Regulatory Documents

Although some documents are required only for NDA submission, the major types of analytical reports for regulatory submission are very similar for IND and NDA submissions. The differences in these reports for IND or NDA submission primarily concern the amount of data (e.g., number of batches, duration of stability studies) and level of detail. Also, the requirements for amendment of the information are different. The major types of analytical documents common to IND and NDA submissions are the following  

Physical-chemical characterization Reference standard characterization Specifications and analytical methods Certificates of analysis 

Stability (stress, accelerated and long-term conditions) 

Typically, an opening IND is submitted before the first clinical study for EIH. As more firms undertake global development, EIH studies may be performed outside of the United States. An IND may not be required if the first clinical trial(s) are performed outside of the United States with volunteer subjects. The U.S. IND must still be filed before the first use of the investigational drug product in the United States but may begin with phase 2 clinical studies. 

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We would like to gratefully acknowledge EMEA, ISO, EDQM, PIC/S, IMB, ISPE and Health Canada that granted us permission to reproduce selected copyrighted material. We reserve a special acknowledgement and thanks to the European Commission, the FDA and the ICH secretariat, the VICH and the GHTF, who have placed their regulatory documentation in the public domain, and we have reproduced several documents from these sources herein. 

A current list of regulatory documents available by e-mail (including the most recent PTCs, or points to consider) can be found at DOC LIST Al.FDA.GOV... 

It is worth noting that, presently, in silico prediction of hERG liability is not considered in regulatory documents, although this is an area of intense investigation... 

Rozet, E., Ceccato, A., Hubert, C., Ziemons, E., Oprean, R., Rudaz, S., Boulanger, B., Hubert, P. Analysis of recent pharmaceutical regulatory documents on analytical method validation. J. Chromatogr. A., 1158, 2007, 111-125. 

CRAs achieve these tasks through frequent visits to the clinical trial site. During these visits, the monitor will verify source data, audit regulatory documents for accuracy and completion, perform drug accountability assessments, and communicate any concerns, problems, or new information with the study staff. 

The scope of this book does not allow a discussion of all the requirements for GCE Readers are referred to Exhibit 6.7 for the headings in the relevant regulatory documents to gain further understanding of the requirements. Some important issues, however, are discussed to clarify the important aspects and requirements for clinical trials in accordance with GCP. Some of these aspects are ... 

This would obviously save unnecessary duplication and reworking and would decrease the time and resources required for submission of the regulatory documents, ultimately benefiting patients in the three regions and in the rest of the world. 

A recent European regulatory document (CHMP (2006) Reflection Paper on Methodological Issues in Confirmatory Clinical Trials with Flexible Design and Analysis Plan ) has given more thought to what is acceptable and what is not, in terms of flexible design. Several common themes are seen to run through this paper ... 

Compiling all relevant regulatory documents for use by the FDA inspectors at the potential inspection sites This should be done by the regulatory affairs group of the firm the efforts... 

Reference all relevant regulatory documents that are important for implementing the system. 

The parameter is recorded as part of the batch record, lot release record, or any other GMP regulatory documentation. 

Finally the Raman spectroscopy approach for API identification is not widely used in regulatory documentation. As previously detailed a major reason is that interpretation of Raman spectra is not as advanced as FT-IR. Additionally, Raman spectrometers are relatively more expensive than FT-IR spectrometers, so are more likely to be found in R D labs rather than QC facilities. However, moving forward the benefits of using a Raman spectroscopy approach will ensure that its usage will become more common and may be adopted into regulatory packages. 

Before responding to the FDA-483, there are some preliminary facts that should be understood about this regulatory document. Such an understanding will help in reacting and responding to an FDA-483. 

Like other potential biopharmaceutical products, FDA, Center for Biologies Evaluation and Research (CBER) regulates the production, testing and use of AAV vectors in human clinical trials, in the US. Many regulatory documents are available to help guide the researcher. These documents are available via the Internet on http //www.fda.gov.cber/guidelines.htm. Review of these documents prior to significant work towards production of vector for... 

All regulatory documents presumably are subject to a tripartite review process. The submission is reviewed by the corporate Regulatory group, which proofs, considers issues of conformity to internal policy and to FDA guidance and checks the factual statements. A Quality Assurance review then rechecks all the previous items and independently confirms all facts and statements. Finally, a corporate review (at or near the top of the organization) precedes the final signatures and confirms conclusions and plans. 

Based on the recommendation of Rocci et al. s publication and other regulatory documentations, the following section summarizes the main features which are essential for ISR practice ... 

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