Alprazolam(Aquestive Therapeutics, Inc.)

2月16日，山西省药监局印发《2023年度药品生产监督检查计划》，检查范围包括：持有《药品生产许可证》的药品上市许可持有人、药品生产企业；持有《医疗机构制剂许可证》的医疗机构制剂室；特殊药品定点经营企业和使用单位。检查方式分为常规检查、专项检查和有因检查常规检查包括：药品生产企业日常监督检查；医疗机构制剂室日常监督检查；药品生产企业符合性检查；特殊药品定点生产经营企业和使用单位日常监督检查。专项检查分为：1、 中药生产专项检查2、 国家集采中选品种专项检查3、 委托生产专项检查4、 药物警戒专项检查5、 特殊药品需用计划执行情况专项检查6、 放射性药品使用专项检查原文如下：市市场监督管理局、综改示范区市场监督管理局，各检查分局，省药品检查中心：为贯彻落实全国药品监督管理工作会议和全省药品监督管理工作会议精神，进一步加强药品生产和特殊药品监督管理，规范药品生产经营活动，强化药品上市许可持有人、药品生产企业（以下统称药品生产企业）和特殊药品企业主体责任落实，依据《中华人民共和国药品管理法》、《药品生产监督管理办法》、《麻醉药品和精神药品管理条例》等法律法规相关规定，省药监局制定了《2023年度药品生产监督检查计划》，现印发给你们，请认真贯彻执行。山西省药品监督管理局办公室2023年2月15日2023年度药品生产监督检查计划一、工作目标以习近平新时代中国特色社会主义思想为指导，贯彻党的二十大精神，落实“四个最严”要求，强化风险排查治理，落实监管主体责任，筑牢药品安全底线，严厉打击违法行为，全面提升药品安全保障能力。二、检查时间2023年2月至2023年11月三、检查范围（一）持有《药品生产许可证》的药品上市许可持有人、药品生产企业。（二）持有《医疗机构制剂许可证》的医疗机构制剂室。（三）特殊药品定点经营企业和使用单位。四、重点监管生产企业（一）高风险药品生产企业血液制品，放射性药品，医疗用毒性药品，无菌药品，多组分生化药，儿童用药。（二）重点关注药品生产企业1、国家集中带量采购中选药品生产企业。2、《新型冠状病毒肺炎诊疗方案（试行第十版）》中解热镇痛、止咳消炎及重症治疗等对症治疗药品生产企业。3、中药饮片生产企业。4、委托生产企业。（三）上年度有安全风险的药品生产企业1、被省药监局行政处罚的药品生产企业。2、被省药监局实施暂停生产销售等安全风险控制措施的药品生产企业。3、国家药监局探索性研究发现提示有风险的药品生产企业。4、国家公共信用综合评价结果较差的药品生产企业。五、检查方式、频次和重点（一）常规检查1、药品生产企业日常监督检查药品生产企业日常监督检查以本计划确定的重点监管生产企业为重点对象，做到全覆盖监督检查1次，对原辅包供应商、生产企业延伸检查不少于20%。对原辅料购进、处方工艺控制、质量检验把关以及偏差调查、变更控制等关键环节开展深入检查，强化药品生产全过程监督和动态检查，重点关注数据和记录的真实可靠、可追溯。对新办企业、新增生产车间（生产线）以及委托生产的持有人强化检查，督促上市许可持有人建立健全追溯管理制度，将药品信息化追溯工作纳入质量管理体系，不断完善药品全生命周期质量保证体系，切实担负质量主体责任。检查责任单位：各检查分局2、医疗机构制剂室日常监督检查医疗机构制剂室以疫情防控用制剂为重点品种，做到全覆盖监督检查1次。对配制制剂原辅料和直接接触药品的包装材料和容器是否符合药用要求，是否严格按照注册（备案）的配方、工艺和制定的配制规程组织配制，成品是否按照质量标准全项检验，配制、检验记录是否真实、完整、可追溯，配制环境、工艺用水是否定期监测，设施设备的使用和维护保养是否有记录进行重点检查，强化受委托配制制剂的检查。检查责任单位：各检查分局3、药品生产企业符合性检查对本计划确定的高风险药品生产企业、新冠诊疗对症治疗药品生产企业、中药饮片生产企业、2022年有安全风险的药品生产企业和国家公共信用综合评价结果较差的药品生产企业为重点开展至少1次药品生产质量管理规范符合性检查。省局制定符合性检查企业和重点检查品种名单。检查以品种为主线，从人、机、料、法、环五个方面，对药品生产是否符合核准的工艺和处方，原辅料采购和投料是否符合质量要求，各类生产检验数据是否真是、完整、可追溯，无菌保障管理是否到位，产品放行是否符合要求，偏差调查、质量回顾是否深入充分，变更管理是否符合规定等执行药品生产质量管理规范情况进行重点检查，严厉打击违法违规行为，监督企业严格按照药品生产质量管理规范组织生产。其中新冠诊疗对症治疗药品生产企业和中药饮片生产企业符合性检查在5月底前完成。检查责任单位：省药品检查中心4、特殊药品定点生产经营企业和使用单位日常监督检查特殊药品以芬太尼、聪明药（哌醋甲酯、莫达非尼）、咖啡因、阿普唑仑、咪达唑仑、曲马多、佐匹克隆、氨酚羟考酮、麻黄碱、A型肉毒毒素、锝标记和氟18药品为重点品种，第二类精神药品原料药和制剂生产企业、麻醉药品和第一类精神药品区域性批发企业以及药品类易制毒化学品原料药定点批发企业每半年检查一次；第二类精神药品定点经营企业和使用精神药品的食品生产企业、药品检验机构全覆盖检查一次；医疗用毒性药品生产经营企业和使用A型肉毒毒素的医疗机构全覆盖检查一次；放射性药品生产经营和医疗机构全覆盖检查一次。麻精药品和药品类易制毒化学品重点检查从安全制度制定、购销质量审验、双人制度执行、专库（柜）设施维护、到货确认付款等方面存在的安全管理风险和漏洞，推进全过程信息化追溯管理，严防流入非法渠道。在医疗机构药品检查中发现的安全问题和违规行为要及时通报当地卫健部门，存在非法渠道购进和非法销售等违法行为要及时移交公安部门。医疗用毒性药品重点对定点批发企业和医疗机构（医美机构）注射用A型肉毒毒素的购进资质票据、销售使用渠道的合法性及储运环境进行检查，督促企业和医疗机构建立或入驻第三方信息化追溯系统，通过扫码实现全程追溯和追溯到人。检查责任单位：各检查分局和各市市场局依工作职责开展检查。（二）专项检查省药监局负责制定专项检查方案（另行下发），各市市场局、省局各相关处室、各检查分局、省药品检查中心按照方案要求开展检查。1、中药生产专项检查对全省中药生产企业开展专项检查。重点检查中药饮片、中药生产过程中是否掺杂使假、非法添加、染色增重、虚假投料，是否违规购进使用原辅料，是否编造生产检验记录，严控药品质量风险，强化中药变更管理，严厉打击违法违规行为，着力提高中药生产质量管控能力和水平。2、国家集采中选品种专项检查对我省国家集中招采中选品种生产企业开展全覆盖专项检查。重点检查企业是否严格按照核准的处方工艺进行生产，批量变更、场地变更、原辅料变更等变更管理是否合法合规，生产过程数据管理、偏差管理、放行管理等质量控制是否持续合规，督促企业落实全程追溯、三方储运、药物警戒等上市许可持有人主体责任。3、委托生产专项检查对委托生产企业的供应商审核、变更管理、偏差管理、上市放行、追溯管理、药物警戒等职责履行情况，特别是关键岗位人员履职情况等进行重点检查，督促持有人落实对受托生产企业的质量管理责任，确保委托双方质量管理体系有效对接，质量协议落到实处。4、药物警戒专项检查推进《药物警戒质量管理规范》的实施和宣贯，按照省局《药物警戒检查要点细则（试行）》，对全省制剂持有人开展药物警戒专项检查，督促指导持有人建立健全药物警戒体系，强化企业药物警戒主体责任落实。5、特殊药品需用计划执行情况专项检查对全省使用麻醉药品、精神药品、药品类易制毒化学品原料药生产药品和食品的企业开展专项检查。重点检查特殊药品需用计划的采购、运输、储存、使用等全环节安全管理情况，特别对特殊药品生产购用审批量涨幅较大、发生变更、安全管理制度落实不到位企业要加大监督检查力度，严防流入非法渠道。6、放射性药品使用专项检查对全省使用放射性药品的企业和医疗机构开展专项检查，重点核对《放射性药品使用许可证》类别、科室与实际使用放射性药品的一致性，是否存在超范围使用情况，重点检查放射性药品的购进、储存、安全管理以及锝标记、氟18等放射性药品的制备、检验、记录等情况开展重点检查，规范放射性药品使用和安全防护行为。（三）有因检查一是针对投诉举报、监督抽检、药物警戒、探索性研究以及药品安全风险研判等发现的药品生产质量风险隐患为线索，由检查分局组织开展有因检查；二是国家药监局安排部署的有因检查，由省局组织进行。要通过有因检查着力提升检查的针对性、靶向性，对检查发现的违法违规行为依法严厉查处。六、工作要求（一）各单位要加强组织领导，坚持问题导向，落实监管工作责任，按照检查计划，统筹安排检查力量，加强药品上市后监管，确保按期保质完成各项检查任务。（二）各单位要坚持风险管理，按照省局《药品质量安全风险研判会商制度》有关要求，加强药品安全风险研判会商，及时有效防范化解药品风险，积极探索创新监管方式方法，提升药品安全监管能力。（三）各单位要强化监管工作协同，横向同卫健、公安、医保等部门加强沟通协调，纵向同各级药品监管部门和技术支撑部门加强信息互通，形成多部门多层级的监管合力，确保监督检查取得实效。（四）各单位要及时汇总监督检查信息，分析研判安全风险。检查分局和省药品检查中心请在检查完成7日内将检查报告等材料报送省局药品生产监管处；各市局请于每季度末报送特殊药品经营企业/使用单位检查情况，6月25日、12月25日前分别报送半年和全年工作总结。联 系 人：李焰（19135317253）电子邮箱：shengjuajc@163.com

Extends Intellectual Property Protections to 2039LAKE FOREST, Ill., Jan. 09, 2023 (GLOBE NEWSWIRE) -- Assertio Holdings, Inc. (“Assertio” or the “Company”) (Nasdaq: ASRT), a specialty pharmaceutical company offering differentiated products to patients, today announced that U.S. Patent, No. 11541002 for Sympazan® oral film is now listed in the U.S. Food and Drug Administration (“FDA”) publication, Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. The patent, which is valid until 2039, is assigned to Aquestive Therapeutics, Inc. and exclusively licensed to Assertio. It covers an oral film for delivering clobazam and methods for using the film to treat epilepsy and/or seizures. Aquestive will continue to prosecute additional US patent application(s) to further strengthen the portfolio on this product. “We are pleased to see this patent listed in the Orange Book, as originally anticipated in our Sympazan licensing agreement with Aquestive. This patent is complementary to two other Sympazan patents already listed in the Orange Book and extends patent coverage until 2039 for this innovative and attractive oral film delivery system for clobazam,” Dan Peisert, President and Chief Executive Officer of Assertio. “Sympazan exemplifies the type of longer duration assets we are seeking to add to the portfolio as we continue to diversify and expand our platform,” said Vanessa Fox, Vice President, Business Development and Commercial Analytics. “We continue to work a robust pipeline of business development projects in support of our goal to add $50 million of incremental gross profit by 2024, of which we have now secured $18 million from the combination of our Otrexup and Sympazan transactions, both of which include notable growth opportunities.” About Sympazan Trade NameSympazan® (clobazam) oral film formulationIndicationFor the adjunctive treatment of seizures associated with Lennox‐Gastaut Syndrome (LGS) in patients aged 2 years of age or olderLast to Expire Orange Book Listed PatentSeptember 2039Trailing 12 Months Revenue Ended 6/30/22Approximately $9.5 Million WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. • The use of benzodiazepines, including SYMPAZAN, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing SYMPAZAN and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.• Abrupt discontinuation or rapid dosage reduction of SYMPAZAN after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue SYMPAZAN. Important Safety Information SYMPAZAN is a benzodiazepine medicine. Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system (CNS) depressants (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma, and death.Get emergency help right away if any of the following happens: shallow or slowed breathingbreathing stops (which may lead to the heart stopping)excessive sleepiness (sedation) Do not drive or operate heavy machinery until you know how taking SYMPAZAN with opioids affects you. Please see full Prescribing Information including Boxed Warning on risks from concomitant use with opioids; abuse, misuse and addiction; and dependence and withdrawal reactions at www.sympazan.com/pdfs/pi.pdf About Assertio Assertio is a specialty pharmaceutical company offering differentiated products to patients utilizing a non-personal promotional model. We have built and continue to build our commercial portfolio by identifying new opportunities within our existing products as well as acquisitions or licensing of additional approved products. To learn more about Assertio, visit www.assertiotx.com. Investor Contact Matt KrepsManaging DirectorDarrow AssociatesAustin, TX M: 214-597-8200mkreps@darrowir.com Forward Looking Statements Statements in this communication that are not historical facts are forward-looking statements that reflect Assertio's current expectations, assumptions and estimates of future performance and economic conditions. These forward-looking statements are made in reliance on the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements relate to, among other things, future events or the future performance or operations of Assertio, including our ability to realize the benefits from our operating model, successfully acquire and integrate new assets including Sympazan and explore new business development initiatives, as well as Aquestive’s ability to successfully prosecute the pending patent application and timing of allowance by the USPTO. All statements other than historical facts may be forward-looking statements and can be identified by words such as "anticipate," "believe," "could," "design," "estimate," "expect," "forecast," "goal," "guidance," "imply," "intend," "may", "objective," "opportunity," "outlook," "plan," "position," "potential," "predict," "project," "prospective," "pursue," "seek," "should," "strategy," "target," "would," "will," "aim" or other similar expressions that convey the uncertainty of future events or outcomes and are used to identify forward-looking statements. Such forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and other factors, some of which are beyond the control of Assertio, including the risks described in Assertio's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the U.S. Securities and Exchange Commission ("SEC") and in other filings Assertio makes with the SEC from time to time. Investors and potential investors are urged not to place undue reliance on forward-looking statements in this communication, which speak only as of this date. While Assertio may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to update or revise any forward-looking-statements contained in this press release whether as a result of new information or future events, except as may be required by applicable law. Nothing contained herein constitutes or will be deemed to constitute a forecast, projection or estimate of the future financial performance or expected results of Assertio.