My name is Mohsen Rajabi. I am a Pharmacologist in the Division of New Drug Bioequivalence Evaluation (DNDBE), Office of Study Integrity and Surveillance, Office Translational Science, Center for Drug Evaluation and Research, US FDA. I conduct study-directed and comprehensive surveillance inspections of firms that conduct pharmacokinetic and bioavailability/bioequivalence (BA/BE) studies submitted to the FDA.
1. What do you think are the main challenges you face in your role?
To detect data integrity and to be able to verify the accuracy and completeness of data generated to meet applicable regulatory requirements.
2. What is your favorite aspect of your work?
Traveling and learning about new science in the area of drug development and regulatory science.
3. Could you describe the different stages of how therapeutic proteins gain FDA approval? And the typical timescale of these stages?
The regulatory basis for therapeutic proteins comes from section 351 of the Public Health Service (PHS) Act, which states that the biologic product must be safe, pure and potent. The manufacturing facility must meet the standards to assure the product is safe, pure and potent. Some therapeutic protein products are approved under section 505 of the Food, Drug and Cosmetic (FDC) Act, not under the PHS Act.
There are several steps to gain FDA approval for therapeutic protein products. Following initial laboratory and animal testing, which shows that investigational use in humans is reasonably safe, the sponsor submits an Investigational New Drug (IND) application to the Center for Drug Evaluation and Research (CDER) for review. The sponsor must wait 30 calendar days before initiating any clinical trials. During this time, the FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk. Once the IND application is approved, the sponsor can begin their clinical trials.
The sponsor submits the Biologics Licence Application (BLA) as soon as the sponsor analyzes the clinical trial data and concludes that enough evidence exists on the drug’s safety and effectiveness to meet the FDA’s requirements for marketing approval. The BLA contains complete information on efficacy and safety, manufacturing specifications, stability and bioavailability data, method of analysis of each of the dosage forms the sponsor intends to market, packaging and labeling for both physician and consumer, and the results of any additional toxicological studies not already submitted in the IND. The IND period for a therapeutic protein product typically is 5– 7 years, and the current timeline for BLA review is 12 months.
4. Why are immunogenicity assays so important in bioanalytical studies?
Assessing immunogenicity against protein therapeutics is important because there have been real life examples in which immune responses to therapeutic proteins have had devastating consequences for healthy volunteers and patients.
5. What is important to consider when performing ADA assays?
ADA assays are qualitative and results are not reported in absolute values.
6. How often are FDA guidelines reviewed and how is your work regulated and standardized?
The FDA guidelines are reviewed continuously based on internal agency policy and feedback from industry. There are working groups that discuss different topics and revise the guidelines to meet regulatory and industry expectations. Our office largely relies on Compliance Program 7348.001, in addition to 21 CFR 320.29a, 320.38, and 320.63.
7. How do you stay on top of new technologies?
By attending conferences and scientific meetings.
8. What does the future hold for immunogenicity testing?
Applying more sensitive and robust techniques in immunogenicity assays.
Current regulations and resources:
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