One of the major differences between FDA GxP regulations and the ISO/IEC 17025 Quality Standard has always been measurement uncertainty. While it is a strong ISO 17025 requirement to estimate and report measurement uncertainty, it has never been an FDA requirement. This seems to been changing now. Not through regulations and official guidance documents but through inspections. Measurement uncertainty has been cited in a recent Warning Letter: "You fail to challenge the analytical balances for minimum weight, measurement for uncertainty, and drift value". The Warning Letter can be downloaded from the Labcompliance Usersclub. Non members can preview excerpts. Scroll down to W-246. To learn more about other inspection trends, sign up for the audio seminar "Learning from Recent Warning Letters Related to GMP Laboratory Controls". To learn everything about measurement uncertainty, attend the audio seminar "Measurement Uncertainty in Chemical Analysis".

New FDA Draft Guidance: Electronic Source Documentation in Clinical Investigations

The document provides guidance to sponsors, contract research organizations (CROs), data management centers, and clinical investigators on capturing, using, and archiving electronic data in FDA-regulated clinical investigations. It is intended to ensure the reliability, quality, integrity, and traceability of electronic source data and source records maintained at the site for FDA inspection. This guidance is intended to promote the capture of source data in electronic form, which will help to eliminate unnecessary duplication of data, reduce the opportunity for transcription errors, promote the real-time entry of electronic source data during subject visits, and to ensure the accuracy and completeness of data (e.g., through the use of electronic prompts for missing or inconsistent data). The guidance can be downloaded from the FDA website

FDA 483 for Insufficient Number of Qualified People

The FDA expects that laboratories have enough qualified people to do the assigned tasks. This became obvious in a recent 483 inspectional observation going to an OTC drug manufacturer. The letter states: "The number of qualified personnel is inadequate to perform and supervise the manufacture, processing, packing, and holding of each drug product. According to the Laboratory Manager, they do not have the staff to adequately investigate OOS test results, refer to observation #27 for a list of OOS investigations that were not timely. In addition, the Quality Control Manager stated they need people to conduct all of the testing." In addition several observations were related to "No or in-sufficient training for permanent and temporary employees, non-completed method validation and non-completed formal method transfer. The 483 can be downloaded from the Labcompliance Usersclub. Non members can preview excerpts. Scroll down to W-248. To learn more about recent lab control related warning letters and how to avoid them, sign up for the audio seminar "Learning from Recent Warning Letters Related to GMP Laboratory Controls".".

USP Proposes to Update Chapter on Verification of Compendial Methods

USP proposed revising the General Chapter <1226> "Verification of Compendial Methods". The title has changed to" Verification of compendial methods" and USP has a new definition for the verification process: "The verification process for compendial test procedures is the assessment of whether the procedure can be used for its intended purpose, under the actual conditions of use for a specified drug substance and/or drug product matrix.“ The new revision leaves it open what and how much to test during the verification process. "The process of assessing the suitability of a compendial analytical test procedure under the conditions of actual use may or may not require actual laboratory performance of each analytical performance characteristic." Most interesting are a couple of additional criteria that should be considered for the type and extent of testing. The revision of the General Chapter <1226> will be published in the USP 35. For more information look at Pharmacopeial Forum 36(6).

"SOP does not Ensure Sample Integrity" cited in FDA 483

The integrity of test samples should be maintained from sampling to sample testing. During inspections FDA check if SOPs are available and adequate. During an inspection of an API manufacturer FDA investigators found that there is no SOP that ensures maintaining sample integrity throughout the testing of the sample. The letter reads: "The SOP 'Maintenance of Integrity of Sample' is inadequate in that it does not assure complete integrity of documentation related to sample analysis. It specifies the assignment of a “booking number” to each sample, but no further procedures regarding subsequent documentation are included. Certain elements of sample integrity are addressed in other SOPs, but none of the procedures explicitly call for maintaining sample integrity throughout the testing of the sample" In addition the FDA found that "In-house laboratory procedures for various laboratory tests were either non-existent or inadequate" and Performance of test methods such as loss on drying, residue on ignition, and sulfated ash was not adequately documented. The Warning Letter can be downloaded from the Labcompliance Usersclub. Non members can preview excerpts. Scroll down to W-247. To learn more about recent lab control related warning letters, sign up for the audio seminar "Learning from Recent Warning Letters Related to GMP Laboratory Controls".

73 New Documents in the Labcompliance Usersclub

We have added 73 new documents to the Labcompliance Usersclub. They include 14 new SOPs, 20 examples for practical validation and compliance including checklists . 10 forms/templates, 3 important FDA presentations and 22 recent FDA warning letters/483's related to GMP/GLP or GCP. To see the new titles, click here.. User club members can instantly download the new additions. To see the complete list and ordering the users club, click here, and scroll down to 'new additions'. With these additions, the Usersclub has more than 500 documents ready for download.

Can Vendors Offer 'FDA Compliant' or "Part 11 Compliant" Software?

With FDA's increasing focus on computers and Part 11 during inspections companies want to do a good job in preparation and software suppliers . User companies with little understanding of the regulations prefer to purchase "Part 11 compliant" or 'FDA approved software" which is advertized by some vendors. Already 10 years ago in the early days of Part 11 the question has been discussed whether vendor can deliver such software. Advice came from FDA officials at conferences and industry trainings. For an example and recommendations from Labcompliance click here.

Free Document of the Month

As a 'Thank You' for our visitors Labcompliance offers every month one document for free. This month's document is the SOP "Risk assessment for Laboratory Systems". To download your free copy, go to the Laboratory Compliance Package website. Scroll down and click on the corresponding ICON on the left (offer expires on April 1, 2011). Labcompliance offers more than 120 SOPs that help to comply with FDA and ISO 17025 compliance. For titles and ordering, click here.

Conference

Analytica Vietnam, Hoh Chi Minh City, Vietnam, April 7-9, 2011
April 8: Full day Workshop by Dr. Ludwig Huber
Validation of Analytical Methods for FDA and EU Compliance

Audio Seminar Schedule

Learning from Recent Warning Letters Related to GMP Laboratory Controls
For Preparation of FDA and International GMP Laboratory Inspections
Recorded, available on demand
Auditing Computer Systems for Part 11 and Annex 11 Compliance
Prepare your organization for upcoming FDA and EU inspection
Recorded, available on demand
Validation and Use of Excel® Spreadsheets in Regulated Environments
Comply with FDA Part 11, the PIC/s Good Practice Guide and the EU Annex 11
Recorded, available on demand
Developing a Risk Management Master Plan
A must for efficient and consistent implementation of risk management projects
Recorded, available on demand