Information Request, May 9, 2013 - ROCUNEST

DEPARTMENT OF HEALTH & HUMAN SERVICES    
 Public Health Service

Food and Drug Administration
 1401 Rockville Pike
 Rockville, MD 20852-1448

Our Reference:  BL 125495/0

Pharming Group NV
 Attention: Ms. Kelly T. Boyle
 May 9, 2013
 Sent by email:

Dear Ms. Boyle:

We are reviewing your April 15, 2013 biologics license application (BLA) for C1 Esterase Inhibitor (Recombinant).  We determined that the following information is necessary to continue our review:

Pharmacovigilance Plan:
1.Please submit the product Safety Specification portion and a more detailed description of Pharming’s proposed routine and enhanced safety surveillance methods in the Pharmacovigilance Plan (PVP), in accordance with the ICH E2E Pharmacovigilance Planning Guidance (http://www.fda.gov/RegulatoryInformation/Guidances/ucm129411.htm).  The major components of the pharmacovigilance plan are: (a) the product safety specification, and (b) the risk management plan that outlines the important identified risks, important potential risks, and important missing information. The risk management plan should detail the specific action plans to address each of these concerns after licensure.
2.Additional details that will help FDA in assessing the adequacy of the PVP include:a.Within the Safety Specification, please provide more detailed information regarding the following components of the ICH guidance:

i.Toxicity
ii.General pharmacology
iii.Drug interactions
iv.Other toxicity-related information or data
v.Limitations of the human safety database
vi.The extent of worldwide exposure to the product
vii.Any new or different safety issues identified
viii.Any regulatory actions related to safety
ix.Populations not studied in the pre-approval phase (in addition to those already listed, i.e., pregnant or nursing women), such as the elderly, patients with relevant co-morbidity such as hepatic or renal disorders, patients of different racial and/or ethnic origins
x.A summary of the clinical safety data (as opposed to a reference to those sections of the application), to highlight the important identified and potential risks that will require further characterization or evaluation
xi.The epidemiology of hereditary angioedema (HAE), including incidence, prevalence, mortality, and relevant co-morbidity, stratifying by age, sex, race/ethnicity, if possible, as well as regional differences.
xii.A brief epidemiology (e.g., background rates) of important adverse events that may require further investigation
b.Within the PVP, please provide more detailed information regarding the specific actions proposed to address each important identified or potential risk.
i.Please provide more details on the signal detection methods and activities that will be used in routine pharmacovigilance.
ii.Please provide a template or more detailed description of how the Data Capture Aids will function.
iii.Please provide more details on the benefit-risk evaluations that will be performed as a part of routine pharmacovigilance.

The review of this submission is on-going and issues may be added, expanded upon, or modified as we continue to review this submission. 

Please submit your response to this information request as an amendment to this file by May 31, 2013 referencing the date of this request.  If you anticipate you will not be able to respond by this date, please contact the Agency immediately so a new response date can be identified.

If you have any questions, please contact me at (301) 827-6174.

Sincerely,

/s/

Nannette Cagungun, MS, PD, RAC
FDA/CBER/OBRR/DBA/RPMB
	