Scientific classification to ensure safety and service innovation——Analysis of "Principles of Classification and Definition of Recombinant Collagen Medical Products"

Medical Network News on June 10 A few days ago, the State Food and Drug Administration issued the "Classification and Definition Principles for Recombinant Collagen Medical Products" (hereinafter referred to as the "Classification and Definition Principles") to further clarify the management attributes of recombinant collagen medical products and the basis for determining management categories.
, To provide guidance documents for the classification and definition of recombinant collagen medical products and the development and compliance of innovative products, which will promote the high-quality development of the recombinant collagen medical device industry
.

 

Facing industry and regulatory issues

 

Collagen is an important structural protein in human and animal tissues.
It is widely found in tendons, ligaments, cartilage, skin and other connective tissues.
It is the most abundant and widely distributed functional protein in mammals
.

 

Collagen biomaterials have been widely used in food, medicine , tissue engineering, cosmetics and other fields because of their good biocompatibility, biodegradability and biological activity
.
According to the source and processing method, collagen biomaterials can be divided into two categories: collagen extracted from animal tissues and recombinant collagen
.
Among them, the application history of extracting collagen from animal tissues has a long history
.
The collagen that people usually call refers to the collagen product prepared by animal tissue extraction technology
.

 

At present, the collagen products used in the medical device field mainly include collagen sutures, collagen-based orthopedic filling and repair materials, collagen implants for plastic surgery, collagen tissue engineering scaffold materials, and collagen dressings
.
Collagen medical devices are animal-derived products.
Due to the risks of immunogenicity and virus transmission, and some products have high risks, some collagen medical devices are managed as Class III medical devices
.
Recombinant collagen refers to the use of genetic engineering technology, using human collagen gene sequence as a template for design, and recombinant expression to obtain collagen biomaterials similar to human collagen
.
Recombinant collagen has good biocompatibility and biological activity, and is one of the research hotspots in the field of biomaterials in recent years
.

 

　　Collagen is widely present in human tissues and plays an important role in physiological activities
.
In recent years, with China's emphasis on the field of biomedicine, basic research and application development of collagen have attracted much attention
.
Innovative medical products based on human-derived recombinant collagen show huge market potential
.

 

　　China's research and industrialization in the field of recombinant collagen is at the forefront of the world.
At present, large-scale production has been initially realized, and it has been applied in many fields such as medical equipment and cosmetics
.
After inquiries, China has 43 recombinant collagen medical device products completed or in the process of registration or filing, which are mainly used as human tissue repair materials and medical wound dressings
.
However, it should be noted that the naming principles of some products on the market are not uniform.
For example, the terms used in the product names are "human-like collagen", "yeast recombinant collagen", "medical recombinant human collagen", and "medical type III collagen".
"Wait
.
At the same time, the provincial drug regulatory authorities are not uniform in grasping the principles of classification of existing marketed products.
There are second-class medical device registered products and first-class registered products, but no third-class registered products and imported products are seen
.
The inconsistency in the naming and classification principles of recombinant collagen medical device products causes difficulties in product identification, is not conducive to the high-quality development of the industry, and also brings difficulties to supervision
.

 

　　Multi-party cooperation to quickly complete the preparation

 

　　As more and more recombinant collagen products are available, the classification and definition of medical products containing recombinant collagen has attracted public attention
.

 

　　Recombinant collagen is used as a raw material in medicine, cosmetics and other fields because of its good biological properties, degradability and low immunogenicity
.
During the research and development of such products, the management attributes should be judged according to the intended use and utility realization method of the development and design, that is, according to the management of drugs , medical devices, cosmetics, or other types of products, otherwise there may be a risk of compliance with market access
.

 

　　For example, are skin care products containing recombinant collagen a medical device or a cosmetic? If it is a product managed by a medical device, the management category needs to be determined according to the degree of risk
.
The collagen products included in the "Medical Device Classification Catalogue" (2017 edition) are mainly written and formulated for collagen medical devices extracted from animals.
There is currently no guidance document for the classification and definition of recombinant collagen medical devices
.

 

　　The State Food and Drug Administration attaches great importance to the innovation and development of the recombinant collagen biomaterial industry
.
In April 2019, the State Food and Drug Administration listed the regulatory scientific research of new medical device materials, including recombinant collagen, as one of the first regulatory scientific research topics, laying the foundation for promoting the transformation of innovative achievements in the field of new materials
.
In June 2020, the State Food and Drug Administration held a special exchange meeting on the transformation and application of recombinant human collagen biomaterials innovation results to make specific arrangements for accelerating the transformation of scientific research results and leading the development of new industries, innovating working models, and actively promoting recombinant collagen innovation biology Material term naming, standards, classification and other tasks
.
Among them, the most important basic work is the deployment and formulation of the "Principles of Classification and Definition
.
"

 

　　In order to make up for this shortcoming as soon as possible and standardize the classification and definition of medical products containing recombinant collagen, in accordance with the deployment of the State Food and Drug Administration, it is led by the Medical Device Standards Management Center of the State Food and Drug Administration, and the Oral Medical Device Inspection Center, Peking University School of Stomatology, Tianjin Medical Device Quality Supervision and Inspection Center, Shandong Medical Device Product Quality Inspection Center and other technical units participated in the drafting working group
.
The working group optimized the work process under the conditions of not lowering the standards and standardizing procedures, and completed the compilation of the "Principles of Classification and Definition" in less than one month
.

 

　　Scientifically formulate the principles of classification

 

　　The "Classification and Definition Principles" are scientifically formulated based on the risk management principles of the "Regulations on the Supervision and Administration of Medical Devices" (hereinafter referred to as the "Regulations")
.

 

　　The term meaning of recombinant collagen medical products is given in the scope of application of the "Principles of Classification and Definition", that is, the recombinant collagen medical products stipulated in this principle refer to products with recombinant collagen as the main component and for medical purposes
.
This article clearly states the main components and intended purpose of such products, and distinguishes between non-recombinant collagen as the main component and products for non-medical purposes
.

 

　　The "Principles of Classification and Definition" clarified the principles for determining the management attributes of recombinant collagen medical products, setting out the specific circumstances of not being managed as a medical device, managing as a combination of medicines and devices, and managing as a medical device, and guiding the determination of the management attributes of such products
.
If it is considered that some cosmetics or health foods containing recombinant collagen may be easily misunderstood as medical devices when their expected effects are exaggerated, the "Principles of Classification and Definition" stipulates that recombinant collagen products do not meet the definition of medical devices in the Regulations.
In addition to the principles of medical device management, there are further examples of recombinant collagen products that are not managed as medical devices, such as recombinant collagen products used to improve vaginal dryness
.
Because vaginal dryness is not a disease, this product has no clinical significance and does not meet the definition of a medical device
.

 

　　In order to further guide the determination of the management categories of recombinant collagen medical products under the management of medical devices, the "Classification and Definition Principles" give the principles for defining the management categories of recombinant collagen medical products
.

 

　　Recombinant collagen is a new type of biological material, which is processed by recombinant technology in genetic engineering and has certain potential risks
.
According to the principle of risk management, the current first-class medical device supervision measures are not enough to ensure the safety and effectiveness of recombinant collagen medical devices
.
Therefore, the "Classification and Definition Principles" clarify the general principles of management categories, and stipulate that the management of recombinant collagen medical devices should not be lower than the second category
.

 

　　Based on the research on the management category of collagen medical devices and the existing marketed recombinant collagen medical devices, the most likely application of recombinant collagen biomaterials in the field of medical devices is passive implants, surgical hemostasis and anti-adhesion For products in the form of materials, medical dressings, etc.
, the "Classification and Definition Principles" clarify the specific principles for determining management categories, and stipulate the principles for determining classification codes, making the "Classification Definition Principles" more instructive
.

 

　　The implementation of the "Principles of Classification and Definition" also has specific requirements
.
Products that have accepted registration applications in accordance with medical devices will continue to be reviewed and approved in accordance with the original accepted categories
.
For recombinant collagen products that have been approved to be registered as medical devices, their registration certificates will continue to be valid during the validity period
.
If the registration application is filed within the validity period of the registration certificate, if the registration certificate expires during the product category conversion period, the registrant can apply to the original examination and approval department for the extension of the original registration certificate
.
If the extension is granted, the validity period of the original registration certificate shall not exceed December 31, 2023 in principle
.

 

　　The "Principles of Classification and Definition" was released and implemented, which defines the standards for the classification and definition of standardized recombinant collagen medical products and maintains market order, which is conducive to the scientific formulation of regulatory measures and lays the foundation for the scientific supervision of such products
.
At the same time, it helps to guide the research and development personnel of recombinant collagen medical products to correctly understand the regulatory policies of related products, determine appropriate compliance channels, and scientifically and reasonably set product design, development, production, quality control and other requirements to avoid compliance risks.
Reduce unreasonable capital investment, improve timeliness, and promote the transformation and application of new technologies and new materials of recombinant collagen research results and the high-quality development of the industry
.
(Author's unit: China Institute for Food and Drug Control)

　　Medical Network News on June 10 A few days ago, the State Food and Drug Administration issued the "Classification and Definition Principles for Recombinant Collagen Medical Products" (hereinafter referred to as the "Classification and Definition Principles") to further clarify the management attributes of recombinant collagen medical products and the basis for determining management categories.
, To provide guidance documents for the classification and definition of recombinant collagen medical products and the development and compliance of innovative products, which will promote the high-quality development of the recombinant collagen medical device industry
.

 

　　Facing industry and regulatory issues

 

　　Collagen is an important structural protein in human and animal tissues.
It is widely found in tendons, ligaments, cartilage, skin and other connective tissues.
It is the most abundant and widely distributed functional protein in mammals
.

 

　　Collagen biomaterials have been widely used in food, medicine , tissue engineering, cosmetics and other fields because of their good biocompatibility, biodegradability and biological activity
.
According to the source and processing method, collagen biomaterials can be divided into two categories: collagen extracted from animal tissues and recombinant collagen
.
Among them, the application history of extracting collagen from animal tissues has a long history
.
The collagen that people usually call refers to the collagen product prepared by animal tissue extraction technology
.

 

　　At present, the collagen products used in the medical device field mainly include collagen sutures, collagen-based orthopedic filling and repair materials, collagen implants for plastic surgery, collagen tissue engineering scaffold materials, and collagen dressings
.
Collagen medical devices are animal-derived products.
Due to the risks of immunogenicity and virus transmission, and some products have high risks, some collagen medical devices are managed as Class III medical devices
.
Recombinant collagen refers to the use of genetic engineering technology, using human collagen gene sequence as a template for design, and recombinant expression to obtain collagen biomaterials similar to human collagen
.
Recombinant collagen has good biocompatibility and biological activity, and is one of the research hotspots in the field of biomaterials in recent years
.

 

　　Collagen is widely present in human tissues and plays an important role in physiological activities
.
In recent years, with China's emphasis on the field of biomedicine, basic research and application development of collagen have attracted much attention
.
Innovative medical products based on human-derived recombinant collagen show huge market potential
.

 

　　China's research and industrialization in the field of recombinant collagen is at the forefront of the world.
At present, large-scale production has been initially realized, and it has been applied in many fields such as medical equipment and cosmetics
.
After inquiries, China has 43 recombinant collagen medical device products completed or in the process of registration or filing, which are mainly used as human tissue repair materials and medical wound dressings
.
However, it should be noted that the naming principles of some products on the market are not uniform.
For example, the terms used in the product names are "human-like collagen", "yeast recombinant collagen", "medical recombinant human collagen", and "medical type III collagen".
"Wait
.
At the same time, the provincial drug regulatory authorities are not uniform in grasping the principles of classification of existing marketed products.
There are second-class medical device registered products and first-class registered products, but no third-class registered products and imported products are seen
.
The inconsistency in the naming and classification principles of recombinant collagen medical device products causes difficulties in product identification, is not conducive to the high-quality development of the industry, and also brings difficulties to supervision
.

 

　　Multi-party cooperation to quickly complete the preparation

 

　　As more and more recombinant collagen products are available, the classification and definition of medical products containing recombinant collagen has attracted public attention
.

 

　　Recombinant collagen is used as a raw material in medicine, cosmetics and other fields because of its good biological properties, degradability and low immunogenicity
.
During the research and development of such products, the management attributes should be judged according to the intended use and utility realization method of the development and design, that is, according to the management of drugs , medical devices, cosmetics, or other types of products, otherwise there may be a risk of compliance with market access
.

 

　　For example, are skin care products containing recombinant collagen a medical device or a cosmetic? If it is a product managed by a medical device, the management category needs to be determined according to the degree of risk
.
The collagen products included in the "Medical Device Classification Catalogue" (2017 edition) are mainly written and formulated for collagen medical devices extracted from animals.
There is currently no guidance document for the classification and definition of recombinant collagen medical devices
.

 

　　The State Food and Drug Administration attaches great importance to the innovation and development of the recombinant collagen biomaterial industry
.
In April 2019, the State Food and Drug Administration listed the regulatory scientific research of new medical device materials, including recombinant collagen, as one of the first regulatory scientific research topics, laying the foundation for promoting the transformation of innovative achievements in the field of new materials
.
In June 2020, the State Food and Drug Administration held a special exchange meeting on the transformation and application of recombinant human collagen biomaterials innovation results to make specific arrangements for accelerating the transformation of scientific research results and leading the development of new industries, innovating working models, and actively promoting recombinant collagen innovation biology Material term naming, standards, classification and other tasks
.
Among them, the most important basic work is the deployment and formulation of the "Principles of Classification and Definition
.
"

 

　　In order to make up for this shortcoming as soon as possible and standardize the classification and definition of medical products containing recombinant collagen, in accordance with the deployment of the State Food and Drug Administration, it is led by the Medical Device Standards Management Center of the State Food and Drug Administration, and the Oral Medical Device Inspection Center, Peking University School of Stomatology, Tianjin Medical Device Quality Supervision and Inspection Center, Shandong Medical Device Product Quality Inspection Center and other technical units participated in the drafting working group
.
The working group optimized the work process under the conditions of not lowering the standards and standardizing procedures, and completed the compilation of the "Principles of Classification and Definition" in less than one month
.

 

　　Scientifically formulate the principles of classification

 

　　The "Classification and Definition Principles" are scientifically formulated based on the risk management principles of the "Regulations on the Supervision and Administration of Medical Devices" (hereinafter referred to as the "Regulations")
.

 

　　The term meaning of recombinant collagen medical products is given in the scope of application of the "Principles of Classification and Definition", that is, the recombinant collagen medical products stipulated in this principle refer to products with recombinant collagen as the main component and for medical purposes
.
This article clearly states the main components and intended purpose of such products, and distinguishes between non-recombinant collagen as the main component and products for non-medical purposes
.

 

　　The "Principles of Classification and Definition" clarified the principles for determining the management attributes of recombinant collagen medical products, setting out the specific circumstances of not being managed as a medical device, managing as a combination of medicines and devices, and managing as a medical device, and guiding the determination of the management attributes of such products
.
If it is considered that some cosmetics or health foods containing recombinant collagen may be easily misunderstood as medical devices when their expected effects are exaggerated, the "Principles of Classification and Definition" stipulates that recombinant collagen products do not meet the definition of medical devices in the Regulations.
In addition to the principles of medical device management, there are further examples of recombinant collagen products that are not managed as medical devices, such as recombinant collagen products used to improve vaginal dryness
.
Because vaginal dryness is not a disease, this product has no clinical significance and does not meet the definition of a medical device
.

 

　　In order to further guide the determination of the management categories of recombinant collagen medical products under the management of medical devices, the "Classification and Definition Principles" give the principles for defining the management categories of recombinant collagen medical products
.

 

　　Recombinant collagen is a new type of biological material, which is processed by recombinant technology in genetic engineering and has certain potential risks
.
According to the principle of risk management, the current first-class medical device supervision measures are not enough to ensure the safety and effectiveness of recombinant collagen medical devices
.
Therefore, the "Classification and Definition Principles" clarify the general principles of management categories, and stipulate that the management of recombinant collagen medical devices should not be lower than the second category
.

 

　　Based on the research on the management category of collagen medical devices and the existing marketed recombinant collagen medical devices, the most likely application of recombinant collagen biomaterials in the field of medical devices is passive implants, surgical hemostasis and anti-adhesion For products in the form of materials, medical dressings, etc.
, the "Classification and Definition Principles" clarify the specific principles for determining management categories, and stipulate the principles for determining classification codes, making the "Classification Definition Principles" more instructive
.

 

　　The implementation of the "Principles of Classification and Definition" also has specific requirements
.
Products that have accepted registration applications in accordance with medical devices will continue to be reviewed and approved in accordance with the original accepted categories
.
For recombinant collagen products that have been approved to be registered as medical devices, their registration certificates will continue to be valid during the validity period
.
If the registration application is filed within the validity period of the registration certificate, if the registration certificate expires during the product category conversion period, the registrant can apply to the original examination and approval department for the extension of the original registration certificate
.
If the extension is granted, the validity period of the original registration certificate shall not exceed December 31, 2023 in principle
.

 

　　The "Principles of Classification and Definition" was released and implemented, which defines the standards for the classification and definition of standardized recombinant collagen medical products and maintains market order, which is conducive to the scientific formulation of regulatory measures and lays the foundation for the scientific supervision of such products
.
At the same time, it helps to guide the research and development personnel of recombinant collagen medical products to correctly understand the regulatory policies of related products, determine appropriate compliance channels, and scientifically and reasonably set product design, development, production, quality control and other requirements to avoid compliance risks.
Reduce unreasonable capital investment, improve timeliness, and promote the transformation and application of new technologies and new materials of recombinant collagen research results and the high-quality development of the industry
.
(Author's unit: China Institute for Food and Drug Control)