FDA警告信-原始数据

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FDA Warning Letter - Raw Data


Date: 23 February 2012
Link FDA 483 (New Window)
Observation4. Your firm has not established appropriate controls over computer or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. Your firm also fails to maintain a backup file of data entered into the computer or related system [21 CFR § 211.68(b)].


For example,

a) There is no system in place to ensure that all electronic raw data from the laboratory is backed up and/or retained.（自动电脑镜像备份和其他离线备份）

During the inspection, you informed our investigators that electronic raw data would not exist for most HPLC assays over two years old because data is not backed up and storage space is limited（不知道这个储存空间好小！！）.

Data is deleted to make space for the most recent test results. You also informed our investigators that printed copies of HPLC test results are treated as raw data.（针对于HPLC这种dynamic data是一般不允许进行打印的static data作为raw data的）

Printed copies of HPLC test results from your firm’s systems do not contain all of the analytical metadata (for example: instrument conditions, integration parameters) that is considered part of the raw data. We acknowledge that your response indicates that you have created a procedure in order to implement the back-up and retention of HPLC data. This electronic HPLC data supports testing, disposition, and other significant quality control decisions, and it is essential that you maintain this information for each batch. In your response, please provide a detailed update on your firm’s implementation of this correction. Also describe your firm’s policy for retaining HPLC raw electronic data associated with pending applications.

b) You have not implemented security control of laboratory electronic data. All laboratory analysts share the same password for the HPLCs in the QC analytical chemistry lab and Omnilog in the microbiology lab. In addition, analysts have access to the HPLCs which allow them to create and/or modify validated methods.

Your response indicates that SOP EDS-084: Procedure to Assign User Access Levels and Privileges for Computerized Analytical System has been issued and training has been provided. Please clarify in the response to this letter how you define the levels of authorization or the user access and privileges for analysts. Your response also explains that analysts now have their own passwords and that changes will be captured by audit trail. We also note that your SOP does have provisions for any audit trail reviews to ensure that deletions and/or modifications do not occur. Please provide an explanation of your firm’s procedures regarding audit trails.
CommentAs discussed in many other posts relating to Warning Letters the FDA are still citing against 21 CFR 211.68 rather than directly to 21 CFR Part 11 for the security and integrity of data. This post looks the first part of the observation relating to Raw Data, security has been covered under Applying Computer Systems Security (GAMP).

In the intial findings the Raw Data for a HPLC is not being backed up and the paper record (results) are not considered to be complete in that all the metadata is not included within the printed results.

These are quoted as:

• instrument conditions
• integration parameters
  

which is considered part of the raw data.

In the post Deleting Electronic Data it was discussed based on the FDA Final Guidance "Part 11, Electronic Records; Electronic Signatures — Scope and Application” that electronic version of the records can be deleted.

In the previous article i wrote

Removing (deleting) the electronic record removes the need to maintain the record and the additional overhead (effort) required to maintain the record compliantly. However the regulated company must ensure that the record is complete (that is does not rely on the electronic data).

this is key to this observation. The regulated company should have documented its decision and determined what records are required to be maintained to support the paper record. In the areas covered under the FDA observation (instrument conditions and integration parameters) these two could have been maintained as paper records either via log books or including printout of the configuration settings.(纸质记录即使可以原始记录，也应该充分记录相关的设置参数，比如设备型号，积分参数等等？？？）

The regulated company did not show that due care and consideration had been taken in the decision to delete electronic records. The decision was based on the available storage and the completness of the record not considered.

When deciding whether to maintain the electronic records in electronic or paper formats ensure that the records are complete and include the required metadata to demonstrate the integrity of the records. Most importantly document the decision and the rationale.

Posted by Barry Tedstone      

Labels: 21 CFR Part 11, Electronic Records, FDA Warning Letters

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§211.68   Automatic, mechanical, and electronic equipment.

(a) Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.

(b) Appropriate controls shall be exercised over computer or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel. Input to and output from the computer or related system of formulas or other records or data shall be checked for accuracy. The degree and frequency of input/output verification shall be based on the complexity and reliability of the computer or related system. A backup file of data entered into the computer or related system shall be maintained except where certain data, such as calculations performed in connection with laboratory analysis, are eliminated by computerization or other automated processes. In such instances a written record of the program shall be maintained along with appropriate validation data. Hard copy or alternative systems, such as duplicates, tapes, or microfilm, designed to assure that backup data are exact and complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained.

(c) Such automated equipment used for performance of operations addressed by §§211.101(c) or (d), 211.103, 211.182, or 211.188(b)(11) can satisfy the requirements included in those sections relating to the performance of an operation by one person and checking by another person if such equipment is used in conformity with this section, and one person checks that the equipment properly performed the operation.

[43 FR 45077, Sept. 29, 1978, as amended at 60 FR 4091, Jan. 20, 1995; 73 FR 51932, Sept. 8, 2008]

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