Release date: 2009-10-20
With the development and integration of modern medical high-tech, researchers have combined medicines, biological products and medical devices to develop a new form of medical products - pharmaceutical and mechanical products. It can be a combination of medicines and medical devices, a combination of biological products and medical devices, a combination of biological products and medicines, or a combination of medicines, biological products, and medical devices. This combination has the potential to make treatment safer, more effective, and more convenient or more comfortable for the patient, effectively improving the performance of the original single product.
After entering the 21st century, in order to meet the medical needs, countries have deepened their research in this area, such as drug-coated stents, catheters, artificial biological livers, orthopedic implants with growth factors, Organized products with cell components, etc., have emerged in an endless stream, especially biological tissue engineering has become one of the major hotspots in the field of life science research.
However, the development of new technologies has objectively increased certain use and management risks, which has brought certain challenges to product supervision, policy formulation and technical review. How to conduct technical review and effective risk management for such products? ?
Treating the right and left, monitoring the dilemma
“Pharmaceutical combination products are mostly innovative high-tech products and belong to new medical products. Due to the diversity and complexity of such products, it is decided that the classification of their management cannot be divided simply, clearly and clearly.†National Bureau Medical Device Technology The responsible person of the evaluation center and the person in charge of the relevant department of the Medical Device Supervision Department of the National Bureau agreed.
For this combination product, the United States, the European Union and other developed countries and regions have established an effective management model. For example, in the United States, according to the principle of product primary mode of action (PMOA), the combined product is distributed to one or two centers of the FDA, which is responsible for the primary pre-market review responsibility of the product; the EU is in accordance with the Medical Device Directive (MDD) Appendix I. Before making a registration decision, consult the competent authority of the member state on the drug part of the device. The competent authority reviews the safety, quality and effectiveness of the drug according to 65/65/EEC, and feeds the review opinion to the certification body. .
However, there has been no final conclusion on the classification of composite products in China. Some believe that it should be reviewed and supervised according to the equipment. Some suggestions are reviewed and supervised according to the drug, but in practice, neither of these methods can be combined with the product. Implement effective review and supervision. A product that can play both drugs and devices at the same time puts the management department in a dilemma. This cannot be said to be a very difficult problem.
In fact, management has been paying attention to and exploring effective management methods for this issue. As early as five years ago, the State Food and Drug Administration issued a regulatory document "Notice on Issues Concerning the Registration and Management of Drugs and Medical Devices Combined Products" (National Food and Drug Administration [2004] No. 94), on drugs and The registration management problem of medical equipment combined products has the following provisions: First, for the main functions of such products, the medical equipment plays a supporting role (such as syringes preloaded with drugs), and is registered and managed according to drugs. Responsible by the Drug Registration Division. 2. For the main products of this type of products, which play a major role in medical equipment and auxiliary functions (such as drug-containing stents, catheters with antibacterial coatings, drug-containing condoms, drug-containing birth control rings, etc.), registration and management according to medical devices It is the responsibility of the Medical Devices Division; in the registration work, drug review experts are invited to participate. The regulatory document also stipulates that: wounds containing antibacterial and anti-inflammatory drugs and traditional Chinese medicine external application agents are registered and managed according to drugs, and the drug registration department is responsible.
“The documents seem to be very clear and specific, but the reality is very complicated. It is often difficult to determine which factors play a major role in the combination of drugs, biological products and medical devices. Which factors play a supporting role, or There is no distinction between primary and secondary effects. Furthermore, in the patch administered under the registration of drugs, if a magnetic disk or a heating element is added to the product, how should it be classified? These bring the supervision of the combined product. Difficulties.†The reporter found in the interview that many frontline reviewers and supervisors have a negative attitude towards the operability of this document.
According to the person in charge of the relevant department of the Medical Device Supervision Department of the National Bureau, the supervision of the medical device combination products in China is still in the initial stage, which is mainly reflected in two aspects:
On the one hand, there are no relevant management regulations and administrative regulations, resulting in a more confusing classification of medical and pharmaceutical products. The same type of combination products may enter into two different registration procedures according to the device and the drug, or the drug or medical device is not clearly judged in the previous period, and the product accepted by the medical device registration is found, and the drug is found in the evaluation stage. Management, thus withdrawing from the medical device review process, and re-registering according to drugs, and more is to declare the enterprise to go back and forth between the drug and medical device authorities in order to clearly classify management, repeated consultations but no clear answer Case. This not only increases the cost of supervision, but also wastes social resources and reduces work efficiency.
On the other hand, even if the pre-classification is clear, a single review model cannot fully adapt to the requirements of the combined product. China's pharmaceuticals and medical devices are implemented in two completely different regulatory systems, with different requirements in terms of product standards, registration tests, clinical trials, and production quality systems. In this way, the first problem encountered is the preparation of the registration data. If the enterprise prepares the data in any one mode, it cannot meet the needs of the other model. For example, when a drug-containing device is applied for registration, the enterprise submits the registration information in accordance with the “Administrative Measures for the Registration of Medical Devicesâ€, but when it needs to be jointly reviewed with the drug evaluation center or hired a drug expert to participate in the review, it can be used for drug evaluation. The technical data is obviously insufficient, which leads to the need for the company to replenish, and even the clinical plan design is unreasonable, and the enterprise is required to re-run the clinical trial. This will not only extend the time limit for review, but also cause many complaints from administrative counterparts.
Is a special issue, why not treat it specially
"If we can't fully clarify the attribution of the combined products, why don't we consider the problem from another angle? There is no need to make a one-size-fits-all. Which category should we divide the combined products into? Why can't we classify them flexibly? Why can't we build such products? An independent review and approval mechanism?†The reporter found that no matter whether it is the evaluation agency, the regulatory department, the research institution or the armed unit, more and more people in the industry are jumping out of the category of “is a drug or a deviceâ€. It is more conducive to the perspective of supervision and explores special solutions to special problems.
The relevant person in charge of the Medical Device Technical Evaluation Center of the National Bureau said that with the increase in the number and types of medical device products, the current incompatibility of the relevant laws and regulations on drugs and medical devices in China has become more and more prominent, and the competent authorities have begun to pay attention to this. The problem, and put the research work of the solution on the agenda. In 2009, one of the measures taken by the State Food and Drug Administration to strengthen medical device supervision was to establish a review and approval mechanism for drug and drug combination products and promote the application of new technologies in the field of medical devices. Under such a favorable policy environment, it is completely feasible to formulate regulations for the classification and management of medical and pharmaceutical products that are in line with China's national conditions. At present, the two jobs bear the brunt.
First of all, to solve the problem of classification. This includes four aspects: First, establish the classification rules and judgment principles of the combined products, and clarify the definition, scope and types of the medical and mechanical combination products. The second is to establish a classification agency. Since the combined product involves both the pharmaceutical and medical device management departments, the classification and determination process requires coordination between the two departments. At present, in view of the fact that it is unlikely to form a separate medical and drug combination office, the two parties may designate a full-time or part-time staff to form a joint working group responsible for the classification of the combined products, and give them the authority to finally assign the corresponding evaluation center. The third is to establish a classification process. The main contents are: (1) Clearly submit the information to be submitted for classification. The enterprise application classification judgment shall submit at least the following materials: a detailed description of the performance and composition of the combined product; the intended purpose/effect of the combined product; the mode of action of each component of the combined product; determining a certain mode of action as the primary of the combined product The principle or reason of the mode of action; the applicant company proposes the management of drugs or medical devices and the reasons. (2) Identify the timing and means of applying for classification. It is recommended that companies start to apply for classification before preparing the registration materials to ensure the integrity and standardization of the registration materials. (3) The time limit for the classification and the manner and form of publication of the classification results. The fourth is to establish a catalogue catalogue of pharmaceutical and pharmaceutical products. The catalogue of the medical and pharmaceutical combination products of the confirmed categories will be summarized, a database will be established and published on the official website to facilitate the inquiry by enterprises and regulatory authorities. Similar medical equipment combination products can be operated according to the classified varieties, and no further classification is required. The description of the catalogue of the medical equipment combination catalogue shall include at least the following contents: a description of the performance and main components of the combined product; a description of the mode of action of the product and a description of the primary mode of action; a description of the intended purpose of the product; and a management of the drug or medical device.
Second, we must solve the problem of joint review. There are three aspects to this: First, the requirements for the application materials. Due to the characteristics of the medical device combination, whether it is registered according to drugs or registered with medical devices, in theory, the application materials submitted by the company must cover the relevant contents of drugs and medical devices and meet the registration requirements for drugs and medical devices. This requires the management department to formulate the “requirement for the registration of medical and pharmaceutical productsâ€. It should reflect the requirements for the safety, effectiveness and quality control of the medical and pharmaceutical combination products. It should not be a simple superposition of the two sets of registration materials for medicines and medical devices. . In addition, different requirements for the combination of pharmaceutical and mechanical products and new drug-medicine combination products that have a clear mechanism, clear use of the market, no substantial changes, and no adverse event reports should be considered to reflect the fundamental principles of product risk management. The second is the requirements for the joint review process. When a drug combination product is assigned to a device evaluation center or drug review center, it is led by the center and has primary review responsibility. The lead center shall, based on the specific conditions of the medical and pharmaceutical combination products, raise the questions that need to be consulted, and transfer the registration related materials to the coordination center, and cooperate with the center to provide evaluation comments to the lead center, and then the lead center will summarize and issue the final review opinions. The third is the time limit for joint review. The overall time limit for the review and approval of the medical device combination product shall be subject to the requirements for the registration form of the drug or medical device entered by the product.
With the rapid development of science and technology, the combination of medical equipment and products has become more and more popular, and the combination of medical equipment and medicines will become more and more close. Only by integrating the technical review resources of medicines and medical equipment supervision, it is more in line with the special nature of the medical equipment combination products. It is more conducive to improving the efficiency of administrative supervision.
Related Links
US FDA's management model for medical device products
According to the regulations of the Medical Device User Fee and Modernization Act of 2002, the US FDA established the Office of Pharmaceuticals and Drugs Products (OCP) on December 24, 2002. Its main responsibility is based on the primary mode of action of the combined product (PMOA). (a single mode of action that provides the most important therapeutic effect of the combination, ie, the mode of action that contributes the most to all expected therapeutic effects or objectives in the combined product), classifies the drug and medical combination products to which the application is dispensed, and combines each combination The product is accurately assigned to a certain center of the FDA, which is primarily responsible for the review of the product.
The FDA Office of Pharmaceutical and Dental Products (OCP) reviews the product distribution application (RFD) submitted by the company based on the principles of combined product classification management, and distributes the products to various FDA centers (CBER, CDER, CDRH). The primary review authority before the negative listing is reviewed. As part of the review process, the center with the primary review authority needs to consult or collaborate with another regulatory body in the portfolio. For example, according to the primary mode of action, the product of the drug-containing device (the combination product based on the device function) is classified into the Device Radiology Center (CDRH) for review. The drug-containing part is reviewed by the Center for Drug Evaluation and Research (CDER) and the review comments are provided to the CDRH. For registered drugs, CDER needs to confirm whether the drug production process control, chemical composition of the drug, drug synthesis changes, potential efficacy is reduced, and drug degradation is confirmed. If the drug has not changed in the above aspects, CDER will no longer review the safety of the drug. If the drug is not registered in the United States, it must be registered as a new drug in accordance with the drug review process. The FDA has issued standard operating practices for consultation and collaborative review between centers, including consulting and collaborative review definitions, procedures, policies, and more.
EU management model for pharmaceutical and pharmaceutical products
The European Union issued the Medical Device (MDD) Directive 93/42/EEC in 1993, which clearly states that if the device is used for the purposes of the 65/65/EEC Directive, the device is subject to this Directive, but may not Violation of the provisions of the 65/65/EEC Directive on medicines. However, if the device is integrated with the drug when it is placed on the market and can only be used in combination and cannot be reused, then the drug should be subject to the 65/65/EEC Directive. However, the basic requirements of Appendix I to this Directive still apply in terms of the safety and performance characteristics of the device. If a device is combined with a substance that is a component thereof, and if it is used alone, it can be regarded as a drug according to the 65/65/EEC directive, but the drug is more prone to the effect of the medical device on the human body. For ancillary effects, the device must be assessed and approved in accordance with the Medical Device Directive 93/42/EEC.
In the European Union, when the CE certification body receives an application for registration of a drug-containing device, according to the relevant regulations, it is necessary to consult the competent authority of the member state (CornpetentAuthority) before the registration decision is made. The competent authority is based on 65/65. The /EEC reviews the safety, quality and effectiveness of the drug and feeds the review comments back to the certification body. The effectiveness of the drug here relates to the expected function and mechanism of action of the drug in the device, and relates to the stability of the drug and its potential risks. According to the Medical Device Directive (MDD) Appendix I, the consultation process is the only way to review the drug-containing part.
Shanghai Medical Device Industry Association
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