The Drug development process - Pharmaceutical Biotechnology: Concepts and Aapplications - page 96

Table 4.10 An overview of the contents of a typical new NDA

Section 1 Index

Section 2 Overall summary

Section 3 Chemistry, manufacturing and control section

Section 4 Sampling, methods of validation, package and labelling

Section 5 Non-clinical pharmacology and toxicology data

Section 6 Human pharmacokinetics and bioavailability data

Section 7 Microbiology data

Section 8 Clinical data

Section 9 Safety update reports

Section 10 Statistical section

Section 11 Case report tabulations

Section 12 Case report forms

Sections 13 and 14 Patent information and certifi cation

Section 15 Additional pertinent information

4.14.3 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 'fi le' the NDA; or, if
more information/better information management is needed, they refuse to fi le until such changes
are implemented by the sponsor.
Once fi led, an NDA undergoes several layers of review (Figure 4.12). A primary review panel
generally consists of a chemist, microbiologist, pharmacologist, biostatistician, medical offi cer
and biopharmaceutics scientist. Most hold PhDs in their relevant discipline. The team is organized
by a project manager or consumer safety offi cer (CSO). The CSO initially forwards relevant por-
tions 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 offi cers,
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 aver-
age, 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 ad-
verse response to the drug.