Import Alert 57-20
(Note: This import alert represents the Agency's current guidance to FDA field personnel regarding the manufacturer(s) and/or products(s) at issue. It does not create or confer any rights for or on any person, and does not operate to bind FDA or the public).
Import Alert # 57-20 Published Date: 10/02/2009 Type: DWPE
Import Alert Name: "Imported Dura Mater Regulated Under Section 361 Of The Public Health Service Act (PHS Act)"
Reason for Alert: Human cells, tissues, and cellular and tissue-based products (HCT/Ps), particularly HCT/Ps such as dura mater that are closely associated with the central nervous system, may transmit some human transmissible spongiform encephalopathies (TSEs) such as CJD and vCJD. Currently, FDA does not recommend testing for human TSEs such as CJD and vCJD and there are no FDA-approved donor screening tests.
However, manufacturers must screen donors of dura mater by reviewing the donor?s relevant medical records for risk factors for and clinical evidence of TSE, including vCJD and CJD ((? 1271.75(a)). Such factors include residence in a country where there is a geographic risk of BSE and, related, vCJD. In addition, manufacturers must perform an adequate assessment for donors of dura mater to detect evidence of TSE (? 1271.85(e)).
Guidance: Districts may detain without physical examination all imported Dura Mater due to the possible risk of CJD and vCJD transmission.
1. Districts may request documents to determine if entries of dura mater are:
a. Imported from a country of geographical risk of BSE (See the updated list below for your reference);
b. Imported following transshipment from a country of geographical risk of BSE.
2. Dura mater that is directly imported from a country of geographical risk of BSE or imported following transshipment from a country of geographical risk of BSE may be refused entry.
3. Districts encountering Dura Mater that is not directly imported from a country of geographical risk of BSE, or imported following transshipment from a country of geographical risk of BSE should contact OCBQ/DCM, Import/Export Staff to determine admissibility.
Countries List Based on Geographic Risk of BSE:
Albania(AL), Andorra (AD), Austria(AT), Belgium(BE), Bosnia-Herzegovina (BA), Bulgaria(BG), Croatia(HR), Czech Republic(CZ), Denmark(DK), Finland(FI), France(FR), Germany(DE), Greece (GR), Hungary(HU), Ireland(IE),Israel(IL), Italy(IT), Japan (JP), Liechtenstein (LI), Luxembourg(LU), Macedonia(MK), Monaco (MC), Netherlands(NL), Norway(NO), Oman (OM), Poland(PL), Portugal(PT), Romania(RO), San Marino(SM), Slovak Republic(SK), Slovenia(SI), Spain(ES), Sweden(SE), Switzerland(CH), United Kingdom (GB), and Yugoslavia(YU).
Product Description: Dura Mater
Charge: "This Human Cell, Tissue, and Cellular and Tissue-Based Product is in violation of section 361 of the Public Health Service Act." OASIS charge code - TISSUE
Countries (AL) ALBANIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(AD) ANDORRA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(AT) AUSTRIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(BE) BELGIUM
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(BA) BOSNIA-HERCEGOVINA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(BG) BULGARIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(HR) CROATIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(CZ) CZECH REPUBLIC
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(DK) DENMARK
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(FI) FINLAND
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(FR) FRANCE
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(DE) GERMANY
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(GR) GREECE
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(HU) HUNGARY
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(IE) IRELAND
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(IL) ISRAEL
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(IT) ITALY
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(JP) JAPAN
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(LI) LIECHTENSTEIN
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(LU) LUXEMBOURG
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(MK) MACEDONIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(MC) MONACO
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(NL) NETHERLANDS
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(NO) NORWAY
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(OM) OMAN
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(PL) POLAND
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(PT) PORTUGAL
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(RO) ROMANIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(SM) SAN MARINO
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(SK) SLOVAKIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(SI) SLOVENIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(ES) SPAIN
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(SE) SWEDEN
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(CH) SWITZERLAND
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(GB) UNITED KINGDOM
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
(YU) YUGOSLAVIA
(57 T - - 01) Dura Mater (Human Dura Mater)
(84 L - - EM) Dura Mater, Human, Lyophilized
http://www.accessdata.fda.gov/cms_ia/importalert_158.html
Import Alert 84-03
(Note: This import alert represents the Agency's current guidance to FDA field personnel regarding the manufacturer(s) and/or products(s) at issue. It does not create or confer any rights for or on any person, and does not operate to bind FDA or the public).
Import Alert # 84-03 Published Date: 10/02/2009 Type: DWPE Import Alert Name: "Lyodura (Dura Mater)"
Reason for Alert: A recent reported case of Creutzfeldt Jakob Disease (CJD) in a 28 year old patient who had received a human dura mater graft indicates that the graft may have been the source of this always fatal disease. The woman died 22 months after receiving the lyophilized, irradiated human cadaveric dura mater graft. The dura mater used in the graft was packaged in October 1982 under lot #2105 by B. Braun Melsungen AG of West Germany, shipped to Tri Hawk International, Inc., Montreal, Quebec, Canada and sold to Saint Francis Hospital, Hartford, Connecticut, on April 4, 1985.
This is the first known case of CJD transmission associated with a dura mater graft. Present methods of sterilizing the dura mater do not completely inactivate the CJD agent.
The dura mater is manufactured by the West German firm under the trade name Lyodura. Although the material is primarily used in neurosurgery, it is also used in orthopedic, otologic, dental, urologic, gynecologic, and cardiac surgical procedures.
We have been unable to determine the total number of packages of Lyodura that were imported into the United States because the Canadian distributor failed to maintain adequate records of distribution for all lots which may have been distributed by mail to hospitals in the United States and Canada.
As stated in the FDA Safety Alert which issued April 28, 1987, we strongly recommend that users of dura mater choose only products from known sources which retrieve, process and handle the material according to guidelines such as those of the American Association of Tissue Banks.
Guidance: Detain all shipments of Lyodura (dura mater) received from Tri Hawk International, Inc., Montreal, Quebec, Canada, or from B. Braun Melsungen AG of West Germany.
Alert your local Customs office to be aware of this import alert and to monitor mail shipments for this product.
Product Description: Lyodura
Charge: "The article is subject to refusal of admission pursuant to section 801(a)(1) in that it appears to be adulterated under section 501(h), because the methods and controls used for the storage and distribution of Lyodura (dura mater) are not in conformance with current good manufacturing practice requirements under section 520(f)(1)."
OASIS charge code - DEVICE GMP
List of firms and their products subject to Detention without Physical Examination (DWPE) under this Import Alert (a.k.a. Red List)
(14415) Tri Hawk International IncDate Published : 09/16/2009 1570 Rue Bane , Saint-Laurent, QC CA 84 - - - -- Neurological Date Published: 09/16/2009
(3002806469) B. Braun MelsungenDate Published : 09/16/2009 Carl Braun Strasse 1 , Melsungen, DE 84 - - - -- Neurological Date Published: 09/16/2009
-
http://www.accessdata.fda.gov/cms_ia/importalert_232.html
also see North America BSE GBR risk factor for Canada, USA, and Mexico ;
The most recent assessments (and reassessments) were published in June 2005 (Table I; 18), and included the categorisation of Canada, the USA, and Mexico as GBR III. Although only Canada and the USA have reported cases, the historically open system of trade in North America suggests that it is likely that BSE is present also in Mexico.
http://www.oie.int/boutique/extrait/06heim937950.pdf
Tutogen Medid,U.S.,Inc.
December 9,2002
Dockets Management Branch (HFA-305)
Food and Drug Administration 5630 Fishers Lane, Rm. 1061 Rockville, MD 20852
RE: Docket No. 02D-0266, CBER 150. Draft Guidance for Industry: Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob disease (CID) and Variant Creutzfeldt-Jakob Disease (vCJD) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Availability. Pages 42789--42790 FR Dot. 02- 158981
Tutogen Medical Inc. ("Tutogen") appreciates the opportunity to comment on the draft document issued by the FDA in June 2002 entitled: "Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob Disease (vCJD) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) " In particular, we wish to use this venue to respond to your request for data assessing the impact of the recommendations contained therein to reduce the risk of CJD and vCJD on the availability of HCT/P.
snip...
1. # of Tissue Banks reporting 63
2. # of tissue donors recovered (HCT/P domw population) 18,021
3. # of Bone allografts dlstributed in U.S. 675,370
4. Volume of Skin grafts distributed in U.S. 11,222 ft2
1Excerpt Corn "Background" statement contained in the American Association of Tissue Banks Membership Directory 2001-2002.
snip...
II. Impact of donor deferral upon the availability of HCT/ps: During the year 2001, Tutogen processed 3,500 donors recovered by our contract recovery agencies from various locations including Europe. In the 12 months from July 1, 200l to June 30, 2002, Tutogen distributed a total of 21,639 musculoskeletal allograft products to patients in the U.S. Based upon the data above, this represents approximately 3% of the total number of bone allograft products distributed by AATB accredited Banks in the United States.
The implementation of the FDA's proposed guidance would immediately reduce the number of available HCT/P donors by approximately 10% in the U.S. due to country of origin exclusion. The direct impact to Tutogen would be an approximate 50% reduction in our donor base or approximately 10,820 musculoskeletal allograft products. Therefore, the impact of this proposal from the FDA upon Tutogen would be greater than upon any other U.S. based tissue bank. Among the remaining 16,271 HCT/P donors (approximately) recovered by other AATB accredited organizations annually, a large percentage would be eliminated under the proposed FDA rule that would disqualify any donor who has visited a listed country for a cumulative period of 6-months or more. Not only would frequent travelers be considered deferred donors, but a large share of military veterans and their immediate family members due to being stationed overseas. Tutogen does not have verifiable data concerning these figures, however, it is not inconceivable that this would adversely impact the donor pool by at least an additional 6% or more, based on the blood bank industry experience, this would translated to a 976 HCT/P donors. The combination of Tutogen's and the rest of the tissue banks would total approximately 2,726 HCT/P donors. .
III. Musculoskeletal allografl tissue has been scientijiiaUy classified as low risk for CVZWCJD transmission. As with other AATB certified organizations, Tutogen allograft products are used across a multitude of medical applications. Currently, none of Tutogen HCT/Ps in the United States are so-called high-risk tissue such as dura mater or corneas (refer to Appendix 1).
Not all tissue has the same infectivity risk. The HCT/Ps utilized by Tutogen in allografi products, distributed in the US, are classified as Category IV tissue (i.e., "No detectible @Jo-) infectivity") by the World Health Organization in its March 19972 study. Tutogen has not processed or distributed in the United States high-risk Category II tissue such as dura mater since June 2000. Tutogen has never processed or distributed comeal tissue. Therefore the effect of any donor deferral ruling by the FDA on HCT/Ps limited to high-risk Category II tissue, will not have any effect upon Tutogen's ability to continue providing HCT/Ps in the United States as shown in the table above.
2 World Health Organization, Emerging and other Communicable Diseases Report of a WHO consultation on medicinal and other products in relation to human and animal transmissible Spongiform Encephalophathies.
2
IK Tutoplast safe@ claims are supported by a long-hktory (25 consecutive years) of successful allograft implants:
Tutogen HCT/Ps are recovered following a very stringent donor selection criterion in accordance with AATB standards and FDA regulations. The current industry standard concerning CJD significantly reduces the risk of harvesting tissue from a potentially infected HCT/P donor. All Tutogen HCT/Ps are processed using a proprietary system known as the Tutophst 8 process. Tutogen's single donor tissue processing methods (no pooling of donors) have been shown to ensure viral/bacterial inactivation in controlled studies. The Tutopht 8 process has been validated, specifically for the inactivation of prions and other transmissible agents. Two independent studies have confirmed that the Tutophst 8 process is capable of removing infectious Prion agents from sol? tissue as a result of treating soft tissue with sodium hydroxide. '4
Recommendations:
Tutogen recognizest hat the spread of bovine spongiform encephalopathy, or mad cow disease, has prompted debate concerning the possible modification of recent deferral criteria Tutogen urges the FDA to continue inviting scientists, physicians and patient groups to participate in this policy discussion. Physicians must be given accurate information about the benefits and risks, both real and theoretical associatedw ith HCT/P transplantations o that they can effectively educate every patient when an HCT/P transplant is needed.
While Tutogen also recognizes that studies about the potential for transmission of TSEs in animal models continue, however, evidence is still lacking of such transmission among patients who have received human tissues, blood transfusions and clotting factor concentrates. Tutogen respectfully requests that the Food and Drug Administration, before any final ruling, address issues sited herein, by limiting its definition of deferred donor to those cases where high-risk Category II tissue is being implanted (e.g., dura mater, corneas), and/or to those cases where tissue recovery and processing methods being used pose additional risks.
Conclusion:
The very low incidence of human CJDMXD and our current screening criterion already poses a low risk that an infected donor may enter the process. The Centers for Disease Control and Prevention reports that the incidence of CJD is one case per million people each year. 3Robert Koch Institut in Berlin (Department of the German FederalI nstitute of Health) Diringer H, Braig H, Infectivity of unconventional viruses in duramater,The Lancet, February 25, 1989 4L aboratorieso f RBM, Ivrea, Italy and expert opinion by Dr. Masullo (NurosurgeonM) asullo, 1994, Estimate of the theoretical risk of transmission of Creutzfeld-Jacob Disease by human duramater grafts manufactured by the Tutoplast process.R MB, Studienbericht1, 994, Determination of the clearance factor for unconventional slow viruses during the processing of duramater.
3
Based upon the track record of safety, quality, and clinical effkacy of TutopZast@ and the product approval protocols adhered to by Tutogen, and already audited by the FDA, relating to the import of HCT/Ps into the U.S. from Europe, we do not believe that there is any additional risk associated with HCT/Ps recovered and processed by Tutogen. Given the scientific data available today, Tutogen does not believe that a blanket ruling to defer HCT/P donors from specific counties would reduce CJD and vCJD risk in cases where a validated recovery and processing procedure is being used. Indeed, the impact of a deferred donor ruling as presently proposed would significantly reduce the availability of HCT/Ps in the United States (up to 20% or more based upon the data contained herein) without a commensurate and measurable risk reduction in CJD and vCJD transmission.
Very truly yours,
Wade S, Tetsuka
Tutogen Medical U.S., Inc. General Manager
P.J. Pardo Tutogen Medical U.S., Inc. Director, Regulatory Affairs/ Quality Management
Appendix 1: Tutoplast@P rocessedA llografks Distributed
Spinal / Trauma Sulzer SpineTech, Minneapolis MN Ophthalmology IOP, Inc., Costa Mesa, CA ENT Urology Mentor Corp., Santa Barbara, CA Dental Sulzer Dental, Carlsbad, CA Spinal Fusion, ACL, Rotator Cuff repair Glaucoma patch, eyebrow slings, enucleation wraps, poterior segment, eyelid spacers Tymp~oplasty, CholesteomaR esection Pelvic Floor repair, urinary incontinence Peridontal implants Femur, Ulna, Radius, Humurous with cuff, anterior cruciate ligament. Sclera, Pericardium, Fascia Lata Sclera, Pericardium, Fascia Temporalis Fascia Lata, Pericardium,D ermis Cancellousb onec hips from femur, ulna, radius 4,000 grafh 8,000 grafts 2,000 grafls 9,000 grafts 17,000 grafts
http://www.fda.gov/ohrms/DOCKETS/dailys/02/Dec02/121002/02d-0266.pdf
Monday, August 31, 2009
HUMAN BODY PARTS FOR SALE TO THE HIGHEST BIDDER Inside a Creepy Global Body Parts Business SPIEGEL ONLINE - News - International ~~ August 28 2009
42.90 Euros Per Arm
Inside a Creepy Global Body Parts Business By Martina Keller and Markus Grill
see full text ;
http://creutzfeldt-jakob-disease.blogspot.com/2009/08/human-body-parts-for-sale-to-highest.html
Update: Creutzfeldt-Jakob Disease Associated with Cadaveric Dura Mater Grafts --- Japan, 1979--2003 MMWR Weekly December 5, 2003 / 52(48);1179-1181
http://www2.niddk.nih.gov/AboutNIDDK/CommitteesAndWorkingGroups/HGH_CJD_Dec_11_2003_TAB_A.htm
Thursday, October 23, 2008
Creutzfeldt-Jakob Disease Associated with Cadaveric Dura Mater Grafts - Japan, 1979-2008 : UPDATE
http://creutzfeldt-jakob-disease.blogspot.com/2008/10/creutzfeldt-jakob-disease-associated.html
http://www.wellsphere.com/cjd-article/medical-procedures-and-risk-for-sporadic-creutzfeldt-jakob-disease-japan-1999-2008-warning-to-neurosurgeons-and-ophthalmologi/641229
Thursday, January 29, 2009
Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number 2-February 2009 Research
http://creutzfeldt-jakob-disease.blogspot.com/2009/01/medical-procedures-and-risk-for.html
Wednesday, August 12, 2009
Unique clinicopathological features and PrP profiles in the first autopsied case of dura mater graft-associated Creutzfeldt-Jakob disease
http://creutzfeldt-jakob-disease.blogspot.com/2009/08/unique-clinicopathological-features-and.html
Sunday, May 10, 2009
Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)
http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html
SEE 2001 SUBMISSION BELOW ;
Freas, William TSS SUBMISSION
Page 1. J Freas, William From: Sent: To: Subject: Terry S. Singeltary
Sr. [flounder@wt.net] Monday, January 08,200l 3:03 PM freas ...
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
Thursday, January 28, 2010
Multiorgan Detection and Characterization of Protease-Resistant Prion Protein in a Case of Variant CJD Examined in the United States
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/multiorgan-detection-and.html
Saturday, June 13, 2009
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html
*** CJD USA RISING, with UNKNOWN PHENOTYPE ;
5 Includes 41 cases in which the diagnosis is pending, and 17 inconclusive cases; 6 Includes 46 cases with type determination pending in which the diagnosis of vCJD has been excluded.
http://www.cjdsurveillance.com/pdf/case-table.pdf
CJD Following up: Patients never contracted brain disorder UW Hospital patients
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/cjd-following-up-patients-never.html
Sunday, January 17, 2010
Human tissue, recovered from a donor history indicated increased risk factors for Creutzfeldt-Jacob disease Lions Eye Bank
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/human-tissue-recovered-from-donor.html
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
my comments to PLosone here ;
http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd
Friday, January 29, 2010
14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)
http://bse-atypical.blogspot.com/2010/01/14th-international-congress-on.html
TSS