The control of impurities in Pharmaceutical Products can be daunting. Impurities, degradants, genotoxic impurities, residual solvents, elemental impurities — the requirements keep changing, and it can be challenging to keep up with the changes and make sure you are in compliance. Just recently, the USP published new General Chapters <476> and <1086> on Impurities in Drug Substances and Drug Products, ICH issued a new guideline M7 on Genotoxic Impurities (now being referred to as DNA Reactive or Mutagenic Impurities), USP has an Expert Panel working on updating the General Chapter on Residual Solvents, and ICH and USP have proposed conflicting requirements for Elemental Impurities.
No wonder it’s challenging keeping up with compliance expectations! As a result of the complexity, many companies choose to react in an overly conservative manner, and end up spending much more money and resources then they really need to. You need to be able to interpret the guidances and understand what the Regulators require, so that you can minimize resource expenditures while maintaining compliance. There are definitely strategies that can help you accomplish this.
If you want to make sure your understanding of the Guidances on Impurities are up to date, and also to learn strategies to save time and money but still be in compliance, plan to attend the one day course, “Control of Impurities in Pharmaceutical Products: Impurities, Degradants, Residual Solvents & Elemental Impurities” on June 18, 2014 in North Brunswick, NJ
When an OOS (Out of Specification) result is generated, it creates a lot of stress! Immediately there are many questions: Is it real? Will it prevent us from shipping the product? Why did this happen? What do we need to do next?
In most laboratories, the number of OOS incidents is relatively small. This means that the labs have relatively little experience addressing them effectively. For individual chemists, the frequency is even smaller.
On the other hand, the impact of having an OOS investigation can be huge. Let’s start with the cost. In one laboratory of a major pharmaceutical company, it was estimated that lab investigations cost a minimum of $3000 – and that was for an investigation with an obvious assignable cause which could be concluded very quickly. Worse yet, there is always the possibility that an OOS investigation cannot be resolved, even if the lot is acceptable, which could lead to a production lot being rejected, or force a recall if the lot is already in the field.
What can you do? Give your Chemists and Lab Managers the tools they need to do the job well. Develop a process for addressing OOS investigations consistently, which can help everyone involved. Use the FDA Guidance for Industry to lead you through the initial laboratory investigation, and if necessary, through the full scale laboratory and production investigations. Learn some of the techniques that help to solve investigations effectively, especially Root Cause Analysis and Effective Use of CAPA (Corrective and Preventative Actions).
By carefully designing your investigation process, and providing useful tools for these procedures, you can reduce the time and anxiety, and improve the probability of identify the true Root Cause. You can help to assure your investigation will have the appropriate outcome, and avoid having the same problem crop up again!
If you want some help in setting up this process, plan to attend the one day course, “Effective Investigation of Out of Specification, Out of Trend or Atypical Results” on May 14, 2014 in North Brunswick, NJ.
The Eastern Analytical Symposium celebrated its 30th anniversary in November, 2013 at Somerset, NJ. This is an excellent scientific meeting for pharmaceutical scientists, especially those on the East Coast. With a theme this year of ‘Analytical In Motion’, there were symposia, posters, short courses and an exposition. This Symposium has a unique character to it, in part due to the regional nature of the meeting and its relatively affordable cost. Since the meeting is more manageable in size than some of the major, national meetings, attendees feel more comfortable in attending the sessions and asking questions. Hope to see you next year at EAS!
The AAPS held its annual meeting on Nov. 10-14, 2013 in the Gonzales Convention Center in San Antonio, Texas. This is one of the top scientific meetings for pharmaceutical scientists, including active professionals and graduate students. There are tracks related to Analysis and Pharmaceutical Quality, Biotechnology, Drug Discovery and Development, Formulation Design and Development, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Regulatory Sciences and other disciplines. Over the course of the meeting hundreds of reviewed posters are presented. There is an extensive exposition at which most of the major vendors for the pharmaceutical industry are present. In addition, there are excellent, timely workshops offered prior to the meeting, for a reasonable cost.
Check out “Lifecycle Management of Analytical Procedures: Method Development, Procedure Performance Qualification, and Procedure Performance Verification” in Pharmacopeial Forum, 39(5), October, 2013. The article proposes a lifecycle approach for analytical methods, linking method development, validation, verification and transfer by means of an Analytical Target Profile (ATP). The ATP is a relatively new concept, not yet widely accepted, which identifies the requirements for certain analytical performance characteristics to demonstrate the method is suitable for its intended purpose. This approach could have major implications for the future of pharmacopeial methods. USP is seeking comments on this approach.
Using a QbD approach to Analytical Methods, from design to validation to transfer has significant advantages. See “QbD for Better Method Validation”, P. Nethercote, et al., Pharmaceutical Manufacturing, April, 2010.
There are currently two alternative approaches to qualifying baths: the new revised USP Performance Verification Test and the FDA-endorsed Enhanced Mechanical Calibration. Look for a discussion on the advantages of both in the upcoming issue of Journal of Validation Technology.