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Labcompliance News, January 2005

January 10, 2005

Links to 26 FDA 'Predicate Rules'

Predicate rules are the requirements that can be found in part 21 CFR Food and Drugs regulations. They are basically promulgated under the authority of the Food Drug and Cosmetic Act or under the authority of the Public Health Service Act. The most well-known FDA regulations are the GLP and GMP regulations but there are many more. All FDA regulations can be downloaded from the FDA website but sometimes they are not easy to find. Labcompliance has a new site with a list of and links to 26 FDA regulations.

January 10, 2005

Update from David Horowitz, US FDA, on FDA's 21 st Century GMP Initiative

David Horowitz, Director, Office of Compliance, FDA CDER, gave an update on current status, future plans and upcoming announcements on FDA's drug GMP initiative at the joint FDA/PDA joint regulatory conference. "The initiative is shifting from assessment to implementation", Horowitz said. He gave specific examples for topics such as "Encouraging best manufacturing practices", "Risk-based approaches", "Enhanced coordination", "Consistency and predictability " and "International Collaboration". He also gave an overview of FDA's Steering Committee and 15 active working groups. They plan to publish new White Papers and at least five new Guidance Documents (some final, some draft).

January 10, 2005

Recent FDA Warning Letter for Missing Software Revalidation Protocols

In a warning letter from September 2004 the FDA cited a firm for not providing revalidation protocols: Your response (to Form FDA 483, List of Inspectional Observations) indicates that the computer software was initially validated in April 2001 and that it was going to be revalidated in May 2004. You also included the validation report of the software used for maintenance of the complaint. However, the adequacy of the challenges to the computer systems cannot be fully assessed since the validation protocols were not provided. Other deviations include: No or inadequate failure investigation to determine the route cause of the failure, failure to assure that test procedures are scientifically sound, failure to reject drug products to meet established standards or specification, no or inadequate scientifically sound specifications, standards, sampling plans, inadequate stability test program, no or inadequate cleaning validation. The warning letter can be downloaded from the Labcompliance Usersclub. (136) Non members can preview excerpts.

January 10, 2005


USP Announces Harmonization of General Chapters

One of the biggest concern of global pharmaceutical companies are different regulations and pharmacopeias in target markets. While there is some progress to harmonize regulations and inspection practices there have been not much progress to harmonize compendial methods. Therefore an article on some harmonization success is quite interesting. According to the article the Pharmacopeia Discussion Group (PDG) has agreed to the final harmonization of several general chapters. The group made the announcement at its Washington, DC, meeting. The general chapters include “Extractable Volume of Parenterals” and “Particulate Matter in Injectables.” Both were recently revised and harmonized by the three pharmacopoeias: The United States Pharmacopeia (USP), the Japanese Pharmacopoeia (JP), and the European Pharmacopoeia (EP). The chapters were also cited in the International Conference on Harmonization (ICH) Q6A guidelines. In addition to extractable volume and particulate matter, the PDG harmonized chapters cover dissolution and disintegration. Those chapters will provide procedures acceptable for evaluating dosage form performance. The PDG hopes that will simplify development and product testing.

January 10, 2005


Principles of Computer Validation

Computer validation confuses people. The question is: why is this so complicated? The main problem is that users expect from the FDA checklists or a step by step instruction with clear deliverables. This is not practical because each situation is different. The extent of validation very much depends on the use of the system, mainly how it impacts final product, e.g., drug, quality and patient safety. There are two more factors that impact the extent of validation: 1) the system complexity. The higher the complexity and interaction with other modules or systems, the more likely is the system to fail. 2) The level of customization and widespread use of the system. Systems that are developed for a specific user require more testing at the user's site than systems that are in compute. The recommendation is to understand and follow a couple of validation principles.