We have discussed the registration requirement of high-risk cosmetic implants in Indonesia, Philippines, Malaysia and Singapore in the previous (August 2019) issue. We received several responses from the readers who are interested in China market. Thus, in this issue, we have included China registration experience, along with some information on United States FDA and Europe’s requirement for high-risk cosmetic implants.

If you wish to review our previous issue on this topic, the link may be found here.

CHINA

In China, medical devices are classified based on intended use categories. High-risk medical devices used for aesthetic purposes such as implants, are classified under a broader category – “Plastic and general surgical implants”. Examples of devices included under this category include breast implants and dermal fillers. NMPA publishes specific guidance documents for breast implants and dermal fillers.

Table 1: Specific Guidance Documents for Breast implants and Dermal Fillers issued by NMPA

Specific Guidance

Guidance content

Breast implant (regarding the guidance of breast implant issued in 2011):

  1. The manufacturer shall submit these necessary information in the submission document: Shell surface, shape, volume (or adjustable), single cavity fill / double cavity fill, width, height, crown, shell thickness.
  2. The raw materials shall meet the verification data of YY0484 "Surgical Implants Two-component Addition Vulcanized Silicone Rubber"
  3. The manufacturer shall provide these performance test reports: Exudation test, Degree of vulcanization, Leaching test, Analysis of volatiles in silicone rubber shells, Heavy metal residue, Determination of viscosity and degree of vulcanization of silicone gels
  4. The clinical trial in China shall follow up to 5 years at least, if manufacturer has previous product in China, then the manufacturer can use the foreign clinical trial report of the registered device to exempt from holding the clinical trial in China.

Dermal filler (based on registration guidance of dermal filler issued in 2016 and clinical trial guidance of dermal filler issued in 2019)

Registration part:

  1. Manufacturer shall provide recognized material chemical name, chemical structure formula/molecular formula, physical and chemical property information, material trade name (if any), material code (if any) and quality standards of raw materials (including components and pre-assembled equipment added in any production process such as cross-linking agent).
  2. If the raw materials are purchased, applicant should provide the qualification documents, supply and marketing agreements, procurement standards and verification reports.
  3. Manufacturer shall provide quality standards and verification reports for injection water, which shall meet with the current Pharmacopoeia of the People's Republic of China.
  4. Manufacturer shall provide below test report:
  1. Relevant research data on degradation cycle, degradation products and metabolism in the body.
  2. Research data on the molecular weight and molecular weight distribution of sodium hyaluronate (provided cross-linking of sodium hyaluronate before cross-linking).
  3. Product viscoelastic energy and push force relationship.
  4. Provide research data on product dose/frequency.
  1. If the product is made through a chemical crosslinking, containing the particles made of non-absorbable materials or made by the microorganism, then the manufacturer shall submit particular documents listed in the guidance to ensure the safety.

Guidelines for clinical trials of sodium hyaluronate facial injection filling materials (No. 13 of 2019)

This Guideline was implemented in March 2019, which is asking for the clinical trials were designed with the product of correcting nasolabial folds as the intended use. This Guideline clarify the scope of primary endpoint, secondary endpoint and safety endpoint in the clinical trial. In addition, NMPA has an illustration on how to set up the observation time and sample size of each clinical trial.

During the market stage of the product, NMPA requests for Post Market Clinical Follow-up (PMCF) for each patient. This requirement is specifically indicated in the Product Certificate.

 

Qualtech has assisted several biotech companies to get the product license of high-risk cosmetic implants, for instance, collagen implant, HA filler, breast implant and such like stuff. Qualtech has our own comprehensive clinical trial team and registration team. Moreover, the team members are the expert/PhD from the fields of plastic medical, statistics, and clinical physician. Feel free to contact us to know more about our service!

 

Europe

As we have tackled the key information on how authorities regulate medical aesthetic devices, it is also noteworthy to mention that the European and US authorities also have established guidelines in regulating these types of devices.

The New European Regulations entitled Regulation (EU) 2017/745 on Medical Devices has just broadened the definition of medical devices to include non-medical and cosmetic devices which were previously not regulated. The included devices are summarized in Table 3. In reference with the new guideline, it was mandated that manufacturers should be able to demonstrate conformity of devices belonging under this category, with regards to application of risk management and clinical evaluation if necessary. Generally, devices with non-medical intended purpose should fulfill the requirements applicable to devices with- and to devices without intended medical purposes

List of Groups of Products Without an Intended Medical Purpose Referred to in Article 1(2) of Regulation (EU) 2017/745:

1.    Contact lenses or other items intended to be introduced into or onto the eye.

2.    Products intended to be totally or partially introduced into the human body through surgically invasive means for the purpose of modifying the anatomy or fixation of body parts with the exception of tattooing products and piercings.

3.    Substances, combinations or substances, or items intended for facial or other dermal or mucous membrane filling by subcutaneous or intradermal injection or other introduction, excluding those for tattooing.

4.    Equipment intended to be used to reduce, remove or destroy adipose tissue, such as equipment for liposuction, lipolysis or lipoplasty.

5.   High intensity electromagnetic radiation (e.g.  Infra-red, visible light and ultra-violet) emitting equipment intended for use on the human body, including coherent and non-coherent sources, monochromatic and broad spectrum, such as lasers and intense pulsed light equipment, for skin resurfacing, tattoo or hair removal or other skin treatment.

6.    Equipment intended for brain stimulation that apply electrical currents or magnetic or electromagnetic fields that penetrate the cranium to modify neuronal activity in the brain. 

 

United States

In the US, specific guidelines for dermal fillers and breast implants belong under the category of “Cosmetic Devices”, which was defined by USFDA as devices used to improve appearance and do not impart any health benefits, e.g. soft dermal filler. The USFDA approves dermal fillers that are made from absorbable or temporary material for specific usage in the correction of moderate to severe facial wrinkles and skin folds, such as nasolabial folds. The agency also approves several absorbable dermal fillers for use as lip and cheek augmentation in patients over the age of 21, and the correction of contour deficiencies, such as acne scars. Fillers for hand augmentation are also approved by FDA.

FDA has NOT approved the dermal fillers to:

increase breast size (breast augmentation)

increase size of the buttocks

increase fullness of the feet

implant into bone, tendon, ligament, or muscle

 

With regards to breast implants, USFDA has only approved two types of breast implants for sale in US, there are saline-filled and silicone gel-filled. Both types have a silicone outer shell and vary in size, shell thickness, shell surface texture, and shape (contour).

 

CONCLUSION

Boost demand on medical aesthetic devices in Asia contributes to the development of health care. In the meantime, the health authority of some countries starts to regulatory of this kind of devices, especially the high-risk device. The post market surveillance of the product would become more and more important for the manufacturer. Here we suggest the manufacturer build up itself PMS plan as much as earlier.

 

Reference:

1.           Regulation (EU) 2017/745 of the European Parliament and of the Council

2.           US Food and Drug Administration: Dermal Fillers (Soft Tissue Fillers)

3.           US Food and Drug Administration: Breast Implants

4.           Breast implant product registration technical review guidelines (Food and Drug Administration Letter [2011] No. 116)

5.           Guiding Principles for the Registration of Sodium Hyaluronate Facial Injection Filling Materials (No. 7 of 2016)

6.           Guidelines for clinical trials of sodium hyaluronate facial injection filling materials (No. 13 of 2019)

7.           Summary of Medical Device-Drug-Cosmetic Interphase (MDDCI) Product Classification Decision

8.           Regulatory Guideline for *Devices For Modification of Appearance or Anatomy

9.           FDA Memorandum Circular 2014-005: Updated List of Medical Devices required to be registered prior to sale, distribution and use

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