A biologics license application is a request to distribute a biologic across states. It generally is submitted after an Investigational New Drug (IND) or an Investigational Device Exemption (IDE) and after the appropriate studies have been conducted.
A biologics license application generally applies to vaccines and other allergenic drug products, blood products, and cellular and genetic therapies.
1. Apply for a biologics license application
Anyone who is involved in the manufacture of biologics or who takes responsibility for the regulatory compliance of a biologic can apply for a biologics license application. Applicants should identify a review committee and arrange a meeting with the Food and Drug Administration (FDA) before they submit the application.
They also should schedule a bioresearch monitoring inspection. When determining the timing of the submission, they should take into consideration the schedule and needs of the advisory committee. In some cases, the manufacturer may also want to consider whether they want submit a validation plan for the FDA to review or to meet with the FDA regarding the validation plan before they submit the application.
2. Submit a Form FDA 356th
Next, applicants must submit a Form FDA 356h to the document control center at the Center for Biologics Evaluation and Research (CBER), a division of the FDA that specifically handles biologics. Both paper and electronic submissions are acceptable. However, as with New Drug Applications (NDA), an electronic Common Technical Document (eCTD) can be used to submit a biologics license application.
A Form FDA 356h is an application to market a new drug, biologic, or antibiotic drug for use in humans. The Form FDA 356h contains the following information:
· A summary of information submitted as part of the application.
· Information on the applicant submitting the biologics license application.
· A preclinical data section.
· A clinical data section that includes safety and efficacy data on the product.
· Draft labeling of the product to be licensed.
· Information on the manufacturing, chemistry, and controls of the product.
· A data summary of validation of important processes and assays involved in the manufacture of the product.
· A description of the facility where the product is manufactured.
· Case report form tabulations on the manufacturer’s clinical experience with the product.
· Case report forms and serious event narratives.
· An index.
The information on the chemistry, manufacturing, and controls should also contain copies of important standard operating procedures related to the manufacture of the drug. In some cases, manufacturers are required to submit information regarding whether they are ready for an inspection by the FDA.
4. Await FDA review
After the FDA receives the biologics license application, they will review it to determine whether it is complete. This review includes an initial review of the standard operating procedures and the validation data. They will then hold a filing meeting to identity any issues that could result in issuance of a Refuse to File (RTF), such as missing data or information on the manufacturing.
If the manufacturer has not provided all the appropriate information, the FDA will discuss what information needs to be provided by the manufacturer within seventy-four days. They will then issue a filing letter or a Refuse to File (RTF) on the basis of their findings.
If they issue a filing letter, advisory committee will then conduct a complete review. This process includes a scientific review of the data by personnel form various disciplines and can vary on the basis of the compound submitted and the manufacturing process involved. In some cases, the FDA may request a prelicensing inspection to verify that the manufacturer is in compliance with the appropriate regulations.
They may also request additional information from the manufacturer as appropriate. In some cases, a discipline review letter may be issued after personnel from a given discipline have completed their review but before the entire review has been completed.
After the complete review has finished, the review committee will meet and identify any issues, agreements, and other commitments.
Some of the negative outcomes that can happen include issuing a Refuse to File (RTF) and placing a hold on the Investigational New Drug (IND) or an Investigational Device Exemption (IDE). They may also determine that the product is not ready for approval and request that the application be resubmitted. However, if the FDA approves the biologics license application, they will issue an approval letter. This approval letter authorizes the manufacturer to distribute the product and itemizes any agreements and other commitments.
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