Publications

Data Analysis • Statistics

It is important to distinguish between out-of- specification (OOS) and out-of-trend (OOT) results in stability studies. The authors discuss three methods for identification of OOT results—the regression-control-chart method, the by-time-point method, and the slope-control-chart method—and further compare the z-score method and the tolerance interval in OOT analysis. The results highlight the need for issuing a regulatory confirmed guideline for identification of OOT results for ongoing stability data. The two terms out-of-trend (OOT) and out-of-specification (OOS) results are in many cases confused by pharmaceutical companies and regulatory agencies. OOT results are defined as a stability result that does not follow the expected trend, either in comparison with other stability batches or with respect to previous results collected during a stability study (1). OOT results are not necessarily OOS, but they do not look like a typical data point. Although OOT results are a serious problem, the scientific literature and regulatory guidelines do not fully address this issue. According to FDA's Guidance for Industry: Investigating Out-Of-Specification (OOS) Test Results for Pharmaceutical Production (2), OOT results should be limited and scientifically justified. The guideline, however, does not define the process for identification of OOT results in stability data. The CMC Statistics and Stability Expert Teams of the Pharmaceutical Research and Manufacturers of America made an attempt to address this problem by suggesting several statistical methods for the identification of OOT results (3). The proposed statistical methods were redesigned and analyzed for the purposes of this study. The aim of this study was to make a statistical confirmation of the statistical methods, which will prove their functionality in identification of OOT results in ongoing stability data within a batch or data among batches. In addition, a comparison was made between the z-score method and the tolerance interval (TI) in terms of defining the limits for identification of the present OOT result.

Guidances • Parameters • Planning • Regulations • Regulatory • Study Design

Introduction: This year [(2013)] marks the 10th anniversary of the introduction of the International Conference on Harmonisation (ICH) guidance on stability testing of new drug substances and products (ICH Q1A(R2)) and the ancillary guidance on storage conditions (ICH Q1F). In 2003, the pharmaceutical industry thought that it had achieved its goal of globally acceptable stability requirements, but unfortunately, that early optimism rapidly dissipated. Less than two years later, the ASEAN (Association of South East Asian Countries) group had broken ranks with ICH guidance and introduced their own guideline on stability requirements. In particular, they mandated the use of 30°C/75%RH for the long-term storage conditions for climatic zone IV (hot and wet).

Best Practices • Efficiencies • Study Design

Abstract: The second edition of Pharmaceutical Stress Testing: Predicting Drug Degradation provides a practical and scientific guide to designing, executing and interpreting stress testing studies for drug substance and drug product. This is the only guide available to tackle this subject in-depth. The Second Edition expands coverage from chemical stability.

Chain of Custody • Sample Control • Storage • Transit

Abstract: Many pharmaceutical or biotechnological products require transport using temperature-controlled systems to keep their therapeutic properties. There are presently no official guidelines for testing pharmaceutical products in order to define suitable transport specifications. After reviewing the current guidance documents, this paper proposes a methodology for testing pharmaceutical products and defining appropriate transport conditions.

Best Practices • Methods • Testing • Types

Introduction: Several intrinsic and extrinsic factors influence microbial growth. Two important factors include the presence of available moisture and a supportive temperature. The conditions described in ICH Topic Q1A (R2)1 do not allow the organisms of interest in pharmaceutical solids to grow, due to either an unfavourable temperature or humidity. For this reason, testing either microbial limits or measuring water activity as part of the stability program is considered of little value in determining microbial stability.

Best Practices • Best Practices • Data Analysis • Determination • Extrapolation • Parameters • Protocols • Shelf-Life • Statistical • Statistics • Study Design

Predict stability using data collected at higher temperatures.

Planning • Study Design • Testing

Introduction: This article examines the decisions to be made regarding the design of a stability strategy during development and some alternative approaches, compared to those traditionally followed, are proposed as being more scientifically rigorous. Following these approaches would lead to better product understanding and robustness as well as to a reduction in the number of scientifically redundant stability studies.

Best Practices • Shelf-Life

Best Practices • Best Practices • Best Practices • Best Practices • Data Analysis • Determination • Excursions • Extension • Extrapolation • Guidances • Methods • Parameters • Planning • Regulations • Regulatory • Shelf-Life • Specifications • Statistics • Study Design • Testing

This book provides an understanding of the regulatory perspective of Stability Testing and positions the stability program for the 21st century globally. It comprises several sessions organized in dual tracks to explore different stability related challenges, such as monitoring impurities, evaluating shipping excursions, setting specifications and estimating expiry. Stability is a crucial sector of the Drug Development Process. Companies rely on the stability data to establish an expiry for marketed pharmaceutical products. Many guidelines have been developed around this arena; however, many continue to be raised and challenge our practices.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Extrapolation • Guidances • Regulations • Regulatory • Shelf-Life • Specifications • Submissions

Abstract: This chapter from the book "Handbook of Stability Testing in Pharm Development" discusses the evaluation of stability data. It follows the study information from the point that raw data is generated in the lab, calculations are performed to give test results, and test results are entered in the stability summary sheets, until data is finally entered into a stability report for submission purposes. This chapter also includes a summary of data evaluation addressed in ICH Q1E and a discussion of Out-of-Specification (OOS) and Out-of-Trend (OOT) investigations. Specification setting and shelf-life extrapolation, which are performed after evaluating stability data, are also described in this chapter.

Batch Selection • Best Practices • Best Practices • Best Practices • Compliance • Data Analysis • Determination • Extension • Extrapolation • Guidances • Investigations • Methods • Parameters • Planning • Quality • Regulations • Regulatory • Shelf-Life • SOPS • Specifications • Statistics • Study Design • Testing

This practical handbook is needed in this area to serve pharmaceutical scientists who handle responsibilities in a variety of functions relating to the drug stability, including R&D, formulation, analytical development, QA/QC, regulatory affairs and production.

Best Practices • Laboratory Issues • Methods • Testing

Introduction: During stability, product testing is performed to ensure the product will continue to meet specified criteria of quality and strength through its expiration or shelf-life at the temperature and humidity required by specific markets. This article will not address the other stability requirement of continued efficacy during consumer use which is done by “in-use testing”, an important subject for another article.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Climate Zones

This article lists countries and their respective climate zone assigned for regulatory purposes.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Best Practices • Determination • Expiry • Extension • Extrapolation • Retest • Shelf-Life • Statistics

Industry, government, and academia collaboration for excellence in pharmaceutical research and product quality.

Chain of Custody • Qualification • Quality • Transit

Historically, the terms 'qualification' and 'validation' have been used interchangeably within the cold chain industry. This has led to a significant amount of confusion in the pharmaceutical industry, which could be avoided by standardising the definitions of both 'qualification' and 'validation'.

Packaging • Planning • Sample Control • Storage

Abstract: The authors evaluate the implications of product photosensitivity and how it influences various aspects of product development. They discuss a product photosensitivity classification system and present a photosensitive pharmaceutical product case study.

Best Practices • Excursions • Parameters • Protocols • Sample Control • Storage • Study Design • Transit

This article outlines distribution stability studies designed to generate additional data to complement pre-formulation development and routine International Conference on Harmonization (ICH) Q1A registration studies. If results from routine studies indicate that the product stability profile is very stable, then one may decide that distribution studies are not warranted. If additional distribution stability studies are needed, they can be developed to test the product’s temperature limitations. In the event that a temperature excursion is higher or lower than the recommended storage condition, these data would be examined to evaluate the effect on product quality.

Best Practices • Guidances • Regulatory • Study Design

This article summarizes the collective views of industry participants at a Pharmaceutical Research and Manufacturers of America Analytical Research and Development Steering Committee workshop on acceptable analytical practices on the topic of forced degradation studies. The article includes an overview of available guidance and some suggestions for best practices.

Data Integrity • Laboratory Issues • Quality • Systems

Event Overview (This is an on-demand webinar): The increased use of electronic data and computerized systems has introduced new challenges to maintaining data integrity. With regulated companies under increased scrutiny by regulatory authorities, companies need to ensure they have a thorough understanding of their regulated systems and how to assess them for gaps. Waters will provide insight on the current focus for data integrity with specific examples of how to monitor Waters Empower data. We will also provide additional tools and services that can help prepare for internal and external audits.

Best Practices • Calibration • Chambers • Sample Control • Study Design

This presentation explains essential photostability testing requirements for small (traditional pharmaceutical) molecules and large (biotechnology products) molecules according to the ICH Q1B and Q5C guidelines. It also explains the basics of what needs to be tested (such as active pharmaceutical ingredient, final finished product, product as packaged, etc.), when it needs to be tested, the light exposure devices used per the ICH requirements, sample presentation and general tips.

Pharmacopoeia • Regulatory

This Free ON DEMAND Webinar provides an overview of the interplay of pharmacopoeias and a company’s quality assurance and regulatory affairs functional areas to assist in establishing effective processes, partnerships, and tools for pharmacopeia compliance. This course can also help you determine whether additional customized training – which is available through CfPA – could enhance your understanding and improve the approaches taken by your company to maintain appropriate and timely compliance with pharmacopoeia requirements.

Pharmacopoeia • Regulatory

This comprehensive 2-day course will provide an understanding, including practical examples of compliance with compendial requirements, as published by pharmacopoeias. The course includes an introduction to the pharmacopoeias, with an emphasis on the USP-NF, Ph. Eur. and BP. A global perspective is presented, with consideration also given to the pharmacopoeias in other important countries. Details of the content, organization and use of the pharmacopoeias are presented, along with regulatory considerations and applicability of compendial requirements. There is a detailed exploration of the development and revision processes for compendial standards, with real-life case studies offered. Efforts toward compendial harmonization are described, with information on the activities of the Pharmacopoeial Discussion Group (PDG) and prospective harmonization of drug substance/product monographs. The course concludes with an exploration of approaches to compendial surveillance, opportunities for advocacy, and – ultimately – compliance with the requirements in the pharmacopoeias.

Methods • Testing

Many types of packaging materials are involved in the production and containment of drug products, such as the elastomeric closure, vials, or another containment device. Each of these items may impact the drug product over time. The typical process of evaluating E&L begins with identifying the extractables, which are chemical compounds that can be released from containers, closures, and packaging materials under exaggerated or extreme conditions. While extractable testing is a necessary starting point, it does not provide all the required information to determine drug compatibility. Therefore, further testing is needed to investigate leachables, which are the subset of extractables that migrate into the drug product under normal conditions. In an ideal situation, the only leachable compounds detected in a drug are compounds present in the extractables profile, however, the leachable profile can contain additional compounds. These additional leachables can be the result of environmental influences or reactions between compounds and the drug, generating new compounds not previously detected.