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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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October 7, 2009 Corrected Approval Letter

October 7, 2009

Our STN:  BL 125329/0

Bio Products Laboratory
Attention:  Mr. Howard Smith
650 Peter Jefferson Parkway, Suite 200
Charlotteville, VA  22911

Dear Mr. Smith:

This letter supersedes our letter of September 17, 2009.  The licensure date remains September 17, 2009. This letter corrects the storage temperature stated on page 1, paragraph 5.

We are issuing Department of Health and Human Services U.S. License No. 1811 to Bio Products Laboratory (BPL),  Hertfordshire, United Kingdom, under the provisions of section 351(a) of the Public Health Service Act controlling the manufacture and sale of biological products. The license authorizes you to introduce or deliver for introduction into interstate commerce, those products for which your company has demonstrated compliance with establishment and product standards.

Under this license, you are authorized to manufacture the product Immune Globulin Intravenous (Human).  Immune Globulin Intravenous (Human) is indicated for the treatment of primary humoral immunodeficiency (PI).

Under this license, you are approved to manufacture Immune Globulin Intravenous (Human) at your facility in  Hertfordshire, United Kingdom. You may label your product with the proprietary name Gammaplex® and will market it in 50 mL, 100 mL and 200 mL sizes.

We did not refer your application to the Blood Products Advisory Committee because our review of information submitted in your BLA, including the clinical study design and trial results, did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.

The dating period for Immune Globulin Intravenous (Human) shall be 24 months from the date of manufacture when stored at 2-25 ºC.  The date of manufacture shall be defined as the date of final sterile filtration of the formulated drug product.  Following the final sterile filtration, no reprocessing/reworking is allowed without prior approval from the Agency.

Please submit final container samples of the product in final containers together with protocols showing results of all applicable tests.  You may not distribute any lots of product until you receive a notification of release from the Director, Center for Biologic Evaluation and Research (CBER). 

You must submit information to your biologics license application for our review and written approval under 21 CFR 601.12 for any changes in the manufacturing, testing, packaging or labeling of Immune Globulin Intravenous (Human) or in the manufacturing facilities.

You must submit reports of biological product deviations under 21 CFR 600.14.  You promptly should identify and investigate all manufacturing deviations, including those associated with processing, testing, packing, labeling, storage, holding and distribution.  If the deviation involves a distributed product, may affect the safety, purity, or potency of the product, and meets the other criteria in the regulation, you must submit a report on Form FDA-3486 to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448.

Please submit all final printed labeling at the time of use and include implementation information on FDA Form 356h and FDA Form 2567 as appropriate.  Please provide content of labeling in Structured Product Labeling format. Please provide a PDF-format electronic copy as well as three original paper copies.

In addition, you may wish to submit two draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448.

All promotional claims must be consistent with and not contrary to approved labeling.  You should not make a comparative promotional claim or claim of superiority over other products unless you have submitted data to support such claims to us and had them approved.

You must submit adverse experience reports in accordance with the adverse experience reporting requirements for licensed biological products (21 CFR 600.80) and you must submit distribution reports as described in 21 CFR 600.81.  You should submit postmarketing adverse experience reports and distribution reports to the Center for Biologics Evaluation and Research, Office of Biostatistics and Epidemiology HFM-210, Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448.  Prominently identify all adverse experience reports as described in 21 CFR 600.80.  Per 21 CFR 600.2(f), please refer to http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm106001.htm for updated mailing address information.

In addition, you must submit adverse event reports for any infectious disease transmission within 15 days after learning of the event.  Infectious disease transmission refers to an adverse event that involves suspected or confirmed transmission of an infectious agent, whether the recipient develops the infectious disease or only has serologic or other evidence.  If an infectious disease transmission event is serious and unexpected, you must submit a 15-day "alert report," as required under 21 CFR 600.80(c)(1)(i).  Infectious disease transmission events that do not meet criteria for expedited submission require periodic reports and must be submitted as individual case reports within 15 days, as authorized under 21 CFR 600.80(c)(2)(i).  You should submit reports for all other non-expedited adverse events under the periodic reporting requirements specified in 21 CFR 600.80(c)(2).

PEDIATRIC REQUIREMENTS

Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication in pediatric patients unless this requirement is waived, deferred, or inapplicable.

We are waiving the pediatric study requirement for patients 0 to <2 years of age because the necessary studies are impossible or highly impracticable. It is rare for primary humoral immunodeficiency to be diagnosed in this age group.

We are deferring submission of your pediatric study for patients >2 to 16 years of age for this application because this product is ready for approval for use in adults and the pediatric study has not been initiated.

Your deferred pediatric study, required under 505B(a) of the Federal Food, Drug, and Cosmetic Act, is a required postmarketing study.  The status of this postmarketing study must be reported according to 21 CFR 601.70 and section 505B(a)(3)(B) of the Federal Food, Drug, and Cosmetic Act.  This required study is listed below:

1.         Deferred pediatric study under PREA for the treatment of primary humoral immunodeficiency in pediatric patients >2 to 16 years of age :  A Phase 3, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Gammaplex® in Primary Immunodeficiency Diseases in Children and Adolescents

Besides safety and efficacy endpoints, the study design should include pharmacokinetic evaluation in both the children (>2 to <12 years of age) and adolescent (>12 to 16 years of age) age groups.

Protocol Submission: November 2009

Study Initiation: January 2010

Study Completion: September 2012

Final Report Submission: December 2012

Submit final study reports to this BLA.  For administrative purposes, all submissions related to this required pediatric postmarketing study must be clearly designated, “Required Pediatric Assessment.”

We acknowledge your written commitments as described in your letter of August 13, 2009 as outlined below:

Postmarketing Studies not subject to reporting requirements of 21 CFR 601.70.  

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We request that you submit information concerning nonclinical and chemistry, manufacturing, and control postmarketing commitments and final reports to your BLA, STN BL 125329/0.

Sincerely yours,  

Mary A. Malarkey
Director
Office of Compliance and 
 Biologics Quality
Center for Biologics
 Evaluation and Research  

 

Jay S. Epstein, M.D.
Director
Office of Blood Research and Review
Center for Biologics
Evaluation and Research