By Rose Pagano and Suzanne M. Sensabaugh, MS, MBA
The intention of this guidance is to clarify FDA expectations related to facility information that must be included in original new drug applications (NDA), abbreviated new drug applications (ANDA), original biologics license applications (BLA), controls supplements (CMC), and resubmissions related to these categories. Completion of Form FDA 356h satisfies the requirement for applicants to submit an application form. This form is a summary of administrative information and details manufacturing, packaging, and control site information for the drug substance and drug product facilities affiliated with the application.
The FDA fields many questions related to manufacturing information for these applications. This guidance is meant to address some of the most frequently asked questions. For example, the facility information that needs to be included in the establishment field on Form FDA 356h should entail all drug product manufacturing and testing sites, all intermediate and final drug substance manufacturing and testing sites (including sterilization and micronization sites), facilities involved with any aspect of constituent drug parts, and all storing facilities.
One aspect of drug development and production that does not need to be included on the form is facilities that do not impact or inform the commercial control strategy. However, submissions do need to include complete facility information for existing facilities and any changes to previously submitted information. If a facility is being withdrawn, simply detail that on the Form FDA 356h.
A key factor in keeping track of this manufacturing application process is the use of FDA Establishment Identifier (FEI) number and Data Universal Numbering System (DUNS) number. These numbers help with registration and help the Agency in proceeding with the facility evaluations. The FDA recommends that at the time of establishing a center registration, the applicant should obtain an FEI number. The absence of the FEI number may hinder the application timeline, but do not delay in submission because of it. Rather, request the FEI number as soon as possible. This can be done by emailing (here) for a Generic Drug User Fee Act (GDUFA)-related facility, or Prescription Drug User Fee Act PDUFA BSUFAFEIRequest@fda.hhs.gov for a PDUFA or Biosimilar User Fee Act (BsUFA)-related facility.
The absence of a facility on the Form FDA 356h is not linked to the assignment of a user fee. Instead, the function performed by the establishment determines the assessment of a user fee.
Additionally, Module 3 of this process should include all facilities listed on Form FDA 356h and research and development manufacturing and testing sites that created data supporting the application. Testing labs that aided in control strategy should also be included in this module. These facilities can be listed under the drug substance or drug product sections of Module 3.
Overall, the FDA is very receptive to answering any more questions applicants have concerning information related to facility processing.
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Suzanne is the President and Principal Consultant of HartmannWillner LLC. She is an FDA regulatory affairs consultant who assists companies in advancing biologics, biosimilars, and biologic/device combination products through the FDA.
She formed HartmannWillner in 2009 as a regulatory affairs consultant. Since then, Suzanne has:
- Assisted in the development of over 130 biologics, biosimilars, and biologic/device combination products
- Conducted over 30 FDA GMP audits, including preapproval inspections (PAI), which allowed for FDA approval
- Provided GMP compliance consulting to successfully address Form FDA 483 observations and Warning Letters
- Prepared expert witness opinions and testimony in the areas of FDA regulatory affairs and GMP compliance
- Wrote and reviewed hundreds of original INDs and BLAs and amendments and supplements