Journal of Plastic, Reconstructive & Aesthetic Surgery (2014) 67, 1457e1459
Letter from America: Selling silk surgical scaffolds Stop the presses! I had mixed feelings about going to last night’s meeting of the Miami Society of Plastic Surgeons. On the one hand, I enjoy its collegiality, getting to see colleagues whom I have known for decades but with whom I no longer interact either because they have retired or are not practicing at the same hospitals as I do. On the other hand, I had a selfimposed deadline to finish my latest “Letter From America” on a complex yet relevant topic. Fortunately, I was able to achieve both goals by attending the meeting, I did have a chance to see friends from years gone by, but the sponsor’s speakers’ presentations were certainly interesting enough for to me postpone my planned essay and write about last night’s topic. A major drug and device manufacturer, currently listed on the New York Stock Exchange, sponsored the meeting.a Its billions of dollars in annual sales include many products used by plastic surgeons including implants, tissue expanders, and neurotoxins. The sponsor had two speakers, an employee and a plastic surgeon from El Paso, Texas. The employee presented in detail how the product was manufactured from the cocoon of the Bombyx mori silkmoth. This included helical twisting to form a multi-filament fiber, followed by using a proprietary method to remove the sericin from the fiber leaving fibroin protein behind. The fiber was then knitted into a patterned scaffold. The manufacturing process included large pores to provide drainage and a proprietary weave to allow cutting the material without unraveling. The material is gas sterilized and does not require rehydration. Experiments in sheep have shown that while the material is eventually replaced by native tissue,
a As of today, the company is the subject of a hostile takeover bid by another health conglomerate and it may no longer be independent by the time that this is published.
the support strength of the material and its replaced tissue is stronger than sheep fascia. Using either CT or MRI, no residual material was present at 12 months.
510(k) Before describing what the plastic surgeon said, I must digress to explain the US Food and Drug Administration’s (FDA) 510(k) regulatory process. It is named after the: “Section of the Food, Drug and Cosmetic Act that requires device manufacturers . to notify FDA of their intent to market a medical device at least 90 days in advance. This is known as Premarket Notification - also called PMN or 510(k)”.1 This is an important distinction. Under section 510(k) FDA does not approve devices, it merely determines if a device is “substantially equivalent” to a device that has been previously cleared for sale. Thus, if I were have a new volar plate for treating distal radius fractures, I would not need to prove that it is safe and effective, I would only need to file a 510(k) notification claiming that it is “substantially equivalent” to other volar plates that FDA has previously approved. Clearly, I would save substantial time and costs if I could avoid having to fund randomized control trials to prove that my plate is safe and effective. On April 23, 2013 FDA informed the manufacturer that: “We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices”.2 What were the “substantially equivalent devices” that the manufacturer used in its 510(k) notification? They were Vicryl mesh and TEI Biosciences’ SurgiMend [bovine] Collagen Matrix. At the time, neither Vicryl mesh nor SurgiMend Collagen Matrix had FDA approval for use in breast reconstruction. Indeed, not until June 5, 2013 did TEI
http://dx.doi.org/10.1016/j.bjps.2014.06.015 1748-6815/ª 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
1458
Table 1
Search results for “surgical scaffold” at clinicaltrials.gov June 19, 2014. Recruitment Number of Updated Start Date Patients
Primary Completion Date
Study Completion Date
Study Results Conditions
Primary Outcome Measure
Surgical Scaffold Use in Reconstruction Post Market Study for Tissue Support and Repair in Breast Reconstruction Surgery Surgical Scaffold Postmarket Study of Soft Tissue Support and Repair in Breast Reconstruction Use in Reconstruction Post Market Study for Tissue Support and Repair in Breast Reconstruction Surgery in Europe Clinical and Economic Outcomes With the Use of Surgical Scaffold in Direct-toimplant Breast Reconstruction Surgical Scaffold Support of the Lower Pole of the Breast
Active, not 160 recruiting
4/16/14 October-10
October-12
October-14
Has Results
Breast Reconstruction
Investigator satisfaction NCT01256502 at 6 months
Active, not recruiting
60
4/17/14 June-13
December-16 December-16 No Results Available
Breast Reconstruction
Incidence of Implant Loss NCT01914653 [Time Frame: 24 months postoperatively]
Active, not 100 recruiting
12/17/13 June-11
August-13
June-15
No Results Available
Breast Reconstruction
Investigator satisfaction NCT01389232 at 6 months
Not yet recruiting
109
1/10/14 March-14
June-16
June-17
No Results Available
Breast Reconstruction
Incidence rate of implant NCT02033590 loss [Time Frame: 52 weeks]
Not yet recruiting
150
12/19/13 December-13 December-15
No Results Available
Surgical Scaffold for Soft Recruiting Tissue Support in Revision Augmentation Surgery
50
NCT02016612 Recurrent Ptosis Nipple to Fold of the Breast Measurement on Stretch [Time Frame: 1 year post op] NCT02030938 Reoperation rate (per Subjects implanted breast) for the Requiring Revision Breast presenting condition at Augmentation 12 months. [Time Frame: 12 months] Surgery Ventral Hernia Rate of hernia NCT01981044 Repair recurrence [Time Frame: 24 months postoperatively]
Active, not 100 Surgical Scaffold Postmarket Study of recruiting Soft Tissue Support in Ventral Hernia Repair
3/26/14 December-13 May-15
4/17/14 October-13
May-15
No Results Available
December-16 December-16 No Results Available
Identifier
M.F. Freshwater
Title
M.F. Freshwater
1459
Biosciences announce that the FDA had approved a clinical trial of SurgiMend in women undergoing breast reconstruction after failed lumpectomy and radiation.3 This TEI trial, which was registered in September 2013, was not supposed to begin until January 2014 and will not be completed until June 2019.4
Ethics approval
Where’s the beef?
The author has no financial interest in any of the products discussed.
The sponsored plastic surgeon presented some individual patients’ results. While he did show some of his own abdominal hernia patients, he readily acknowledged that the majority of the breast patients that he showed were from other surgeons. The “Procedure Guide” that was provided to each dinner guest had many of the same photos as the presentation with the longest follow-up being 8 months. I was reminded of “Where’s the beef?” the 1980’s catchphrase used to signify the factual deficiencies of a product’s or politician’s claims.5 On this night, the beef was being presented on a plate and the only substantive data being presented was on sheep. In 2007, FDA legislation was revised and several major changes were enacted.6 Drug and device manufacturers were required to register trials within a certain time period and post updated results at clinicaltrials.gov, otherwise they could face substantial financial penalties.7 Table 1 shows all relevant studies that I could locate at clinical trials.gov. Note the dearth of data; the only study with data is NCT01256502, a post-marketing study in breast reconstruction whose primary outcome measurement was surgeon satisfaction and secondary outcome measurement was ease of use, not patient satisfaction.8 The other studies, including those measuring explantation post-reconstruction and recurrent ptosis, will not be completed for years. Yet, the indications that the FDA approved and for which the manufacturer sells the product are:
Financial disclosure
“Use as a transitory scaffold for soft tissue support and repair to reinforce deficiencies where weakness or voids exist that require the addition of material to obtain the desired surgical outcome. This includes reinforcement of soft tissue in plastic and reconstructive surgery, and general soft tissue reconstruction”.9 Until clinical trial results are available, I believe that we should remember the saying about the feasibility of making silk purses out of sows ears.
Not required.
Competing interests
The author believes that the manufacturer of the silkmoth product subsidized the cost of the Miami Society of Plastic Surgeons dinner, which he attended.
References 1. http://www.fda.gov/medicaldevices/productsandmedical procedures/deviceapprovalsandclearances/510kclearances/ default.htm [accessed 19.06.14]. 2. http://www.accessdata.fda.gov/cdrh_docs/pdf12/K123128. pdf p. 2 [accessed 19.06.14]. 3. http://www.teibio.com/news-releases/tei-biosciencesgranted-fda-approval-to-initiate-a-human-clinical-trial-withsurgimend-prs-in-patients-undergoing-breast-reconstructionfollowing-mastectomy/ [accessed 19.06.14]. 4. http://clinicaltrials.gov/ct2/show/record/NCT01959867 [accessed 19.06.14]. 5. http://en.wikipedia.org/wiki/Where’s_the_beef%3F [accessed 19.06.14]. 6. http://www.gpo.gov/fdsys/pkg/PLAW-110publ85/pdf/PLAW110publ85.pdf#pageZ82 [accessed 19.06.14]. 7. http://clinicaltrials.gov/ct2/manage-recs/ fdaaa#AreTherePenalties [accessed 19.06.14]. 8. http://clinicaltrials.gov/ct2/show/results/NCT01256502? sectZX01256 [accessed 19.06.14]. 9. http://www.accessdata.fda.gov/cdrh_docs/pdf12/K123128. pdf p. 4 [accessed 19.06.14].
M. Felix Freshwater Voluntary Professor of Surgery, University of Miami School of Medicine, 9155 S. Dadeland Blvd, Suite 1404, Miami, FL 33156-2739, USA E-mail address: [email protected] 20 June 2014
Letter from America: Selling silk surgical scaffolds Stop the presses! I had mixed feelings about going to last night’s meeting of the Miami Society of Plastic Surgeons. On the one hand, I enjoy its collegiality, getting to see colleagues whom I have known for decades but with whom I no longer interact either because they have retired or are not practicing at the same hospitals as I do. On the other hand, I had a selfimposed deadline to finish my latest “Letter From America” on a complex yet relevant topic. Fortunately, I was able to achieve both goals by attending the meeting, I did have a chance to see friends from years gone by, but the sponsor’s speakers’ presentations were certainly interesting enough for to me postpone my planned essay and write about last night’s topic. A major drug and device manufacturer, currently listed on the New York Stock Exchange, sponsored the meeting.a Its billions of dollars in annual sales include many products used by plastic surgeons including implants, tissue expanders, and neurotoxins. The sponsor had two speakers, an employee and a plastic surgeon from El Paso, Texas. The employee presented in detail how the product was manufactured from the cocoon of the Bombyx mori silkmoth. This included helical twisting to form a multi-filament fiber, followed by using a proprietary method to remove the sericin from the fiber leaving fibroin protein behind. The fiber was then knitted into a patterned scaffold. The manufacturing process included large pores to provide drainage and a proprietary weave to allow cutting the material without unraveling. The material is gas sterilized and does not require rehydration. Experiments in sheep have shown that while the material is eventually replaced by native tissue,
a As of today, the company is the subject of a hostile takeover bid by another health conglomerate and it may no longer be independent by the time that this is published.
the support strength of the material and its replaced tissue is stronger than sheep fascia. Using either CT or MRI, no residual material was present at 12 months.
510(k) Before describing what the plastic surgeon said, I must digress to explain the US Food and Drug Administration’s (FDA) 510(k) regulatory process. It is named after the: “Section of the Food, Drug and Cosmetic Act that requires device manufacturers . to notify FDA of their intent to market a medical device at least 90 days in advance. This is known as Premarket Notification - also called PMN or 510(k)”.1 This is an important distinction. Under section 510(k) FDA does not approve devices, it merely determines if a device is “substantially equivalent” to a device that has been previously cleared for sale. Thus, if I were have a new volar plate for treating distal radius fractures, I would not need to prove that it is safe and effective, I would only need to file a 510(k) notification claiming that it is “substantially equivalent” to other volar plates that FDA has previously approved. Clearly, I would save substantial time and costs if I could avoid having to fund randomized control trials to prove that my plate is safe and effective. On April 23, 2013 FDA informed the manufacturer that: “We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices”.2 What were the “substantially equivalent devices” that the manufacturer used in its 510(k) notification? They were Vicryl mesh and TEI Biosciences’ SurgiMend [bovine] Collagen Matrix. At the time, neither Vicryl mesh nor SurgiMend Collagen Matrix had FDA approval for use in breast reconstruction. Indeed, not until June 5, 2013 did TEI
http://dx.doi.org/10.1016/j.bjps.2014.06.015 1748-6815/ª 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
1458
Table 1
Search results for “surgical scaffold” at clinicaltrials.gov June 19, 2014. Recruitment Number of Updated Start Date Patients
Primary Completion Date
Study Completion Date
Study Results Conditions
Primary Outcome Measure
Surgical Scaffold Use in Reconstruction Post Market Study for Tissue Support and Repair in Breast Reconstruction Surgery Surgical Scaffold Postmarket Study of Soft Tissue Support and Repair in Breast Reconstruction Use in Reconstruction Post Market Study for Tissue Support and Repair in Breast Reconstruction Surgery in Europe Clinical and Economic Outcomes With the Use of Surgical Scaffold in Direct-toimplant Breast Reconstruction Surgical Scaffold Support of the Lower Pole of the Breast
Active, not 160 recruiting
4/16/14 October-10
October-12
October-14
Has Results
Breast Reconstruction
Investigator satisfaction NCT01256502 at 6 months
Active, not recruiting
60
4/17/14 June-13
December-16 December-16 No Results Available
Breast Reconstruction
Incidence of Implant Loss NCT01914653 [Time Frame: 24 months postoperatively]
Active, not 100 recruiting
12/17/13 June-11
August-13
June-15
No Results Available
Breast Reconstruction
Investigator satisfaction NCT01389232 at 6 months
Not yet recruiting
109
1/10/14 March-14
June-16
June-17
No Results Available
Breast Reconstruction
Incidence rate of implant NCT02033590 loss [Time Frame: 52 weeks]
Not yet recruiting
150
12/19/13 December-13 December-15
No Results Available
Surgical Scaffold for Soft Recruiting Tissue Support in Revision Augmentation Surgery
50
NCT02016612 Recurrent Ptosis Nipple to Fold of the Breast Measurement on Stretch [Time Frame: 1 year post op] NCT02030938 Reoperation rate (per Subjects implanted breast) for the Requiring Revision Breast presenting condition at Augmentation 12 months. [Time Frame: 12 months] Surgery Ventral Hernia Rate of hernia NCT01981044 Repair recurrence [Time Frame: 24 months postoperatively]
Active, not 100 Surgical Scaffold Postmarket Study of recruiting Soft Tissue Support in Ventral Hernia Repair
3/26/14 December-13 May-15
4/17/14 October-13
May-15
No Results Available
December-16 December-16 No Results Available
Identifier
M.F. Freshwater
Title
M.F. Freshwater
1459
Biosciences announce that the FDA had approved a clinical trial of SurgiMend in women undergoing breast reconstruction after failed lumpectomy and radiation.3 This TEI trial, which was registered in September 2013, was not supposed to begin until January 2014 and will not be completed until June 2019.4
Ethics approval
Where’s the beef?
The author has no financial interest in any of the products discussed.
The sponsored plastic surgeon presented some individual patients’ results. While he did show some of his own abdominal hernia patients, he readily acknowledged that the majority of the breast patients that he showed were from other surgeons. The “Procedure Guide” that was provided to each dinner guest had many of the same photos as the presentation with the longest follow-up being 8 months. I was reminded of “Where’s the beef?” the 1980’s catchphrase used to signify the factual deficiencies of a product’s or politician’s claims.5 On this night, the beef was being presented on a plate and the only substantive data being presented was on sheep. In 2007, FDA legislation was revised and several major changes were enacted.6 Drug and device manufacturers were required to register trials within a certain time period and post updated results at clinicaltrials.gov, otherwise they could face substantial financial penalties.7 Table 1 shows all relevant studies that I could locate at clinical trials.gov. Note the dearth of data; the only study with data is NCT01256502, a post-marketing study in breast reconstruction whose primary outcome measurement was surgeon satisfaction and secondary outcome measurement was ease of use, not patient satisfaction.8 The other studies, including those measuring explantation post-reconstruction and recurrent ptosis, will not be completed for years. Yet, the indications that the FDA approved and for which the manufacturer sells the product are:
Financial disclosure
“Use as a transitory scaffold for soft tissue support and repair to reinforce deficiencies where weakness or voids exist that require the addition of material to obtain the desired surgical outcome. This includes reinforcement of soft tissue in plastic and reconstructive surgery, and general soft tissue reconstruction”.9 Until clinical trial results are available, I believe that we should remember the saying about the feasibility of making silk purses out of sows ears.
Not required.
Competing interests
The author believes that the manufacturer of the silkmoth product subsidized the cost of the Miami Society of Plastic Surgeons dinner, which he attended.
References 1. http://www.fda.gov/medicaldevices/productsandmedical procedures/deviceapprovalsandclearances/510kclearances/ default.htm [accessed 19.06.14]. 2. http://www.accessdata.fda.gov/cdrh_docs/pdf12/K123128. pdf p. 2 [accessed 19.06.14]. 3. http://www.teibio.com/news-releases/tei-biosciencesgranted-fda-approval-to-initiate-a-human-clinical-trial-withsurgimend-prs-in-patients-undergoing-breast-reconstructionfollowing-mastectomy/ [accessed 19.06.14]. 4. http://clinicaltrials.gov/ct2/show/record/NCT01959867 [accessed 19.06.14]. 5. http://en.wikipedia.org/wiki/Where’s_the_beef%3F [accessed 19.06.14]. 6. http://www.gpo.gov/fdsys/pkg/PLAW-110publ85/pdf/PLAW110publ85.pdf#pageZ82 [accessed 19.06.14]. 7. http://clinicaltrials.gov/ct2/manage-recs/ fdaaa#AreTherePenalties [accessed 19.06.14]. 8. http://clinicaltrials.gov/ct2/show/results/NCT01256502? sectZX01256 [accessed 19.06.14]. 9. http://www.accessdata.fda.gov/cdrh_docs/pdf12/K123128. pdf p. 4 [accessed 19.06.14].
M. Felix Freshwater Voluntary Professor of Surgery, University of Miami School of Medicine, 9155 S. Dadeland Blvd, Suite 1404, Miami, FL 33156-2739, USA E-mail address: [email protected] 20 June 2014
