearly includes Type III DMFs,” explains Peter Schmitt, managing director and cofounder of Montesino Associates. “While the pharmaceutical industry is fully engaged in preparing their regulatory submissions in accordance with this binding guidance, it is not clear that holders of Type III DMFs realize that ‘the clock is ticking.’”
There are “layers of risk to manufacturers,” explains Bieganousky. “For instance, if suppliers are not ready to use the eCTD system, there could be delays in issuing Letters of Authorization, because copies of the LOAs need to be submitted electronically to FDA in the eCTD format.”
Dwain L. Sparks of Sparks Consulting Services (and an Eli Lilly and Company retiree) expects the DMF changes to be “confusing to all parties, and drug companies need to take a proactive position to understand how they will impact drug submissions, including annual reports and supplements.”
Schmitt explains there will be significant differences in the process of submitting DMF documents as well as the organization and structure of the content. For example, as of May 5, 2017, any and all submissions relating to a Type III DMF, including Annual Reports, LOAs, amendments, and new submissions, are required to:
- Use the version of eCTD publishing software currently supported by the FDA as specified in the FDA Data Standards Catalogue.
- For new DMF submissions, obtain a pre-assigned application number by contacting the appropriate Center.
- Follow the FDA eCTD technical specification Table of Contents Headings and Hierarchy.
- Adhere to the formats and versions specified in the FDA Specifications for File Format Types Using eCTD Specifications.
- Adhere to the FDA Portable Document Format (PDF) Specifications.
Sparks points out that, according to FDA, “there is no requirement to resubmit anything that has already been submitted in paper.” In addition, “if holders choose to resubmit their entire DMF upon conversion to eCTD format, that is acceptable, but it is NOT required."
However, Annual Reports must be filed electronically, emphasizes Bieganousky. “They show that the DMF is current; if no report is filed in three years, the DMF may be closed by the FDA and the DMF status becomes inactive.” Adds Sparks: “Inactive DMFs cannot be referenced in drug applications.”
If FDA’s new electronic requirements haven’t mobilized DMF holders yet, Health Canada’s may already have. Sparks and Bieganousky point out that by March 31, 2016, DMF holders must “convert submissions to a Web-based eCTD format or use the non eCTD electronic format.” Bieganousky adds that some suppliers may be reconsidering supporting DMFs in Canada.
For packaging suppliers that are not equipped to submit files electronically, there could be delays in maintaining their DMFs, and this situation will impact their customers. Bieganousky lists the following potential risks to pharma companies:
- There could be delays in the LOA process.
- Submission of DMF Annual Reports may not be current.
- Some suppliers may decide to no longer hold a DMF, resulting in additional information required to be included in the drug product registration.
- The cost associated with the conversion may be passed along in the cost of packaging components.
Each of these risks could hold up drug product registrations, says Bieganousky.
Schmitt advises that “preparation needs to begin as soon as possible.”
Adds Bieganousky: “For suppliers to be in this market long term, they should seriously consider converting their paper DMFs to the eCTD format in order to make it easier for FDA reviewers to find the information they need. This will reduce the likelihood of questions or deficiency letters from the FDA. Why force the FDA reviewer to piece together information that will be in a mix of paper and electronic amendments and other documents?”
To learn more about the U.S. FDA’s new eDMF rules, please join us June 16 at EastPack. At EastPack, Schmitt, Bieganousky, and Sparks will explain how the new eDMF rules could impact you and will offer steps you can take today to minimize risks. On June 16, they will present “Successfully Preparing for the New Electronic Drug Master File System.”