Ref l ections on the Management of Preventing lnterest Conf l ict among Pharmacopoeia Members

Zhao Jianfeng , Zhang Wei, Yu Hai

(1. School of Business Administration, Shenyang Pharmaceutical University, Shenyang 110010, China;2. China Pharmacopoeia Commission, Beijing 100061, China;3. Liaoning Health Industry Group, Shenyang 110000, China)

AbstractObjective To provide reference for strengthening the management of preventing interest conflicts among pharmacopoeia members. Methods The procedures of the United States Pharmacopoeia (USP) Committee, and the actions taken by members or experts of US food and drug administration to prevent interest con fl icts were referred to analyze the problems in the management of preventing interest conflicts in China pharmacopoeia committee, and corresponding suggestions were put forward. Results and Conclusion Although the interest and risk avoidance system and dismissal measures were mentioned in the measures for the administration of Chinese pharmacopoeia commissioners, no detailed rules and specific procedures were formulated to prevent interest con fl icts of Chinese pharmacopoeia commissioners. It is suggested that preventing the interest con fl icts of pharmacopoeia members should be included into the drug formulation and revision system as soon as possible. In addition, the management measures for pharmacopoeia members should be further perfected to avoid the interest con fl icts. The scope of publicity for the formulation and revision of drug standards should be expanded and the supervision and implementation must be strengthened. Therefore, the members of pharmacopoeia can participate in the formulation and revision of drug standards in a fair or just manner.

Keywords: risk management; pharmacopoeia member; con fl ict of interest; precaution

Conflict of interest was originally a political concept. In the 1960s, the Canadian government fi rst introduced it into the fi eld of clean government.It was believed that public servants must serve the national interest or public interest one hundred percent and should not seek personal gain through public service[1]. The term "conf l ict of interest" was proposed and used by China in the fourth plenary session of the central commission for discipline inspection on January 3, 2000. At the meeting, it was proposed that "spouses and children of leading cadres at the provincial (ministry) and prefecturelevel (office) levels shall not be allowed to engage in business or enterprise activities that may conflict with public interests within the business scope under the jurisdiction of the leading cadre". The fourth plenary session of the seventeenth CCP central committee adopted "the Decision of the CCP Central Committee on Several Major Issues Concerning Strengthening and Improving the Party Building Under New Circumstances", which for the first time explicitly put forward the idea of "establishing and improving the system for preventing conflicts of interest". Conflict of interest is a game between the public right representing the public interest and the private right representing the individual interest.Improving the system of preventing conf l ict of interest is an important part of the construction of the clean government. The fundamental problem is to prevent the risk of corruption through system construction to maximize the public interest. Therefore, as long as it involves the decision-making of the conflict of personal interests and public interests, it is necessary to build a system to prevent the conf l ict of interests.

The national pharmacopoeia committee is a statutory body that organizes and carries out the revision work of national drug standards. During the process of revising drug standards, the constitution of the pharmacopoeia committee and the management measures for the members of the pharmacopoeia have been preliminarily formulated[2-3], but the concept of risk management has not been effectively integrated with the concept of prevention of conf l icts of interest.On August 29, 2017, the 11th pharmacopoeia committee was established in Beijing, involving in a total of 26 committees in general principles, traditional Chinese medicine, chemical medicine, biological products, pharmaceutical excipients and medicine packaging materials. Bi Jingquan, the former director of the food and drug administration and the chairman of the eleventh pharmacopoeia committee, proposed the requirements for pharmacopoeia committee members to stick to a clean and honest professional ethics with the scientific attitude and courage. He also required pharmacopoeia commission should strengthen the system construction, which meant to set up a withdrawal system for conf l icts of interest[4]. This paper analyzed the practice of preventing conflicts of interest taken by drug evaluation and research centers of USP and FDA, and then we put forward some corresponding management suggestions for the management and supervision of preventing conf l icts of interest among pharmacopoeia committee members.

1 The importance of establishing a mechanism for the committee of pharmacopoeia to prevent conf l icts of interest

National drug standards refer to the technical regulations made by the State on the quality indicators,inspection methods and production processes of drugs in order to ensure the quality of drugs. They are the mandatory guidelines and legal basis for all links of drug research, production, management, use, and supervision. "The Drug Administration Law of the People's Republic of China" clearly stipulates that"drugs must meet the national drug standards". The pharmacopoeia of the People's Republic of China and the pharmaceutical standards promulgated by the drug supervision and administration department under the State Council are the national drug standards. The formulation of drug standards includes the collection of standard subjects, the initiation of standard research work, the drafting, review, examination and publicity of the standards, which are finally approved by the pharmacopoeia committee to form the Chinese Pharmacopoeia (Draft). Then it is approved by the pharmacopoeia committee and submitted to the drug regulatory department under the State Council for approval, promulgation and implementation.According to the articles of association of the pharmacopoeia committee and the administrative measures for pharmacopoeia committee members,they shall be responsible for the examination and approval of the drug standards and their research projects as well as the formulation and revision of the drug standards. They also participate in the examination and approval of the drug standards of the professional committee to review and vote on the draft for drug standards. At present, the standing body of the pharmacopoeia committee generally organizes professional committee meetings for pharmacopoeia members to review related topics,variety standards, etc., and then they put forward opinions and make decisions. It can be seen that the drug standard evaluation still depends on the opinions of the professional committee members to a large extent. Drug standard review is based on the current situation of China's social and economic development,the people's drug safety needs and the application of new instruments and methods, which is an effective means to reevaluate safety, effectiveness and quality of listed drugs. Drug standards are scientific and rigorous, and the level of drug standards will aあect the interests of enterprises and the safety of the people's medication. On the basis of their working experience and cognition, various members of professional committees provide medical, pharmaceutical and other support in the process of drug approval. Though they are not civil servants, they are actually entrusted by the pharmacopoeia committee to review drug standards. Therefore, they will be inevitably involved in a conflict of interest and may be tempted by enterprises.

In addition, as the committee members come from all over the country, they are involved in drug research and development, production and research institutes and other institutions etc. For example, the 11th pharmacopoeia committee has a total of 346 members from each professional committee, and 146 members from national drug testing institutions at all levels, accounting for 42%. A total of 117 members from universities and research institutes, accounting for 33%, 40 members from medical institutions,accounting for 11%, 31 members from the enterprises,accounting for 9%, 12 members from the management department, accounting for 3%. Some members are engaged in the formulation and revision of drug standards themselves, while others have positions or have part-time jobs in enterprises. Therefore, it is necessary to avoid the deviation of drug standards from the purpose of public welfare due to the multirole of members. Solving conflicts of interest is the premise to formulate and revise drug standards efficiently and fairly. If conflicts of interest cannot be effectively managed and controlled, corruption is likely to occur which will seriously aあect public drug safety.

2 Problems in the prevention mechanism of interest of conflict for pharmacopoeia committee members

According to the administrative measures for pharmacopoeia committee members, they shall not participate in the examination and verification of the relevant varieties or topics in which they have an interest. If invited, they shall take the initiative to withdraw. If there is any private agreement among members of the pharmacopoeia, which violates the principles of fairness, impartiality and openness and affects the audit results, measures shall be taken to dismiss the members of pharmacopoeia committee according to the provisions of the drug regulatory authority under the State Council and the provisions of the pharmacopoeia committee on conf l icts of interest.Although the measures mention the interest and risk avoidance system as well as dismissal, no detailed rules and specific procedures have been formulated to prevent conflicts of interest for pharmacopoeia committee members.

Conflict of interest is defined by the USP as a matter of direct or indirect economic or other personal interest to a committee member, which may or may not prevent a member from exercising a public decision or affect the best interests of the member. The member of pharmacopoeia committee shall serve as an independent expert for the USP and shall not provide any help to external interests,nor in any way use his membership to obtain any personal or external gains. Before doing any work,discussing the issue, or reviewing the matter, any member of the professional committee who thinks that he has a clear or potential interest shall notify USP staあ and the experts committee in advance. And then the USP secretariat shall confirm whether the individual has a conf l ict of interest. The minutes of the meeting shall disclose the conf l ict of interest and resolutions, including disqualification from voting and deliberations.

In addition, each member shall submit a disclosure statement to the USP to disclose all information related to the practice, professional research, and other interests. The disclosure statement shall be kept up to date or updated regularly in accordance with USP regulations. The member shall be obligated to provide the committee of experts and USP staff with information about ongoing changes or emerging interests, and the information in the disclosure statement shall be kept confidential. If a committee member fails to fi le a disclosure statement,that member cannot participate in the activities of the professional committee until a statement is filed with the USP. The USP shall periodically review the disclosure statement to identify potential conflicts of interest and ensure that other members of the professional committee are informed of all interests revealed in the disclosure statement. Any obvious or potential conflict of interest identified by the professional committee shall not be resolved by recusal or intervention of the chairman of the professional committee. The problem shall be submitted to the USP executive secretariat for resolution. Minutes of any meeting related to conf l ict of interest should ref l ect the disclosure and solutions of the problems, including the withdrawal of an expert due to conf l icts of interest[5].

China has not established an avoidance mechanism for the management of conflict of interest for pharmacopoeia committee members, nor formulated corresponding procedures on identifying and solving conflicts of interest for the members. In the current practice of drug standard evaluation in China, the members of pharmacopoeia committee are not constrained to disclose relevant information of economic interests to pharmacopoeia committee for their own interests. Therefore, it is necessary to further refine the system of conflict of interest and formulate procedures to solve conf l icts of interest for pharmacopoeia committee members.

3 Suggestions on establishing a prevention mechanism for conflict of interest of the pharmacopoeia committee members

3.1 Setting up a withdrawal system for pharmacopoeia committee members

Foreign successful experience shows that the establishment of a sound avoidance system is an important institutional guarantee to prevent conflicts of interest. In the fi eld of drug supervision in China, a series of systems have been formulated to prevent the risk of conf l icts of interest. In 2014, "the Management of Conflicts of Interest of External Experts in Drug Supervision (Trial)" was formulated by the former Food and Drug Administration. In the field of drug approval, the management of national drug review expert promulgated by the Ministry of Health in 2000 stipulates that if a national drug review expert is also a participant in the research and development of a drug to be evaluated, the expert should inform Drug Approval Center to withdraw from the review.If the national drug evaluation expert has any other interests with the applicant enterprise, and there are other factors that may affect the scientific and fair evaluation, he shall also withdraw from the evaluation.In the USA, when the drug review experts hold the applicant enterprise shares or have investment in the applicant enterprise, or work for the applicant enterprise, or provide advice for the applicant enterprise in the form of contract, research funding,it means the expert and the applicant enterprise have specific economic interests. In the process of drug approval, such an expert should withdraw from the evaluation. But given the present close link between academia and industry, the expert can be exempt from the avoidance if his professional knowledge exceeds his existing economic interests[6].

This paper is on the practice of the avoidance system in the field of drug evaluation based on the rules and regulations of the US pharmacopoeia commission, as well as the research of the conflict of interest between experts and the applicant enterprises made by Professor Song Hualin of Nankai University. The withdrawal system for members of the pharmacopoeia committee is initially identif i ed as the following two stages:

The first is the screening of the pharmacopoeia committee members. Before the professional committee meeting on pharmaceutical standards is held, the standing body of the pharmacopoeia committee shall provide the meeting materials to the committee members to be invited. After receiving the materials, the committee member shall fi ll in the statement of conf l ict of interest according to the requirements if they are able to attend the meeting. In addition, information about their economic activities should be submitted, including but not limited to their participation in the research projects of the corresponding varieties, or their direct interests in the research projects of similar products. If they have a kinship relationship with the corresponding administrative staff, or have an interest relationship between them or their immediate family members and the corresponding administrative counterpart, or the experts participate in the commissioned research work of the corresponding products and collect fees, or experts have received sponsorship or fi nancial support from administrative counterparts in other work, they should take the initiative to make a statement to the pharmacopoeia committee and withdraw from the evaluation[7].

The second is a conf l ict of interest identif i cation and confirmation. After receiving the members'information on economic activities and participation in the meeting, the standing body of the pharmacopoeia committee will use the information to judge whether there is an interest relationship between experts,evaluation varieties and applicant enterprises. Then they will tell if the experts should withdraw from the evaluation and disclose the reasons for the withdrawal. When necessary, the potential interests of the committee members can be studied and judged according to the actual situation by the standing body.After weighing the interests of the pharmacopoeia members and the needs of the standard review, the decision of avoiding can be made. But the reasons for not withdrawing and the interests of the drug review department need to be made public.

3.2 Expanding the scope of information disclosure in the formulation of standards and smoothing the reporting channel

The implementation of the prevention system for conflict of interest among pharmacopoeia committee members is inseparable from public supervision.Transparency is the best policy for anti-corruption. On the one hand, making the drug standards revision public can strengthen the self-discipline of pharmacopoeia committee members. On the other hand, it also can avoid the information asymmetry between related pharmaceutical departments and pharmacopoeia committee, which can provide information basis for social supervision. At present, in order to solicit opinions from all sectors of society and strengthen the applicability of quality standards from pharmaceutical enterprises, the revised draft amendment to the specif i c varieties of drug quality standard system approved by professional pharmacopoeia committee will be published on the national pharmacopoeia committee website for public comments. The publicity period is generally 3 months. However, the content on the website is only limited to the draft of the revised standards and the contact information of the person in charge of various drugs. Therefore, it is necessary to further publicize the selection of varieties, the approval of standard research projects, the drafting and review of standards, the list of professional committee members and experts participating in the meetings, and the information of enterprises and varieties applied for.These can guarantee the supervision from all walks of life.

In addition, there should be open channels for concerned parties to make complaints and they should timely respond to the public's queries. Disclosing the key information of the drug standard review meeting is a good way to ensure the pharmacopoeia committee to be supervised by the public. Therefore, the committee members can be prevented from corruption and giving suggestions against the conscience[5].

3.3 Establishing the management system of pharmacopoeia members and improving their management level

The establishment of the management system for pharmacopoeia committee member can not only provide a channel for communication between pharmacopoeia committee members and the standing body, but also set up a platform for the prevention system of conf l icts of interest. First of all, the standing body of the pharmacopoeia committee requires members to update the information of their economic activities every year and update it timely according to the changing situation. Before each meeting of the professional committee, the standing body sends the deliberative materials to the members through the management system of the pharmacopoeia committee members.The members confirm whether they have conflicts of interest by reviewing the materials and combining their own information of economic activities. The standing body of the pharmacopoeia committee will review and confirm if the experts must withdraw from the committee. After receiving the conf i rmation of meeting the requirements, the committee management system will inform the members. In addition, a member's credit system can be put into the management system. That is,after the member has conf i rmed that he has no conf l ict of interest, but the standing body fi nds the member has a conf l ict of interest or is reported to have a conf l ict of interest during the publicity period and it is true, the member will be recorded in the credit system and given a warning. The relevant member will be disqualified from the meeting according to the situation of the time limit, and in serious case, the member will be directly disqualified from the pharmacopoeia committee. By embedding the credit system of the pharmacopoeia members into the management system, it is a constraint on the members and an eあective measure to guarantee the management of the pharmacopoeia committee members.

Pharmacopoeia member is one of the core elements of the revision of drug standards. The management of pharmacopoeia members is equivalent to the foundation of the revision of drug standards. Therefore, based on the premise of risk,it is necessary to include the prevention of interest conflicts of pharmacopoeia committee members into the drug standard system. We will further improve the management measures for pharmacopoeia committee members, refining the specific measures for the prevention system of pharmacopoeia committee members, and strengthening the supervision and implementation. Through the construction of the credit system for pharmacopoeia committee, the formulation and revision of drug standards can be carried out in the sun.