Attachments, report document format

I hereby certify that l have reviewed the attached documents and that, to the best of my kr>owledge ar>d belief, the submitted formation a c complete and that the amounts and values in this report are accurate based on reasonable estimates usir>g data avaiiaoie to tne oreoarers o tnis i-eocr ... 

A variety of mammalian cellular systems have been used as experimental models for documenting the in vitro effects of cannabinoids on immune responsiveness to viruses, bacteria, and amoebae. Blevins and Dumic (1980) indicated that THC had a protective effect against HSV infection in vitro. It was found that both HSV-1 and HSV-2 failed to replicate and produce extensive cytopathic effect (c.p.e.) in human cell monolayer cultures exposed before infection, at infection, or post infection to various concentrations of THC. In contrast, other studies indicate that THC compromises resistance to virus infection. It has been reported that THC inhibits macrophage extrinsic anti-viral activity (Cabral and Vasquez 1991 Cabral and Vdsquez 1992) whereby macrophages normally suppress virus replication in cells to which they attach (Morahan et al. 1980 Stohlman et al. 1982). Noe et al. (1998) reported that a variety of cannabinoid receptor agonists enhanced syncytia formation in human T cell leukemia virus-I (HTLV-I)-transformed human T (MT-2) cells infected with cell free human immunodeficiency virus (HIV-IMN). It was found that CP 55,940, THC, WIN 55,212-2, and WIN 55,212-3 significantly increased syncytia formation, a phenomenon that has been reported to serve as an indicator of HIV infection and cytopathicity. 

The CTD format allows other, regional specific information, to be provided in a separate section of the application. The requirements for this section are often described in detail in the individual agency guidance documents. The CTD format also specifies sections for inclusion of references and attachments, as appropriate. Additionally, the CTD includes a quality overall summary (QOS) of the more detailed information provided in the application. The contents of the QOS related to API are fully described in ICH M4Q, and represent a brief overview of the main API section. The QOS may be used during the review of the application by other reviewing disciplines (e.g., clinical, pharm/tox, etc.). The QOS in essence has eliminated the need for a specific expert opinion report and summary tables in the EU however, it is expected that the contents of the document submitted to the EU have been reviewed and accepted by an appropriate quality expert, and that this expert is suitably identified in the application. 

The document on preliminary findings (or interim report) shall also include, inter alia, the list of results of analysis, if conducted on site, records of seals, results of inventories, copies of photographs to be retained by the inspection team, and results of certified measurements. It will be prepared in accordance with the standardised format referenced in Attachment 27. Any substantive changes to this format will be made only after consultation with the inspected State Party. 

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