Chemistry, Manufacturing, and Controls CMC document

Quality control and assurance Final product must be made under current good manufacturing process (cGMP)— emphasis placed on the final bulk product The product is the manufacturing process —cGMPs from seed stock or first step onward evaluated with equal scrutiny Regulated under analytical procedures and method validation, chemistry, manufacturing and control (CMC) documentation... 

As well as GCP site inspections, an examination is imdertaken of the raw or source data and records of Chemistry Manufacturing and Control (CMC), non-clinical and clinical reports that are the basis of the application. This is to ensure that the application dossier accurately reflects the source data. The procedure issued by PMDA details that list of raw data and records must be provided. The applicant is required to bring the data and records to PMDA on the specified days and when the examination finishes they should be retrieved. Therefore, the raw data and records stored at overseas sites are usually categorised as documents not to be submitted and not subject to reliability review by PMDA. Instead, the MHLW may investigate the data from non-Japanese studies at the site of storage since submission of a photocopy of the data is not permitted. 

Folders. Inside the main folder, you should provide five folders, Administrative (admin), Chemistry, Manufacturing and Controls (cmc), Pharmacology and Toxicology (pharmtox), Clinical (clinical), and Other (other) to organize the documents and data sets provided in the original submission and subsequent amendments to your IND (Fig. 4.1). See Table 4.1 for the types of documents that would reside in each folder. In addition, the main folder should contain an indindex folder (see Folder and File Names ). 

Then, preferably at an off-site location (to avoid any interruptions) the panel should meet with the corporate regulatory NDA team [presumably Regulatory Director, Medical Director, Chemistry, Manufacturing, and Control (CMC) Director, and others as appropriate] with a detailed grilling and discussion. The idea is to dissect the entire document and to closely question the corporate team on all aspects. 

Food and Drug Administration (FDA) (August 2000) Draft guidance for industry, analytical procedures and methods validation chemistry, manufacturing, and controls documentation (CMC)... 

The stability portion of the Chemistry and Manufacturing Controls (CMC) dossier contains the sections from the stability report described above. The requirements for the CMC sections can be found in 21 CFR Part 312 for IND application and Part 314 for NDA and Abbreviated New Drug Application (ANDA). Tables 13.1 and 13.2 provide the requirements for the CMC, and the location of the stability related documents within the CMC are highlighted in Table 13.2. 

---