Submission to the Senate Community Affairs Committee: Number of Women in Australia Who Have Had Transvaginal Mesh Implants and Related Matters

Johnson & Johnson Medical Pty Ltd

Submission to the Senate Community Affairs Committee: Number of women in Australia who have had transvaginal mesh implants and related matters

May 2017

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Introductory comments

Johnson & Johnson Medical Pty Ltd (JJM) appreciates the opportunity to contribute to the inquiry into transvaginal mesh implants in Australia. JJM provides a range of innovative medical devices and solutions used primarily by healthcare professionals in the fields of orthopaedics, neurological disease, surgery and surgical instruments, diabetes, infection prevention, diagnostics, cardiovascular disease, and aesthetics. We are the largest medical technology provider in Australia working across public and private sectors.

We empathise with all women suffering from stress urinary incontinence and pelvic organ prolapse, conditions that can be serious and debilitating, and we are always concerned when a patient believes they have experienced an unexpected or undesirable outcome. While treatment options with varying degrees of efficacy exist for these conditions, surgical treatment for stress urinary incontinence and pelvic organ prolapse remains an important option. The use of implantable mesh is supported by clinical research and is often the preferred option to treat certain female pelvic conditions, including stress urinary incontinence and pelvic organ prolapse.

There is presently a representative action in the Federal Court that has been brought against JJM and two affiliated companies. The Federal Court has allocated 24 weeks to hear the matter, commencing on 4 July 2017. The factual and legal issues raised in those proceedings are comprehensive and complex. Some 35 national and international experts across a range of medical and scientific disciplines are expected to give evidence at trial. A number of the matters and issues which this Committee will consider and report upon through this Inquiry directly relate to matters and issues that will be fully heard and determined by the Federal Court in those proceedings.

While JJM respects the decision of the applicants (and the group members they represent) to bring legal proceedings such as these, JJM is defending the claims that have been made and will continue to do so. Having regard to the jurisdiction of the Federal Court and its powers in relation to both the proceedings and the litigants (and the imminent commencement of that matter), JJM will not make submissions on matters regarding the specific issues in contention in the litigation. While we recognise that the Senate has an important role to play in exploring issues that impact the Australian community and constituencies, the Federal Court is the forum chosen by the applicants to hear and determine these matters and we respect that decision.

To assist the Committee, we have provided background to the conditions treated by mesh medical devices and some history of the development of those medical devices. We have also provided submissions in response to the Terms of Reference (to the extent possible, having regard to the Federal Court litigation).

Background to the conditions and medical devices

Pelvic mesh medical devices were developed in conjunction with surgeons seeking to address the shortcomings of other treatment options for stress urinary incontinence and pelvic organ prolapse, and they have helped a significant number of women worldwide suffering from these conditions.

While the terms of reference refer to “transvaginal mesh”, this term requires some definition and explanation to understand the medical conditions being treated and the devices that are treatment options. As we interpret the terms of reference, the Committee is concerned with mesh medical devices used to treat two separate and distinct medical conditions – stress urinary incontinence and pelvic organ prolapse. While medical devices comprising polypropylene mesh (in various forms and structures) are an option used to surgically treat the conditions, the surgical approach to implantation may vary – such that surgery may be conducted where the devices are implanted in one of two ways depending on surgeon choice. Implantation may be accomplished through an incision in the vaginal wall (that is, a “transvaginal” implantation) or through an incision in the abdomen (that is, either a “laparoscopic” or an “open” (laparotomy) implantation).

JJM was the sponsor and distributor of a number of medical devices which can be used to treat stress urinary incontinence and pelvic organ prolapse, and those devices were (at various times) indicated for use using a transvaginal surgical technique. In broad terms, JJM supplied a family of medical devices known as “TVT” to the Australian market for stress urinary incontinence, and “Gynemesh PS”, “Prolift”, "Prolift+M" and “Prosima” branded medical devices to the Australian market for the treatment of pelvic organ prolapse. The TVT medical devices were first supplied in Europe pursuant to CE marking (that is, compliance with European Directive 93/68/EEC) in 1997, were cleared by the US Food and Drug Administration in 1998 and supplied in Australia in 1999 (in compliance with Australian regulations at the time). The Gynemesh PS, Prolift, Prolift+M and Prosima medical devices were also supplied in Europe and the US (in compliance with their regulations) before supply in Australia (again, in compliance with Australian regulations) in 2003, 2005, 2009 and 2010 respectively.

Where we refer in this submission to JJM “tape” devices, we are referring to the TVT medical devices used for the treatment of stress urinary incontinence and where we refer to JJM “mesh” devices, we are referring to Gynemesh PS, Prolift, Prolift+M and Prosima medical devices used for the treatment of pelvic organ prolapse.

Stress urinary incontinence

Stress urinary incontinence (SUI) is an increasingly prevalent condition among women and has an adverse impact on health-related quality of life. Although estimates vary, a recent population study estimated the prevalence of SUI in women to be 26 %, with prevalence of SUI increasing with age.1 Estimates indicate that the number of procedures for SUI may increase by approximately 50% from 210,700 in 2010 to 310,050 by 2050.2

1 Reynolds WS, Dmochowski RR, Penson DF. Epidemiology of stress urinary incontinence in women. Curr Urol Rep. 2011;12(5): 370-6. 2 Wu JM et aL Predicting the number of women who will undergo incontinence and prolapse surgery, 2010 to 2050. AFT1 J Obstet GynecoL 2011;205(3):230 el-5

The current gold standard for surgical management of SUI is the synthetic mid-urethral sling.3 Since its introduction in 1995, the synthetic midurethral sling has increasingly become the preferred surgical treatment for SUI, with a resultant decrease in autologous slings, laparoscopic or open Burch colposuspensions, and collagen injections.4

The discovery of tension-free vaginal tape (TVT) began in 1986 with two unrelated observations: pressure applied unilaterally at the mid-urethra controlled urine loss on coughing; and implanted Teflon tape caused a collagenous tissue reaction.

This led to a paradigm shift of understanding of the mechanism of stress incontinence. The theory was put into practice by a team led by Professor Ulf Ulmsten by developing a new minimally invasive, ambulatory, standardized surgical procedure to be named tension-free vaginal tape (TVT) at the time of its launch in Europe at the end of 1997, in the USA at the end of 1998 and in Australia at the end of 1999.

Several modifications of the procedure were tested using Gore-Tex, Mersilene and Nylon meshes before arriving at the final one, which included the use of Ethicon's monofilament polypropylene Prolene tape. Gore-Tex, Mersilene and Nylon meshes had complication rates that were higher than Prolene polypropylene mesh.

Once the TVT procedure was finalized the first prospective clinical trial was conducted at the Department of Obstetrics and Gynecology of the University Hospital of Uppsala, Sweden, of which Professor Ulmsten was the chairman. The trial included 75 primary cases of stress urinary incontinence that were followed for 24 months. The results, published in 1996, were very encouraging and prompted further prospective clinical trials conducted in normal clinical settings.

A multicenter trial including six clinics in Finland and Sweden enrolled 130 primary cases of stress incontinence that were followed for a minimum of 12 months showed the same high rate of success as Professor Ulmsten's initial clinical study. This prospective multicenter study was published in 1998. This multicenter study demonstrated that trained gynecologists achieved the same high cure rates and low complication rates as found in the original training centers, and were consistent with Professor Ulmsten's results. Two independent studies with a 3-year follow-up were published in 1999, revealing the same high success rates as the earlier studies.

By 2001, results of trials with a follow-up of four years in women suffering from recurrent stress incontinence, intrinsic sphincter deficiency, and mixed urinary incontinence were published. TVT was initially recommended as a primary surgery for genuine stress incontinence; however, it was quickly used and adopted by many surgeons in primary cases and more complicated cases, such as recurrences after traditional anti-incontinence surgery. Also in 2001, the five-year follow-up results of TVT were published showing an overall cure rate of 85%.

3 Cox A, Herschom S, Lee L. Surgical management of female SUI: is there a gold standard? Nat Rev Urol. 2013;10(2):78-89. 4 4 Anger JT et al. Trends in surgical management of stress urinary incontinence among female Medicare beneficiaries. Urology. 2009;74(2):283-7. Cox A, Herschom S, Lee L. Surgical management of female SUI: is there a gold standard? Nat Rev Urol. 2013;10(2):78-89. Rogo-Gupta L et al. Trends in the surgical management of stress urinary incontinence among female Medicare beneficiaries, 2002-2007. Urology. 2013;82(1):38-41.

In 2013, results were published of a 17-year follow-up of the performance of the TVT procedure, which showed that no significant decline in cure rate had developed throughout the years and that no late onset problems occur with the Prolene polypropylene tape.5 These results have been achieved and published in hundreds of clinical studies, including more than ten studies reporting results after follow- up at 10 years or longer.

The minimal invasiveness of the TVT procedure and the idea of performing the operation under-local anaesthesia were aimed at reducing the risk of complications. Utilising local anaesthesia allowed an intra-operative cough stress test to be performed, the purpose of which was explicitly to avoid postoperative voiding problems seen with traditional incontinence procedures.

Training was thought to be important to the success of performance of the operation, and the procedure was therefore carefully standardised to facilitate training.

The US FDA cleared the first synthetic mesh for SUI in 1996, but the use of slings was not widespread until the introduction of the tension-free vaginal tape (TVT) by Ethicon (Gynecare) in 1998. Ethicon's TVT revolutionised the fields of urology and urogynecology, allowing for a minimally invasive, outpatient procedure to treat stress incontinence.

Professional societies across the world have issued statements in support of synthetic midurethral slings as the first-line treatment of choice and gold standard repair for stress urinary incontinence. The American Urological Association (AUA) released a position statement in 2011, which was revised in 2013, strongly supporting the MUS, noting that mesh slings have similar efficacy but lower morbidity than conventional non-mesh approaches and that "any restriction of the use of synthetic polypropylene MUS would be a disservice to women who choose surgical correction of SUI". The AUA described synthetic midurethral polypropylene slings as "the most common surgery currently performed for SUI" The AUA described the advantages of midurethral slings to include: "shorter operative time/anesthetic need, reduced surgical pain, reduced hospitaliation, and reduced voiding dysfunction." Importantly, the AUA noted that "[m]esh-related complications can occur following polypropylene sling placement, but the rate of these complications is acceptably low. Furthermore, it is important to recognize that many sling-related complications are not unique to mesh surgeries and are known to occur with non-mesh sling procedures as well."

In 2012, the European Association of Urology (EAU) published its guidelines on the surgical treatment of urinary incontinence and described the synthetic polypropylene midurethral sling (MUS) as the first-line treatment for stress urinary incontinence. The EAU further noted that "[t]here has been a rapid adoption of midurethral synthetic sling insertion as the first-line surgical option for SUI because it is effective, it is less invasive, and patients recover more quickly."

Shortly thereafter, in 2013, the National Institute for Health and Care Excellence (NICE) issued a clinical guidance document on the management of urinary incontinence in women. NICE recommended offering either synthetic mid-urethral tape, open colposuspension, or autologous rectus fascial sling for women with stress urinary incontinence who have failed conservative treatment. The NICE clinical guideline recommended that when using a midurethral slings, surgeons use a device for which there is current high quality evidence of efficacy and safety: and in this respect, specifically listed two of the medical

5 Nilsson, C.G, Palva, K, Aarnio, R, Morcos, E, Falconer, C. Seventeen years’ follow-up of the tension-free vaginal tape procedure for female stress urinary incontinence. Int Urogynecol J: 2013

6 devices distributed by JJM – being TVT (for a retropubic surgical approach) and TVT-O (for a transobturator surgical approach).

In 2014, to provide clarity about the safety and efficacy of the midurethral polypropylene sling (MUS), a number of professional societies released statements. The American Urogynecologic Society (AUGS) and The Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) released a joint position statement, strongly reaffirming their support for the use of multi-incision synthetic midurethral sling, noting:

"...We are concerned that the multimedia attention has resulted in confusion, fear, and an unbalanced negative perception regarding the MUS as a treatment for SUI. This negative perception of the MUS is not shared by the medical community and the overwhelming majority of women who have been satisfied with their MUS ...any restriction of mesh slings for the treatment of SUI is clearly not supported by any professional organization or the FDA."

AUGS and SUFU listed four main points supported by citations to demonstrate their support for synthetic midurethral slings:

"(1) Polypropylene material is safe and effective as a surgical implant; (2) The monofilament polypropylene mesh MUS is the most extensively studied anti-incontinence procedure in history; (3) Polypropylene mesh midurethral slings are the standard of care for the surgical treatment of SUI and represent a great advance in the treatment of this condition for our patients; and (4) The FDA has clearly stated that the polypropylene MUS is safe and effective in the treatment of SUI."

The position statement also describes how more than three million midurethral slings have been placed worldwide, and a recent study indicates that more than 99% of AUGS members perform midurethral sling procedures. They also note that "there are greater than 2000 publications in the scientific literature describing the MUS in the treatment of SUI."

AUGS and SUFU concluded the position statement with the following:

"The polypropylene midurethral sling has helped millions of women with SUI regain control of their lives by undergoing a simple outpatient procedure that allows them to return to daily life very quickly. With its acknowledged safety and efficacy it has created an environment for a much larger number of women to have access to treatment. In the past, concerns over failure and invasiveness of surgery caused a substantial percent of incontinent women to live without treatment. One of the unintended consequences of this polypropylene mesh controversy has been to keep women from receiving any treatment for SUI. This procedure is probably the most important advancement in the treatment of stress urinary incontinence in the last 50 years and has the full support of our organizations which are dedicated to improving the lives of women with urinary incontinence."

Several other professional societies and organizations endorsed the AUGS/SUFU Position Statement on Mesh Midurethral Slings in 2016, including The American Association of Gynecological Laparoscopists (AAGL), The American College of Obstetricians and Gynecologists (ACOG), The National Association for Continence (NAFC), The Society of Gynecologic Surgeons (SGS), and Women's Health Foundation (WHF).

Similarly, in 2014, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) and the Urogynaecological Society of Australasia (UGSA) issued a position statement

7 supporting the use of synthetic midurethral slings for the treatment of stress urinary incontinence. RANZCOG and UGSA described how midurethral slings:

"have been shown to be as effective as more invasive traditional surgery with major advantages of shorter operating and admission times, and a quicker return to normal activities, together with lower rates of complications. This has resulted in MUS becoming the operation of choice in Europe, the United Kingdom, Australasia and the USA for treatment of SUI."

The common theme in these responses is the recognition of the public’s confusion about type, uses, and safety concerns associated with mesh for pelvic organ prolapse and mesh for SUI. Despite the noted confusion, all of these societies strongly recommended the first-generation MUS as best practice for the treatment of SUI.

In 2015, the European Commission issued the SCENIHR Report evaluating the safety of surgical meshes used in urogynecological surgery and found that "use of a synthetic mesh (called a `tape') is currently considered the standard of care" for the treatment of stress urinary incontinence. Similarly, the Medicines and Healthcare products Regulatory Agency (MHRA) based in the United Kingdom concluded in 2014 that "the overall benefit outweighs the relatively low rate of complications" associated with synthetic midurethral slings for the treatment of stress urinary incontinence.

Also in 2015, The American College of Obstetricians and Gynecologists (ACOG) and American Urogynecologic Society (AUGS) issued a clinical management guideline for the management of urinary incontinence in women. They assigned the highest level of evidence to the conclusion and recommendation for the following:

"Synthetic midurethral slings demonstrate efficacy that is similar to traditional suburethral fascial slings, open colposuspension, and laparoscopic colposuspension. Compared with suburethral fascial slings, fewer adverse events have been reported with synthetic midurethral slings. Voiding dysfunction is more common with open colposuspension than with synthetic midurethral slings. There are substantial safety and efficacy data that support the role of synthetic mesh midurethral slings as a primary surgical treatment option for stress urinary incontinence in women."

Attached as Appendix 1 are links to the statements referenced above (that are publicly accessible).

Pelvic organ prolapse

Pelvic organ prolapse occurs when the muscles, fascial and tendinous tissue in the female pelvis can no longer fully support various abdominal organs, like the bladder, rectum, and uterus. As a result, the organs descend, or prolapse.

There are different types of prolapse. A prolapse may arise in the front wall of the vagina (anterior wall prolapse), back wall of the vagina (posterior wall prolapse), the uterus or top of the vagina (apical or uterine prolapse). Many women have a prolapse in more than one compartment at the same time.

Millions of women worldwide experience pelvic organ prolapse. Treatment options for prolapse depend upon a number of factors, including the severity of the condition and patient's desires. Sometimes non- surgical treatment options are appropriate. Other times surgical treatment options are necessary.

Prolapse can be surgically repaired either through the abdomen or the vagina; using stitches to repair the body's own tissue (traditional surgery) or implants (including synthetic mesh) to add support to weakened tissues.

Initial surgical treatments developed involved native tissue repairs — using the woman's own tissue to bolster support of the descending organs with sutures. Native tissue repairs have high reported failure/recurrence rates frequently exceeding 30%, primarily because the surgeon attempting to repair tissue which has already been weakened or compromised.

In answer to these failure/recurrence rates of native tissue repair, surgeons developed operations that used mesh implanted with open abdominal surgery. The goal of a mesh implant is to reinforce natural tissue which has failed to support the pelvic organs, restoring support to the bladder, uterus or bowel and so preventing further bulging of these organs towards the vagina.

Different techniques are used to implant the graft and to keep it in place, some of which include fixation arms that exit through small incisions at the inner thigh and/or the buttocks or special anchors that fixate the mesh to firm structures in the pelvis (such as the sacrospinous ligament). If synthetic mesh is used, tissue grows through the pores in the graft and the mesh becomes fully incorporated.

By 2005, surgeons had several surgical options available to them for treating pelvic organ prolapse. They could surgically repair the condition via an incision in the abdomen or the vagina; they could use mesh with either approach, or no mesh, or perform combination procedures.

In October 20086, the US Food and Drug Administration (FDA), after reviewing complaints made to the agency in the USA, issued a statement regarding vaginal mesh. They recommended that surgeons should undertake specialized further training before attempting vaginal mesh repairs and that they should notify patients that mesh is a permanent implant and 'complications can occur which may not resolve even with further corrective surgery. However, they still considered these serious complications "rare".

In July 20117, the FDA update stated that adverse events with the use of vaginal mesh were no longer considered rare. The FDA conducted a literature search from 1996 to 2010 comparing mesh surgeries to treat prolapse to non-mesh surgeries and concluded that there was no evidence that mesh provided any greater clinical benefit than non-mesh surgeries, with the exception that there was some evidence of greater efficacy with the use of mesh in the anterior compartment (bladder prolapse). The FDA recommended that all patients be advised that convincing long term data on the safety of mesh was limited and that all alternatives to the use of mesh should be also discussed in detail with patients prior to its use.

Systematic reviews, meta-analyses, and clinical studies continue to demonstrate that there is no difference in quality of life or de novo dyspareunia when comparing outcomes after traditional prolapse procedures to prolapse procedures utilising mesh.8

6 See https://www.fda.gov/medicaldevices/safety/alertsandnotices/ucm262435.htm 7 https://www.fda.gov/medicaldevices/safety/alertsandnotices/ucm262435.htm 8 See Svabik, K, Martan, A, Masata, J, El-Haddad, R and Hubka, P. Comparison of vaginal mesh repair with sacrospinous vaginal colpopexy in the management of vaginal vault prolapse after hysterectomy in patients with

Lowman JK, Jones LA, Woodman PJ, et al. Does the Prolift system cause dyspareunia? Am J Obstet Gynecol 2008;199:707.e1-707.e6.910

The International Urogynecological Association (IUGA) published a patient brochure in 2011 describing the success rate for vaginal mesh repairs as 80% to 95%. IUGA describes chronic vaginal pain and painful intercourse as having a low incidence, noting that these complications can occur following both mesh surgery and traditional surgery.

In 2011, The American College of Obstetricians and Gynecologists (ACOG) issued a Committee Opinion on the Vaginal Placement of Synthetic Mesh for Pelvic Organ Prolapse and concluded that many patients undergoing mesh-augmented vaginal repairs heal well without problems, but there is a small but significant group of patients who experience permanent and life-altering conditions, including pain and dyspareunia, from the use of vaginal mesh.

In 2013, The Royal Australian and New Zealand College of Obstetricians and Gynaecologists and (RANZCOG) and the Urogyneaecological Society of Australasia (UGSA) issued a statement on the use of polypropylene vaginal mesh implants for vaginal prolapse. They noted that the introduction of vaginal mesh augmented repairs was driven by a pervasive perception that conventional native tissue repairs had unacceptably high anatomical failure rates in the short to medium term. RANZCOG and UGSA discussed the importance of surgeon training and noted that experienced surgeons have fewer complications than those with less experience.

The American Urogynecologic Society (AUGS) also issued a position statement on prolapse mesh in 2013. The AUGS statement determined that: "Restrictions that prohibit the use of synthetic mesh in the treatment of prolapse or incontinence do not represent the findings of the FDA investigation," and that levator ani avulsion: a randomized controlled trial. Ultrasound Obstet Gynecol. 2014:1-7; Dandolu, V, Pathak, P. Mesh complications in US after transvaginal mesh repair surgery versus abdominal or laparascopic sacrocolpopexy. Int Urogynecol J. 2015: 26 (Suppl 1):S23–S174; Singh, R, Cornish, A, Carey M.P. Native tissues repair versus mesh for trans-vaginal prolapse surgery: 5 year follow-up RCT. Int Urogynecol J. 2014: 25 (Suppl 1):S1–S240

9 “ASC” means abdominal sacral colpopexy, “SSLF” means sacrospinous ligament fixation, “USS” means uterosacral ligament vault suspension, “APR” means anterior colporrhaphy. 10 Handa, V.L. et.al. Sexual Function Before and After Sacrocolpopexy for Pelvic Organ Prolapse. Am J Obstet Gynecol. 2007 December: 197(6): 629.e1–629.e6; Maher, C. et.al Surgical Management of Pelvic Organ Prolapse in Women: A Short Version Cochrane Review. Neurourology and Urodynamics. 2008: 27:3–12; Silva, W.A. et.al. Uterosacral Ligament Vault Suspension Five Year Outcomes. Obstetrics & Gynecology.2006: Vol 108, No.2: 255- 263; Weber, A.M, Walters, M.D, Piedmonte, M.R. Sexual function and vaginal anatomy in women before and after surgery for pelvic organ prolapse and urinary incontinence. Am J Obstet Gynecol.2000: 182: 1610-5.

"[n]either the FDA Advisory Panel, the NIH, the American College of Ob/Gyn (ACOG), nor AUGS has recommended removing any mesh products from the market or withholding them from surgeon use. They further found that "No one approach has proven to be superior in all cases and it is particularly essential that specialists who regularly treat advanced and/or recurrent prolapse are able to maintain a complete set of treatment options in order to provide the most effective and individualized care." They also determined that "in some circumstances transvaginal mesh for pelvic organ prolapse may be the most appropriate surgical option."

Attached as Appendix 2 are links to the statements referenced above (that are publicly accessible).

Terms of reference submissions

Terms of Reference 1:

The number of women in Australia: a. who have had transvaginal mesh implants; b. who have had transvaginal mesh implants who have experienced adverse side effects; and c. who have made attempts to have the mesh removed in Australia or elsewhere.

In the table below, we have provided data on the supply of tape and mesh medical devices JJM has made into the Australian market up to April 2017, and the number of product events that have been recorded in our management system (for Australia and New Zealand). However, we are not able to detail the total number of women that have had transvaginal mesh implants, the number who have experienced adverse side effects nor the number who have made attempts to have transvaginal mesh removed (in Australia or elsewhere). We do not hold or have access to data for all devices distributed in this market - only those devices for which we are the sponsor and that we have distributed. We do not hold or have access to data concerning complications or their treatment for patients. As the sponsor for medical devices, we do have responsibility to ensure that each device continues to meet all of the safety and performance criteria that were required for the approval and we do record potential product events for the devices for which we are the sponsor. We have included the data we hold in this respect below.

The sales data below has been extracted from several sources, including retired data systems. We should also note that while the sales data does represent JJM's medical devices which would be in the market, it does not follow that each medical device represents a single (or any) surgical use. It is possible that more than one device was used in any given surgery, and it is possible that no device at all was used (for example, it may have been opened and during the surgery a decision was made to take an alternative approach to treatment or an alternative device was used).

In relation to the final column “Total reported events”, we note that for our recording purposes an “event” may be a product complaint, or a safety or adverse event. Such events are reported to JJM primarily through four sources:

1 Field based employees 2 Patients

3 Healthcare Practitioners 4 Health Authority (TGA)

A product event is reported by our employees when they become aware of an actual or suspected deficiency related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is released for distribution. As a consequence, an “event” does not automatically correlate to an “adverse side effect” or even a potential adverse event or adverse event. For instance, an “event” may be damaged packaging for the device, or it may be a report of an expiry date issue. It should also be noted that an “adverse event” for the purposes of the regulations is not necessarily an “adverse side effect” which is the term used in the terms of reference.

Most product events for JJM’s relevant mesh and tape medical devices are received from either field based employees or healthcare practitioners. It is not common for patients to report product events directly to JJM. All product events, irrespective of their origin, are included in our management system.

JJM’s product event reporting procedure and processes are a part of the Johnson & Johnson global medical safety and quality management systems and ensure that JJM is able to meet its continuing obligations for post-market vigilance for medical devices for which it is the sponsor.

Product Medical devices Dates of supply Total Australian Total reported group sales product events (Australia and New Zealand)

Tape TVT Tension-free Vaginal Tape October 1999 - 81,356 129 System, TVT OBTURATOR, TVT current ABBREVO, TVT EXACT, TVT SECUR

Mesh PROLIFT*, PROLIFT+M*, July 2003-current 22,086 52 PROSIMA*, GYNEMESH PS

*Prolift, Prolift +M and Prosima decommercialised in August 2012

Of the 181 product events, we note that 67 product events which JJM assessed were reportable to the TGA and Medsafe pursuant to the requirements of those regulators: 41 of these were related to tape medical devices, and 26 were related to mesh medical devices.

Terms of Reference 2:

Information provided to women prior to surgery about possible complications and side effects.

Information provided to patients by their surgeon in relation to the medical devices and the procedure forms the basis for informed consent and, by its nature, is confidential between each patient and their health care practitioner. As a result, JJM is not in a position to comment on this aspect.

JJM produced material and made it available to surgeons interested in or contemplating using the medical devices, should they wish to avail themselves of such material. As is standard for medical devices, this information was not generally or publicly available but instead, made available directly to surgeons.

We have attached to this submission as Appendix 3 patient facing materials prepared by the International Urogynecological Association:

 “Mid-Urethral Sling (MUS) Procedures for Stress Incontinence”  “Pelvic Organ Prolapse”  “Vaginal Repair with Mesh”

We note each of these patient facing leaflets has a section titled “How successful is surgery?” and in the case of “Vaginal Repair with Mesh” and “Mid-Urethral Sling (MUS) Procedures for Stress Incontinence” have sections titled “What complications can happen?”

We note that this term of reference is a matter which is in contention in the litigation that will be fully heard and determined by the Federal Court, and as such, JJM does not make any further submission.

Terms of Reference 3:

Information provided to doctors regarding transvaginal mesh implants and possible complications and side effects

The information provided to surgeons concerning the devices, possible complications and side effects are matters which are in contention in the litigation. As we note above, we will respect that process.

To assist the Committee, we have attached representative versions of the instructions for use for JJM’s tape medical devices and mesh medical devices at Appendix 4. Similar instructions for use accompanied each medical device at the time of supply. We draw your particular attention to the sections titled: “Contraindications”, “Warnings”, “Precautions” and “Adverse Reactions”.

Terms of Reference 4:

Any financial or other incentives provided to medical practitioners to use or promote transvaginal mesh implants

JJM complies with a company-wide, internal International Health Care Business Integrity Guide (the Guide) that contains standards for compliance with a number of legal regimes. It is intended to supplement national and international legislation and applicable industry codes. Where local laws or regulations or codes of conduct to which we ascribe are more stringent or specific than the provisions of the Guide, the stricter standards apply and must always take precedence.

The Guide sets out how JJM interacts with healthcare professionals (HCPs) including the following principles:

 When engaging a HCP to act on behalf of the company, the services paid for by the JJM must fill a legitimate, documented business need and such services must be obtained from individuals who possess demonstrable special knowledge or capabilities to perform the services;

 These services must be properly documented in a written agreement, and that agreement must specify the complete compensation arrangements. Compensation paid must be fair market value for the services provided. JJM must document how fair market value was determined;

 Performance of services received must be documented and invoices from service providers must have sufficient detail to enable proper recordkeeping; and

 The agreement must contain a representation and warranty by the HCP that, in the event the HCP is or attains a position to influence purchasing decisions by a government entity or the HCP’s employer, the HCP shall notify the purchase decision-maker of the HCP’s financial relationship with JJM and otherwise comply with applicable requirements of local law. In such circumstances, the agreement will also permit JJM to terminate the agreement

The Guide also sets out the requirements for arrangements under a Product Development Agreement or a licence for intellectual property rights. Again, such arrangements must be properly documented in a written contract that includes the complete compensation arrangements with the HCP. In addition, if royalties are to be paid, the HCP’s contribution to the development of the product at issue must be documented. Further, the Guide requires that purchases by the applicable HCP be excluded in the calculation of appropriate royalties to avoid the potential for improper influence.

In addition to the requirements of the Guide, JJM expects the surgeons with whom it interacts to abide by their professional standards of conduct and ethics, including:

 The Australian Medical Council Good Medical Practice: A Code of Conduct for Doctors in Australia (the AMC Code) which applies to all doctors nationally registered within Australia.

Section 8.11 sets out the requirements of a doctor to adhere to when a conflict of interest arises which may affect their care of a patient.11

 The Royal Australasian College of Surgeons (RACS) has a Code of Conduct, which defines the standards of professional behaviour applicable to surgeons who are fellows of RACS. Section 8.1(4) specifies that surgeons will be honest and transparent with respect to any potential conflicts of interest.12

In complying with the Guide, JJM has not provided any financial or other incentive to medical practitioners to use or promote transvaginal mesh implants.

Terms of Reference 5:

The types and incidence of health problems experienced by women with transvaginal mesh implants and the impact these health problems have had on women’s lives

We empathise with all women suffering from stress urinary incontinence and pelvic organ prolapse, and we are always concerned when a patient believes they have experienced an unexpected or undesirable outcome. However, JJM is not able to make a submission to this term of reference: the type and incidence of any health problems, and their impact, are matters which we anticipate would be best dealt with through submissions from the relevant surgical and medical colleges and patients themselves.

Terms of Reference 6:

The Therapeutic Goods Association’s: a. role in investigating the suitability of the implants for use in Australia;

b. role in ongoing monitoring of the suitability of the implants; and

c. knowledge of women suffering with health problems after having transvaginal mesh implants.

While JJM is not able to answer as to the state of knowledge of the Therapeutic Goods Administration (term of reference (c)), we have made numerous submissions concerning the current regulatory regime for medical devices in Australia. Attached as Appendix 5 are papers prepared by JJM (or its affiliated companies) in response to the following consultations (since 2015):

 Expert Review of Medicines and Medical Devices Regulation (2015)  Consultation: Draft clinical evidence guidelines - Medical devices | Therapeutic Goods Administration (TGA) (2016)  The regulatory framework for advertising therapeutic goods (2016)  Designation of Australian conformity assessment bodies for medical devices (2016)

11 The AMC Code can be found at: http://www.amc.org.au/images/Final_Code.pdf. 12 The RACS Code can be found at: http://www.surgeons.org/media/30110/pos_2011_02_24_code_of_conduct_2011.pdf.

We would encourage the Committee to consider the detail of those submissions with regard to the role of the Therapeutic Goods Administration.

The role of the Therapeutic Goods Administration is to ensure the quality, safety and performance of medical devices supplied in Australia and is based on a benefit/risk management approach designed to ensure public health and safety. We endorse this role for the Therapeutic Goods Administration and acknowledge their on‐going work in this area.

In this section of our submission, we outline some of the key considerations for the Committee in relation to the role of Therapeutic Goods Administration in regulating medical devices, including the current regulatory practice and our recommendations.

Current Regulatory Practice

The current regulatory framework is based on a risk management approach directed toward higher risk devices and a robust post‐market surveillance system covering all devices. Johnson & Johnson Medical supports greater acceptance of third party conformity assessment and reduced TGA pre-market assessment for all classes of medical devices supplied in Australia. This approach builds upon the strengths of the TGA’s current regulatory structure and experience with accepting conformity assessment certificates from overseas Conformity Assessment Bodies (CAB’s) since the regulatory framework was implemented in 2002. It is also consistent with the TGA’s stated shift in emphasis from pre-market assessment to post-market surveillance and better focuses TGA’s resources to where they will have the most effective impact on public health. It remains consistent with the framework established by the GHTF and would continue to be harmonised with the European Medical Device Directive (MDD).

Recommendations

The position of JJM remains as noted in its January 2015 submission concerning the review of medicines and medical device regulations, being:

 The level of regulation should be commensurate with the risk posed by the regulated products, with the aim being to establish the minimum effective regulation. Disproportionate rigour impacts the costs of products or reduces access to innovation in this market that may already be available in other markets. Ultimately this will impact the Australian consumer and have a negative impact or unnecessary burden on the public health system.  A risk-benefit approach to the regulation of therapeutic goods is appropriate  The regulation of therapeutic goods should take a whole of lifecycle approach. As a result, the regulatory system must: o Have capacity to source and analyse data as it becomes available. o Recognise and respond in a timely way to changes in the risk profile of products across their lifecycle. o Provide for whole of life solutions, from product development to withdrawal/disinvestment o Be transparent and understood by all stakeholders, including manufacturers and sponsors of therapeutic goods, health professionals, and consumers.

 The ultimate responsibility for medical devices regulation should remain with the Commonwealth. o Australia should maintain its capacity to undertake assessments of medicines and medical devices for safety, quality, and efficacy. o The role of the regulator undertaking this assessment should be considered in light of approaches taken internationally.

Terms of Reference 7:

Options available to women to have transvaginal mesh removed

JJM is not able to make a submission to this term of reference. The treatment of pelvic organ prolapse and stress urinary incontinence, the use (or not) of medical devices to treat those conditions, the decision on surgical approach to implant a medical device (if used) and the options available to have such medical device removed (in whole or in part), are decisions made by individual patients with advice from their expert medical advisers.

Appendix 1: Links to professional societies and organizations’ statements relating to SUI

 American Urological Association (2011) https://www.auanet.org/guidelines/use-of- vaginal-mesh-for-the-surgical-treatment-of-stress-urinary-incontinence

 European Association of Urology (2012) https://uroweb.org/wp- content/uploads/Lucas-MG-et-al.-Eur-Urol-2012-6261118.-EAU-guidelines-on- surgical-treatment-of-urinary-incontinence..pdf

 the National Institute for Health and Care Excellence (2013) https://www.nice.org.uk/guidance/cg171

 The American Urogynecologic Society (AUGS) and The Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (2014) http://sufuorg.com/docs/news/augs-sufu-mus-position-statement.aspx

 American Urogynecologic Society (2014) https://www.augs.org/assets/1/6/AUGS- SUFU_MUS_Position_Statement.pdf

 The American Association of Gynecological Laparoscopists (2016) https://www.aagl.org/aaglnews/from-the-desk-of-the-aagl-president-2/

 The National Association for Continence (2016) https://www.nafc.org/bhealth- blog/2016/6/15/augs-sufu-sling-position?rq=midurethral%20sling

 Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) and the Urogynaecological Society of Australasia (UGSA) (March 2014) http://www.ugsa.org.au/data/Position_statement_on_midurethral_slings_C- Gyn_32_2.pdf

 European Commission Scientific Committee On Emerging And Newly Identified Health Risks, Final Opinion on the Safety of Surgical Meshes Used in Urogynecological Surgery (December 2015) http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_049.pdf

Appendix 2: Links to professional societies and organizations’ statements relating to POP

 The International Urogynecological Association (IUGA) published a patient brochure: http://c.ymcdn.com/sites/www.iuga.org/resource/resmgr/leaflet/Vaginal_Repair_with_Mesh .pdf

 The American College of Obstetricians and Gynecologists (2011): https://www.ncbi.nlm.nih.gov/pubmed/22105294

 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists and (RANZCOG) and the Urogyneaecological Society of Australasia (2013): https://www.ranzcog.edu.au/RANZCOG_SITE/media/DOCMAN-ARCHIVE/C- Gyn_20_Polypropylene_Vaginal_Mesh_Implants_for_Vaginal_Prolapse_Rewrite_UGSA%20Exec utive_Mar_13.pdf

 [Note that RNAZCOG has issued a 2016 statement https://www.ranzcog.edu.au/getattachment/Statements- Guidelines/Gynaecology/Polypropylene-Vaginal-Mesh-Implants-for-Vaginal- Pr/Polypropylene-vaginal-mesh-implants-for-vaginal-prolapse-(C-Gyn-20)-Review- November-2016.pdf?lang=en-AU&ext=.pdf ]

 American Urogynecologic Society (2013): https://www.augs.org/assets/1/6/Position_Statement_Surgical_Options_for_PFDs.pdf

Appendix 3 Patient facing materials prepared by the International Urogynecological Association

 “Mid-Urethral Sling (MUS) Procedures for Stress Incontinence”  “Pelvic Organ Prolapse”  “Vaginal Repair with Mesh”

the middle portion urethra and the skin of the vagina. The urethra is the pipe through which the bladder empties. Normally the muscle and ligaments, which support the urethra, close firmly when straining or exercising to prevent leakage. Damage or weakening of these structures by childbirth and/or the aging process can result in this mechanism failing, leading to urine leakage. Plac- Mid-Urethral Sling (MUS) ing a sling underneath the urethra improves the support and re- Procedures for Stress duces or stops leaking. Incontinence How are the operations done? There are three main routes for placing the sling: the retro-pubic A Guide for Women route, the transobturator route, and the “single incision” or “mini- sling”. There is no clear advantage of one over the other, except 1. What are midurethral slings? for some women with severe stress incontinence where the retro- 2. How are the operations done? pubic route appears to be more successful. Minislings are still in the initial phases of investigation. Although they are less invasive 3. How do they work? than the other methods they may not be quite as effective in con- 4. Do I need an anesthetic for the operation? trolling stress incontinence in the longer term, or in women with 5. When will I be able to go home after the operation? severe incontinence. During the retropubic operation the sling is placed through a 6. What are the chances of success of the operation? small cut made in the vagina over the mid-point of the urethra. 7. When can I return to my normal routine? Through this the two ends of the sling are passed from the va- 8. What complications can happen? gina, passing either side of the urethra to exit through two small cuts made just above the pubic bone in the hairline, about 4-6 cm 9. My bladder isn’t too bad at the moment, but should I apart. The surgeon will then use a camera (cystoscope) to check have an operation now to prevent it getting worse in that the sling is correctly positioned and not sitting within the bladder. The sling is then adjusted so that it sits loosely under- the future? neath the urethra and the vaginal cut stitched to cover the sling 10. I haven’t finished my family yet, can I still have a over. The ends of the sling are cut off and they too are covered MUS? over. The transobturator approach to the operation also requires a small 11. How will the operation affect my sex life? incision to be made in the vagina at the same place as for the 12. Is there anything else I can do instead of an retropubic operation. The ends of the sling are passed through operation? two small incisions made, this time, in the groin. Each end of the sling passes through the obturator foramen, which is a gap between the bones of the pelvis. The ends are cut off once the What are midurethral slings? sling is confirmed to be in the in the correct position and the skin Mid-urethral sling procedures are operations designed to help closed over them. women with stress incontinence. Stress incontinence is the The mini-sling procedure is similar to the initial part of retropu- leakage of urine with every day activities such as coughing, bic approach, except that the ends of the sling do not come out sneezing or exercise. It is a very common and embarrassing onto the skin and are anchored in position by one of a number of problem affecting up to 1 in 3 women. Stress incontinence may different fixation techniques. be cured or improved with pelvic floor exercises and lifestyle modifications, but if these strategies fail then surgery may be Figure 2: Retropubic Sling recommended for you. The most frequently offered type of operation is a mid-urethral sling procedure, a simple day case procedure that has been performed for more than 3 million women worldwide to date. The operation involves placing a sling of polypropylene mesh about 1cm wide (suture material that is woven together) between Figure 1: Normal Anatomy

uterus rectum

bladder vagina How do they work? The sling (or tape) prevents leakage by supporting the urethra and mimicking the ligaments that have been weakened by having babies and the aging process. Once the sling is in position your tissues grow through the holes in the weave and so anchor it in position. This may take 3 to 4 weeks.

IUGA Office | [email protected] | www.iuga.org ©2011, 2016 Do I need an anesthetic for the operation? The most common retropubic operation to be carried out is the Although it is possible to do the operations just with local anes- TVT (Tension-free Vaginal Tape). This is also the operation that thetic, most surgeons would supplement this with a strong seda- has been done for the longest time, and research suggests that if tive or, sometimes, a full general anesthetic. Occasionally, the it is initially successful in controlling stress incontinence then operation is done using a spinal or an epidural anesthetic, de- it is still likely to be working up to at least 17 years later. The pending on the preference of the patient, anesthetist and surgeon. other retropubic and transobturator procedures are likely to have similar long term success rates. When will I be able to go home after the operation? Most surgeons will allow patients to go home after a mid-urethral When can I return to my usual routine? sling operation once they are emptying their bladders efficiently You should be able to drive and be fit enough for usual daily activities within a week of surgery. We advise you to avoid Figure 3: Transobturator Sling heavy lifting and sport for 6 weeks to allow the wounds to heal and the sling to be firmly held in place.

What complications can happen? There is no completely “risk free” operation for stress incontinence. The three methods of placing the sling have their own specific risks (see below) but all can be complicated by: • Urinary tract infections – These are not uncommon after any procedure and should respond to antibiotics. Symptoms of a urinary tract infection include burning, stinging, the need to pass urine frequently and in some cases bloody, cloudy or offensive smelling urine. If you notice these symptoms contact your doctor. • Bleeding – Bleeding, sufficient to require a blood transfusion, is very rare. Sometimes bleeding can happen where the tape from a retropubic operation passes behind the pelvic bones. This is normally self-limiting and only very rarely needs an operation to fix. Figure 4: Mini-sling • Difficulty passing urine (voiding difficulty) – Some women have difficulty emptying their bladder following sling surgery; this is often because of swelling around the urethra or discomfort and will usually settle quickly (within a week). During this time your doctor may recommend a fine tube or catheter be used to drain the bladder. If your urine stream remains very slow or you cannot empty the bladder well even after the swelling has settled, your care provider will discuss other bladder possibilities, such as cutting or stretching the sling, with you. urethra • Sling exposure – Very occasionally the sling can appear in the wall of the vagina a few weeks, months or years after an operation. Your partner may notice a rough area during intercourse, or you may feel an un- mini-sling comfortable prickling sensation in the vagina. Occa- sionally there can be some blood-stained discharge. In this case, you should consult your surgeon who will be able to advise which method of resolving the situation is best. Usually this would involve either re-covering the tape or removing the section of tape that is exposed. and after any pain has been adequately controlled. Normally this The risks of this happening are about 1 in 100 after time will vary from a few hours to a couple of days, depending a retropubic operation or mini-sling and more slightly on the facilities available. frequent than this after a transobturator operation. What are the chances of success of the operation? • Bladder or urethral perforation – Bladder perforation Our research tells us that, in the short term, this operation is as occurs most often during a retropubic operation, whilst successful as any more invasive procedure used for controlling the urethra is most at risk of damage during a transob- stress incontinence, but with a quicker recovery and less chance turator procedure. Your surgeon will check for damage of needing surgery for prolapse in the first two years after the during the operation by looking inside the bladder and surgery. Between 80 - 90% of women are happy with their op- urethra using a special telescope (cystoscope). Remov- eration and feel that their incontinence is either cured or much ing and correctly relocating the needle to which the better. However, there are a small group of women for whom the sling is attached should resolve the situation. The blad- operation does not seem to work. The operation is less likely to der is normally then drained by a catheter for 24 hours be a success if you have had previous surgery to your bladder to allow the hole in the bladder to heal itself. Damage (such as a repair operation). to the urethra is more difficult to deal with, and should

IUGA Office | [email protected] | www.iuga.org ©2011, 2016 be discussed with your surgeon should it occur. Both urge incontinence worse whilst reducing weight can result are relatively rare, and bladder perforation, as long as it is in an improvement in incontinence symptoms. Maintaining recognized, does not affect the success of the operation. a good general health, quitting smoking, and having good • Urgency and urge incontinence - Women who have bad control of medical conditions such as asthma can also be stress incontinence often experience urgency and urge helpful. incontinence, the leakage of urine associated with the sensation of urgency. About 50% of women notice an For more advice and information check out our leaflet on stress improvement in urgency symptoms but for about 5% the urinary incontinence: http://c.ymcdn.com/sites/www.iuga.org/ symptoms may worsen following a MUS procedure. resource/resmgr/Brochures/eng_sui.pdf • Pain – Long term pain following sling surgery is unusual. Studies suggest that after the retropubic operation about 1 in 100 (1%) will develop vaginal or groin pain. Similar pain in the vagina or at the site of the cuts where the tape is put in can occur in as many as 1 in 10 women after a transobturator approach. In most cases pain is short lived and does not occur for more than 1 to 2 weeks. Rarely pain may not settle and removal of the sling is required.

My bladder isn’t too bad at the moment, but should I have an operation now to prevent it getting worse in the future? It is difficult to predict what will happen to your bladder in the future; doing regular pelvic floor exercises improves stress incontinence in up to 75% of women and may mean surgery is never required. You should have the operation only if you feel the stress incontinence is affecting the quality of your life now, not to prevent it deteriorating in the future.

I haven’t finished my family yet, can I still have a MUS? Many surgeons would want to avoid surgery until a woman’s family is complete because future pregnancy may compromise the results of the initial surgery.

How will the operation affect my sex life? We usually advise you to wait for 4 weeks after the operation before having sexual intercourse. In the long term there is no evidence that the operation will make any difference to your sex life. If you previously leaked urine during intercourse, the operation might make this better, but this is not always the case.

Is there anything else I can do instead of an operation? • Pelvic Floor Exercises (PFE). Pelvic floor exercises can be a very effective way of improving symptoms of stress urinary incontinence. Up to 75% of women show an improvement in leakage after PFE training. Like all training, the benefits of pelvic floor exercises are maximised if practice is carried out regularly over a period of time. Maximum benefit usually occurs after 3 to 6 months of regular exercising. You may be referred to a physical therapist (physiotherapist) specialising in teaching PFEs to supervise this. If you also have a problem with urge urinary incontinence your doctor may also advise bladder retraining exercises. http://c.ymcdn. com/sites/www.iuga.org/resource/resmgr/Brochures/eng_ btraining.pdf • Continence Devices. Continence devices are available which fit in the vagina and help control leakage. These can be inserted prior to exercise or, in the case of a vaginal pessary, can be worn continuously. Some women find inserting a large tampon prior to exercise may prevent or reduce leakage. These types of device are most suitable for women with more minor degrees of urinary incontinence or who are waiting definitive surgical treatment. • Lifestyle Changes. Being overweight can make stress and

The information contained in this brochure is intended to be used for educational purposes only. It is not intended to be used for the diagnosis or treatment of any specific medical condition, which should only be done by a qualified physician or other health care professional.

IUGA Office | [email protected] | www.iuga.org ©2011, 2016 • Some women may have an inherited risk for prolapse, while some diseases affect the strength of connective tissue, e.g. Marfan syndrome and Ehlers-Danlos syndrome

Pelvic Organ Prolapse Where can a prolapse occur? A prolapse may arise in the front wall of the vagina (anterior compartment), or back wall of the vagina (posterior compart- A Guide for Women ment), the uterus or top of the vagina (apical compartment). 1. What is pelvic organ prolapse? Normal anatomy, no prolapse 2. What causes pelvic organs to prolapse? 3. Where can a prolapse occur? 4. How bad is my prolapse? uterus rectum 5. How can pelvic organ prolapse be treated? 6. What surgical approach is right for me? 7. Is it necessary to use a graft material during the surgery? 8. How successful is surgery? bladder 9. What if I haven't completed my family? pelvic floor pubic bone muscle What is pelvic organ prolapse? This condition refers to the bulging or herniation of one or more pelvic organs into or out of the vagina. The pelvic organs consist of the uterus, vagina, bowel and bladder. Pelvic organ prolapse occurs when the muscles, ligaments and fascia (a network of supporting tissue) that hold these organs in their correct posi- tions become weakened. Symptoms include: Many women have a prolapse in more than one compartment at • a heavy dragging feeling in the vagina or lower back the same time. • feeling of a lump in the vagina or outside the vagina Prolapse of the Anterior Compartment • urinary symptoms such as slow urinary stream, a feeling This is the most common type of prolapse and involves the blad- of incomplete bladder emptying, urinary frequency or urgent desire to pass urine, and urinary stress incontinence Anterior compartment prolapse • bowel symptoms, such as difficulty moving the bowel or a feeling of not emptying properly, or needing to press on the vaginal wall to empty the bowel uterus rectum • discomfort during sexual intercourse

What causes pelvic organs to prolapse? The main cause is damage to the nerves, ligaments and muscles bladder which support the pelvic organs and may result from the following: • Pregnancy and childbirth are considered to be major factors leading to weakening of the vagina and its supports. Prolapse affects about one in three women who have had one or more children. A prolapse may occur during or shortly after a pregnancy or may take many years to develop. However, it is important to emphasize that only 1 out of 9 women (11%) will ever need surgery for prolapse in their lifetime. • Aging and menopause may cause further weakening of der and/or urethra bulging into the vagina. Your doctor may re- the pelvic floor structures. fer to it as cystocele or cysto-urethrocele. • Conditions that cause excessive pressure on the pelvic Prolapse of the Posterior Compartment floor like obesity, chronic cough, chronic constipation, This is when the lower part of the large bowel (rectum) bulges heavy lifting and straining into the back wall of the vagina (which your doctor may refer to as rectocele) and/or part of the small intestine bulges into the

IUGA Office | [email protected] | www.iuga.org ©2011, 2016 Posterior compartment prolapse Non-surgical Treatment Options • Do nothing: Prolapse is rarely a life-threatening condition and many women will choose not to have any treatment if they have no symptoms or discomfort. If you have been diagnosed with a prolapse, try to avoid heavy lifting, chronic straining e.g. with constipation, and gaining rectum excess weight as these can cause your prolapse to worsen. • Pessary: Pessaries are vaginal devices that come in various shapes and sizes. Pessaries help by providing mechanical support to the prolapsed organs, thus relieving symptoms. Pessaries are most suitable if you wish to delay or avoid surgery, e.g. if your family is not yet complete or if you have medical problems that will make surgery a risk. Pessaries require fitting by your health care provider and may require some trial and error before the most suitable

Ring Pessary upper part of the back wall of the vagina (which your doctor may refer to as enterocele). Prolapse of the Apical Compartment Uterine prolapse. This occurs when the uterus (womb) drops or uterus Uterine prolapse rectum

rectum bladder

bladder uterus

pubic bone size and type is found for you. It is possible to remain sexually active with some types of pessaries in situ. • Pelvic floor exercises (Kegel exercises): Exercising your weakened pelvic floor muscles may help improve or prevent the worsening of early stages of prolapse. Just as any exercise program, pelvic floor exercises require time, mo- tivation and proper technique. Please see the pelvic floor herniates into the vagina. This is the second most common form exercises leaflet for more information. of prolapse. Surgical Treatment Options Vaginal vault prolapse – following a hysterectomy, the top of the vagina may collapse downwards, (rather like the toe of a sock) For women with symptomatic prolapse, a surgical repair may turning inside out) falling towards or out of the vaginal opening. be offered. Your surgeon will recommend the most appropriate surgical treatment for you based on a number of factors including your age, previous surgical history, severity of prolapse and How bad is my prolapse? your general health. There are two main options: reconstructive Many women (up to 40%) have a minor degree of prolapse with surgery and vaginal closure surgery. minimal or no symptoms. Your physician will take a complete medical history and perform a vaginal examination to deter- • Reconstructive Surgical Repair: The purpose of pelvic mine prolapse severity and grade. Different physicians utilize reconstructive surgery is to restore your pelvic organs different grading systems and your doctor will explain this to to their natural position while retaining sexual function. you. There are many different ways to accomplish the surgery including: • Vaginal approach How can pelvic organ prolapse be treated? Treatment options can be categorized into non-surgical and sur- • Abdominal approach (through an abdominal incision) gical options. • Laparoscopic (keyhole) • Robotic

IUGA Office | [email protected] | www.iuga.org ©2011, 2016 • Vaginal Closure Surgery (Colpocleisis) Sacrocolpopexy Your doctor may recommend this surgery if you have a severe prolapse, are not sexually active and have no intention of becoming sexually active in the future, or if L5 you are medically unfit for reconstructive surgery. Dur- ing this procedure your surgeon will stitch the vaginal walls together thus preventing the prolapse from recur- ring. The main advantage of this procedure is its short surgical time and quick recovery. Success rates for this hip bone sacrum type of procedure are 90 – 95%.

What surgical approach is right for me? There is no single best approach for all patients. The approach for your particular surgery will depend on many factors, includ- rectum ing your history, your surgeon’s training and experience with different approaches, and your preference. Your surgeon will discuss with you the various options and will recommend the type of surgery best suited to your condition and needs. Each re- bladder pair is individualized, even two different women with the same prolapse may have different needs. • Vaginal approach: This usually involves making an incision in the vagina, separating the prolapsed organ involved from the vaginal wall and using stitches and / or mesh to vagina strengthen and repair the vagina. Permanent stitches may also be placed into the top of the vagina or into the cervix servative management such as pelvic floor exercises or the use and attached to strong ligaments in the pelvis to provide of vaginal pessary may be employed. support to the uterus or vaginal vault (these are termed sacrospinous or uterosacral ligament suspensions). • Abdominal approach: This involves making an incision in the abdomen and using sutures and / or graft materials to support the vagina, vaginal vault or uterus. In a sacrocolpopexy, a prolapsed vaginal vault is supported using mesh attached to the sacrum. Again, there are many different procedures and your doctor will explain these in detail to you. • Laparoscopic and robotic approaches: These procedures offer repairs similar to the open abdominal approach but often with quicker recovery time and smaller scars. At present, robotic surgery is only available in a few centers.

Is it necessary to use a graft material during the surgery? Not all repairs require a graft. Traditionally, grafts are used in repeated surgeries and where significant risk factors for failure exist. The graft may be absorbable or made from animal tissue (biologic) and will disappear gradually over time, or nonabsorbable synthetic material which stays permanently in your body. Some grafts are a combination of absorbable and non-absorbable materials. You should discuss the pros and cons of their use in detail with your surgeon.

How successful is surgery? Approximately 75% of women having vaginal surgery, and 90- 95% having an abdominal approach, will have a long-term cure of their prolapse symptoms. Recurrent prolapse may be due to continued factors which have caused the initial prolapse e.g. constipation and weak tissues.

What if I haven’t completed my family? It is generally advised to withhold the definitive prolapse repair surgery until completion of your family. In the meantime, con-

IUGA Office | [email protected] | www.iuga.org ©2011, 2016 An incision is made through the vaginal skin and fascia and the mesh placed to add additional support to the bladder and. vaginal walls synthetic mesh vagina Vaginal Repair with Mesh

A Guide for Women bladder 1. Why are mesh implants used to repair prolapse? 2. How is the surgery performed? cystocele 3. Is mesh good for me? 4. What will happen to me after the operation? 5. What are the chances of success? fascial layer 6. Are there any complications? 7. When can I return to my usual routine?

Introduction Fig. 1 Prolapse repair anterior compartment (cystocele repair) Prolapse of the vagina or uterus is a common condition causing using synthetic mesh. Mesh is placed under the skin and fascia to symptoms such as vaginal bulge, a sensation of dragging or full- provide additional support. ness in the vagina, difficulty emptying the bowels or bladder and additional small incisions at the inner thigh and/or the buttocks back ache. Up to 11% of women may require surgery for pelvic or special anchors that fixate the mesh to firm structures in the organ prolapse during their lifetime. Prolapse often occurs as pelvis (such as the sacrospinous ligament). If synthetic mesh is a result of damage to the support structures of the uterus and used, tissue grows through the holes in the graft and the mesh vagina. It can be surgically repaired either through the abdomen becomes fully incorporated in the body. Most biological grafts or the vagina using stitches to repair the body’s own tissue (tra- are reabsorbed slowly over about 6-9 months to be replaced by ditional surgery) or mesh implants to add support to weakened new support tissue produced by the body. tissues. Is mesh good for me? Why are mesh implants used to repair prolapse? Currently available evidence suggests that surgery with mesh Vaginal prolapse may recur after it has been treated by conven- may be more effective than traditional surgery, in certain cir- tional surgery. This is especially true when the prolapse involves cumstances, in reducing the chance of recurrent prolapse. Mesh the front wall of the vagina and in the presence of risk factors can be particularly useful in the treatment of cystocele and vagi- such as obesity, chronic cough, constipation or occupations that nal vault prolapse. However, there is not much good evidence involve excessive abdominal straining or heavy lifting. This is about how well this procedure works in the long term (over known as a recurrent prolapse. two years) and there is some concern regarding potential complications that are unique to permanent synthetic mesh placed The aim of a mesh implant is to reinforce natural tissue which through the vagina (see further details in complications section). has failed to support the pelvic organs, restoring support to the bladder, uterus or bowel and so preventing further bulging of these organs towards the vagina. There are different opinions among surgeons with regard to The term ‘mesh’ may refer to different types of materials includ- when mesh should be used. Some prefer to save the mesh only ing biologic grafts (derived from humans or animals), synthetic, for selected situations like failure of a previous traditional sur- absorbable (dissolves slowly over time), or permanent (stays in gery, management of a particularly large prolapse or in women the body forever). Mesh can be used to repair cystocele (a pro- with risk factors for recurrence. Others would use mesh for the lapse of the bladder downwards through the front wall of the initial surgery even without any particular risk factors. There vagina) or rectocele (a prolapse of the rectum through the back is a consensus, however, that mesh surgery should only be per- wall of the vagina), in isolation or both during the same surgery. formed by a specialist who has undergone training for perform- It can also be used to support the uterus (womb) in women suf- ing these procedures. Prior to the surgery your doctor should fering from uterine prolapse or to treat vaginal vault prolapse fully explain what is involved in having the procedure and dis- (descent of the vaginal apex after hysterectomy). cuss the possible benefits and risks of complications with you as well as alternative ways (both surgical and non-surgical) of managing your prolapse. How is the surgery performed? An incision is made in the vaginal skin and supporting tissue (fascia). The tissue is then separated from the underlying organ What will happen to me after the operation? (bladder or bowel, depending on the site of prolapse). The mesh When you wake up you will have a drip to give you fluids and implant is placed underneath the vaginal skin and fascia. (Fig. may have a catheter in your bladder. Often the surgeon will 1 and 2) place a gauze pack inside the vagina to reduce any bleeding into the tissues. Both the pack and the catheter are usually removed Different techniques are used to implant the graft and to keep within 24 to 48 hours after the operation. it in place. These include fixation arms that exit through a few

IUGA Office | [email protected] | www.iuga.org ©2011, 2017 An incision is made through the vaginal include an unpleasant smelling vaginal discharge, fever and skin and fascia and the mesh placed to pelvic pain or abdominal discomfort. Modern meshes used add additional support to the bladder and for prolapse repairs rarely become infected. vaginal walls. • Bladder infections (cystitis). Cystitis occurs in about 6% of women after surgery and is more common if a catheter rectum has been used. Symptoms include burning or stinging when passing urine, urinary frequency and sometimes blood in the urine. Cystitis is usually easily treated by a course of antibiotics. rectum • Injury of the urinary bladder, bowel or blood vessels. Surgi- vagina cal repair of prolapse involves the use of sharp instruments close to vital organs such as the urinary bladder, large bowel and major blood vessels that can potentially be injured. When surgery is performed by an experienced surgeon, the chances of this happening are small. Most injuries, if identified, can be immediately repaired although occasionally further surgery is required.

The following complications are more related to synthetic mesh implantations: rectocele • Mesh exposure. Some women who have had a vaginal repair with mesh will develop exposure of the mesh in the vaginal walls. It is estimated that this occurs following ap- mesh proximately 10-15% of surgeries using mesh. This can lead Fig. 2 Prolapse repair posterior compartment (rectocoele/ to vaginal discomfort, especially during intercourse (for ei- enterocoele) using synthetic mesh. Mesh is placed under the skin ther partner) and blood-stained ‘spotting’. Mesh exposure and fascia to provide additional support. through the vaginal skin is not considered a major complication. If mesh exposure occurs, it can be taken care of It is normal to get a white discharge for 4 to 6 weeks after sur- with the use of vaginal estrogen cream or a minor office or gery. This is due to the presence of stitches in the vagina. As the surgical procedure to re-cover the mesh. This may require stitches absorb the discharge will gradually reduce. If the dis- another surgical procedure. charge has a bad smell, contact your doctor. You may get some • Buttock and groin pain. When mesh is used to repair the blood-stained discharge immediately after surgery or starting back wall of the vagina, it is not uncommon to have some about a week after surgery. This blood is usually quite thin and pain in the buttock for the first few weeks after surgery. old, brownish looking and is the result of the body breaking This will get better by itself, and you will be given pain kill- down stitches and blood trapped under the skin. ers. It is also quite common to get some stabbing or burning rectal pain that settles within a short time. If the pain is What are the chances of success? severe or not improving you should contact your surgeon. The rate of success varies depending on the type of prolapse When mesh is used to support the anterior wall of the va- (cystocele versus rectocele, vaginal wall or vaginal apex), sever- gina, mesh arms may be passed through the groin area and ity of the prolapse and the presence of risk factors for recurrence. this can cause short term pain along the inner thighs/groin Quoted success rates for vaginal mesh repairs are 80% to 95%. area. Rarely, this can become a longer term problem. If you suffer from chronic pelvic or bladder pain or have a pain- sensitive condition such as fibromyalgia, you should inform Are there any complications? your surgeon during the pre-operative visits. With any operation there is always a risk of complications. • Constipation. Constipation is a common short term prob- The following general complications can happen after any sur- lem after pelvic surgery. Your doctor may prescribe stool gery: softeners and/or laxatives for this. Try to maintain a high • Anesthetic problems. With modern anesthetics and moni- fiber diet and drink plenty of fluids to help as well. toring equipment, complications due to anesthesia are very • Chronic vaginal pain and painful intercourse. Some wom- rare. Surgery can be performed using a regional (spinal or en may develop chronic pain or discomfort in the vagina, epidural) or general anesthetic; your anesthetist will discuss either constantly or during sexual intercourse. Whilst every what will be most suitable for you. effort is made to prevent this from happening, it is some- • Bleeding. Serious bleeding requiring blood transfusion is times unavoidable. The incidence of this complication is unusual following vaginal surgery. Mesh implantation may low and can occur following both mesh surgery and tradi- be associated with a higher rate of bleeding than traditional tional surgery. Treatment may require further surgery if it vaginal surgery according to previous clinical trials. does not improve with time or conservative therapy such as pelvic floor physical therapy. • Postoperative surgical site infection. Although antibiotics are routinely given just before surgery and all attempts are made to keep surgery sterile, there is a small chance of When can I return to my usual routine? developing an infection in the vagina or pelvis. Symptoms You should be able to drive and be fit enough for light activities

IUGA Office | [email protected] | www.iuga.org ©2011, 2017 such as short walks within 2 weeks of surgery. You are advised to avoid heavy lifting and sport for at least 6 weeks to allow the wounds to heal. It is usually advisable to plan to take 2 to 6 weeks off work. Your doctor can guide you as this will depend on your job type and the exact surgery you have had. You should wait six weeks before attempting sexual intercourse. Some women find using additional lubricant during intercourse to be helpful following pelvic surgery. Lubricants can easily be bought at supermarkets or pharmacies. There are different opinions among surgeons with regard to use of local estrogens after mesh surgery. Your doctor may advise you to use local estrogen both to decrease mesh erosion risk and to relieve discomfort during sexual intercourse. We hope you have found this leaflet helpful. For more information on prolapse, urinary incontinence or post-operative recovery visit our website at www.IUGA.org and click on the patient information section.

GYNECARE TVT™ Tension-free Vaginal Tape GYNECARE TVT™ Single Use Device GYNECARE TVT™ Reusable Introducer GYNECARE TVT™ Reusable Rigid Catheter Guide GYNECARE TVT™ anordning til engangsbrug GYNECARE TVT™ indfører til flergangsbrug GYNECARE TVT™ stift guiding kateter til flergangsbrug GYNECARE TVT™ hulpmiddel voor eenmalig gebruik GYNECARE TVT™ herbruikbare introducer GYNECARE TVT™ herbruikbare starre kathetervoerder GYNECARE TVT™ -laite, kertakäyttöinen GYNECARE TVT™ -sisäänviejä, kestokäyttöinen GYNECARE TVT™ -katetrinohjain, kestokäyttöinen, jäykkä Dispositif GYNECARE TVT™ à usage unique Introducteur réutilisable GYNECARE TVT™ Guide de sonde rigide réutilisable GYNECARE TVT™ GYNECARE TVT™ Einmal-Implantat GYNECARE TVT™ wiederverwendbares Einführungsinstrument GYNECARE TVT™ wiederverwendbare starre Katheterführung Συσκευή μιας χρήσης GYNECARE TVT™ Επαναχρησιμοποιήσιμος εισαγωγέας GYNECARE TVT™ Επαναχρησιμοποιήσιμος άκαμπτος οδηγός καθετήρα GYNECARE TVT™ Dispositivo monouso GYNECARE TVT™ Introduttore riutilizzabile GYNECARE TVT™ Guida rigida riutilizzabile per catetere GYNECARE TVT™ Dispositivo de utilização única GYNECARE TVT™ Introdutor reutilizável GYNECARE TVT™ Guia rígido de cateter reutilizável GYNECARE TVT™ Sistema para un solo uso GYNECARE TVT™ Introductor reutilizable GYNECARE TVT™ Guía de catéter rígida reutilizable GYNECARE TVT™ GYNECARE TVT™ produkt för engångsbruk GYNECARE TVT™ återanvändbar införare GYNECARE TVT™ återanvändbar stel kateterguide

Ethicon SÀRL Puits Godet 20 P15506 Neuchâtel LAB0012841v5 CH-2000 01/2015 Switzerland Made in Switzerland 1-877-ETHICON © Ethicon, Inc. 2009 +1-513-337-6928 GYNECARE TVT™ Tension-free Vaginal Tape GB USA System – Instructions For Use GYNECARE TVT™ Single Use Device GYNECARE TVT™ Reusable Introducer GYNECARE TVT™ Reusable Rigid Catheter Guide

Please read all information carefully. Failure to properly follow instructions may result in improper functioning of the device and lead to injury. Important: This package insert is designed to provide instructions for use of the Tension-free Vaginal Tape single use device, Reusable Introducer, and Reusable Rigid Catheter Guide. It is not a comprehensive reference to surgical technique for correcting Stress Urinary Incontinence (SUI). The device should be used only by physicians trained in the surgical treatment of Stress Urinary Incontinence and specifically in implanting the GYNECARE TVT™ Device. These instructions are recommended for general use of the device. Variations in use may occur in specific procedures due to individual technique and patient anatomy. DESCRIPTION (System) GYNECARE TVT consists of the following: GYNECARE TVT™ Single Use Device, provided sterile (available separately) GYNECARE TVT™ Reusable Introducer, provided non-sterile (available separately) GYNECARE TVT™ Reusable Rigid Catheter Guide, provided non-sterile (available separately) GYNECARE TVT DEVICE The GYNECARE TVT Device is a sterile single use device, consisting of one piece of undyed or blue (Phthalocyanine blue, color index. Number 74160) PROLENE™ Polypropylene Mesh (tape) approximately 1/2 x 18 inches (1.1 x 45 cm), covered by a plastic sheath cut and overlapping in the middle, and held between two stainless steel needles bonded to the mesh and sheath with plastic collars. The GYNECARE TVT Device is available in either mechanical cut or laser cut versions for the physician’s preference. To determine if the GYNECARE TVT Device implant is mechanical or laser cut, consult the product code on the device packaging; an (L) at the end of the number indicates the laser cut mesh. PROLENE Mesh is constructed of knitted filaments of extruded polypropylene strands identical in composition to that used in PROLENE™ polypropylene nonabsorbable surgical suture. The mesh is approximately 0.027 inches (0.7 mm) thick. This material, when used as a suture, has been reported to be non-reactive and to retain its strength indefinitely in clinical use. PROLENE Mesh is knitted by a process which interlinks each fiber junction. GYNECARE TVT INTRODUCER The GYNECARE TVT Introducer is provided non-sterile and is reusable. The Introducer is made of stainless steel. It consists of two parts, a handle and an inserted threaded metal shaft. The Introducer is intended to facilitate the passage of the GYNECARE TVT Device from the vagina to the abdominal skin. It is connected and fixed to the needle, via the threaded end of the shaft, prior to inserting the needle with the tape. GYNECARE TVT RIGID CATHETER GUIDE The GYNECARE TVT Rigid Catheter Guide is a non-sterile reusable instrument intended to facilitate the identification of the urethra and the bladder neck during the surgical procedure. It is inserted into a Foley catheter (recommended size 18 French) positioned in the bladder via the urethra. To facilitate insertion, it can be lubricated with gel. INDICATIONS The GYNECARE TVT Device is intended to be used as a pubourethral sling for treatment of Stress Urinary Incontinence (SUI), for female urinary incontinence resulting from urethral hypermobility and/or intrinsic sphincter deficiency. The GYNECARE TVT Introducer and Rigid Catheter Guide are available separately and are intended to facilitate the placement of the GYNECARE TVT Device. PATIENT FACTORS Physicians should use their surgical experience and judgment to determine if PROLENE Mesh is appropriate for certain patients. Patient-specific factors may impair wound healing, which may increase the likelihood of adverse reactions.

2 INSTRUCTIONS FOR USE 1. The procedure can be carried out under local anesthesia, but it can also be performed using regional or general anesthesia. 2. Before the patient is prepped and draped, she should be placed in the lithotomy position taking care to avoid hip flexion greater than 60°. 3. Insert an 18 French Foley catheter and leave it to open drainage. 4. At the level of the mid urethra, inject a small amount of local anesthesia submucosally to create a space between the vaginal wall and the periure- thral fascia. The extent of dissection required for placement is minimal. Only a small paraurethral incision is required over the mid urethra to position the tip of the Needle. Using forceps, grasp the vaginal wall at each side of the urethra. Using a small scalpel, make a sagittal incision about 1.5 cm long starting approximately 1.0 cm cephalad from the urethral meatus. This incision will be positioned over the mid-urethral zone and will allow for subsequent passage of the Implant. 5. With a small pair of blunt scissors, make two small paraurethral lateral dissec- tions (approximately 0.5 to 1.0 cm) to accommodate the tips of the Needle. 6. Identify the two Needle exit sites, which should be 2-2.5 cm on each side of the midline, immediately above the pubic symphysis. Either mark these sites or, if desired, place two small 3-4 mm transverse stab incisions at the intended exit site. In order to avoid the inferior epigastric vessels it is important that the intended exit sites be not more than 2.5 cm from the midline. It is important that the exit sites for the Needle passages be near the midline and close to the superior aspect of the pubic bone, in order to avoid anatomic structures in the abdomen, inguinal area and lateral pelvic sidewall. 7. If retropubic infiltration of local anesthesia is not performed then consider infiltrating the retropubic space with two injections of normal saline on either side of midline. Starting at the needle exit sites pass an 18 gauge needle along the back of the pubic bone until the tip of the needle touches the endopelvic fascia. As the needle is withdrawn inject 30 to 50 cc. By so doing it opens up the retropubic space to minimize the risk of bladder puncture during retropubic Needle passage. 8. Confirm that all urine has been drained from the bladder. Once the bladder is empty, insert the GYNECARE TVT Reusable Rigid Catheter Guide (available separately) into the channel of the 18 French Foley catheter. The handle of the GYNECARE TVT Reusable Rigid Catheter Guide should be fixed around the catheter at its proximal end. The purpose of placing the GYNECARE TVT Reusable Rigid Catheter Guide into the catheter is to allow contralateral displacement of the bladder, bladder neck and urethra away from the tip of the Needle as it passes through the retropubic space. 9. The threaded end of the Introducer is screwed into the end of one of the needles. 10. Gently push the tip of the 18 French Foley catheter toward the posterior lateral wall of the bladder opposite to the intended Needle passage. For example, by pushing toward the patient’s left side the bladder will go from a spherical to a spheroid configuration. This moves the bladder away from the back of the pubic symphysis. Additionally, it moves the bladder neck and the urethra to the left as the Needle is passed on the patient’s right side, thereby minimizing the risk of bladder perforation. 11. Hold the Introducer Handle using your dominant hand. Pass the tip of the Needle that is mounted on the GYNECARE TVT Introducer, paraurethrally through the urogenital diaphragm at the level of the midurethra. Initial insertion of the device is controlled by using the tip of the index finger of the non-dominant hand, which is placed in the vagina under the anterior vaginal wall, just lateral to the suburethral incision. The curved part of the Needle should rest in the palm of the non-dominant hand. Pass the Needle through the urogenital diaphragm into the retropubic space. During the initial placement into the paraurethral dissected space the Needle tip should be oriented horizontally, i.e. in the frontal plane. During passage through the urogenital diaphragm lower the Introducer handle to ensure that the Needle tip passes vertically while staying in close contact to the back of the pubic symphysis. After passage through the urogenital diaphragm resistance to the passage of the Needle is significantly reduced once it enters the retropubic space.

3 12. At this point, the non-dominant hand is moved from the vagina to the supra- pubic exit site. The Needle tip is guided through the retropubic space staying as close to the back of the pubic symphysis as possible. This is achieved by lowering the GYNECARE TVT Introducer Handle, thereby pressing the Needle tip against the back of the pubic bone. 13. During passage through the retropubic space aim the Needle tip towards the pre-marked abdominal exit site. 14. When the needle tip has reached the abdominal incision unscrew the GYNECARE TVT Introducer from the Needle. Before the Implant is pulled into place, remove the 18 French Foley catheter and perform a cystoscopy (70 degree lens recommended). 15. Once bladder integrity is confirmed, pull the Needle upward to bring the Implant out through the abdominal exit site. Clamp the Implant just below the Needle. Cut the Implant between the connection to the Needle and the clamp. 16. The procedure is now repeated on the patient’s other side while repeating steps 9 – 15. NOTE: IN ORDER TO MINIMIZE THE RISK OF BLADDER INJURY, IT IS IMPORTANT THAT THE BLADDER BE DISPLACED TO THE CONTRALATERAL SIDE USING THE MANEUVERS OUTLINED IN STEP 10. 17. The ends of the implant are then pulled upward to bring the implant (sling) loosely, i.e., without tension, under the midurethra. Adjust the Implant so that leakage is reduced, allowing only a few drops of urinary leakage to occur under stress. For this, use patient feedback, i.e. coughing with a full bladder (approximately 300 mL). 18. Grasp the Implant Sheaths that surround the Implant with clamps, taking care not to grasp the Implant. Then individually remove the Implant Sheaths by gently pulling up on the clamps, away from the abdomen, one at a time. To avoid putting tension on the Implant, a blunt instrument (scissors or forceps) should be placed between the urethra and the Implant during removal of the Implant Sheaths. 19. NOTE: Premature removal of the sheath may make subsequent adjustments difficult. 20. After proper adjustment of the tape, close the vaginal incision. The abdominal ends of the tape are then cut and left in subcutis. Do not suture the implant. 21. Close the skin incisions with suture or surgical skin adhesive. 22. Empty the bladder. Following this procedure, postoperative catheterization is not typically required. The patient should be encouraged to try to empty the bladder 2-3 hours after the operation. CONTRAINDICATIONS As with any suspension surgery, this procedure should not be performed in pregnant patients. Additionally, because the PROLENE Mesh will not stretch significantly, it should not be performed in patients with future growth potential including women with plans for future pregnancy. WARNINGS AND PRECAUTIONS • Do not use GYNECARE TVT in patients who are on anti-coagulation therapy. • Do not use GYNECARE TVT in a patient who has a urinary tract infection. • Users should be familiar with surgical technique for bladder neck suspensions and should be adequately trained in the GYNECARE TVT implantation procedure before employing the GYNECARE TVT Device. It is important that the tape be located without tension under mid-urethra. • Acceptable surgical practice should be followed for the procedure as well as for the management of contaminated or infected wounds. • The procedure should be performed with care to avoid large vessels, nerves, bladder and bowel. Attention to local anatomy and proper passage of needles will minimize risks. • Retropubic bleeding may occur post-operatively. Observe for any symptoms or signs before releasing the patient from the hospital. • Cystoscopy should be performed to confirm bladder integrity or recognize a bladder perforation. • The Rigid Catheter Guide should be gently pushed into the Foley catheter so that the catheter guide does not extend into the holes of the Foley catheter. • When removing the Rigid Catheter Guide, open the handle completely so that the catheter remains properly in place. • Do not remove the plastic sheath until the tape has been properly positioned.

4 • Ensure that the tape is placed with minimal tension under mid-urethra. • PROLENE Mesh in contaminated areas should be used with the understanding that subsequent infection may require removal of the material. • The patient should be counseled that future pregnancies may negate the effects of the surgical procedure and the patient may again become incontinent. • Since no clinical experience is available with vaginal delivery following the procedure, in case of pregnancy delivery via cesarean section is recommended. • Post-operatively, the patient is recommended to refrain from heavy lifting and/or exercise (i.e., cycling, jogging) for at least three to four weeks and intercourse for one month. The patient can return to other normal activity after one or two weeks. • Should dysuria, bleeding or other problems occur, the patient is instructed to contact the surgeon immediately. • All surgical instruments are subject to wear and damage under normal use. Before use, the instrument should be visually inspected. Defective instruments or instruments that appear to be corroded should not be used and should be discarded. • As with other incontinence procedures, de novo detrusor instability may occur following the procedure. To minimize this risk, make sure to place the tape tension-free in the mid-urethral position. • Do not contact the PROLENE Mesh with any staples, clips or clamps, as mechanical damage to the mesh may occur. • Do not resterilize/reuse. Reuse of this device (or portions of this device) may create a risk of product degradation, which may result in device failure and/or cross-contamination, which may lead to infection or transmission of blood-borne pathogens to patients and users. • Discard opened, unused devices. ADVERSE REACTIONS • Punctures or lacerations of vessels, nerves, structures or organs, including the bladder, urethra or bowel, may occur and may require surgical repair. • Transitory local irritation at the wound site may occur. • As with any implant, a foreign body response may occur. This response could result in extrusion, erosion, exposure, fistula formation and/or inflammation. • Mesh extrusion, exposure, or erosion into the vagina or other structures or organs. • As with all surgical procedures, there is a risk of infection. As with all foreign bodies, PROLENE Mesh may potentiate an existing infection. • Over correction, i.e., too much tension applied to the tape may cause temporary or permanent lower urinary tract obstruction. • Acute and/or chronic pain • Voiding dysfunction • Pain with intercourse which in some patients may not resolve. • Neuromuscular problems, including acute and/or chronic pain in the groin, thigh, leg, pelvic and/or abdominal area may occur. • Recurrence of incontinence • Bleeding including hemorrhage, or hematoma. • One or more revision surgeries may be necessary to treat these adverse reactions. • PROLENE Mesh is a permanent implant that integrates into the tissue. In cases in which the PROLENE Mesh needs to be removed in part or whole, significant dissection may be required. OTHER ADVERSE REACTIONS • Seroma • Urge incontinence • Urinary frequency • Urinary retention • Adhesion formation • Atypical vaginal discharge • Exposed mesh may cause pain or discomfort to the patient’s partner during intercourse. • Death

5 ACTIONS Animal studies show that implantation of PROLENE Mesh elicits a minimal inflam- matory reaction in tissues and stimulates the deposition of a thin fibrous layer of tissue that can grow through the interstices of the mesh, thus incorporating the mesh into adjacent tissue. The material is not absorbed, nor is it subject to degradation or weakening by the action of tissue enzymes. INSTRUCTIONS FOR CLEANING REUSABLE INSTRUMENTS (GYNECARE TVT Introducer, GYNECARE TVT Rigid Catheter Guide) To ensure the reliability and functionality of the GYNECARE TVT Introducer and GYNECARE TVT Rigid Catheter Guide, clean the instruments before initial use and after each procedure. The following are suggested manual and automated methods for cleaning the instruments. Prior to cleaning, the GYNECARE TVT Introducer should be separated into its component parts (handle and threaded shaft). The Introducer is reassembled after cleaning and before sterilization. Manual Method: 1. Soak the instrument components in an enzyme cleaner suitable for stainless steel instruments. 2. Wash in a surgical detergent and disinfecting solution at a temperature of 86°F to 95°F (30°C to 35°C). Remove any contamination from body fluids or tissues using a soft brush. 3. Place the instrument components in an ultrasonic bath with fresh detergent solution for approximately 10 minutes or follow the instructions below if using an automatic washing cycle. 4. Rinse thoroughly in a stream of fresh tap water followed by towel drying. The instrument components may be treated with instrument lubricant. Automated Method: Automatic washing cycles are suitable for stainless steel instruments. One recommended cycle is described below: • Rinse/Wet Cycle Cold Water – 1 minute • Wash 176°F (80°C) – 12 minutes • Rinse Cycle – 1 minute • Rinse Cycle – 12 minutes • Final Rinse – 2 minutes • Rinse with Demineralized water 176°F (80°C) – 2 minutes • Dry 199.4°F (93°C) – 10 minutes STERILIZATION RECOMMENDATIONS FOR REUSABLE INSTRUMENTS (GYNECARE TVT Introducer, GYNECARE TVT Rigid Catheter Guide) The GYNECARE TVT Introducer and GYNECARE TVT Rigid Catheter Guide are supplied non-sterile. To sterilize, steam autoclave prior to each use. Steam autoclave at a temperature of 270°F to 284°F (132°C to 140°C) for a minimum of 4 minutes (pre-vacuum). It is the responsibility of the end user to assure sterility of the product when using sterilization process recommended, since bioburden and sterilization equipment will vary. INSTRUMENT MAINTENANCE • GYNECARE TVT Introducer Before each use, inspect the threaded parts of the inner shaft. • GYNECARE TVT Rigid Catheter Guide Before each use, inspect the instrument. Check to ensure that the long end which traverses the catheter channel has no sharp edges or burrs. HOW SUPPLIED The GYNECARE TVT Device is provided sterile (ethylene oxide) for single use. Do not re-sterilize. Do not use if package is opened or damaged. Discard opened, unused devices. The reusable GYNECARE TVT Introducer and GYNECARE TVT Rigid Catheter Guide are supplied separately and are non-sterile. These accessories are to be cleaned and sterilized prior to each use as described above. STORAGE No special storage conditions required. Do not use after expiration date. Caution: Federal (U.S.A.) law restricts this device to sale by or on the order of a licensed healthcare practitioner.

6 Symbols Used on Labeling

Do not reuse

Do not resterilize

Use by date

Catalogue number

Caution

Manufacturer CE mark and identification number of Notified Body. Product conforms to the essential requirements of the Medical Device Directive 93/42/EEC Caution: Federal (U.S.A.) law restricts this device to sale by or on the order of a licensed healthcare practitioner.

Do not use if package is damaged

Sterilized using Ethylene Oxide

Batch code

PPE Specification LAB-0012841 | Rev:5 Labeling Specification Released: 17 Sep 2015 RMC P15506 Gynecare TVT Device IFU (main) CO: 100300298 Release Level: 4. Production

IFU PRINTING SPECIFICATION SHEET

PAGE LAYOUT FOLD PATTERN

6" 6" (152.4 mm) (152.4 mm)

Binding Method: Stitched/ Stapled (2 staples)

4.5" (114.3 mm) 2.25" (57.15 mm)

Flat Size Folded Size

TITLE DESCRIPTION LAB NUMBER SPECIAL INSTRUCTIONS/COMMENTS BINDING Stitched/ COLORS Gynecare TVT™ Booklet IFU LAB0012841v5 n/a Stapled (2 staples) Black FLAT SIZE FOLDED SIZE RMC NUMBER PAGE COUNT LANGUAGES SELF COVER PLUS COVER SEALING METHOD WAFER SEAL 4.5" x 6" 2.25" x 6" P15506 64 DA, DE, EL, ES, FI, FR, GB, IT, NL, PT, SV X n/a 114.3 mm x 152.4 mm 57.15 mm x 152.4 mm BLEED SIZE .5" (12.7 mm) .125" (3.175 mm) NONE BLEED ALL SIDES BLEED TOP BLEED RIGHT BLEED LEFT BLEED BOTTOM DRAWING IS NOT TO SCALE: DRAWINGS REFLECT INFORMATION FOR PRODUCTION OF PRINTED PIECES AND DO NOT CONTAIN ACTUAL ARTWORK. X This document or data herein or herewith is not to be reproduced, used or disclosed in whole or part without the permission of Ethicon, Inc. STOCK 100 g/m2 Wood Free Gloss Paper PPE Specification LAB-0012266 | Rev:3 Labeling Specification Released: 03 Feb 2015 389766R02 Gynecare Gynemesh PS IFU CO: 100257301 Release Level: 4. Production

0086 PPE Specification LAB-0012266 | Rev:3 Labeling Specification Released: 03 Feb 2015 389766R02 Gynecare Gynemesh PS IFU CO: 100257301 Release Level: 4. Production PPE Specification LAB-0012266 | Rev:3 Labeling Specification Released: 03 Feb 2015 389766R02 Gynecare Gynemesh PS IFU CO: 100257301 Release Level: 4. Production PPE Specification LAB-0012266 | Rev:3 Labeling Specification Released: 03 Feb 2015 389766R02 Gynecare Gynemesh PS IFU CO: 100257301 Release Level: 4. Production PPE Specification LAB-0012266 | Rev:3 Labeling Specification Released: 03 Feb 2015 389766R02 Gynecare Gynemesh PS IFU CO: 100257301 Release Level: 4. Production

0086 Appendix 5: Papers prepared by JJM (or its affiliated companies) in response to the following consultations (since 2015)

Consultation: Draft clinical evidence guidelines – medical devices

Submission to Consultation: Draft clinical evidence guidelines – Medical devices

June 2016

Consultation: Draft clinical evidence guidelines – medical devices

Our Credo

Consultation: Draft clinical evidence guidelines – medical devices

Submission Information

Organisation: Johnson & Johnson Medical Pty Ltd

Address: 1 – 5 Khartoum Road, Macquarie Park NSW 2113

Email and phone contact: Rebecca Gaudin Director of Regulatory Affairs Johnson & Johnson Medical Ph: +61 2 9815 4186 Email: [email protected]

Consultation: Draft clinical evidence guidelines – medical devices

Overview On behalf of Johnson & Johnson (J&J), we appreciate the opportunity to submit comments in response to the Draft Clinical Evidence Guidelines- Medical Devices

J&J is the world’s most comprehensive and broadly based manufacturer of healthcare products. Our family of healthcare companies brings together innovative ideas, products, and services to advance the health and well-being of people around the world. Our more than 250 companies located in 57 countries work with partners in health care to touch the lives of over a billion people every day. We routinely perform clinical trials and studies related to the medical devices, pharmaceuticals, consumer products, and diagnostics we develop and bring to market. Clinical trials and studies we perform with patients and human subjects include but are not limited to randomized controlled trials (RCTs), observational studies, registries, comprehension studies, and patient preference studies. Our commitment to patients and research subjects drives us to ensure that all of J&J’s research is done with integrity and in an ethical and scientifically sound manner. We strive to advance science and medicine through research and to ensure that all products have a comprehensive and continuous evaluation of clinical evidence to ensure safety and efficacy prior to and following market authorization

J&J fully supports efforts to protect research subjects, promote research, leverage available clinical evidence and to ultimately protect patients and enhance and preserve health. We welcome your commitment to reviewing and proposing updates to the Clinical Evidence Guidelines for Medical Devices. We support in principle the intent to streamline and modernise it. Our goal, as is yours, is to afford maximum protection to patients, while at the same time making sure that clinical evaluation, clinical evidence generation and analysis in all segments of a product lifecycle can proceed in a timely and efficient manner. We have kept these goals uppermost in mind as we evaluated the proposed draft.

In these comments we will focus on the areas where we believe enhancements or clarifications need to be made to the proposal set forth. We commend your work in identifying key issues and presenting thoughtful approaches. We have reviewed the submission made by the Medical Technology Association of Australia and we generally support their comments.

As more and more countries work to strengthen their regulatory systems, there happens to be great variety in regulatory standards from one country to the next. These often divergent regulatory standards have resulted in major challenges to the medical device innovation ecosystem. As a global leader, we applaud the TGA’s strong advocacy and participation in global regulatory convergence efforts. While the resources invested in global convergence organizations like ICH and International Medical Device Regulators Forum have been valuable, real progress will require a sustained effort and commitment from global leaders.

J&J continues to support alignment with the EU regulatory system, particularly as the new Medical Devices Regulations (MDR) is implemented. We strive to ensure that the TGA do not impose any unique requirements through the release of their Clinical Evidence Guidelines ahead of the EU Commission finalising MEDDEV guidance 2.7/1 Rev.4 Clinical Evaluation: A Guide for Manufacturers and Notified Bodies.

A list of specific comments on the draft guideline is tabulated in the following pages.

Consultation: Draft clinical evidence guidelines – medical devices

Provision Recommendation

Section 2. Legislative Basis Suggest to change to “predicate or similar Principle six: Benefits must outweigh marketed device” to align with definition in undesirable side-effects (P11) Section 3. “It may also be appropriate, on occasion, to argue for safety based upon data for a predicate or similar device which is already marketed.”

Section 3. Clinical evidence This sentence could be clarified to note that Key definitions and concepts (P15) PMCF, with a formal protocol and completion “Routine post-market surveillance may report, is proactive post-market surveillance that not constitute a clinical investigation (e.g. qualifies as post market clinical investigation. investigation of complaints, individual vigilance reports, literature reviews).”

Section 3. Clinical evidence Suggest to add “if necessary” to allow Review and critical analysis (P18) manufacturer to estimate if it’s necessary to “The method of synthesising the results combine the included study results. of included studies, including methods of handling data and combining results of studies should be described. “

Section 3. Clinical evidence Suggest to also include “unit demand” as some Post-market data (P19) systems may only capture this data. “The number of units sold…”

Section 3. Clinical evidence Suggest to correct “The total number of adverse Post-market data (P19) events reported to regulatory agencies” to “The The total number of adverse events total number of reportable complaints to reported to regulatory agencies… regulatory agencies”

Section 3. Clinical evidence Further clarification is required around the Post-market data (P19) definition of adverse event versus complaint. “Together, this data should be compiled into an adverse event rate and a device complaint rate which will allow the clinical assessor to better evaluate the benefit-risk profile of the device. “

Consultation: Draft clinical evidence guidelines – medical devices

Provision Recommendation

Section 3. Clinical evidence Clarification of “clinically validated”. Data from pre-clinical assessment (P20) This may include biocompatibility testing, bench testing, animal studies and computer simulation and/or modelling data that have been clinically validated.

Section 4. Clinical evaluation report and Correct to Appendix 2: Constructing the clinical supporting documents evaluation report Clinical evaluation report (P21)

2nd paragraph Appendix 5: Constructing the clinical evaluation report provides …

Section 4. Clinical evaluation report and Correct to Appendix 5: Clinical evaluation report supporting documents and supporting documents Clinical evaluation report 3rd paragraph (P21) The recommended structure of the components of the clinical evaluation report is provided in Appendix 6: Clinical evaluation report and supporting documents

Section 4. Clinical evaluation report and Suggest limiting to regulatory status in IMDRF supporting documents member countries for relevance and currency. Clinical evaluation report (P21) The status in all countries may be difficult to “3. Regulatory status in other countries” maintain.

Section 4. Clinical evaluation report and Correct to Appendix 6: Collection and Evaluation supporting documents of clinical data. 7. Evaluation of clinical data (P24) Guidance on the recommended reporting requirements for clinical studies and examples of validated tools that can be used to guide the quality appraisal of both clinical investigations and literature reviews are provided in Appendix 4: Evaluation of clinical data.

Consultation: Draft clinical evidence guidelines – medical devices

Provision Recommendation

Section 4. Clinical evaluation report and Suggest to add “if necessary” , and only provide supporting documents the full text for which evaluators want to refer Supporting documents during the review. D. Full text articles from literature review (P27)

Philip Desjardins, JD

Vice President, Global Regulatory Affairs Policy & Intelligence

Medical Devices , Johnson & Johnson

David Cain

Government Affairs & Policy Manager

Johnson & Johnson Medical Pty Ltd

Review of Medicines and Medical Device Regulations

Submission to the Review of Medicines and Medical Device Regulations

January 2015

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Review of Medicines and Medical Device Regulations

Contents

Review of Medicines and Medical Devices Regulation Submission Cover Sheet ...... 1 Our Credo ...... 5 Submission Information & Company Overview ...... 6 Executive Summary ...... 8 Recommendations from the Johnson & Johnson Family of Companies ...... 9 Prescription Medicines ...... 9 Non-Prescription Medicines ...... 9 Medical Devices ...... 11 Chapter One – Review Details ...... 12 Chapter Two – Environmental Factors...... 13 Chapter Three – Principles Underpinning the Review...... 14 Principle 1 ...... 14 Principle 2 ...... 14 Principle 3 ...... 14 Principle 4 ...... 14 Principle 5 ...... 15 Question for consideration: ...... 16 Chapter Four – Regulation of Prescription Medicines ...... 17 Considering the Global Regulatory Framework in Addressing Identified Themes: ...... 17 New Chemical Entities (NCE) and Expanded Indication Pathway: ...... 18 Good Manufacturing Practice (GMP) Clearances: ...... 19 Application Entry Team (Case Managers): ...... 19 Chapter Five – Regulation of Generic Medicines and Biosimilars ...... 20 Biosimilars: ...... 20 Bioequivalence of Generic Medications: ...... 20 Variations to Prescription Medicines: ...... 20 Chapter Six – Regulation of Over the Counter Medicines ...... 21 Theme 1: Regulatory requirements are not commensurate with risk ...... 21 Issue 1 – Scheduling Framework ...... 21 Issue 2– Direct-to-consumer advertising of Schedule 3 Medicines ...... 26 Issue 3 – Regulation of low-risk therapeutic goods ...... 27 Issue 4 – Variations to registered OTC medicines ...... 33 Theme 2: Overly Burdensome Processes ...... 33 1. Overseas Evaluation Reports ...... 33 2. Application Processing ...... 34 3. International Harmonisation ...... 35 Theme 3: Complex Regulatory Framework ...... 35 Issue 1 – New product applications which require a related scheduling decision ...... 35 Issue 2 – Applications to reschedule substances which require evaluation of new product labels ...... 35

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Chapter Seven – Regulation of Medical Devices ...... 36 Theme 1: Duplication of Regulatory Processes ...... 36 Current regulatory framework and recognition of trusted international standards: ... 36 TGA Confidence Building: ...... 38 Other International Regulators: ...... 38 Classification Alignment: ...... 38 Theme 2: Lack of flexibility ...... 39 Converging Technologies: ...... 39 Biologics: ...... 39 Theme 3: Regulatory requirements are not commensurate with risk ...... 40 Variations to Medical Devices: ...... 40 Post-Market Focus: ...... 41 Access to Unapproved Medical Devices: ...... 41 Theme 4: Overly Burdensome Processes ...... 41 Multiple Systems and Manual processes ...... 41 Process for Inclusion of Devices on the ARTG...... 42 Instructions for Medical Devices...... 42 Theme 5: Complex Regulatory Framework ...... 42 Categorisation of Medical Devices...... 42 Transparency of Regulatory Decisions...... 43 Consumer Understanding of Medical Devices Regulation ...... 43 Other Considerations ...... 44 Differences between Prostheses List Advisory Committee (PLAC) and TGA: ...... 44 Australian Unique Requirements – Regulation of Tampons ...... 44 Clinical Trials: ...... 46 Chapter Eight – Framework for Advertising Therapeutic Goods ...... 47 Issue 1 – Advertising of Schedule 4 prescription medicines to consumers ...... 47 Issue 2 – Advertising of Schedule 3 medicines to consumers ...... 47 Issue 3 - Co-regulation and the pre-approval process ...... 47 Issue 4 – Management of complaints and enforcement powers ...... 48 Issue 5 – Advertising of medical devices ...... 49 Advertising of Samples of Therapeutic Goods ...... 49

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Our Credo

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Submission Information & Company Overview

Organisation: Johnson & Johnson Pty Ltd

Type of Organisation: Proprietary Limited Company

Address: 1 – 5 Khartoum Road, Macquarie Park NSW 2113

Email and phone contact: Mr David Cain Government Affairs & Policy Manager Johnson & Johnson Medical Ph: +61 2 9815 3847 Email: [email protected]

Declaration of Interest: Johnson & Johnson Pty Ltd is a subsidiary of Johnson & Johnson, the world’s most comprehensive and broadly based healthcare company. The organisation is engaged in business located in Australia and is the sponsor of thousands of products and services within medical devices, diagnostics, pharmaceuticals and consumer healthcare products.

Our Family of Companies operating under the Johnson & Johnson Pty Ltd banner consists of: Johnson & Johnson Pacific (JJP), known for its portfolio of leading consumer health brands; • Johnson & Johnson Medical (JJM), a medical devices and technology business; Janssen (JC), the pharmaceutical companies of Johnson & Johnson; and • Tasmanian Alkaloids (TA) an advanced agricultural production and pharmaceutical • ingredient manufacturing company. •

We employ approximately 1,800 Australians who are passionate about bringing innovative ideas, products and services to advance the health and well-being of people. Driven by our commitment to patients, we bring innovative products, services and solutions to people throughout the world. We recognise the impact of serious conditions on people's lives, and we aim to empower people through disease awareness, education and access to quality care. Our research and development strategy focuses on identifying medical needs and harnessing the best science in the world, whether from our own laboratories or through strategic relationships and collaborations.

Johnson & Johnson Pacific is a leading provider of consumer health and wellbeing products, offering families in Australia and New Zealand more than 650 trusted solutions for their most common health and wellbeing needs. Many of our brands are #1 in the categories in which they compete and have earned consumers’ trust over generations.

Johnson & Johnson Medical produces a range of innovative products and solutions used primarily by healthcare professionals in the fields of orthopaedics, neurological disease, vision care, diabetes care, infection prevention, diagnostics, cardiovascular disease, and aesthetics. We are the

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Review of Medicines and Medical Device Regulations

largest medical technology provider in Australia and work across both the public and private sectors.

The Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Janssen has a long-standing history in making a meaningful difference in global public health, dating back to Dr Paul Janssen’s pioneering work in mental health and pain medications, as well as the development of more than 80 medicines, four of which are included on the World Health Organisation’s List of Essential Medicines. Inspired by his legacy, we aim to help more people in more places have access to our medicines and to sustainable, effective healthcare solutions.

Tasmanian Alkaloids Pty Ltd is an advanced agricultural production and R&D company located in Westbury, near Launceston. It extracts alkaloids used in the manufacture of opiate-based pain- control medicines from poppy straw. Around 99% of this product is exported, making Tasmanian Alkaloids the largest manufacturer of active pharmaceutical ingredients in Australia, supplying 45-50% of the world’s demand for medicinal opiates. Tasmanian Alkaloids contracts with approximately 530 Tasmanian farmers to grow the poppy crop, and 50 additional contractors also linked to the agricultural operations.

In summary the Johnson & Johnson Family of Companies (JJFC) in Australia is driven by a commitment to patients. We develop sustainable, integrated healthcare solutions by working side-by-side with healthcare stakeholders, and investing in partnerships based on trust and transparency. We provide education materials to healthcare professionals throughout the country – from student doctors and nurses through to registrars and consultants. We also have a broad range of products in baby care, skin care, oral care, wound care and women’s health, as well as over-the-counter pharmaceutical products.

Johnson & Johnson Industry Group Memberships: Please find below a list of the relevant industry associations in which our Companies maintain membership. It should be noted that our Companies have contributed to submissions by many of the organisations listed.

• ACCORD – an advocate association for the Consumer, Cosmetic, Hygiene & Specialty Products Industry • API Manufacturers Australia • Australian Self Medication Industry (ASMI) • AusBiotech – Australia’s Biotechnology Association • Australian Food & Grocery Council (AFGC) • Medical Technology Association Australia(MTAA) • Medicines Australia (MA)

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Executive Summary Regulation of medical devices and medicines exists as an important safeguard for the population. Agencies, such as the TGA, provide assurance to the community that products are assessed for safety, efficacy and quality with sufficient rigour. Evaluation of products globally is evolving towards expedient assessment of data generated during clinical development and partnership in post-market surveillance.

Investment in prescription medicine has largely progressed from the blockbuster interventions developed in the 1980s and 1990s to treat broad sectors of society to current developments that tend to be in high impact diseases with limited patient populations. This limits the ability to generate quality data and compels developmental partnership between sponsors, regulators and clinicians.

Regulators have shown willingness to expedite novel interventions and unlock additional resources in the process. This sharing of developmental risk enhances understanding of interventions and ultimately benefits individual patients and public health.

This review allows for the examination of the regulations that govern therapeutic goods and represents an opportunity to ensure that the regulatory burden is commensurate with the risk of the product. Ideally any recommendations stemming from this review should be in line with international best practices and strives for the minimal effective regulation.

Specifically in regard to medical devices the proposal for greater acceptance of third party conformity assessment and reduced TGA pre-market assessment for all classes of medical devices supplied in Australia builds upon the strengths of the TGA’s current regulatory structure and experience with accepting conformity assessment certificates from overseas Conformity Assessment Bodies (CAB’s) since the regulatory framework was implemented in 2002. This approach is consistent with the TGA’s stated shift in emphasis from pre-market assessment to post-market surveillance and better focuses TGA’s resources to where they will have the most effective impact on public health. It remains consistent with the framework established by the GHTF and would continue to be harmonised with the European Medical Device Directive (MDD).

Overall, JJFC believe that there is no “good reason” to impose additional or unique requirements for medicines and medical devices, when compared with the requirements of other well regarded regulators. The TGA should continue focusing on confidence building activities, reducing the regulatory burden for low risk products, with the aim of achieving the minimum effective regulation and focus on greater post-market surveillance.

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Review of Medicines and Medical Device Regulations

Recommendations from the Johnson & Johnson Family of Companies JJFC has addressed a number of issues highlighted in the discussion paper, along with other issues. Below is a summary of recommendations that have been made throughout the JJFC response.

1. JJFC supports a framework whereby there is Commonwealth responsibility for all aspects of regulation and supply of therapeutic goods in Australia.

Prescription Medicines 2. The TGA adopt a system which allows products automatic listing on the ARTG providing the following can be fulfilled: a. FDA Breakthrough designation and subsequent approval b. Fast track designation and subsequent approval 3. The TGA adopt a streamlined review program for listing on the ARTG providing the following can be fulfilled via the FDA: c. Priority evaluation; or d. accelerated approval 4. The TGA remove the requirement to review GMP clearance certificates where GMP certificates have been issued by a trusted authority agency, irrespective of the location of the site. 5. That TGA adopt a customer focused portal to assist in application entry team managers employ a flexible and solutions-based approach

Non-Prescription Medicines 6. The current scheduling framework is risk averse and lacks transparency. JJFC recommends the adoption of a system based on consistent and transparent methodology for assessing risk versus benefit (such as the model proposed by Brass et al). 7. The existing guidelines to help sponsors make effective re-scheduling applications are poor and lack detail. The guidelines are in desperate need of review and updating. 8. The reasons for the Delegate’s decisions are light on detail when compared with the ratified minutes of the now defunct NDPSC. The reasons for the Delegates decisions need to be more detailed such that sponsors are able to adequately address the concerns of the Delegate in subsequent application if required. 9. Under the relatively new scheduling framework the pathway that allowed parallel scheduling and registration (Schedule 10) was removed. JJFC recommends that parallel scheduling and registration applications be reinstated. 10. There is little reward for sponsors or individuals who invest in switching molecules. JJFC recommends that a period of exclusivity exist for sponsors or individuals that investing time, money and resource into rescheduling molecules.

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11. JJFC recommends that the Delegate’s decisions with regard to the scheduling of a molecule be subject to both merits and judicial review. 12. JJFC recommends that details of proposals for scheduling of molecules contain sufficient detail to allow companies and individuals to have meaningful submissions at the public consultation phase. 13. JJFC recommends that direct to consumer advertising for Schedule 3 medicines is permitted with the exception of molecules that are prone to abuse or misuse. 14. JJFC supports a framework of regulating sunscreens that simplifies the classification of primary and secondary sunscreens and reduces regulatory burden. Ideally there should be one product classification for sunscreens in our market. 15. Difference in product classification in different countries often makes it difficult to introduce innovation into Australia. JJFC recommends the removal of the requirement of a default pharmacopoeial standard for low risk medicines, particularly topical products. 16. JJFC recommends the adoption of an automatic (or administrative process) for including an ingredient in the Register that has been assessed for safety by another regulator with similar regulatory standards. 17. JJFC recommends for novel ingredients not yet approved for use by another regulator, a period of exclusivity is issued to the applicant or the application is fee exempt, with the evaluation fee being covered by combined revenue from annual fees. 18. A comprehensive review of the current proprietary ingredient system needs to be undertaken. The current system introduces complexity and adds to the regulatory burden, particularly for low risk medicines. 19. Reintroduce the self-assessable variation/notification system as existed prior to 2013 for minor quality and non-quality related changes, to bring Australia back in line with international regulatory practices. 20. The TGA should adopt an approach of recognising evaluation reports from other regulators of similar standard, thereby allowing increased speed to market and reduction in TGA resource burden, particularly for products containing well known/characterised actives. 21. If combinations of well-known actives, novel to the Australian market, exist in the countries of regulators of similar standard to the TGA, there should be no need to provide safety and efficacy data for the purposes of registration if there is a history of safe use by consumers in those markets. 22. A review of the GMP clearance system for international manufacturers is required: *Greater recognition and alignment of alternative GMP regimes and inspection frequencies for low risk products *Remove duplication of GMP preclearance reviews: Currently all sponsors that use an international manufacturer must apply for a GMP clearance. This is highly inefficient as the same data is being reviewed several times by the TGA for different sponsors. A better system that frees up TGA resource and allows for a single review for all sponsors should be considered.

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Medical Devices 23. The TGA should adopt the role of a designating authority for domestic Conformity Assessment Bodies (CABs) which can demonstrate competence to evaluate all medical devices requiring pre‐market assessment for supply in Australia. The TGA should expand the scope of devices for which it fully accepts evidence of EU assessment to include those devices which currently undergo a mandatory application audit. 24. The TGA should also fully accept evidence of EU assessment for those devices which currently require a TGA Conformity Assessment Certificate. 25. JJFC supports the intent of the current confidence building program the TGA are undertaking with specified EU Competent Authorities and Notified Bodies and welcomes greater recognition of this trusted international regulatory system as an outcome of the program. 26. The TGA should consider acceptance of the US FDA Premarket Approval (PMA) for Class III devices and Health Canada Class IV Product License. 27. The TGA should align the Australian classification rules and their interpretation so that medical devices have the same classification as in Europe. 28. The TGA should reduce its level of involvement in direct assessment and concentrate resources on post-market regulatory supervision. 29. TGA processes should continue to be digitised building upon the work currently proposed through the Business Improvement Program (BIP). 30. The TGA should continue to be responsible for making the final decision about which products should be included in the ARTG for general supply in Australia. 31. The TGA should remove the current requirement for including Class III devices on the ARTG at the UPI level and allow for flexibility of grouping a broader range of devices within a product family as determined by the manufacturer. 32. JJFC supports the proposal to provide information about the degree to which a medical device has been assessed prior to inclusion on the ARTG. 33. JJFC does not support publication of decisions on medical devices for which applications were not approved. 34. JJFC supports the publication of post-market decisions which are relevant to patient safety only following consultation with the manufacturer and sponsor of the device. 35. JJFC supports removing the Australian specific requirements for the regulation of Tampons and supports a move to fully harmonise with international standards and accept tampons manufactured to the EDANA and FDA requirements.

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Review of Medicines and Medical Device Regulations

Chapter One – Review Details JJFC welcome the review and agree that there are significant opportunities to streamline and simplify requirements and processes in the regulation of therapeutic goods in Australia that would increase access to new and innovative products without compromising quality or consumer safety in any way.

Given our businesses have substantial operations across multiple sectors (pharmaceuticals, medical devices and over the counter medicines) we are in an excellent position to contribute to the review of the medicines and medical device regulations. Our broad healthcare offering affords us unique perspectives on the inter-relationships of Australian healthcare sectors. In addition we are leading contributors to numerous industry groups which gives us a good understanding of impacts for the wider industry. We welcome the opportunity to further contribute to this review or subsequent consultations that might result from the recommendations that will be made by the expert panel.

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Chapter Two – Environmental Factors Given the detail of our recommendations are split across all the Chapters, we have elected not to populate this section so as to avoid duplication.

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Chapter Three – Principles Underpinning the Review. JJFC supports the principles underpinning the review as described in the discussion paper. Comments specific to each principle are provided below.

Principle 1 The role of regulation is to manage risk in order to protect public health and safety.

JJFC comment JJFC supports this principle.

Principle 2 The level of regulation should be commensurate with the risk posed by the regulated products.

JJFC comment JJFC supports this principle however in line with proposal from ASMI, JJFC support the amending of the principle to:

The level of regulation should be commensurate with the risk posed by the regulated products, with the aim being to establish the minimum effective regulation.

Disproportionate rigour impacts the costs of products or reduces access to innovation in this market that may already be available in other markets. Ultimately this will impact the Australian consumer and have a negative impact or unnecessary burden on the public health system.

Principle 3 A risk-benefits approach to the regulation of therapeutic goods is appropriate.

JJFC comment JJFC supports this principle.

Principle 4 The regulation of therapeutic goods should take a whole of lifecycle approach. As a result, the regulatory system must: • Have capacity to source and analyse data as it becomes available. • Recognise and respond in a timely way to changes in the risk profile of products across their lifecycle. • Provide for whole of life solutions, from product development to withdrawal/disinvestment.

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Be transparent and understood by all stakeholders, including manufacturers and sponsors of therapeutic goods, health professionals, and consumers.

JJFC comment JJFC supports this principle.

Principle 5 The ultimate responsibility for medicines and medical devices regulation should remain with the Commonwealth. • Australia should maintain its capacity to undertake assessments of medicines and medical devices for safety, quality, and efficacy. • The role of the regulator undertaking this assessment should be considered in light of approaches taken internationally.

JJFC comment JJFC supports this principle.

It is worth stating that with this review represents tremendous opportunity to remove all complexity in the supply of therapeutic goods with in Australia. The various states legislation introduces a plethora of challenges in terms of supply of therapeutic goods which could be simplified if all aspects of therapeutic good regulations are moved to the commonwealth level.

By way of example, a state issue that could be harmonised at a commonwealth level is the location of scheduled products in the retail environment. In some states, all scheduled medicines are effectively behind the counter medicines (including schedule 2 medicines) and requires interaction with a pharmacy assistant (at a minimum) or a pharmacist to purchase S2 medicines. One could argue that for S2 medicines there is more benefit to the public health system in having a harmonised retail model more aligned to that of NSW and Victoria where consumers can take the time to read label of a medicine and determine if an S2 Medicine is appropriate for their use (whilst maintaining the option of discussing their choice with a pharmacist or pharmacy assistant).

Another good example of complexity that is introduced by not having Commonwealth legislation is the issue of sampling of therapeutic goods. In some states sampling to the general public of unscheduled medicines is permitted (ACT, SA, QLD, TAS) whilst in other states (NSW, WA, NT, VIC) this practiced is not allowed. In some cases exemptions may exist (NSW) and in other cases permission can be obtained on justification and provision of sampling details (NSW, VIC).

Appropriate sampling activities for suitable therapeutic goods can provide consumers the opportunity to try a product at no cost to determine whether the product is suitable for their needs. This may be particularly useful for some higher cost consumer goods such as Nicotine

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replacement therapies, where the format of the therapeutic good can have a huge impact to consumer compliance to a regimen and ultimately the cessation of smoking. The benefits to the public health system for successful attempts at smoking cessation are significant and do not need to be quantified for the purposes of this review.

As a final example, Part 4 of the Poisons Standard is a record of decisions regarding the classification of medicines and chemicals into Schedules. States and territories can then adopt the Poisons Standard in a variety of ways: either by reference or by specific stipulation in legislation. However, each jurisdiction reserves the right to implement a different scheduling decision from that included in the Poison standard. As a result of this practice, there is a degree of complexity for sponsors and a resource impost on the TGA as they currently maintain a list of variances in each state and territory from Part 4 of the Poisons Standard; http://www.tga.gov.au/australian-state-territory-variations-part-4-poisons- standard.

JJFC advocates for commonwealth responsibility for all aspects of regulation of therapeutic goods in Australia

Question for consideration: Are there any additional principles that should be considered?

JJFC comment JJFC believe the principles outlined above, with the inclusion of the amendments described are adequate for the purposes of the review.

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Chapter Four – Regulation of Prescription Medicines It should be noted that JJFC have contributed to and broadly supports the submission made by Medicines Australia but wishes to provide further recommendations in this submission.

Considering the Global Regulatory Framework in Addressing Identified Themes: JJFC understands the need to separate assessments of regulatory and reimbursement agencies despite the fundamental connection between the two. The discussion paper neatly summarises the relationship:

“…timely access by Australian consumers to new medicines is generally dependent on timely decisions about both product registration and subsidy. The TGA and the Pharmaceutical Benefits Advisory Committee (PBAC) currently have parallel processes, whereby a submission to the PBAC may be lodged at any time from the date of lodgement of a TGA registration dossier. Any delay by sponsors in lodging a dossier with the TGA would, therefore, have potential flow on effects to subsidy decisions.”

Regulators play an important role in ensuring safe and effective medicines reach patients. Generally, registration is seen as an appropriate way to protect the interest of Australian citizens. JJFC believe that the TGA holds an exemplary reputation amongst global agencies in terms of quality of assessment. The discussion paper has highlighted areas where regulatory processes inadvertently can delay access to medicines. In addressing these areas, JJFC believe that it is important to both global regulatory frameworks and the evolution of evidence to deliver a robust yet flexible system.

Medical development remains driven by return on investment. Regulatory and reimbursement systems provide market signals based on evidentiary requirements which drive these decisions. Presently, much investment is being made into areas of high unmet clinical need but with limited patient populations.

In oncology, for example, smaller patient populations and the increasing understanding of different genetic profiles within cancer types, reduces the availability of data which can be generated within Phase 3 clinical trials. Furthermore, relevant measures to determine efficacy and safety may take time which is not commensurate with development. As identified, the reduced ability to collect evidence leads inherently to uncertainty regarding a treatment’s risk benefit profile, in a treatment area where the condition can be life-threatening, increasing the tolerance of patients and clinicians for risk. Faster initial approval of products and ongoing partnership between regulators and sponsors to monitor outcomes recognises the changing paradigm for evidence generation globally.

Regulatory agencies have responded to expectations that products which nominally demonstrate significant improvements can be expedited through registration processes to allow

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access. As identified, both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have committed resources to shifting the paradigm for registration with a focus on early entry. Accompanying this acceleration is the recognition that evidence generation is an ongoing process. Through experience, regulators and sponsors of medicines have strengthened the post-market environment, where registration conditions do and will continue to evolve over the product life-cycle. The TGA is well equipped to influence adaptive licensing around the world as it proliferates.

JJFC recognise the need to balance the benefit of earlier access against uncertainty in risk profiles. Keeping this in mind, our recommendations focus on where improvements should be made.

New Chemical Entities (NCE) and Expanded Indication Pathway: Alignment with trusted regulators should be considered to expedite approvals and avoid duplication of review processes. Trusted regulators should be limited to countries with similar populations and aligned regulatory standards i.e. FDA, EMA and Health Canada (HC).

JJFC propose a two-tiered accelerated regulatory system based on the current FDA definitions, given accelerated approvals seem mainly driven by the FDA regulatory agency at this time.

Whereby if a medicine has been granted by the US FDA: - Breakthrough designation and subsequently approved; or - Fast track designation and subsequently approved An Australian sponsor could then opt for automatic approval in Australia - addition to the Australian Register of Therapeutic Goods (ARTG) - based on an assurance that the product is identical to that supplied in US with the exception of artwork and Product Information which would be localised and provided to the TGA for review prior to automatic approval. Localised documents should be reviewed and approved by TGA within 45 working days.

Medicines granted FDA designation of: - Priority evaluation; or - Accelerated approval Should be streamlined for review by the TGA (estimated approval within six months as per FDA) - the details of this process can be open for discussion however would likely involve an increased fee for service to allow resourcing capabilities and moving submission to top of the evaluation queue.

We also propose that the TGA should create an internal fast-track designation to allow for situations where the US clinical practice does not align to AU but where a medicine would still meet the criteria for unmet medical need in the local setting (the definition of this can be discussed in the consultation).

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For submissions automatically approved after review by FDA we propose that the requirement for an RMP be waived as an EU-RMP is unlikely to be available at the time of submission.

If a product is automatically accepted as approved by TGA, using an FDA decision, and a consequential EMA or Health Canada (HC) decision is made to reject the submission, then further supply of the product would be temporarily placed on hold whilst the EMA and/or HC evaluation reports are provided to TGA for independent review. At this point TGA will agree to review the EMA/HC and either ratify or reject the EMA/HC decision within a defined timeframe. Existing patients will continue to receive treatment but no new patients will be initiated until the final TGA decision is reached.

Good Manufacturing Practice (GMP) Clearances: A key area that could be reviewed in the minimising of red tape within the regulatory process is the unnecessary duplication conducted by the TGA to review GMP certificates issued by other trusted overseas authorities. If automatic approval is granted by the TGA using overseas decisions, the ability to obtain GMP clearance to support approval this may be difficult to obtain and may undermine the fast-track approach.

We question the need for the TGA to re-evaluate GMP data already approved by a trusted overseas agency – therefore we propose to remove the need to obtain GMP clearance for sites already audited members covered by MRA or where audits have been conducted by regulators of similar regulatory standard, irrespective of the site’s location.

This is also further discussed in chapter 6 in “Acceptance of Alternate Standards & Inspection Frequency for GMP Requirements”.

Application Entry Team (Case Managers): A key part of accelerated access is a flexible approach at the application entry stage. The TGA’s move to institute a case manager system for prescription medicine submissions has had a negative approach on the sponsor’s ability to obtain accelerated approval as the case managers are often inflexible and rigid according to their understanding of the submission requirements (which are often unclear and subject to interpretation).

JJFC urge the TGA to consider a change to the case manager approach - to ensure that a more customer and solutions focused approach is taken so that accelerated review options are possible. Improved communications would also assist in minimising excessive calls to the case managers and therefore improve resource capabilities – maybe a portal with dates and letters would be an appropriate solution.

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Chapter Five – Regulation of Generic Medicines and Biosimilars

Biosimilars: Our Company has long maintained that biosimilar medicines are similar, but not the same, as those they reference. Given the complexity of these molecules and lack of information regarding interchangeability and extrapolation of use surrounding biosimilars we believe that an accelerated pathway would be inappropriate for these types of medicines.

Since biosimilars would not fulfil an unmet clinical need, given the originator product is already registered, JJFC believe that the current regulation of these products should continue unchanged (i.e. accelerated approvals for these products would not fulfil an unmet medical need).

While Our Company has a long history of supporting efforts to establish an approval pathway for biosimilars, this has only been in circumstances where patient safety is maintained. We note that overseas regulators have taken different approaches to the approval of biosimilars, particularly in relation to the indications for which they will be granted. Therefore it is important that the TGA maintains its ability to undertaken an independent assessment of these medicines.

Bioequivalence of Generic Medications: Currently the TGA requires that a generic medicine demonstrate bioequivalence to the local innovator product prior to registration in Australia. If bioequivalence has been demonstrated to a branded product in EU, US or Canada and this product has demonstrated safety profile in these countries and the two products are similar qualitatively to other products with the same key active ingredient in Australia, then we would propose that bioequivalence to a local innovator should not be required as any deemed risk to patients would be low.

Variations to Prescription Medicines: Timelines and the level of information required for variations to products have regressed recently due to the TGA’s changes in their interpretation of the legislation that allows sponsors to make certain changes to the manufacturing conditions if deemed to be of low risk. Previously certain changes were permitted as self-assessable (Appendix 12) however the TGA has taken a more risk-averse position and now require all variations to be reviewed and approved prior to implementation.

This additional burden can prevent innovation in manufacturing (contrary to the EU Quality by Design approach which allows sponsors to implement pre-defined changes) and can also adversely impact supply chain.

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Chapter Six – Regulation of Over the Counter Medicines It should be noted that JJFC have contributed to and broadly supports the submission made by ASMI and ACCORD but wishes to provide further recommendations in this submission.

Theme 1: Regulatory requirements are not commensurate with risk Issue 1 – Scheduling Framework

1. Reclassification In recent years, Australia has become very risk averse with switch (down-scheduling) activity and there has been a significant decline in the number of switches since 2006. This is also true for applications made to included substances in Appendix H allowing Schedule 3 medicines to be advertised direct to consumers. The intent of Appendix H was to ensure consumers were made aware of treatment options available to them without a prescription. As far as JJFC is aware, the last molecule to be included in Appendix H was Fluconazole in October 2003 (39th Meeting of the NDPSC), despite numerous applications to included substances in Appendix H.

Globally, Australia is not considered to be a lead country in terms of switch. The UK and New Zealand are both viewed as countries that embrace/encourage switching of molecules that would be appropriate for consumers to use without the need for a prescription.

The graph below represents switch activity in Australia since 1993 (adapted from data compiled by ASMI).

Switch History in Australia 60

30 Switch Reverse switch 20 Number of of Number switches

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

JJFC believe that consideration should be given to the switching/reclassification/down- scheduling processes from other countries with equivalent regulatory systems and standards. This review represents an opportunity for Australia to establish a more efficient and streamlined process that can be considered “gold standard”.

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Concerns with the current switch process It should be recognised that improved access to effective medicines, improved clinical outcomes, and improved involvement by consumers in their health represent benefits to the consumer, and should be considered in the assessment. Like ASMI, JJFC supports the adoption of a consistent and transparent methodology for assessing benefit versus risk. ASMI has previously endorsed the adoption of the value-tree framework approach developed by Brass et al1. The framework described by Brass et al has been adopted by a number of other regulators, including the MHRA.

It should be brought to the attention of the expert panel that since the scheduling decisions became the responsibility of the Department of Health (the delegate); the end to end process is now taking longer. Importantly, the implementation date has become inconsistent, leaving sponsors with less time to effectively plan and implement the artwork changes necessary by the scheduling effective date.

Where this becomes critical is when scheduling decisions require the consideration of new warning statements. The delegate refers this to the OTC section of the TGA to determine the final warning statements. In practical terms this means sponsors are required to understand what the new warning statements will be, submit an application to the OTC section (can be “new” application or variation depending on the switch) and gain approval all within the implementation timeframe which is extremely tight and inconsistent from one scheduling item to another.

Under the current system warning statements can all change again once the warning statements are subjected to a separate consultation process prior to the inclusion of the warning statements into the Required Advisory statements for Medicine Labels (RASML).

The current process is disjointed and cumbersome, resulting in unnecessary labelling changes in quick succession which is disruptive, costly and inefficient; leading to a lack of consistency in warning statements for products with the same active and classification until the warnings are ratified in RASML. Detailed below are specific examples of the current disorderly process. These specific examples are being provided in confidence.

(Information on specific company switch activity to remain confidential) LOPERAMIDE

In 2011 loperamide was rescheduled from Schedule 2 to unscheduled, when presented in pack sizes 8 or less. Below were the key dates and milestones:

1 Brass EP, Lofstedt R, Renn O. Improving the Decision-Making Process for Nonprescription Drugs: A Framework for Benefit-Risk Assessment. Clin Pharmacol Ther 2011;90:791-803

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• ACMS meeting: June 2011 • Interim decision: August 2011 • Final Decision: September 2011 • Implementation date: 1 May 2012

What was clear in the Delegates final decision was that label warnings would be referred to the TGA for final determination. As the company submitting the switch application we were privy to the fact that the labelling warning statements were going to be discussed at the December 2011 ACNM meeting following numerous conversations with the OTC section. Following the ACNM meeting we were informed that additional warning statements would be required for “all” OTC loperamide products (both unscheduled and OTC scheduled), which JJP implemented in time for the May 2012 effective date. However, given new warning statements are required to be consulted through RASML, during this period of consultation this brought to light warnings that were not warranted, and as a result the final position which was published in May 2014 did not reflect all warnings initially requested by TGA in December 2011.

JJP is now in a position where additional warnings are included on its loperamide products, even though they are not required. Additionally, these warnings are not included on the packs of competitor products. A C2 application is required initially to remove the signal headings. Following ratification of the warnings in RASML, another C2 application is required to remove unnecessary warning statements. This situation is unique to the company initiating the switch.

When companies are given advice on warning statements right after a switch they are not final as they do not include the consultation period for RASML. JJFC questions the appropriateness of this approach. Using the current scenario it clearly demonstrates how an innovative company, that has invested time, money and resources into a switch that would be to the benefit of the Australian consumer, is commercially disadvantaged i.e. a competitor not involved directly with the switch application is able to remove the signal header only without introducing additional warnings. From a consumer perspective, side by side comparison of the innovator and generic product, the consumer will consider the generic product to be safer on the basis that it has fewer warnings on the pack. This is certainly not the case. This process is ineffective, has a lack of consistency between sponsors and burdens sponsors with making two lots of labelling changes in quick succession.

CETIRIZINE: In 2012 cetirizine was rescheduled from Schedule 2 to unscheduled under certain conditions. Below were the key dates and milestones:

• ACMS meeting: June 2012 • Interim decision: 5 September 2012 • Final Decision: 10 October 2012 • Implementation date: 1 January 2013

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JJP had discussions with OTC section of the TGA following the publication of the Delegate’s Final decision in October 2012. We should note that the implementation date was unusually extremely tight (less than 3 months following the final decision), which also demonstrates the lack of consistency with scheduling implementation dates, giving sponsors very little time to plan effectively.

The advice from the TGA was that a New Medicine application was required for the unscheduled product due to the differing indication to the schedule 2 product, and that additional warnings were required to be added to the label. JJP implemented all TGA required warning statements, however again JJP finds themselves in the situation where unnecessary warning statements, additional to those required by RASML, are on its cetirizine containing product labels.

It is apparent that our competitors have not been required to include the additional warning statements on their product labels, again demonstrating inconsistencies and resulting in the innovator company being commercially disadvantaged. Again, additional applications and packaging changes will be required by JJP to “level the playing field”. JJP is of the opinion that this practice is not acceptable and we request that the expert panel take these examples into consideration and make recommendations that will result in a model that will encourage innovation and reward companies that invest in innovation and down scheduling.

In addition, as noted above, scheduling changes require signal header changes in the majority of cases. Given the inconsistent implementation timings it means that sponsors have very little time to sell through existing products and implement the new artwork with revised signal header by the implementation date or plan for new production runs with new artwork.

The current process to sell through stock with the incorrect signal header is to apply for an exemption through the individual states and territories. JJP suggests that this represent an opportunity to streamline this process by adopting a commonwealth approach which will also ensure consistency.

2. Poor Guidance Documents The guidelines for making a scheduling application are poor and really do not provide sufficient detail to allow companies to make effective applications. This needs to be addressed.

3. Insufficient detail in Reasons for Delegate’s Decisions The level of detail made available in the reasons for the delegates decision is light when compared with the level of detail in the record of reasons previously published by the NDPSC. This is disappointing as it makes it difficult for sponsors to address the concerns of the committee in subsequent submissions.

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4. Lack of Parallel Scheduling Consideration and Registration Evaluations Under the previous scheduling framework the TGA accepted Schedule 10 route of evaluation applications in relation to rescheduling applications. This has now changed, and the TGA OTC Medicines Section will not consider applications to register a new OTC medicine until the Delegate’s final decision has been published. The result of this is that some well-known active ingredients, when presented in different dosage forms (e.g. transdermal vs. topical; oral spray vs. buccal preparations) are required to go through the scheduling process prior to an application for registration being submitted, thus causing delays for sponsors and also provides competitors with intelligence as to future launch plans for these products, given that calls for comment are published prior to the registration applications being considered by TGA.

5. Lack of Exclusivity Under the current model of scheduling there is a lack of exclusivity for any company that invests in switching. JJFC would support a model that allows a period of market exclusivity that is commensurate with the degree of innovation and investment that is required to recoup investment and costs associated with any rescheduling activity. This would act as an incentive to research new therapeutic claims and products. Currently there is no or limited incentives. As stated in the Discussion paper, The Pharmaceuticals Industry Strategy Report in 2008 noted that increasing healthcare costs were driving an increased focus by governments around the world on involving individuals in healthcare, particularly through encouraging the use of OTC medicines. The current framework does not support this thinking and an alternative approach would be to adopt the practice of reclassification/products as opposed to reclassification substances. Such a practice has been adopted in the UK and provides an incentive for sponsors to make submissions to reclassify products appropriate for consumer to use without a prescription.

6. Review of Scheduling Decisions Sponsors or other persons who are adversely affected by a decision relating to scheduling or inclusion of substances in the appendices of the SUSMP ought to have access to a full range of review processes (including both merits review and judicial review). The current framework does not give sponsors or persons adversely affected by a decision any recourse.

7. Lack of Detail to Scheduling Proposals Call for public comments on items on the agenda for scheduling lack detail. This review represents an opportunity to ensure that scheduling agenda items have more detail and background to the proposals, as industry can be left unsure whether a scheduling agenda item affects them, as was the case with the thymol re-scheduling item in 2012.

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With this specific example, in 2012 a scheduling agenda item was referred to the delegate to propose a new Schedule 6 entry for thymol. This was all the information industry were given.

Thymol is an ingredient used in chemicals, veterinary products, cosmetics and in therapeutic products for human use. No back ground to this scheduling item was provided therefore it was impossible for industry to determine whether the scheduling affected them (i.e. for human use) nor was there the opportunity for industry to address the concerns raised in the submission proposing the creation of a new schedule 6 entry for thymol. As the proposal was referred to the ACCS, it seemed appropriate to assume that the concern was more likely to be around thymol used in chemicals and veterinary type products, however due to the nature of the Poisons Standard, a new scheduling entry for thymol under Schedule 6 would impact all types of products containing this ingredient, including therapeutics and cosmetics for human use, therefore it was pertinent for sponsors with products containing thymol to make a submission.

With the benefit of hindsight, we know now that the proposal was for products for veterinary use. More background to the scheduling item would have ensured that industry would have been clear on the scope of the scheduling item, saving them from unnecessarily making submissions.

Issue 2– Direct-to-consumer advertising of Schedule 3 Medicines The current framework of direct to consumer advertising of Schedule 3 medicines is incredibly risk averse and is out of step with international practices. The intent of Appendix H allowing a specific molecule to be advertised direct to consumers was to inform consumers of treatment options available to them without the need of a prescription. This resource has been underutilised as it has been claimed that there is no demonstrated benefit by advertising direct to consumers.

There are some huge potential public health benefits by allowing more Schedule 3 medicines to be advertised direct to consumers. The reality is that if consumers are made aware of the available treatment options without a prescription, there is potential to reduce the burden on primary care physicians. As a result of the continued lack of this awareness of product availability by consumer, consumers continue to consult GPs for conditions which could be safely managed by pharmacists. Poignant examples are: chloramphenicol, an antibiotic in Schedule 3 which is indicated for the treatment of bacterial conjunctivitis or; any of the proton pump inhibitors indicated for the treatment of the symptoms associated gastro oesophageal reflux disease (GORD). It was been well documented that consumers that suffer from the symptoms of GORD do not see a physician until the symptoms start to significantly impact their quality of life. Until such time consumers who suffer from these symptoms tend to take antacids because they are unaware that there may be more appropriate/more efficacious medicines for to manage or treat their symptoms or condition. As a result consumers are being mistreated.

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Australia has the ideal model to permit direct to consumer advertising of Schedule 3 medicine by way of the need to interact with the pharmacist prior to purchase of the medicine. This model is not available in all countries – There are sufficient safeguards in place to ensure consumers are appropriately diagnosed and treated with the appropriate medications.

It should be pointed out that there is now a 16 year track record of direct-to-consumer advertising of a limited number of Schedule 3 Medicines with no evidence of any detriment to public health and safety.

JJFC is aligned with the proposal submitted by ASMI in previous consultations. In brief this proposal suggests the following: • Any product that is deemed suitable for sale without prescription should, because of that approval, be able to be advertised (the default position is that advertising of S3 products is permitted). • The advertising should be under the present regulatory controls over advertising of therapeutic goods (with a consistent and structured communication format balancing the following three components: information about the condition; promotion and reinforcement of the role of the pharmacist; branded product information). • Where the regulators can make a case (based on published evidence or where there is a strong case for applying the precautionary principle, and appealable on administrative law grounds), individual advertising bans in respect of particular products could be considered (so that exceptions are available where warranted).

Issue 3 – Regulation of low-risk therapeutic goods JJFC believe there is opportunity for lower regulatory intervention for low risk therapeutic goods, in particular sunscreens, without compromising product safety, efficacy or quality. A number of opportunities have been identified below.

1. Sunscreen regulation and classification Sunscreens are topical products used to protect consumers from the effects of ultraviolet radiation generated by the sun. They are products used on otherwise healthy individuals and are not used for symptomatic relief or treatment of a disease, ailment, defect or injury. Regardless of classification all sunscreens are required to meet the AU/NZ sunscreen standard 2012 which includes specific requirements for SPF testing. The key quality aspect of a sunscreen is that it can meet its SPF label claim throughout its shelf life. The Australian standard requires all sunscreens to be tested. The SPF requirements set out in the Australian sunscreen standard are the most stringent requirements globally.

The regulation of sunscreens in Australia is unique and the lack of harmonisation poses unnecessary difficulties and burdens on sponsors. JJFC has the following concerns with the current regulatory framework for sunscreens:

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1.1 Complex Classification The classification of sunscreens is complex and difficult to describe to other markets. Sunscreens are divided into Primary and Secondary sunscreens (i.e. secondary sunscreens being those that have a primary cosmetic benefit and a secondary sunscreen benefit). Sunscreens are declared medicines and are regulated as listed medicines. A proportion of secondary sunscreens are regulated as cosmetics if they: • have an SPF no greater than 15, • a pack size no greater than 300 mL, • are not represented to be water resistant • do not include a therapeutic claim e.g. prevention of skin cancer.

Sunscreens are regulated as cosmetics in Europe. In Europe sunscreens are required to meet the ISO or Colipa (International) standard for SPF testing. In the USA sunscreens are regulated under the FDA via an OTC monograph where the manufacturer places the products on the market based on a self-assessment of compliance to that monograph. In Canada the regulation of sunscreens is also being reconsidered.

JJFC believes that the regulation and any sub-classification of sunscreens in Australia should be simplified. Ideally there should be one product classification in our market.

1.2 Proposed changes to in vivo safety testing for cosmetic ingredients The evaluation of ingredients for use in Sunscreens new to Australia will be impacted by the ban on the use of animal testing in ingredients used in cosmetics in the EU and the call for a similar ban in other parts of the world including Australia. Both the cosmetic ingredient regulator (NICNAS) and the TGA rely on traditional toxicological endpoints involving animal data to evaluate new ingredients. Acceptance of other ingredient safety assessments needs to be considered

1.3 Lack of harmonised pharmacovigilance requirements As sunscreens straddle 2 possible classifications, AE reporting requirements are vastly different between the two different regulators (TGA and ACCC). The TGA has a long established, respected record and significant expertise in handling pharmacovigilance reporting for therapeutic goods. We believe that the ACCC should have aligned its definition of a serious adverse reaction (i.e. reportable event) and reporting periods with those of the TGA. Any products that are removed from therapeutic good regulation will become subject to ACCC adverse reaction requirements. It is questionable as to why a relatively small country has 2 separate reporting regimes for this activity. There might be an argument for a single agency to manage the reporting of adverse events or incidents, irrespective of product classification.

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Proposals JJFC suggests the following possible alternative options of sunscreen regulation that recognising that neither is ideal due to potential related changes to other Australian regulation and their unknown impacts:

Option 1 Regulation of all sunscreens as cosmetics as proposed by ACCORD with the following caveats: • a viable and cost effective avenue is made available for the market authorisation of novel or innovative sunscreens that do not fully meet the requirements of the AU/NZ sunscreen standard • pharmacovigilance reporting requirements that are aligned with those of the TGA • automatic acceptance of ingredients in recognised market databases • recognition of IFFRA compliance for fragrance ingredients • cosmetic regulation is product based

Option 2 A model using the definition of Primary and Secondary sunscreens aligned with the Australian Standard AS/NZS 2604:2012: o Primary sunscreen: A product that is represented as being primarily to protect the skin from ultraviolet radiation o Secondary sunscreen: A product that is represented as having a primary function (cosmetic) other than sun protection whilst providing some protection of the skin from ultraviolet radiation (these sunscreens should not claim any water or sweat resistance) • All secondary sunscreens are cosmetic, regardless of SPF or pack size • Primary sunscreens remaining regulated pursuant to the Therapeutic Goods Act with the following changes proposed: o A model requiring less regulatory intervention such as a Sunscreen monograph system which operates distinctly from the current OTC monograph system in place (more aligned with the US OTC monograph system) o An exemption from the requirements of GMP under Part 3-3 of the Therapeutic Goods Act o Raw materials are not required to meet a default pharmacopoeial monograph standard.

JJFC is a member of ASMI and ACCORD and have contributed to their discussions. JJFC endorses the proposals regarding reduction in regulatory burden for sunscreen medicines. As with any regulatory changes, further consultation on any proposed model will be required. JJFC looks forward to contributing to any such future consultations.

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2. Removing the need for PIC/S GMP for topical products or acceptance of alternate standards and inspection frequency for GMP requirements There is a need for greater recognition and alignment of alternative GMP regimes and inspection frequencies for low risk products, particularly topically applied products (including sunscreens).

The US FDA inspects manufacturing premises at a frequency based on risk of product type and process. Thus for listed medicines (including sunscreens) the current GMP preclearance expiry of 3 years is not aligned with the US re-inspection period which varies and commonly is around 5 years for low risk medicines.

This misalignment between the GMP Clearance expiry and inspection frequencies of other regulators can impede the introduction of a new listed product manufactured in other countries. Currently the only option in this instance is to have the TGA inspect the manufacturing facility or the sponsor withdrawing a product from the market or not launching new innovation. As well as funding the inspection, which can be as high as $75,000 AUD, this reduces competition and is not in the best interest of the Australian Public health.

(Information on specific company activity to remain confidential) Australia is a very small market compared with a number of other markets, especially the USA. For one of our Sunscreen manufacturers in the US, product produced for the Australian market represents a total of 0.1% of its total annual income. The GMP Clearance is due to expire, and an FDA Audit is unlikely to occur for another 2 years. Consequently the manufacturer has no need or desire to host the TGA for an inspection of its facility. As a result the innovation that had been planned for the next sunscreen season has been cancelled.

3. Removing the need for pharmacopoeial monograph standards for all ingredients for topical products. One of the current regulatory requirements for listable medicines is that all ingredients whether actives or excipients, must meet the requirements of a pharmacopoeial monograph if one exists. This often causes issues in particular with imported products as this is not a requirement in other markets such as EU or the USA for lower risk topical products such as sunscreens.

In many cases food grade or cosmetic grade excipients are used in these markets, and upgrading testing to pharmacopoeial grade is expensive, onerous and unnecessary for a low risk topical product. If the manufacturer cannot upgrade to a pharmacopoeial grade raw material then the product will not be launched in the Australian market which puts the local consumer at a disadvantage in not having access to safe and effective products that are available in other comparable markets such as the EU or the USA.

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JJFC proposes that the requirement to meet a pharmacopoeial monograph for all ingredients be removed for low risk medicines, in particular for topically applied products, and allow the use of food or cosmetic grade ingredients as an alternative.

4. Pre-approval of excipient ingredients new to Australia by recognition of other country/region ingredient inventories The current system is overly onerous, expensive and time consuming. It can (and has) resulted in the delay of products (some of which are seasonal) for reasons other than quality or safety. In order to include a new ingredient in a listed medicine one must first apply for inclusion of the ingredient in the Register by submitting an application for an approved name and a safety/toxicological assessment. Additionally, the expense is borne by the sponsor company, however, once approved, there is no exclusivity for the sponsor company, the ingredient then becomes available for all companies to use.

Below is a specific example which has created significant business uncertainty and risk to the launch of new sunscreen product in Australia.

(Information on specific company activity to remain confidential) In anticipation of the launch of a new sunscreen for the 2012 summer season (product launched in the US in the previous US sunscreen season) an Ingredient application was submitted and received by TGA 10 May 2011. It concerned 2 new excipient ingredients. The first ingredient was a mixture of 3 polymer type chemical constituents. These were approved 6 July 2011, 22 July 2011 and 26 July 2011 respectively (i.e. approximately 2 months post submission).

The other excipient ingredient included a herbal substance extracted from the lotus flower which has been used traditionally as a medical herb for over 1500 years. It is our understanding that matters concerning the safety of the lotus flower extract for use in topical applications up to 0.1% as included in the intended products were resolved 4 August 2011. The final approval for this ingredient however was not given until 29 November 2011 (i.e. just over 6 months) after diligent follow-up. The delay in this approval was due to the bureaucracy that surrounded whether this ingredient could be included in the Register as an Australian Herbal name (AHN) or an Australian Approved name (AAN). On the 26 October 2011 it was agreed to give this ingredient a temporary AAN to facilitate approval.

The delay in achieving this approval meant uncertainty for our business and to those businesses we supply.

The following additional considerations applied to the supply of the sunscreen concerned:

a. Sunscreens are a seasonal product and the major supply of sunscreen products are through the grocery channels. In order to supply product for the 2012 summer season the

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product had to be provided to grocery on the 1st June or the 15th June 2012 (depending on the retailer). b. The latest production run that would get the product to the trade in time for that season was 26th January 2012. Any later would have missed the grocery sell-in period. (This period is fixed by the retailer and is not negotiable). c. Once produced the product needed to be filled into Australian unique labelling (in this case packaging had to be ordered and printed with Australian unique labelling at risk prior to ingredient approval and product listing with subsequent addition of the AUST L number to the label when known (over-labelling)).

The delayed approval involved substantial direct and indirect costs plus potential loss of shelf space in grocery which is very difficult to retrieve in the current retail environment.

JJFC takes the position that: • Where an ingredient has already been evaluated by other Agencies either in Australia or by other equivalent foreign countries, the process for including the material in the Register should simply be an administrative activity and should not attract an application fee (but should be covered out of the combined revenue from annual fees). • Where an ingredient has not been approved in a comparable market, the process for including the material in the Register should be streamlined and should not attract an application fee (but should be covered out of the combined revenue from annual fees) – Alternatively, a period of exclusivity should be considered for the applicants.

5. Review of the Proprietary Ingredient System If a Proprietary Ingredient that contains active ingredients needs to change to alternative proprietary ingredient, a new ARTG entry is created, even if the quantities of the actives are identical. Consideration should be given on how these can be grouped as opposed to creating a separate and distinct good.

6. Variations of Listed Medicines Minor changes to levels of restricted excipients (excipients for which there is a concentration limit which can be used in listed medicines) within their approved restriction, or changes in excipient of the same function e.g. changing the preservative system automatically result in a new AUST L number for the product. This introduces unnecessary cost and disruption as it requires the sponsor to change the product label to reflect the new AUST L number before the changed product can be supplied.

We propose that sponsors should be able to vary their listed details without generating a new AUST L number where those changes themselves do not directly affect the label. This would involve amending the Therapeutic Goods Groups Order(s).

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Issue 4 – Variations to registered OTC medicines Low risk, changes to medicines should be allowed by way of notification. This was the practice of the TGA until only a few years ago (ca. 2013) when the TGA overturned years of accepted regulatory practice of self-assessable notifications, despite there being no changes to section 9D of the Therapeutic Goods Act.

Prior to their removal, the self-assessable notifications provided both the TGA and sponsors with an efficient and cost-effective mechanism tom implement low risk changes. These changes included, but were not limited to: • Label changes in compliance with revised SUSMP requirements, • Decreasing a product’s shelf-life, • Adopting more restrictive storage conditions, • Adding an additional pack size.

The TGA’s reforms removed the ability for sponsors to affect these changes by way of notification and instead required the TGA to individually approve every change before a sponsor could implement it.

In other countries, including New Zealand, minor non-quality and quality related changes are still considered “self-assessable” and prior approval is not required prior to implementation of the change. However, the notification must precede the implementation of the change and the onus is on the sponsor to ensure that data to support the change are held and could be made available on request. In some other countries, minor changes made to a products on an annual basis after the changes has already been implemented.

Australia is now out of step with international practices.

Theme 2: Overly Burdensome Processes 1. Overseas Evaluation Reports JJFC believes there is an opportunity for the TGA to develop a risk based process to reduce TGA evaluation based on comparable agencies’ evaluation reports, particularly for new indications or routes of administration. Medsafe already have the Abbreviated Process for prescription medicines whereby they will consider evaluation reports from recognised health authorities.

JJFC believes that is a similar approach was considered for the higher risk non-prescription medicines (N4 and above) will reduce duplication and the level of clinical data required, which in turn will streamline and speed up the process.

JJFC also questions the need for the provision of safety and efficacy data for new combinations of existing well known actives (e.g. Ibuprofen and Diphenhydramine – a fixed dose combination

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currently available in the USA and Canada, but not Australia), new dosage forms of existing actives (unless their performance is formulation dependent) especially if there is a history of safe use by consumers in other countries with regulators that have standards to the TGA.

(Information on specific company application to remain confidential) A notable example where there could have been an opportunity for TGA to reduce evaluation based on comparable agencies’ evaluation reports, was an application made by Johnson & Johnson Pacific (JJP) in 2010 for NICORETTE QuickMist Mouth Spray.

This product contains a well-established OTC active ingredient (nicotine) in a novel dosage format (mouth spray). The new medicine application was submitted to the TGA in May 2010 and the submission package was in line with the advice that had been provided in the pre- submission meeting.

However, during the course of the evaluation the TGA requested for additional clinical data which was not required by the UK MHRA, a comparable Health Authority. As a result the product was not registered until May 2012, 2 years after the submission and 6 months later than other comparable submissions.

In comparison in New Zealand, the same submission was submitted to Medsafe in May 2010 with approval granted in December 2011 as Medsafe acknowledged and accepted evaluation reports from the MHRA.

This example highlights an example of where a streamlined process and mutual recognition of evaluation reports for new ingredients, combinations, dosage forms, routes of administration and indications from trusted or comparable regulators. This would have had benefits for JJP, TGA and the Australian consumer.

2. Application Processing Significant process improvements have been made since the introduction of the Business Process Reforms (BPR) as it’s an adoption of a risk based approach. However JJFC believes that further improvements could be made to the process.

The TGA had ensured that, with the introduction of the OTC monographs, the valuable time of evaluators would be freed up considerably ensuring evaluators could spend more time on the higher risk products, thus improving evaluation timelines for these applications. However we question how valuable the monograph route has been, and whether there are opportunities to further improve this route of evaluation to ensure sponsors and TGA can see the benefits.

Currently applications with no clinical data with umbrella branding components fall into the higher category of risk – N4. We do not feel that this route of evaluation is appropriate based on the risk profile of the application. The N4 timeframe is longer and the cost is much higher which

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is not justifiable just because of the umbrella branding component. Arguably if a product would otherwise qualify for inclusion in the ARTG by the monograph route (N2) but is only eligible for entry via the N4 route because of an umbrella branding components, JJFC questions why the same level of scrutiny of the quality aspects of the application are not treated in the same manner. This is more likely to result in the desired outcome of reducing the resource burden on the TGA evaluators.

3. International Harmonisation For OTC medicines there are also opportunities to improve international harmonization, especially in regards to Manufacturing including: • Alignment with clearance review periods to ensure to help ensure that sponsors are not repeatedly requesting for GMP extensions for a site purely because we are waiting for an audit to close out or waiting for the next audit. • Multiple desk-top audits for the same site used by numerous sponsors. JJFC believe that a system needs to be developed where there is only one desk-top audit performed by the TGA and that the cost be recovered through other means e.g. through an annualised fee distributed equally amongst sponsors that utilize the site or have the site listed on the ARTG for individual registrations. • JJFC questions why it is acceptable to provide notarized certificates issued by a regulator that has an MRA with the TGA (e.g. MHRA) as evidence of GMP for a manufacturer in the same country (e.g. UK), yet the TGA require the full gamut of documents required for a desktop audit (accepted on a case by case basis) for audits conducted in facilities outside of the auditing country (e.g. Manufacturer located in India, audited by the MHRA). Arguably there is no change in the standard accepted by the regulators irrespective of the geography of the manufacturing site.

Theme 3: Complex Regulatory Framework Issue 1 – New product applications which require a related scheduling decision JJFC has provided comments to this point above in the “Scheduling Framework” section.

Issue 2 – Applications to reschedule substances which require evaluation of new product labels JJFC has provided comments to this point above in the “Scheduling Framework” section.

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Chapter Seven – Regulation of Medical Devices It should be noted that JJFC have contributed to and broadly supports the submission made by MTAA but wishes to provide further recommendations in this submission.

This response is provided in the context of the following principle: …if a system, service or product has been approved under a trusted international standard or risk assessment, Australian regulators should not impose any additional requirements unless it can be demonstrated that there is a good reason to do so2.

Theme 1: Duplication of Regulatory Processes Current regulatory framework and recognition of trusted international standards: As noted in the paper, the TGA currently recognises to a large extent certification from EU Notified Bodies as a third party conformity assessment body and trusted international standard. Notwithstanding, there is still significant scope to review the TGA processes for administering this framework and for reducing the duplication which currently exists in the form of TGA conformity assessments and application audits.

In 2002 the TGA introduced a new regulatory framework which was based on the guidelines published by the Global Harmonisation Task Force (GHTF) and closely aligned with the regulatory systems of the EU. The aim of these reforms was to introduce a regulatory system which is consistent with contemporary international best practices and by alignment with overseas systems, to minimise regulatory burden on industry through elimination of differences in regulatory requirements or duplication of assessments.

The TGA has effectively implemented third party conformity assessment for 98% of medical devices since the introduction of the new regulatory framework in 2002. Based on figures provided to the Productivity Commission Annual Review of Regulatory Burdens on Business (Productivity Commission) – August 20083, almost one third of all devices requiring pre-market assessment, have been entered onto the register based solely on presentation of CE certification. Only 8% have been subject to further review by the TGA via an application audit, with only 2% of device approvals based on direct TGA assessment.

The TGA should expand the scope of devices for which it fully accepts evidence of EU assessment to include those devices which currently undergo a mandatory application audit per Regulation 5.34 such as Class III implantable medical devices and AIMDs. The necessity in the regulations for the TGA to conduct mandatory application audits of

2 Industry Innovation and Competitiveness Agenda, An action plan for a stronger Australia 3 Annual Review of Regulatory Burdens on Business (Productivity Commission) – August 2008 4 Therapeutic Goods (Medical Devices) Regulations

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documentation supporting these devices is repetitive of the assessment undertaken to gain EU conformity assessment certification.

JJFC also believes that the TGA should fully accept evidence of EU assessment for those devices which currently require a TGA Conformity Assessment Certificate according to Regulation 4.1 such as devices that contain a medicine or material of animal, human or microbial origin and Class 4 IVDs. JJFC does not believe the current level of pre-market scrutiny which requires these devices to undergo full conformity assessment by the TGA is the most appropriate model for ensuring their quality, safety and performance and that the current requirement is again repetitive of the assessment undertaken to gain EU conformity assessment certification.

Only in cases with well‐founded safety concerns should additional or alternate requirements apply.

JJFC supports the proposal outlined in the MTAA’s White Paper5 and believes the TGA should adopt the role of a designating authority for domestic Conformity Assessment Bodies (CABs) which can demonstrate competence to evaluate all medical devices requiring pre‐ market assessment for supply in Australia. JJFC believe this approach may address the concerns raised by the TGA and others, and will improve both public health outcomes and public confidence in the TGA and the Australian regulatory framework.

Rigorous supervision of CABs is critical to ensuring their competence so that regulatory controls are adequate to ensure acceptable safety and performance. The paper identifies specific concerns with the variability of EU Notified Bodies and in particular the capacity of some of the smaller Notified Bodies to deliver adequate standards of assessment. JJFC share these concerns and note the presence in the regulatory system of assessors, which may not meet adequate standards, would not only undermine the regulatory system but would also permit unfair competition. Some manufacturers and suppliers may deliberately seek easier assessments in order to compete unfairly with the large majority of ethical manufacturers who willingly submit to rigorous assessment by properly supervised and reputable Notified Bodies.

Furthermore, concerns with the EU system have led to the European Commission reviewing its regulatory framework for devices which includes implementing stronger supervision of the independent notified bodies. Despite the timeframe for final implementation of this reform extending to 2020, our manufacturers are already experiencing an increase in scrutiny by EU Notified Bodies, particularly in relation to assessment of clinical evidence for high risk devices. The GHTF regulatory framework as implemented in Australia and Europe is self-evidently working well. There is no evidence of systemic regulatory failure or of proliferation of unsafe or substandard medical devices or of significant public health concern associated with medical

5 MTAA White Paper: “Improvements to the Australian Regulatory System for Medical Devices” – May2014

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devices in these jurisdictions. Current European reforms are directed to further strengthening the system by eliminating specific deficiencies in supervisory arrangements rather than any deficiency in the regulatory framework itself.

TGA Confidence Building: JJFC supports the intent of the current confidence building program the TGA are undertaking with specified EU Competent Authorities and Notified Bodies and welcomes greater recognition of this trusted international regulatory system as an outcome of the program.

Understanding a review criterion for designating procedures needs to be set, there is concern whether the TGA would have the capability to assess the EU Competent Authorities against these criteria and in fact be able to meet the same requirements expected of an EU Notified Body as the TGA has never been subject to an independent review of its own conformity assessment procedures.

Overall, there should be transparency around the criteria that CABs would have to meet in order to be designated for each class of device. Where a CAB has already been designated by an overseas Competent Authority such as the MHRA in the UK, this should be accepted by the TGA as meeting Australian requirements for designation once each country’s requirements are clearly articulated and understood. Duplication of the designation process should be avoided.

Other International Regulators: The TGA should also consider acceptance of the US FDA Premarket Approval (PMA) for Class III devices and Health Canada Class IV Product License following a comparative assessment of the equivalence of these systems with the design examination process required for relevant devices under the TGA regulatory framework.

Classification Alignment: To support the above proposal for the TGA to have greater acceptance of EU conformity assessment certification, it is essential that alignment of the classification rules and their interpretation be established so that medical devices in Australia have the same classification as in Europe. Whilst relatively few differences exist, those that do create a significant regulatory barrier particularly in relation to the Australian definition of the Central Circulatory System where peripheral vascular products used in the common iliac are currently Class IIb in Europe and Class III in Australia. More recently there has also been an issue for partial orthopaedic implants which are deemed to be Class III in Australia but often remain Class IIb in Europe. In some instances, manufacturers have been unable to continue supply of these devices due to the additional conformity assessment required for inclusion on the ARTG.

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Another poignant example is the Australian Special rule 5.5 “Devices containing non-viable animal tissues or derivatives, or microbial or recombinant tissues, cells or substances”. This rule automatically classifies products such as lubricant eye drops containing hyaluronic acid as a moisturizing agent, as a class III device in Australia while they are marketed in Europe under a lower medical device classification. The rule does not take into account how processed/removed the ingredient is from the animal or microbial origin of the material.

This difference in classification has been an ongoing issue when manufacturers consider the feasibility of supplying such new devices in the relatively small size Australian market at such increased effort and in some cases has resulted in the products not being supplied in Australia. Arguably, this is not in the best interest of the Australian consumer.

Theme 2: Lack of flexibility Converging Technologies: JJFC promote and advocate for an innovation-friendly and patient-centric approach to regulating combination (medicine/device/biologic) products, with standards and requirements that: • Are rational and scientifically-driven • Follow rational and appropriately balanced pre/post-market requirements • Based on the incremental risk and benefit associated with the combination product • Consider patient preference and benefit/risk acceptance In order to expedite patient access to innovative care, JJFC also seeks enhancements in current regulatory process to achieve predictable, consistent, transparent and timely review.

JJFC advocate for a regulatory framework base on the following three principles: • Primary Mode of Action (PMOA) determines how the combination products should be regulated, either as a medicine (drug or biologic) or a device • Regulatory requirements based on incremental risk, balancing patient benefits and safety risks • Allow the existing non-proprietary knowledge base to contribute to meeting evidentiary standards

Biologics: Redundant State and Territory legislation has and continues to delay TGA approved biologic products being made available for patients. In general the State legislation is very out of date and when it was drafted it was not envisaged that TGA registered and evaluated tissue derived products were going to be supplied to the medical community.

Regrettably, the onus is currently on the Sponsor to attempt to resolve these inconsistencies. The examples outlined below, illustrate the red tape that our companies have encountered regarding the launch of DBX Osteoinductive Human Allograft and FlexHD Pliable Human

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Acellular Dermal Matrixover over the last 18 months. JJFC invested hundreds of hours of legal review in order to work through these challenges. Further detail is available on request. The states that posed significant challenges were Western Australia, Queensland, Victoria and Northern Territory. Below is an example experienced by our company. These examples are being provided in confidence

(Information on specific company application to remain confidential) Queensland: Every hospital needed to apply for an individual permit and our companies were not able to promote or sell prior to the approval by the State Health Department which on average took 3 months per application.

Victoria: Every hospital needed to apply for an individual permit, but after lengthy correspondence and several meetings the Health Minister agreed to issue a blanket permit with several conditions related to promotional material reviews and ongoing reporting of adverse events.

JJFC proposes urgent consultation with State and Territory Governments to identify and repeal redundant and duplicative legislation and regulations which impact the provision of TGA- registered therapeutic goods to patients.

Finally we wish to highlight there are significant differences between regulatory frameworks around the world for human tissue derived products. There is no harmonisation between the regulatory frameworks and how the perceived risks associated with the type of tissue products produced nor the production processes used in processing the tissue are to be handled by manufacturers and suppliers. Of greatest concern and difference is the interpretation of the Quality Systems requirements for the facilities involved in the testing and processing of the tissue. The differences are mostly in the application and evidence required to show compliance between the US 21 CFR Part 1271 and the Australian code of good manufacturing practice for human blood and blood components, human tissues and human cellular therapy products, 2013.

Theme 3: Regulatory requirements are not commensurate with risk Variations to Medical Devices: JJFC would like to reiterate concerns raised in the paper regarding delayed review times for assessment of changes which can ultimately impact the continued supply of affected medical devices to Australian patients. The review should consider the systems used by overseas regulators to manage variations to medical devices on a risk basis, including through notification and/or annual reporting which could result in significantly shorter review times than current TGA practices.

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Post-Market Focus: It is commonly accepted the nature of complex medical technology is that some unexpected outcomes of device use only manifest with extensive post approval clinical use and so post- market surveillance is essential to identify these. The current regulatory framework is based on a risk management approach with review directed toward select higher risk devices but also complemented with a robust post-market surveillance system.

JJFC supports this risk management approach but believes we should continue to build upon the strengths of the current post-market regulatory system through greater utilization of the data which is currently provided by sponsors rather than imposing additional requirements in this area It is recommended that TGA reduce its level of involvement in direct assessment and concentrate resources on post-market regulatory supervision.

Access to Unapproved Medical Devices: JJFC believes increasing the scope of devices which can be included on the ARTG without direct pre-market assessment by the TGA could in fact reduce the need for devices to be accessed through the Special Access and Authorised Prescriber Schemes. Although there will always be a need for Australian patients to access unapproved devices, it is felt the current approach provides timely access to such devices. Further improvements could be made by making the application process available through the TGA’s online eBusiness System (eBS), giving sponsors visibility of the application and subsequent TGA approval.

Theme 4: Overly Burdensome Processes Multiple Systems and Manual processes JJFC agree there is significant scope for TGA processes to be digitised and welcomes and acknowledges the changes currently proposed through the TGA’ s Business Improvement Program (BIP).

Our Companies look forward to collaborating with the TGA further throughout the implementation of this program.

The manufacturing authorisation of a medical device is a 2-step process involving the authorisation of conformity assessment evidence which must be obtained before product authorisation can be obtained. This is currently handled as two separate electronic applications. We believe this is inefficient for both the TGA and industry and a 1-step process that simultaneously allows a sponsor to obtain conformity assessment approval and product approval should be developed.

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Process for Inclusion of Devices on the ARTG. JJFC supports the TGA making the final decision about which products should be included in the ARTG for general supply in Australia.

In aligning with the EU regulatory system it is important to recognise that, while both systems have similar frameworks for applying conformity assessment, Australia has the additional requirement to include medical devices on the ARTG before supply. In particular, the Australian concept of Unique Product Identifier (UPI) and Variants is inconsistent with conformity assessment procedures for Class III devices in Europe and adds an unnecessary layer of complexity which will make it difficult to directly align EU conformity assessment certification with TGA inclusion.

While JJFC support the TGA’s intent to increase visibility and traceability of high risk Class III devices, we have concerns regarding the TGA’s interpretation and ruling on acceptable UPIs which we would submit has, at times, been inconsistently applied. JJFC recommends the TGA remove the current requirement for including Class III devices on the ARTG at the UPI level and allow for flexibility of grouping a broader range of devices within a product family as determined by the manufacturer.

The TGA should also consider low risk medical devices that are not subject to an independent conformity assessment i.e. Class I devices be exempt from inclusion on the ARTG. These devices are still required to meet the Essential Principles of safety and performance based on self-declaration, which JJFC believes is an appropriate level of regulation for what have been deemed as low risk devices.

Their inclusion on the ARTG also holds little value given they are included according to a top level “kind of device” criteria (same sponsor, manufacturer, classification and GMDN code) so the information available on a specific device is limited.

Instructions for Medical Devices. The TGA should allow a broader range of permissible formats for instructions for the use of medical devices such as websites and electronic only formats.

Theme 5: Complex Regulatory Framework Categorisation of Medical Devices. Although it is the medical device manufacturer’s responsibility to classify a medical device under the Australian system in reality many overseas manufacturers request the assistance of the local sponsor. We believe there should be an increased focus on improved guidance and acceptable documentation rationale for device classification.

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In addition we believe the TGA provides a crucial role in providing regulatory advice and this service should specifically address questions asked and be easily accessible. Our experience to date is that questions are responded to however the response is not necessarily specific to the question asked and appears to be a cut and paste of existing guidelines which were previously consulted.

We do not find the current medical device guidance material easy to locate, navigate and understand and JJFC believes there is significant scope for improvement but welcomes and acknowledges the changes currently proposed to the Australian Regulatory Guidelines for Medical Devices (ARGMD). JJFC look forward to collaborating with the TGA further throughout the implementation of the revised ARGMD in 2015.

Transparency of Regulatory Decisions. JJFC acknowledge the TGA currently publishes limited information about medical devices on the ARTG, and supports the TGA’s interests in improving the transparency and accountability in its decision making processes. Our Company also supports the patient’s right to such information with the intent of facilitating better informed consent however the level of information should be appropriate to the type of medical device and intended audience.

JJFC supports the proposal to provide information about the degree to which a medical device has been assessed prior to inclusion on the ARTG. We believe that consultation must occur with the sponsor prior to publication of any such information.

JJFC does not support publication of decisions on medical devices for which applications were not approved. This information should remain commercial‐in‐confidence. The publication of such decisions could potentially be misinterpreted by patients, health professionals or industry and cause unnecessary concern, especially if a similar medical device or variant is subsequently approved.

JJFC supports the publication of post-market decisions which are relevant to patient safety only following consultation with the manufacturer and sponsor of the device.

Consumer Understanding of Medical Devices Regulation We do not believe there should there be a system for medical devices similar to the AUST R and AUST L system for medicines.

However we would support a system where all trade names are included under the relevant ARTG entry. This does not mean we consider it appropriate for each individual trade pack to be listed. For example wound dressings are sold in a variety of different shapes, sizes and pack sizes and some pack sizes are Account/Customer specific. If each variation were entered then the list would be very long, and burdensome for industry to maintain with no proven benefit

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resulting from collecting this information. JJFC recommend that the addition of new products should be via a notification only process using the current eBusiness System. A suitable upgrade to this system should allow sponsors to add new products and maintain information with built in validation negating the need for TGA review and associated fees.

Further, we would not agree with any proposal that suggests the inclusion ARTG numbers on a medical device or on the product labels. This will be very costly for industry at the outset and would achieve the objective of indicating to consumers and health professionals the level of scrutiny to which the medical device has been subjected. Nor would it provide further transparency as medical devices are listed by responsible manufacturer and intended use: there may be more than one ARTG listing for the one product where the product is made at more than one site or, as responsible manufacturers can change over time. This would serve to confuse rather than aid in device identification.

We believe labelling of medical devices supplied directly to consumers can be improved by exempting all medical devices from the Commerce (Imports) Regulations 1940. This legislation requires a country of origin to be included on the label of a medical device while the Medical Device legislation requires the responsible manufacturer name and address on the label. This can cause confusion to the consumer when the responsible manufacturer is not located in the same country as the medical device was produced (as defined by ACCC rules). In this case the desired objective of the Commerce legislation is not met.

Country of origin should not be considered an important factor in the decision to use a medical device.

Other Considerations Differences between Prostheses List Advisory Committee (PLAC) and TGA: There should be no duplication in the current review of clinical evidence that the PLAC and TGA may conduct as part of their respective roles in the health technology assessment process. If there is found to be duplication in the assessment of clinical evidence, then it should be questioned whether the PLAC is acting outside its remit by assessing the clinical evidence against the TGA’s regulatory requirements, rather than limiting its review to a comparative assessment.

Australian Unique Requirements – Regulation of Tampons Tampons are regulated in Australia as an “other therapeutic good” and are classified as a therapeutic device regulated under Therapeutic Goods Order 82 which specifies that tampons must comply with the Australian/New Zealand Standard “AS/NZS 2869:2008 Tampons – Menstrual”. We believe that the process of regulation is appropriate however the requirement to mandatorily comply with the tampon standard which demands unique requirements far above those of other major economies imposes increased cost and regulatory burden to

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industry with no demonstrated public health outcomes over and above those of the US and European markets. This effectively decreases competition in the Australian market as manufacturers based in these markets have to apply the Australian unique requirements to tampons destined to the Australian market.

This standard is not mandatory in New Zealand and is now referred to as the Australian standard.

The tampon standard was first developed in 1986 in response to a greater incidence of toxic shock syndrome occurring in menstruating women compared to other population groups.

In 1998 the standard was revised to harmonise the absorbency test method with that used by manufacturers in the EU and the US, however the interpretation of the absorbency results and permitted absorbency bands are not aligned, particularly with the EU. This means that tampons manufactured in the EU are either not able to be sold in Australia or they must be specifically designed to pass the more rigorous absorbency test criteria of AS/NZS 2869:2008. The differences are: • Australia: at least 90% of a tampon sample must have absorbencies within the specified absorbency band with 90% confidence • EU: at least 67% of a tampon sample must have absorbencies within the specified absorbency band with 90% confidence). The costs of complying with this Australian requirement are both direct in increased production costs and indirect in added complexity of supply.

Within the EU, tampons must follow the General Product Safety Directive 2001/95/EC which holds the manufacturer responsible for providing consumers with products that are safe. Tampons must also be manufactured and labelled in accordance with the EU Tampon Code of Practice (CoP).

Although the initial development of the AS/NZS 2869 was appropriate given the uncertainty of risk at that time we believe it is now appropriate to fully harmonise with international standards and accept tampons manufactured to the EDANA and FDA requirements because: • In the 25 years since the promulgation of the standard there has been no clear link established between tampon use and TSS • Differences between tampon standards has not resulted in a difference in TSS incidence between Australia and the rest of the world • The tight absorbance control is not critical to the functioning of the product • Release of menstruation fluid is inherently variable within and between individuals • Variability in tampon absorbance is not injurious to user health and is not likely to be perceived by the user • The less demanding EU absorbance criteria have not caused any issues in the European environment.

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• The Australian standard unnecessarily restricts the entry of new tampon products onto the Australian market and involves an increased cost of manufacture.

Clinical Trials: The Therapeutic Goods Administration (TGA) Clinical Trial Regulation has been in our experience an efficient and clear process which is seen as an advantage for attracting global clinical trials to Australia. The short turnaround of Clinical Trials Network CTN acknowledgements is perceived favourably by our global colleagues. We appreciate recent progress in making the process Sponsor friendly through initiatives including online payment of fees, email acknowledgements, and timely and comprehensive answers to queries. It is noted that online submissions shall be trialled in 2015 and we would appreciate the opportunity to participate.

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Chapter Eight – Framework for Advertising Therapeutic Goods It should be noted that JJFC have contributed to and broadly supports the submissions made by Medicines Australia, ACCORD and MTAA but wishes to provide further recommendations in this submission.

Issue 1 – Advertising of Schedule 4 prescription medicines to consumers Direct to consumer advertising already exists in countries such as the USA and New Zealand. Proliferation of media resources for health literature, primarily through the internet, means that Australian consumers already have readily available information.

JJFC believes that direct communication with consumers can improve understanding when accompanied with appropriate controls. We support the provision of advertising of Schedule 4 products and would welcome further dialogue on how to implement during the Review.

Issue 2 – Advertising of Schedule 3 medicines to consumers JJFC believe that S3 medicines should be advertisable to consumers unless specifically exempted.

JJFC does not believe that this will create any specific risks to consumers as the scheduling process enforces appropriate conditions of supply (e.g. restricted pack sizes), consumers will not be able to self-select these medicines and counselling by a pharmacist will be still be required. Direct-to-consumer advertising will provide awareness of the availability of S3 medicines and appropriate therapeutic options, facilitate the access of these medicines and reduce unnecessary doctor visits.

These medicines are already advertisable in other countries such as the US, UK and New Zealand and given the ability of consumers to view and purchase similar medicines from these countries over the internet the restriction on advertising S3 medicines locally no longer makes sense.

Further discussion on this issue is provided in our response to Chapter 6 ‘Regulation of Over the Counter Medicines; theme 1: Scheduling Framework; Issue 2: Direct-to-Consumer advertising of schedule 3 medicines’.

Issue 3 - Co-regulation and the pre-approval process The direct to consumer advertising preapproval process has served Australia reasonably well in the past, however it does not provide the advertiser with any protection against complaints (including vexatious and mischievous complaints) and needs revision to cater for the development of new advertising media and the expansion of medicine advertising in fast moving digital media.

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JJFC does not believe that Australia should continue with compulsory pre-vetting of medicine advertising but a recommended pre-vetting service needs to be available. This service needs to be quick, should not rely on the services of a sole reviewer and should cater for all medicines (currently separate approvals are required for OTC and complementary medicines occurring in the same advertisement, unless the advertisements is intended for broadcast media). It should also incorporate the needs of FreeTV Commercials Advice (CAD) to reduce duplication in television pre-advertising approval so that CAD’s review becomes a classification decision only.

JJFC suggest that if self-regulation is found to be problematic for a specific advertiser, a provision to require mandatory pre-approval for a stipulated period could be used to bring that advertiser into compliance.

In order for a self-regulatory system to be successful, JJFC believes it needs to be supported by a swift acting and effective compliant body (see below).

JJFC are of the opinion that the current advertising framework for Therapeutic Goods (The TGAC) is now out of date and requires revision to incorporate more specific considerations of advertising medicines using emerging types of digital media and devices.

Should mandatory pre-approval of advertising remain JJFC believes that the determination of advertisements requiring pre-approval should be based on risk and not media.

Issue 4 – Management of complaints and enforcement powers The currently available processes to resolve an advertising complaint is too slow, lack direct enforcement powers and does not permit an advertiser to enter into dialogue with the panel.

JJFC agrees that there should be a new, single independent authority for complaint handling. The current agencies appear to have too many conflicting interests to effectively manage complaints and are doing a poor job of filtering vexatious and mischievous complaints. In order for the agency to be viable perhaps it could incorporate complaints for other regulated goods, advertising vigilance activities and advertising requirement development responsibilities.

The UK advertising control of therapeutic goods relies heavily on self-regulatory measures and a post advertising vigilance and complaint system that seeks to resolve complaints within 30 calendar days.

To support a self-regulatory regime this complaint body would need to be able to react within a week of the receipt of a complaint.

JJFC believe the existing range of sanctions is sufficient except for the speed in which they are applied.

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The most effective deterrent is the enforcement of quick removal of offending material from the market place. In this case the advertiser will have little opportunity to capitalize on the offending material and potential risk to consumers is minimized. The application of sanctions should be based on risk to the public. In extreme cases where safety is an issue immediate retractions could be required.

Any advertiser initiated appeal of the decision by such a body also needs to be acted upon in a swift and just manner.

Issue 5 – Advertising of medical devices JJFC believe the status quo self-regulatory system advertising compliance is appropriate for consumer medical devices as they are very low risk products (e.g. such as wound dressings).

Similarly we believe commensurate with a risk based approach that advertising for listable medicines regardless of media should not require advertising pre-approval

Advertising of Samples of Therapeutic Goods The Therapeutic Goods Advertising Code section 4(8) prohibits the advertising of the offer of a sample other than for therapeutic devices and sun screening preparations. Whilst there is good reason for this there are circumstances where it is appropriate for consumers to be made aware that a small pack can be obtained to trial a medication to see if it is suitable for their needs.

Currently the consumer must purchase a standard pack size in order to ascertain whether the medicine suits their needs as there is little point providing a trial size pack that cannot be advertised.

Inappropriate or excessive use of samples is as undesirable for the supplier as it is for the consumer as the supplier is endeavouring to obtain a future purchase from the consumer.

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Regulatory Framework for Advertising Therapeutic Goods

THERAPEUTIC GOODS ADMINISTRATION

THE REGULATORY FRAMEWORK FOR ADVERTISING THERAPEUTIC GOODS

SUBMISSION December 2016

Regulatory Framework for Advertising Therapeutic Goods

Contents

Our Credo 3 Submission Information & Company Overview 4 Comments on the consultation document 5

Regulatory Framework for Advertising Therapeutic Goods

Our Credo

Regulatory Framework for Advertising Therapeutic Goods

Submission Information & Company Overview

Organisation: Johnson & Johnson Pty Ltd Type of Organisation: Proprietary Limited Company Address: 45 Jones Street Ultimo NSW 2007 Email and phone contact: Phillip Yu Senior Regulatory Associate Johnson & Johnson Pacific Pty Ltd +61 2 8260 8456/ [email protected]

Johnson & Johnson Pty Ltd is a subsidiary of Johnson & Johnson, the world’s most comprehensive and broadly based healthcare company. In Australia we provide products and services including medical devices, diagnostics, pharmaceuticals and consumer healthcare products.

The Johnson & Johnson Family of Companies in Australia consists of: • Johnson & Johnson Pacific Pty Limited – consumer health brands; • Johnson & Johnson Medical Pty Limited – medical devices and related technology; and • Janssen-Cilag Pty Limited – pharmaceuticals.

We employ approximately 1,500 Australians who bring innovative ideas, products and services to advance the health and well-being of the patients we serve. We recognise the impact of serious conditions on people's lives, and we aim to empower people through disease awareness, education and access to quality care. Our research and development focuses on identifying medical needs and harnessing the best science, whether from our own laboratories or through strategic relationships and collaborations.

Johnson & Johnson Pacific is a provider of consumer health and wellbeing products, offering families more than 650 trusted solutions for their most common health and wellbeing needs. Many of our brands have earned consumers’ trust over generations.

Johnson & Johnson Medical produces a range of innovative products and solutions used primarily by healthcare professionals in the fields of orthopaedics, neurological disease, vision care, diabetes, infection prevention, diagnostics, cardiovascular disease, and aesthetics. We are the largest medical technology provider in Australia working across public and private sectors.

Janssen is dedicated to addressing unmet medical needs in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Janssen has a long-standing history in making a meaningful difference in global public health, dating back to Dr Paul Janssen’s pioneering work in mental health and pain medications, as well as the development of more than 80 medicines.

Regulatory Framework for Advertising Therapeutic Goods

Comments on the consultation document

Overall Comments We support the Government’s endorsement to move to a more self-regulatory framework for the advertising of therapeutic products. In order for a self-regulatory system to be successful, we believe it needs to be supported by a swift acting and effective complaint body. This body needs to be made up of members who have the appropriate expertise including (but not limited to):  advertising healthcare products and solutions,  emerging advertising trends  evaluating scientific data, peer reviewed publications and clinical trials

It is also critical that the committee member(s) that are deemed to be the consumer representatives genuinely represent the interests of consumers and are qualified to accurately represent “the reasonable consumer”.

If self-regulation is found to be problematic for a specific advertiser, we suggest that a provision to require mandatory pre-approval for a stipulated period could be used to bring that advertiser into compliance.

We are of the opinion that the current advertising framework for Therapeutic Goods (The TGAC) is now out of date and requires revision to incorporate more specific considerations of advertising medicines using emerging types of digital media and devices. We would also support the regular (every 2-3 years) update to the TGAC, allowing the code to cater for emerging trends and techniques of advertising as well as the development of an accompanying guideline.

4.1 Moving forward At the time of product listing, sponsors and manufacturers of complementary medicines may not have developed promotional claims and won’t be able to submit any proposed promotional claims for assessment. Additionally, new promotional claims may be developed after the product is listed. Further consideration will need to be given to whether these new claims will be assessed and how the process will look in terms of getting the new claims assessed.

5. Sanctions and penalties We support the Governments proposal to increase the regulator’s enforcement powers with respect to advertising. This proposal however must include a process for a merits and judicial review of any decision made by the committee or delegate (i.e. all decisions should be subject to operation of section 60 of the Act). There should be no publication of any decision until such time that the timeframes for the review process referenced above have been expired.

We believe that sanctions and penalties should not be issued for advertisements that are highly subjective in nature as they are matters that cannot be 100% confirmed e.g. there is uncertainty around likely consumer take out. Sanctions and penalties should only be issued where there is clear objective evidence of a breach of the advertising requirements e.g. advertising that puts the Regulatory Framework for Advertising Therapeutic Goods

consumer’s health at risk or claims that are not scientifically substantiated.

5.1 Civil penalty provisions We support the Governments proposal to include civil penalties as part of the sanctions package, however this should be reserved for breaches that endanger public health and safety or for obstinate and repeat offenders. The issuing of such sanctions must go through the appropriate process and subject to operation of section 60 of the Act.

5.2 Infringement notices We note that infringement notices will only be used where there is a clear objective evidence of a breach of the advertising requirements. We propose that ‘objective evidence’ be clearly defined to ensure decisions that are subjective won’t result to infringement notices being issued.

5.3 Injunctions We support the proposal for the TGA to have the power to apply for an injunction relating to advertising. The injunction should only apply to advertisements of therapeutic goods that pose risks to public health and safety, or if the advertisement contains false or misleading representations that contravene the requirements relating to quality use of medicines or medical devices.

We suggest that all costs relating to the injunction should be paid by the advertiser that has been found to be in breach.

5.4 Substantiation and warning notice powers We have no objection to the TGA being given the discretionary power to publish public warning notices in relation to advertising claims as long as the claims are likely to cause or result in harm or injury.

5.5 Transparency We agree the TGA should publish information on their website if a matter is referred to the Secretary to take action and the advertiser did not provide an appropriate response. However, this information should only be published if the complaints handling process (including any potential legal proceedings) has been closed out. This needs to apply to both advertisements that have been found in breach of the TGAC as well as those referred to the TGA having found to comply with the TGAC.

We also propose that full meeting minutes (from the complaints review committee, including the committee representatives) and a copy of the outcome report (if the assessment of the complaint included an evaluation of clinical or other scientific data) should be made available to the advertiser. This will allow advertisers to have greater transparency of the decisions made from the committee Regulatory Framework for Advertising Therapeutic Goods

that reviewed the information provided during the complaints handling process.

6.3 Future Options: Model 1 – Commonwealth agency Consideration should be given to how this model will be funded and whether the TGA would also assess complaints for non-therapeutic products making therapeutic advertising claims. Additionally, the individuals who assess the complaints need to have both technical expertise and a good understanding of the regulatory framework and are adequately qualified to represent the reasonable consumer.

6.3 Future Options : Model 2 – Independent non-government authority If an independent authority will be handling the complaints process, the individuals within the group must have the right expertise. We suggest that rotating industry members could be included in the independent authority, as long as there is no conflict of interest.

Careful consideration must be given to this option, as it is effectively no different to the existing CRP.

6.3 Future Options : Model 3 – Hybrid government and non-government authorities Consideration should be given to how complaints for advertisements that both contain non- therapeutic and therapeutic advertising claims would be assessed. If the TGA only assesses the therapeutic advertising claims and an external agency assesses the non-therapeutic advertising claims, we have concerns that the timeframe for the outcome of the complaint could be overly long.

7.1 The Therapeutic Goods Advertising Code In addition to the considerations listed in the consultation document, the following points should also be considered:  The Code should be clear so that it is less open to interpretation. Definitions should be aligned with Industry prior to publication of the code (for instance – “Internet marketing” is not a term that is used in Industry)  The Code should be updated and maintained on a regular basis – this will help incorporate advertising requirements for advertising material that use emerging types of digital media and devices  The Code should continue to be written in plain English  The Code should have an accompanying guideline  There is currently no information as to how large mandatory statements and disclaimers should be or how long they should appear in the advertisement for. This should factor in advertisements that are provided via social media and mobile apps. This information could be provided in the accompanying guideline  Examples of what is considered ‘prominent’ should also be provided. This information could be provided in the accompanying guideline  Examples of what is considered to be ‘implied’ endorsement should be given. This Regulatory Framework for Advertising Therapeutic Goods

information could be provided in the accompanying guideline  Examples of what is considered as scientific information should be given. A criterion should also be included so that advertisers are clear of the requirements when using scientific evidence. This information could be provided in the accompanying guideline.

7.2 Future provision of expert advice The committee and expert advisers who will provide the TGA advice on matters relating to advertising should have the appropriate expertise, be completely independent and be up to date with the different advertising channels available. In order to be quorum, the committee should also include members who truly represent the consumers. We also suggest that industry members could be included in the committees, as long as there is no conflict of interest.

Designation of Australian CABs – Submission January 2017

THERAPEUTIC GOODS ADMINISTRATION

DESIGNATION OF AUSTRALIAN CONFORMITY ASSESSMENT BODIES FOR MEDICAL DEVICES

SUBMISSION January 2017

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Designation of Australian CABs – Submission January 2017 Our Credo

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Designation of Australian CABs – Submission January 2017 Submission Information & Company Overview

Organisation: Johnson & Johnson Pty Ltd Type of Organisation: Proprietary Limited Company Address: 1 – 5 Khartoum Road, Macquarie Park, NSW 2113 Email and phone contact: Rebecca Gaudin Director of Regulatory Affairs Johnson & Johnson Medical Pty Ltd +61 2 9815 4186 / [email protected]

Johnson & Johnson Pty Ltd (JJPL) is a subsidiary of Johnson & Johnson, the world’s most comprehensive and broadly based healthcare company. In Australia we provide products and services including medical devices, diagnostics, pharmaceuticals and consumer healthcare products.

The Johnson & Johnson Family of Companies in Australia consists of: Johnson & Johnson Pacific – consumer health brands; Johnson & Johnson Medical – medical devices and related technology; and • Janssen – pharmaceuticals. • We• employ approximately 1,800 Australians who bring innovative ideas, products and services to advance the health and well-being of the patients we serve. We recognise the impact of serious conditions on people's lives, and we aim to empower people through disease awareness, education and access to quality care. Our research and development focuses on identifying medical needs and harnessing the best science, whether from our own laboratories or through strategic relationships and collaborations.

Johnson & Johnson Medical produces a range of innovative products and solutions used primarily by healthcare professionals in the fields of orthopaedics, neurological disease, vision care, diabetes, infection prevention, diagnostics, cardiovascular disease, and aesthetics. We are the largest medical technology provider in Australia working across public and private sectors.

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Designation of Australian CABs – Submission January 2017 Comments on the Proposal

It should be noted that we have contributed to and broadly support the submission made by the Medical Technology Association of Australia (MTAA). Our additional commentary on the questions is summarised below.

Scope Question #1: Should designated Australian conformity assessment bodies (subject to capability etc.) be able to provide conformity assessment certification for all medical device applications? Should some device types or classes continue to be required to hold TGA conformity assessment certification? If the Australian Conformity Assessment Body (CAB) can demonstrate they have the appropriate level of technical expertise and meet all requirements set as part of the designation process, it should be able to provide conformity assessment certification for all medical device applications. The TGA should fully accept evidence of the Australian CAB certification for those high risk devices specified under both Regulation 5.31 and Regulation 4.12 which currently require a mandatory application audit or TGA conformity assessment certification respectively. Outsourcing of medical device assessments could be competently managed through the designation process in the same manner as the European regulatory system. The same approach should also be applied to Pathway Two3 which could allow all devices to be Conformity Assessed by a body that has been designated by a comparable overseas Designating Authority without the need for a either mandatory application audit or TGA conformity assessment.

Question #2: Does your organisation market devices to countries relying on ‘home market’ regulatory approval? How would this proposal impact on this? No, we are currently only required to seek TGA conformity assessment for those devices under Regulation 4.1.

Context Question #3: Are there other key issues which should be considered in developing this proposal? No comments.

1 Therapeutic Goods (Medical Devices) Regulations 2002, Part 4, Regulation 5.3 specifies that certain kinds of medical devices including Class IIIs will be selected for a mandatory application audit. 2 Therapeutic Goods (Medical Devices) Regulations 2002, Part 4, Regulation 4.1 specifies that medical devices containing medicines, tissues of animal, biological or microbial origin and Class 4 IVDs must hold TGA conformity assessment certification. 3 Australian Government Response to the Review of Medicines and Medical Devices Regulation, 15 September 2016, Recommendation Fifteen, Pathway Two - Conformity Assessed by a body that has been designated to undertake Conformity Assessments by a comparable overseas Designating Authority.

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Designation of Australian CABs – Submission January 2017

Cost Recovery Question #4: Should the costs of designation be recovered directly as fees from conformity assessment bodies, or is it appropriate that some or all costs be recovered through other mechanisms such as charge on all medical device sponsors? The designation costs should be fully recovered from the CABs as the main beneficiaries of the designation activity. These private sector competitors can then recover assessment and evaluation costs from applicants at a potentially higher rate than the TGA but with the possible benefit to applicants of guaranteed faster review times.

Question #5: Are there other competitive neutrality concerns for the Designating Authority function that you can identify? No comments.

TGA conformity assessment function Question #6: TGA would continue to offer a full suite of conformity assessment functions. Is this important to you or your organisation? It is important that the TGA continue to offer a full suite of conformity assessment functions in order to maintain the necessary competence and capacity within a government regulator. However we recommend that the TGA should reduce its level of involvement in direct assessment and concentrate resources on post-market regulatory supervision which could be possible with the introduction of other Australian CABs.

Possible interested bodies Question #7: Do you or your organisation have an interest in seeking designation as a conformity assessment body? What are the issues which would affect your decision to apply for designation? We do not have an interest in seeking designation as a CAB.

Designation framework Question #8: Should the designation framework be aligned to MDSAP requirements, European requirements or a hybrid? We support the comments in the paper that the designation framework is likely to be a hybrid given the Medical Device Single Audit Program (MDSAP) process is still in pilot and the European designation framework is already established. However, the designation framework should move towards a globally harmonised model aligned with the framework being established by the International Medical Device Regulators Forum (IMDRF).

Question #9: Should particular aspects of each system be adopted for a hybrid approach? The current status of both the MDSAP and European framework will determine which aspects of each system will be adopted i.e. MDSAP for the Quality Management System (QMS) requirements while the European designation framework would likely cover the assessment of medical device compliance with the essential principles.

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Designation of Australian CABs – Submission January 2017

Question #10: How might alignment to the MDSAP and/or European framework be managed as international regulatory convergence develops? Adoption of the designation framework being established by the International Medical Device Regulators Forum (IMDRF) should occur as soon as practical.

Designation criteria Question #11: Are the listed criteria appropriate and comprehensive? The listed criteria are deemed to be appropriate and comprehensive as they have been taken from the Notified Body Operations Group (NBOG) Best Practice Guides and MDSAP documents.

Question #12: Are there particular issues which should be considered in developing these criteria for the regulatory framework? No comments.

Overall Question #13: In addition to any feedback on specific aspects of the proposed approach to designation of Australian conformity assessment bodies, we are also interested in broader comments on the proposal. Comments might take into consideration the context for change and issues to consider outlined in the introduction, and consider the risks and benefits of this proposal and how these might be managed. We support the overall proposal and believe that the TGA should adopt the role of a designating authority for domestic CABs which can demonstrate competence to evaluate all medical devices requiring premarket assessment for supply in Australia. We believe this approach may address the concerns raised by the TGA and others throughout the Review of Medicines and Medical Device Regulations, and will improve both public health outcomes and public confidence in the TGA and the Australian regulatory framework. We do however share the concerns raised in the paper around the viability of a private sector CAB industry in Australia and the considerable time and resource required to establish this pathway. Overall it is difficult to comment on the full impact of this proposal without considering the details of recommendation 15, Pathway Two which seeks to have greater utilisation of overseas approvals. In particular, if greater confidence in the EU system removes the mandatory application audit requirement for Class IIIs, than assessment by a TGA-designated commercial body in Australia may be a less attractive pathway.

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Accelerated assessment of medical devices – Submission January 2017

THERAPEUTIC GOODS ADMINISTRATION

ACCELERATED ASSESSMENT OF MEDICAL DEVICES – PRIORITY REVIEW PATHWAY

SUBMISSION January 2017

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Accelerated assessment of medical devices – Submission January 2017 Our Credo

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Accelerated assessment of medical devices – Submission January 2017 Submission Information & Company Overview

Organisation: Johnson & Johnson Pty Ltd Type of Organisation: Proprietary Limited Company Address: 1 – 5 Khartoum Road, Macquarie Park NSW 2113 Email and phone contact: Rebecca Gaudin Director of Regulatory Affairs Johnson & Johnson Medical Pty Ltd +61 2 9815 4186 / [email protected]

Johnson & Johnson Medical produces a range of innovative products and solutions used primarily by healthcare professionals in the fields of orthopaedics, neurological disease, vision care, diabetes, infection prevention, diagnostics, cardiovascular disease, and aesthetics. We are the largest medical technology provider in Australia working across public and private sectors.

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Accelerated assessment of medical devices – Submission January 2017 Comments on the Proposal

General Comments We support the introduction of a Priority Review Pathway which enables expedited access to innovative medical technology that meets critical patient needs without compromising safety. However we have concerns that the current proposal does not actually allow for accelerated assessment but rather “front of queue” processing with a designation process that may limit the overall reduction in review times. We are also concerned that only those technologies having substantial clinical data would be considered for priority review. This would seem to exclude promising new technologies that may have limited clinical data at the earliest stages of development, but would benefit from expedited review. For example, in the US, the Expedited Access Pathway (EAP) established by the FDA allows manufacturers whose device meets the specified eligibility criteria for EAP designation to work with the FDA to reduce the time and cost from development to marketing decision without changing the standard of reasonable assurance of safety and effectiveness. This is done through priority review, submission of a data development plan, interactive review, senior management involvement and assignment of a case manager to oversee the process.

Current environment Question #1: Are there any other environmental issues that would inform or benefit the development of this proposal? The paper references the TGA’s acceptance of conformity assessment certification issued by a Notified Body in the European Union (EU) which reduces duplication in assessments. There is still a large degree of duplication for those high risk devices specified under both Regulation 5.31 and Regulation 4.12 which currently require a mandatory application audit or TGA conformity assessment certification respectively. The details of recommendation 15, Pathway Two3 which seeks to have greater utilisation of overseas approvals must also be considered as another mechanism to expedite assessment with the TGA to understand the full impact of the Priority Review Pathway proposal.

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Accelerated assessment of medical devices – Submission January 2017

Question #2: Are there other issues to be considered in developing this proposal? We are concerned about the TGA’s ability to assign additional review resources to this pathway without adversely impacting applications being evaluated under standard mechanisms. We note the TGA’s recent delay in Level 2 Application Audits due to clinical assessor resource constraints as an example of this risk and that there may be further limitations as to the availability of appropriately qualified subject matter experts to evaluate such novel technologies.

Principles and criteria Question #3: Are the criteria appropriate to restrict acceptance for Priority Review to the truly new and novel devices for patients in immediate need? Noting that acceptance of a large number of applications would undermine the viability of Priority Review. Further definition or clarification on key terms such as life-threatening, seriously debilitating and major clinical advantage is required to evaluate the full extent of this proposal. We also have concerns regarding the eligibility criteria which appear to rely heavily on pre-market clinical evidence to demonstrate “major clinical advantage.” As pre-market clinical data may be limited for novel devices, we recommend an evaluation of the benefit/risk profile for the device to support the argument for greater reliance on post-market clinical data where patients will benefit from expedited access to the technology. In these cases, we recommend an option for the TGA to grant provisional approval, as proposed for prescription medicines, which allows sponsors to collect and submit post-market clinical data before the product is granted full approval. Devices could be granted provisional approval where the benefit to a specified patient population of earlier availability outweighs the risk inherent in the fact that additional clinical data is still required.

Question #4: Do the proposed criteria cover all issues which should be considered in assessing a medical device for Priority Review designation? Clarification is needed as the last criterion “early availability in Australia will result in a major public health benefit” only applies to IVDs and not all medical devices.

Question #5: What is your estimated likelihood of making an application for a medical device to have Priority Review designation? It is unlikely but we would need to clarify device eligibility for priority review (especially as it relates to clinical data requirements) and establish whether the TGA Priority Review Pathway would be advantageous compared to standard assessment pathways.

Implementation of Priority Review Question #6: Is the proposed sponsor alert timeframe adequate for industry? We appreciate the TGA’s need for planning and ensuring appropriate resourcing however the proposed pathway should allow for greater flexibility in the sponsor alert timeframe in cases where the TGA have been able to identify the relevant technical and clinical experts to facilitate the Priority Review in less than four (4) weeks.

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Accelerated assessment of medical devices – Submission January 2017

Question #7: Decisions will need to be made promptly, within six (6) weeks. Large submissions will undermine this, as will applications that are incomplete in meeting the criteria. Will applicants be able to present a succinct and compelling argument for Priority Review designation, independent of the full application process? While we trust that all applicants will aim to present a succinct and compelling argument per the guidelines, the TGA must be agreeable to accept the applicant’s medical expert support submitted with the summary of clinical evidence. The TGA’s current increased scrutiny of Clinical Evaluation Reports has shown that clinical assessors are reluctant to make a determination based on the clinical expert’s critical evaluation and conclusions and the supporting documents such as full clinical investigation reports and full text articles from literature reviews are then also required to be submitted. We also have concerns that the six (6) week review timeframe is too lengthy and may reduce any real gain in overall review times given the device will still be required to undergo standard assessment processes. We note the current proposed designation decision time for prescription medicines is 20 working days.

Question #8: In the proposed implementation it is expected that sponsors on receipt of designation advice will promptly submit their full application for conformity assessment or inclusion. Is this a reasonable expectation? We believe this is a reasonable expectation but recommend there be the capacity to request an extension in reasonable circumstances.

Question #9: It is proposed that priority review status will be revoked if timeframes for reply to request for information are not met. Is the existing practice of a twenty (20) working day timeframe appropriate? The due date specified in the request for information (e.g. Section 41JA) should be dependent on the type of information required and should again include the capacity to request an extension in reasonable circumstances.

Question #10: Is the proposed approach to publication of Priority Review applications and decisions appropriate? We understand the TGA’s interests in improving the transparency and accountability in their decision making processes but we do not support the publication of Priority Review applications, requests and decisions. This information should remain commercial‐in‐confidence. Information that a device went through the Priority Review pathway should only be published at the time of inclusion on the ARTG.

Question #11: Is the proposal to publish medical device product information for consumers supported, and what extent of detail would consumers seek? We do not support the proposal for the TGA to publish medical device product information for consumers as this is not a requirement for other devices assessed under standard pathways. The same assessment requirements will apply to Priority Review devices so once included on the ARTG they should not be treated differently. We do on occasions provide device and surgical procedure information to health care professionals and the surgeons sometimes use these materials in communication with their patients.

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Accelerated assessment of medical devices – Submission January 2017

Question #12: Is the Priority Review pathway for designated applications adequately detailed? If not, which areas are unclear or require more detail? Further guidance on the format and detail required for an application for Priority Review designation would be beneficial.

TGA operational impacts Question #13: Are there any gaps in the proposed implementation plan? Further information regarding TGA’s plan for identifying and obtaining the relevant technical and clinical resources to manage the proposed pathway is required.

Question #14: What aspects of the proposed implementation would you suggest for inclusion in a post-implementation review? None further than those already identified on page 16 of the paper.

Question #15: What timeframe would you suggest for the review – 1 year, 2 years or 3 years after commencement? We support a yearly review, particularly to ensure this pathway does not affect TGA business as usual operations.

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