CBER reviews

The decision of whether a given IND is reviewed by CBER or ODER is not clear-cut. The designation BLA or NDA really depends on which branch of the FDA s drug division is assigned review responsi-bihties. ODER reviews all NDAs, while CBER reviews all BLAs. In general, most small peptides and proteins such as insulin,... 

The members of CDER and CBER review teams who apply their special technical expertise to the review of NDAs, and BLAs ... 

In the BLA, a biologic product sponsor submits thousands of pages of nonclinical and clinical data, chemical and biologic information, and product manufacturing descriptions. The submission must allow CBER reviewers to make three principal determinations ... 

To alert CBER reviewers to other documentation that must be referenced during the BLA review, the sponsor should note in the cover letter other documents associated with the application, such as INDs, BLAs, and master files. 

In general, the BLA must provide CBER reviewers with an overview of the manufacturing facility and its operations regarding the product. 

Once the OOPD determines that the proposed compound is for a disease or condition that is rare in the U.S., the request will be forwarded to the responsible division for formal review and direct response. The OOPD monitors the review process within the respective CDER/CBER reviewing division and, where possible, assists in resolving specific issues that may arise during the review process. It should be understood that protocol assistance provided under the Act does not waive the necessity for the submission of an Investigational New Drug Application (IND) by sponsors planning to conduct clinical trials with the product. 

CBER Review of PLAs and ELAs-The CBER review process for new products places added emphasis on the safety and quality of the processes and facilities used to produce a biological drug.12 Also, in contrast to CDER s NDA process, there are no statutory limits on the amount of time CBER reviewers may take to complete their review of PLAs and ELAs (40). As with the CDER process, reviewers may refer the applications to a relevant FDA advisory committee before reaching a final decision. 

In 2001, the CDER approved 66 new drugs, 24 of which were new molecular entities (NMEs) or new chemical entities (NCEs). The median approval time was 14 months. In the same period, the CBER reviewed and approved 16 BLAs. The median approval time was 20.3 months. 

Once the FDA receive the initial submission, an IND reference number is assigned. The application is then passed on to the appropriate review centre either the Center for Drug Evaluation and Research (CDER), or the Center for Biologies Evaluation and Research (CBER). Various experts will then review the submitted documents, the purpose being to ensure that the safety of subjects is not compromised and, in the case of Phase II and III studies, that the quality of study design is scientifically adequate. The FDA are allowed 30 days to complete the initial review, after which the study can commence, provided that it has been approved by an Institutional Review Board (IRB). 

CeUular Therapies. Since 1984 CBER has reviewed close to 300 somatic cell therapy protocols. Examples of the specific categories include manipulation, selection, mobilization, tumor vaccines and other. 

NDA/BLA Review Review is undertaken by FDA staff from different offices within the CDER and CBER. These staff members are trained physicians. 

FDA center responsible for review Center for Drug Evaluation and Research (CDER) Center for Biologies Evaluation and Research (CBER) ... 

Under the revised system, CBER will continue to review blood products and vaccines. These product areas are CBER s strengths and the basis for creation of the biologies division. CBERwill also be responsible for evaluating gene therapy and tissue transplantation products as the development of these novel entities comes to fruition. 

Currently, most recombinant proteins such as erythropoietin, colony-stimulating factors, and interferons are reviewed by CBER. Under the proposed consolidation plan, these well-characterized and recombinant products are likely to be reviewed by CDER. 

In the final analysis, approval of a BLA or NDA comes down to two key questions Do the results of well-controlled studies provide substantial evidence of effectiveness and Do the results show the product to be safe under the conditions of use in the proposed labeling Safe, in this context, means that the benefits of the drug appear to outweigh its risks. On completion of the review, CDER or CBER sends a letter to the applicant sponsor stating that the drug is approved for marketing is approvable,... 

See, for example, Sensabaugh (1998) for a detailed examination of CBER s product review and evaluation process. 

Reviewer Training Introduction to the Regulatory Process, which includes an orientation to CBER, INDs, clinical studies, and postmarketing surveillance... 

Sensabaugh, S. M., A Primer on CBER s Regulatory Review Structure and Process, Drug Information Journal, No. 32, 1998, pp. 1011-1030. 

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