关于水表的相关规定

nature biotechnology volume 29 number 1 january 2011

1Similarity trialsA European guideline on biosimilar monoclonal antibodies suggests smaller trials with homogeneous, younger patient groups may suffice for marketing authorization.The European regulatory authorities continue to make strides for-ward with biosimilars. Indeed, the latest advice from the European Medicines Agency (EMA) to those seeking to produce biosimilar mono-clonal antibodies (mAbs) is really quite straightforward. In its draft Guideline on Similar Biological Medicinal Products Containing Monoclonal Antibodies released for consultation in November, the Committee for Medicinal Products for Human Use (CHMP) of the EMA, in essence, said two things. First, applicants seeking approval of biosimilar mAbs will have to undertake comparative clinical studies; they must show that the safety and efficacy performance of a biosimilar is indeed similar to that of a reference, originator compound. But, second, clinical work doesn’t have to be too onerous, especially if applicants are smart about the way they choose the patient population. This latter point has received remarkably little attention but could be pivotal in shaping the biosimilars marketplace as the cost and complexity of running trials is the biggest barrier to market entry by generics companies.The expensive part of the process of developing biosimilars was always going to be the clinical work. But the overarching guidelines that the CHMP published on biosimilars (not specifically mAbs) in 2005 were rather vague on the nature of those trials. Indeed, the guidelines barely deserved the name, so little guidance did they actually give, and so few lines did they draw. The 2005 CHMP documentation did little more than identify who companies needed to talk to at EMA when taking their prod-uct forward on, in essence, a case-by-case basis.The 2010 antibody guidelines are much more specific. The key passages in the document still steer applicants firmly toward upfront discussion with the European regulator, which might be construed as a return to a case-by-case system. But the document also plants several highly signifi-cant signposts, all of which point in the same direction—that of simpler, smaller clinical studies.The focus of the biosimilarity exercise, says the guideline, is to “demon-strate similar safety and efficacy compared to the reference product, not patient benefit per se.” So the idea is not to reproduce the trial for the origi-nal approval, but to design a trial that shows the compounds are similar.How would such a trial be done? Well the guideline has sage advice there, too.First, choose a sensitive, experimental human model. In other words, select a clinical population where, from knowledge of the reference bio-logic, you would expect the drug to make a big impact. In that way, the similarity trial would be comparing one big impact with (one hopes) a second, similarly big impact. Comparing two large impacts would enable any differences to be more apparent.Second, the guideline suggests using homogeneous patient populations. By taking variability out of the patient set, any variability between the brand and the biosimilar forms of the biologic would be more apparent, the CHMP argues. The guideline also points out that with a homogeneous population, the sample size needed to prove (or disprove) equivalence would be smaller and facilitate simpler interpretation. It warns against using patients who either have different disease severity or have been exposed to different prior treatments because these additional variables could complicate the interpretation of differences seen in the two drug arms of the study. The guideline even recommends using younger groups of patients where possible, because younger people would be less likely to be effected by “concomitant clinical conditions.”In short, a trial to establish similarity is quite unlike a trial designed to measure safety and efficacy.Thus, with its new guideline on biosimilar mAbs, the EMA has not only provided specific and lucid advice to industry but, importantly, kept the debate about biosimilars and brands on a firm and rational footing. The US situation, in contrast, remains rather different.The 2010 Patient Protection and Affordable Care Act passed last March contained a section providing a legal framework for the approval of follow-on biologics. At the beginning of November, the US Food and Drug Administration held a two-day hearing in Silver Spring, Maryland, to discuss some of the issues with different stakeholders.Understandably perhaps for a first meeting, much of the debate was polarized between generics firms, which called for low clinical hurdles to biosimilarity, and innovator companies, which called for high ones. There were polemics over whether a biosimilar approved in more than one indi-cation would require comparative trials in each of those indications. There were distracting discussions on a phenomenon known as drift, wherein the manufacturing processes for a biologic and its biosimilar evolve away from each other. There were debates on whether trials should establish noninferiority or equivalence. And the possibility was discussed that a thorough analysis of post-translational modifications, three-dimensional structure and protein aggregation might obviate the need for clinical work altogether. That seems extraordinarily unlikely given the current state of technology and experience gained so far.It is striking how far behind Europe the US regulatory pathway for follow-on biologics remains. Part of this is due to the weaker political impetus and greater lobbying strength of US-based innovator companies. But governmental momentum to push forward might change if it became evident that healthcare costs could be substantially reduced by means of follow-on products for expensive biologics and mAbs. If, as EMA sug-gests, abbreviated trials with homogeneous patient groups are sufficient to support a marketing authorization of a biosimilar, many more generics companies are likely to enter the biosimilars/follow-on market, increasing price competition and driving down healthcare costs.Thus far, clinical trials for biosimilars in Europe haven’t looked much smaller or less costly than those required for applying for a new marketing authorization. But the guideline on biosimilar mAbs provides the first tantalizing indication that smaller trials may indeed be possible. EdiTorial

关于招待费的相关规定

1、为加强公司内部控制，降本增效，有效节约管理费用，特制订本规定。

2、原则：厉行节约，合理开支，严格控制，超标自负。各部门必须严格遵照这一原则控制好业务招待费用，杜绝不必要的支出。

3、程序：有接待任务的部门应事先填写《业务招待申请单》经分管领导审核及办公室主任批准后，报副总经理以上领导批准，凡不遵照本程序办理的，一律不予报销。

4、标准：

4.1 外出就餐：

（1）凡上级主管部门领导或重要客户来访，可按来宾规格安排在外就餐或安排在海成源农家院就餐；

（2）由部门自行负责接待的，其费用标准为80元/人（含酒水）；

（3）由董事长助理以上领导接待的，费用标准为120元/人（含酒水）；

（4）由总经理接待的，费用标准不超过150元/人（含酒水）；

（5）由董事长或董事长特批人员接待的，实报实销，无需填写《业务招待申请单》，由办公室主任或董事长助理负责协调安排并签单；

（6）由业务员（一对一）接待，费用标准不超过50元/人（含酒水）。

（7）特殊情况需超规格接待的，必须经总经理或董事长特别批准后方可办理，否则超出费用标准的部分自理；

4.2 来宾在公司食堂就餐：由办公室开具《公司食堂进餐卷》到食堂进餐。到食堂就餐的，每人标准按公司员工就餐标准执行。

5、招待费报销：外出就餐的，在公司协议饭店就餐的，由办公室负责联络安排，用餐后接待人员负责确认签单，办公室统一结算；其它饭店就餐的由接待人员先行垫付招待费，之后按公司相关报销流程签字报销，报销时须附上经过领导审批确认的《业务招待申请单》。

6、因公司食堂不提供晚餐，所有夜间需加班公司人员，公司给予福利性餐费补贴，按20元/人标准执行，人数以加班申请单为准，由当日加班最高领导签单确认。

7、本规定自文件下发之日起执行。

8、本规定由办公室负责解释。

附件：1、《业务招待申请单》 2、《公司食堂进餐卷》

内蒙古益世源科技环保有限公司

二O一七年八月一日

1 关于高层住宅地下室水表间水表安装规定

12层以下（包括12层）住宅楼，按一户一管水表在地下室水表间的规定：

1、水表间必须设有照明设施及动力电源。

2、水表间内不允许有煤气管线，如有其他管线，必须统一布置在边缘。

3、水表间内必须采取保温措施（参照相关规范）。

4、水表间内应设有集水坑0.4x0.4x0.4m，水表间室内地坪低于室外0.12m，以保证正常维修。

5、水表宜分层设置，层距0.5m，最低层距地面≥0.2m，最高层≤1.5m，同层管道外壁最小净距≥0.2m,分水器前必须设置闸门。

6、分层设置的水表及水管需设置固定支架，以保证水表的安全使用、维修、更换。

7、主要通道宽度≥1.0m，且水表要靠近通道一侧。同层水表多于8块时，中间要设维修通道≥0.5m。

8、水表预留安装距离为0.34m（误差不超过0.005m），进水端预留DN20外牙接头，出水端安装DN20短节加管箍尺寸0.08-0.085m。

9、水表间的布置应做出一个样板间，待我公司相关人员检查合格后，再进行下步施工，避免做完后不合格整改现象。

10、水表安装要保持水平，不得歪装或反向安装。

11、在我公司安装水表前，委托方需将水表间的钥匙提供给我公司安装人员。 2 12、委托方需在我公司安装人员进场前将用户标识标清（一管一表对应一户）。

13、在我公司工作人员进行水表安装时，委托方需配合相关人员，安装完毕后委托方应对安装情况及时验收，否则安装方对水表丢失等情况不予负责。

唐山市自来水公司

2013年1月9日

3 关于高层住宅管道井内水表安装规定

1、给水管道井应单独设置，须设有照明设施及动力电源。管道井内应保证不结冻，否则应采取适当的保温措施（参照相关规范）。

2、给水管道外壁（或保温层外壁）与其他管道外壁（或保温层外壁）之间的最小净距≥0.1m；。

3、水表应设置在正对管道井出口处，且中间无障碍物或其他管线穿插。

1

成都峨眉山国际大酒店

关于降职、解聘的相关规定

降职

各级员工违反成都峨眉山国际大酒店纪律或工作表现欠佳，或对本职务无法胜任，严重影响工作进行，可受到降职处分。

解聘

对于严重的重复违规或表现差的您可能会被解聘，所有的解聘都会有一个书面的通知并遵循国家的有关法律。作为立即解聘，酒店将不再考虑任何的通知期。另外，两次书面的处罚警告将导致解聘。

导致纪律处分警告直至解聘处分的例子

以下并未列尽行为失当的例子，但不表示其它的不诚实/或失当行为可以不导致采取上述纪律处分。例子的排列不分先后。

·故意不服从或不按酒店政策指导方针工作。

·由于疏忽和大意造成您个人受伤或导致酒店的财产受损。

·擅自迟到、早退和旷工。

·擅离工作岗位或未经许可在工作时间处理个人事务。

·不遵守成都峨眉山国际大酒店食品生产卫生和清洁的标准。

·不及时向上级报告个人受伤和事故。

·犯有任何可能危害其它您和顾客的安全的错误行为或失职情况。

·工作时间干扰其它同事的工作情绪和工作。

·工作拖拉或玩忽职守。

·在非成都峨眉山国际大酒店规定的时间和场所进餐、饮用饮料、抽烟，或未经成都峨眉山国际大酒店允许，将食品或饮料带入工作场所。

·不能或无法按计划上班又不及时通知部门管理人员。

·工作及工作表现不按照规定的目标，或不根据酒店决定的规定做。

·工作态度不严肃，或干劲不足。

·擅自进入对客区域，使用酒店财产、设备等，没有书面批准文件从酒店带出财务（包括食品、文件或其它物品、资料）。或未经批准将顾客和同事的财物带出。

·谎称受伤或诈取伤害赔偿。

·您监管的酒店现金短少。

·不能胜任工作或缺乏效率。

·违反安全规定，违规操作。 2 ·违反酒店仪容仪表规定。

·故意不完成酒店及部门管理人员交办的工作。

·泄露不应向其它人说明的酒店内容资料、信息及会议内容。

·类似上述性质的事例。

★ 导致立即解聘的例子

您犯有任何不忠诚和有意做错的行为，可能导致立即解聘，且酒店不需事先通知或支付费用。导致立即解聘的故意出错的定义是指任何会损害成都峨眉山国际大酒店良好经营的行为。下列不忠实和/或故意出错的事例会导致立即解雇。以下所列并非详尽无遗或意味没有其它会导致立即解雇的不忠实和/或故意出错的事例。例子的排列不分先后。