The new drug application

Upon completion of clinical trials, the sponsor will collate all the preclinical, clinical and other pertinent data (Table 4.10) and submit this to FDA in support of an application to allow the new drug to be placed upon the market. For CDER-related drugs, this submission document is termed an NDA.

The NDA must be an integrated document. It often consists of 200-300 volumes, which can represent over 120 000 pages. Several copies of the entire document, and sections thereof, are provided to the CDER. The FDA then classify the NDA based upon the chemical type of the drug and its therapeutic potential. Generally, drugs of high therapeutic potential (e.g. new drugs capable of curing/alleviating serious/terminal medical conditions) are appraised by the CDER in the shortest time.

After initial submission of the NDA, the FDA has 45 days in which to undertake a preliminary inspection of the document, to ensure that everything is in order. They then 'file' the NDA; or, if more information/better information management is needed, they refuse to file until such changes are implemented by the sponsor.

Once filed, an NDA undergoes several layers of review (Figure 4.12). A primary review panel generally consists of a chemist, microbiologist, pharmacologist, biostatistician, medical officer and biopharmaceutics scientist. Most hold PhDs in their relevant discipline. The team is organized by a project manager or consumer safety officer (CSO). The CSO initially forwards relevant portions of the NDA to the primary review panel member with the appropriate expertise.

Each reviewer then prepares a review report. This is forwarded to their supervisory officers, who undertake a second review. All of the reports are then sent to the division director who, in turn, recommends rejection or approval, or asks the sponsor to provide more information. On average, this entire process takes some 12 months.

Even when the NDA is approved and the product goes on sale, the sponsor must provide the FDA with further occasional reports. These can be in the form of scheduled annual reports, but also unscheduled reports are required in instances such as the occurrence of an unexpected adverse response to the drug.

Supervisers of the individual members of the initial review panel

Multidisciplinary review expert panel

Figure 4.12 The CDER review process for a typical NDA. In addition to the review stages described, the FDA may also consult with a technical advisory committee. The members of the advisory committee are not routinely involved in IND or NDA assessment. The FDA is not obliged to follow any advice given by the advisory committee, but it generally does so

Supervisers of the individual members of the initial review panel

Multidisciplinary review expert panel

FDA Division

Director

Figure 4.12 The CDER review process for a typical NDA. In addition to the review stages described, the FDA may also consult with a technical advisory committee. The members of the advisory committee are not routinely involved in IND or NDA assessment. The FDA is not obliged to follow any advice given by the advisory committee, but it generally does so

A similar general approach is taken by the CBER with regard to drugs being developed under their auspices. The CBER 'licensing process' for a new drug consists of three phases: the IND phase (already discussed), the pre-marketing approval phase (licensure phase) and the postmarketing surveillance phase. The pre-marketing approval phase (i.e. clinical trial phase) aims to generate data that prove the potency, purity and safety of the product. Upon completion of clinical trials, the sponsor collates the data generated and submits it to the FDA in the form of a BLA, which must provide a comprehensive description of both the product and product manufacture (including methods of QC analysis, product stability data, labelling data and, of course, safety and efficacy data).

A small number of biotechnology products are classified as medical devices and, hence, are regulated by the Center for Devices and Radiological Health (CDRH). The first approved biotech product to come under the auspices of the CDRH was OP-1 implant. Marketed by Stryker Biotech, OP-1 implant is a sterile powder composed of recombinant human oestrogenic protein-1 (OP-1) along with bovine collagen. It is used to treat fractured bones that fail to heal. The product is mixed with sterile saline immediately before application, and entails surgical insertion of the paste into the fracture.

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Project Management Made Easy

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