FDA警告信：Adamson Analytical Laboratories（节译）

WARNING LETTER

UNITED PARCEL SERVICE

SIGNATURE REQUIRED

August 2, 2016

  WL # 38-16

Ms. Vicky T. Seto

Laboratory Director and Owner

Adamson Analytical Laboratories, Inc.

220 Crouse Drive

Corona, CA 92879-8093

Dear Ms. Seto:

The U.S. Food and Drug Administration (FDA) inspected your drug contract testing laboratory, Adamson Analytical Laboratories Inc. at 220 Crouse Drive, Corona, Calif., from August 4-14, 2015.

FDA于2015年8月4-14日对你工厂进行了检查。

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, 21 CFR parts 210 and 211, and significant deviations from CGMP for active pharmaceutical ingredients (API).

  此警告信中列出了原料药重大CGMP缺陷。

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drugs are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

  由于你们生产、加工、包装或保存的方法、设施或控制不符合CGMP要求，你们的药品被认为是掺假。

We acknowledge receipt of your firm’s September 25, 2015, response.

我们收到了你们于2015年9月25日发出的回复。

Our investigators observed specific violations and deviations including, but not limited to, the following.

  我们的调查人员在检查期间发现了一些具体的缺陷，包括但不仅限于以下：

Finished Product: CGMP Violations 制剂产品CGMP违规

1.    Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).

你们公司未能对计算机或相关系统实施适当的控制，以保证只有经过授权的人员才能改变主生产和检验记录或其它记录(21 CFR 211.68(b))。

Specifically, your high performance liquid chromatography (HPLC) and gas chromatography (GC) data acquisition systems did not have sufficient controls to prevent deletion or alteration of raw data files. During the inspection, our investigators observed that your laboratory personnel use a shared password to access the HPLC (b)(4) computer system and that your GC (b)(4) computer system requires no password for access.

具体来说，你们的HPLC和GC数据获取系统没有足够的控制来防止原始数据文件的删除和篡改。在检查期间，我们的调查员发现你们化验室的人员共用密码来登录HPLC XX计算机系统，你们的GC计算机系统根据不需要密码登录。

In addition, multiple instruments had no audit trail function to record information about each analytical test, such as:

此外，多个仪器都没有审计追踪功能来记录每次分析检测的信息，如：

• type of injection 进样类型
• date and time 日期和时间
• identity of analyst 化验员身份
• reason for action taken (for example, modifying a record) 采取行动的理由（例如，修改记录）
  

This is a repeat observation from our February 7, 2013, inspection. In 2013, you committed to augmenting the security of your computer systems within six months. However, based on our 2015 inspection, it appears that you have not made appropriate corrective actions such as installing audit trails and ensuring that analysts have unique user names and passwords for your computerized systems.

这是我们在2013年2月7日检查中发现的缺陷的重复。在2013年，你们承诺要在6个月内加强你们计算机系统的安全性。但是根据我们2015年检查的情况，貌似你们并没有实施恰当的纠正措施，如为计算机化系统安装审订追踪和确保化验员有唯一的用户名和密码。

It is essential that your firm keep track of all changes made to your electronic data. The use of audit trails for computerized analytical instrumentation helps to ensure that all additions, deletions, or modifications of information in your electronic records are authorized. It also allows you to verify the quality and integrity of the electronic data your contract testing laboratory generates for your customers.

公司保持追踪对电子数据的所有修改是很重要的。在计算机化分析仪器上使用审核追踪有助于保证所有对电子记录里信息的增加、删除或修改都经过授权。它还能让你们核对你们合同化验室里为你们的客户生成的电子数据的质量和完整性。

We acknowledge your commitment to install and configure appropriate electronic controls to ensure that access to your computerized systems and data is restricted to authorized personnel with access rights specified for each individual. However, your response is inadequate as you did not provide an action plan describing the interim security measures in place prior to your installation of electronic controls. Your response also lacked details regarding the type of electronic controls to be installed, and you did not describe how you will evaluate the effectiveness of these computerized system changes.

我们知晓你们承诺要安装和设置适当的电子控制，保证你们计算机化系统和数据的登录只限制于被授权的人员，让不同人员具有特定的登录权限。但是你们的回复是不充分的因为你们没有提供一份行动计算来描述在你们安装电子控制之前的临时安全措施。你们的回复还缺陷关于要安装的电子控制类型的详细信息，你们没有描述你们要如何来评估这些计算机化系统变更的有效性。

2.    Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b))

你们公司未能建立化验室控制，包括科学合理和恰当的捏标准、取样计划和检验程序，用以保证组分、药品容器、密闭器、中控物料、标签和药品符合适当的鉴别、剂量、质量和纯度标准(21 CFR 211.160(b))

Specifically, your quality control unit failed to ensure completeness and accuracy of your laboratory procedures, analytical data, and test results. For example:

具体来说，你们的质量控制部门未能保证你们化验室程序、分析数据和检验结果的完整性和准确性。例如：

• You did not detect that your secondary reference standards for oxymetazoline hydrochloride were not appropriately qualified as required by your firm’s standard operating procedure (SOP), (b)(4).
• 你们未能发现你们的盐酸羟甲唑啉工作标准品没有按你们公司的SOPXXX进行适当的确认
• You reviewed and approved laboratory notebooks with missing data such as HPLC chromatograms and assay calculations.
• 你们审核和批准的化验室记录本数据缺失，如HPLC图谱和含量计算
  

API: CGMP Deviation  原料药：CGMP偏差

3.    Failure of your quality unit to ensure that materials are appropriately tested and the results are reported.

你们质量部门未能保证物料经过适当的检测，并报告结果。

During the inspection, our investigators discovered that your firm failed to appropriately qualify the secondary reference standard for avobenzone API required by your firm’s SOP, (b)(4).

在检查期间，我们调查员发现你们公司没有按你们公司的SOPXXX适当地确认阿伏苯宗工作标准品。

In your response, you state that you retrained the quality control unit personnel, and that you appropriately qualified your secondary standards. Your response is inadequate because you did not provide a risk assessment of the lots tested with the unqualified secondary reference standards. You used these secondary reference standards for analysis of your customer’s API. Your failure to appropriately qualify your secondary reference standards calls into question the accuracy of the analytical results you provide to your API customers.

在你们回复中，你们声称你们重新培训了QC人员，你们适当地确认了你们的工作对照品。你们的回复是不充分的，因为你们没有提供一份使用未经确认的工作对照品检验的产品批次的风险评估。你们使用了这些工作对照品用于你们客户的原料药的分析。你们没有质疑你们提供给你们原料药客户的采用此未经确认的工作对照品检验的结果的准确性。

In response to this letter, provide a plan describing how your quality control unit will effectively exercise its responsibilities. Include how your quality control unit will verify that all of your secondary reference standards have been appropriately qualified. Also, include how your quality control unit will verify that your laboratory records include complete electronic raw data. Provide assurance that your corrective actions will effectively prevent the types of failures described above from recurring in the future. In addition, include a risk assessment regarding your practice of testing drugs with unqualified secondary reference standards.

在回复此函时，请提供一份计划说明你们QC将如何有效履行其职责，包括你们QC如何核查所有你们的工作对照品均经过适当确认。还应包括你们QC要如何核查你们化验室的记录包括了完整的电子原始数据。要提供保证来保证你们的纠正措施将有效防止上述类型的失败在将来再次发生。另外，还要包括一份关于你们使用未经确认的工作对照品进行药品检测的做法的风险评估。

Conclusion

Violations and deviations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these violations and deviations, for determining the causes, for preventing their recurrence, and for preventing other violations and deviations.

FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your clients. It is essential that you understand your responsibility to operate in full compliance with CGMP, and to inform all of your customers of significant problems or deviations encountered during the testing of these drugs.

After you receive this letter, you have 15 working days to respond to this office in writing. Specify what you have done since our inspection to correct your violations and deviations and to prevent their recurrence. If you cannot complete corrective actions within 15 days, state your completion date and reasons for delay.

Correct the violations and deviations cited in this letter promptly. Failure to promptly correct these violations and deviations may result in legal action without further notice including, without limitation, seizure and injunction. Unresolved violations and deviations in this warning letter may also prevent other Federal agencies from awarding contracts.

Until these violations and deviations are corrected, we may withhold approval of pending drug applications listing your facility. We may also refuse requests for export certificates. We may re-inspect to verify that you have completed your corrective actions.

Send your reply to:

CAPT Larry Howell, Acting Director

Compliance Branch

U.S. Food & Drug Administration

Los Angeles District Office

19701 Fairchild

Irvine, CA 92612

Attn: Dr. Raymond W. Brullo, Compliance Officer

Please identify your response with FEI 3000204955.

Sincerely,

/S/

CDR Steven E. Porter, Jr.

Los Angeles District Director

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