延误、抵制、限制或拒绝药品检查的情况（下）

延误、抵制、限制或拒绝药品检查的情况（下） http://www.zjccd.org/exchange/a/ff8080814cb54fd9014cbf88d2d50025.htm

IV. 抵制检查 FDA对“抵制”这个术语的解释包括药品企业所有者、经营者或药品代理机构阻止FDA授权代表进行检查或阻止FDA完成检查的行为。这包括语言或肢体行为，目的是逃避检查或误导、欺骗、阻碍检查员。以下是构成抵制检查的行为并可根据FD&C法案第501(j)条被视为掺假药的情况举例，包括但不限于：? • 企业拒绝FDA计划安排的预先通知检查。 • 在检查员达到企业后，企业不允许FDA检查员开始检查。 • 企业因为某些员工不在而不允许FDA检查员开展检查，并且没有给出合理解释。 • 企业虚假宣称本厂没有生产、加工、包装、储存药品，从而不允许FDA检查员检查企业。? •  企业在检查日将员工遣散回家，告知FDA检查员本厂没有进行任何生产。 以下是企业给出了合理解释，根据FD&C法案第501(j)条不会被视为掺假药的情形举例，包括但不限于： • 在非预先通知检查的开始阶段，（适当比例的）部分员工无法立即达到准确回答FDA检查员的问题。 • FDA检查员开始非预先通知检查，但是企业由于维修计划正处于停产关闭状态。 V. 限制检查 根据FD&C法案第501(j)条，企业所有者、经营者或药品代理机构在法律允许的程度上阻止FDA授权代表实施检查，将被视为限制检查。以下是构成限制检查的行为并可根据FD&C法案第501(j)条被视为掺假药的情况举例。? A. 限制进入工厂和/或查看生产工艺 阻止FDA授权代表合理进入FDA授权检查的区域，可被认为是限制检查。这包括拒绝公开或允许查看生产工艺，包括但不限于： • 在FDA检查期间，企业下令停止生产，且没有合理的解释。 • 企业声称直接涉及生产工艺的检查（整个或部分生产工艺）必须限制在不合理的较短的时间限度内，从而阻止FDA检查企业。这种情况是比较常见的。 • 企业限制检查员对部分生产工艺直接进行检查，且没有合理解释。 • 企业不合理地限制检查员进入企业的某个特定区域，且没有合理解释。 • 企业员工引导FDA检查员在检查完成之前离开建筑物。 以下是企业给出了合理解释，根据FD&C法案第501(j)条不会被视为掺假药的情形举例，包括但不限于： • 企业不让FDA检查员进行无菌工艺生产区域，直到检查员的更衣操作符合企业规定的更衣程序 • 进入企业特定区域的人员需要接受职业安全和健康管理局的特定培训，而FDA检查员没有接受该特定培训。 B. 限制拍照 拍照是FDA检查的主要组成部分，因为照片能客观、实时反应企业的状况。照片能有效记录以下情况（包括但不限于）：鼠类或虫类侵入的证据、设施设备结构缺陷或维护不当、产品储存条件、产品标签标识、以及原料或成品中的可见污染等。如果检查员认为这些照片对于有效开展检查是必须的，妨碍或阻止FDA检查员拍照可视为限制行为。 以下是企业给出了合理解释，根据FD&C法案第501(j)条不会被视为掺假药的情形举例，包括但不限于： • 企业生产产品的化学性能特殊，拍照可能对产品质量造成不利影响。 C. 限制查看或复印记录 根据本指南III.C部分的解释，查看和复印记录是FDA检查的重要组成部分。不允许FDA授权代表查看或复印FDA有权检查的记录，包括不提供FDA要求的记录，按照FD&C法案第704(a)(4)条，可视为限制检查。限制查看或复印记录记录的举例包括但不限于： • 企业拒绝FDA检查员查看FDA有权审核的企业货运单据。 • 企业仅提供部分（而非全部）FDA检查员要求的且有权检查的记录。 • 企业提供了FDA检查员要求的且有权检查的记录，但记录被不合理地修改过。 • 企业拒绝提供FDA根据第704(a)(4)条款要求查看的记录，或这些记录被不合理地修改过。 D. 限制或阻止取样 取样是FDA检查和法规行为的关键部分。FD&C法案第702(a)条授予FDA开展调查和取样的权力。阻止FDA授权人员取样可视为限制检查。限制取样包括婉拒或妨碍FDA抽取以下样品（但不限于）：环境样品、成品样品、原料样品、中间产品样品、生物等效性和生物分析研究用样品。 VI. 拒绝允许进入或检查 FDA对“拒绝允许进入或检查”这个术语的解释，包括企业所有者、经营者或代理机构的行为、被动行为或不作为导致FDA授权代表无法进入企业或对企业进行全面的检查。根据本指南，如果企业所有者、经营者或代理机构不允许FDA对企业、仓库或其它设施进行检查，应视其拒绝进入或检查。拒绝允许进入或检查的行为包括但不限于： • 企业阻止FDA检查员进入企业或企业特定区域，例如通过对该区域上锁或或采取其它措施阻止检查员进入，且没有合理解释。 •  FDA试图与企业指定的联络员进行联系，但没有回应。 • 即使有明确的证据显示相关工作人员在场，企业不接现场检查的FDA检查员的电话。 英文原文 Guidance for Industry Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection IV. DENIAL OF INSPECTION FDA interprets the word deny to include active behavior by the owner, operator, or agent of a drug facility to prevent an authorized representative of the FDA from conducting an inspection or to prevent FDA from completing an inspection. This includes statements or physical actions intended to avoid inspection or to mislead, deceive, or impede the investigator. Examples of behavior that may constitute a denial that may cause drugs to be adulterated under section 501(j) of the FD&C Act include, but are not limited to: • A facility rejects FDA’s attempt to schedule a pre-announced inspection. • Upon arrival at the facility, the facility does not allow the FDA investigator to begin the inspection. • A facility does not allow the FDA investigator to inspect the facility because certain staff members are not present, without a reasonable explanation. • A facility does not allow the FDA investigator to inspect the facility by falsely alleging the facility does not manufacture, process, pack, or hold drugs. • A facility sends staff home for the day and tells the FDA investigator that the facility is not producing any product. Examples of potentially reasonable explanations that might result in the drugs not being deemed adulterated under section 501(j) of the FD&C Act include, but are not limited to: • At the beginning of an unannounced inspection, appropriate personnel are not immediately available to accurately answer the FDA investigator’s questions. • The FDA investigator arrives for an unannounced inspection, but the facility is closed due to scheduled maintenance. V. LIMITING OF INSPECTION An owner, operator, or agent of a drug facility who prevents an authorized representative of the FDA from conducting an inspection to the extent allowable under the law may be viewed as limiting inspection under section 501(j). Below are examples of behavior that FDA considers to constitute a limitation that may cause drugs to be adulterated under section 501(j) of the FD&C Act. A. Limiting Access to Facilities and/or Manufacturing Processes Preventing an authorized representative of the FDA reasonable access to an area of the site that FDA is entitled to inspect may be considered limiting the inspection. This includes the refusal to disclose or permit observation of the manufacturing processes. Examples include, but are not limited to: • A facility orders the discontinuation of all manufacturing for the duration of the FDA inspection without a reasonable explanation. • A facility states that direct observation of the manufacturing process, in whole or in part, must be limited to an unreasonably short amount of time, thus preventing FDA from inspecting the facility as is usual and customary. • A facility limits direct observation of portions of the manufacturing process without reasonable explanation. • A facility unreasonably restricts entry to a particular portion of the facility without reasonable explanation. • Staff at a facility causes the FDA investigator to leave the premises before the inspection is completed. Examples of potentially reasonable explanations that might result in the drugs not being deemed adulterated under section 501(j) of the FD&C Act include, but are not limited to: • A facility does not provide the FDA investigator access to aseptic processing areas until the investigator accommodates the facility’s documented gowning procedures. • Training specified by the Occupational Safety and Health Administration is required before an individual may enter a particular area of the facility, and the FDA investigator has not completed such training. B. Limiting Photography Photographs are an integral part of an FDA inspection because they present an objective and contemporaneous representation of facility conditions. Examples of conditions or practices effectively documented by photographs include, but are not limited to: evidence of rodents or insect infestation; faulty construction or maintenance of equipment or facilities; product storage conditions; product labels and labeling; and, visible contamination of raw materials or finished products. Impeding or resisting photography by an FDA investigator may be considered a limitation if such photographs are determined by the investigator to be necessary to effectively conduct that particular inspection. An example of a potentially reasonable explanation that might result in the drugs not being deemed adulterated under section 501(j) of the FD&C Act includes, but is not limited to: • The chemical properties of products manufactured at the facility are such that taking photographs would adversely affect product quality. C. Limiting Access to or Copying of Records As explained in section III.C, the ability to access and copy records is a critical aspect of FDA inspections. Not allowing an authorized representative of the FDA access to or copying of records that FDA is entitled to inspect by law, including not providing records that FDA requests pursuant to section 704(a)(4) of the FD&C Act, may be considered limiting an inspection. Examples of records limitations include, but are not limited to: • A facility refuses to allow the FDA investigator to review the facility’s shipping records that FDA has authority to inspect. •A facility provides some, but not all of, the records requested by the FDA investigator that FDA has authority to inspect. • A facility provides the FDA investigator the requested records that FDA has authority to inspect, but they are unreasonably redacted.11 • A facility refuses to provide records that FDA requests pursuant to section 704(a)(4), or such records are unreasonably redacted. D. Limiting or Preventing Collection of Samples Collecting samples is a critical part of FDA’s inspectional and regulatory activities. Section 702(a) of the FD&C Act gives FDA authority to conduct investigations and collect samples. Preventing an authorized representative of the FDA from collecting statutorily authorized samples may be considered limiting the inspection. Examples of sample limitations include, but are not limited to, declining to allow or impeding FDA to collect the following types of samples: environmental samples, finished product samples, raw material samples, in-process material samples, and reserve samples in bioequivalence and bioanalytical studies. VI. REFUSAL TO PERMIT ENTRY OR INSPECTION FDA interprets the term “refuses to permit entry or inspection” to include not only active, but also passive behavior and non-action by the owner, operator, or agent of a drug facility that results in an authorized representative of the FDA not being able to enter or fully inspect the facility. For purposes of this guidance, such an owner, operator, or agent shall be considered to have refused to permit entry or inspection if such owner, operator, or agent fails to take steps to permit an inspection of a factory, warehouse, or other facility. Examples include, but are not limited to: • Without reasonable explanation, the facility bars the FDA investigator from entering the facility or certain areas of the facility by, for example, not unlocking the areas or taking other necessary actions that would permit access by the investigator. • Following FDA’s attempt to contact the facility’s designated contact(s) to schedule an inspection, the facility fails to respond. • The facility does not answer calls from the FDA investigator who is present at the facility, despite clear evidence of the presence of employees engaged in job-related functions.

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