Publications

Planning • Quality

Course Description: This 6-hour, accredited course will provide an understanding of how the pre-market stability programs can be successfully managed while minimizing the overall timeline. Lectures will address the seven key GMP aspects of a stability program along with all of the relevant stability guidelines that cover drug product stability. Accelerated testing that allows the marketing of a new OTC drug product prior to the generation of long-term, real-time stability data and confirmation of the stability projections will also be covered.

Planning • Quality • Study Design

Course Overview: Stability testing is a major requirement in the development of a pharmaceutical product to determine the versatility of a drug substance when exposed to certain conditions such as heat, pH, humidity, and radiation. It is vital for patient safety to know how a drug product will change over time and to provide adequate advice for the storage and disposal of the product. Stability failures are responsible for a third of product recalls, costing pharmaceutical companies millions. The risk of not conducting thorough stability testing, therefore, outweighs the cost of performing it.

This course will provide you with an understanding of the science behind stability testing, a detailed examination of the ICH guidelines, and accurate assessments of the tools and techniques to carry out testing. Crucially you will gain a deeper understanding of the guidelines and how best to create stability protocols to maintain compliance.

Best Practices • Guidances • Laboratory Issues • Methods • Pharmacopoeia • Regulations • Testing

Course Description: This accredited 12-hour intensive course provides comprehensive and up-to-date knowledge of developing and executing compliant and effective stability programs for protein and peptide biopharmaceuticals and biologics. The course covers both US FDA and EU EMA regulatory and technical expectations and activities to fulfill those expectations, with the biotechnology guidelines of the International Council for Harmonization (ICH) receiving special attention.

Audits • Best Practices • Compliance • Guidances • Investigations • Laboratory Issues • Quality • Regulations • Testing

This 90-minute accredited training will benefit manufacturers of cGMP products in designing an effective, robust and compliant OOS investigation process.

Some FDA (form 483’s) and other regulatory bodies’ inspectional findings, FDA warning letters, product recalls and plant shut down (voluntary or involuntary) sometimes relate to incomplete, ineffective and non-compliant OOS investigations that impacts a manufactured product. Per the regulations, all Failures.

Deviation or OOS results investigations regardless of its product impact should be appropriately documented, investigated, analyzed for root cause(s), with a justifiable retest plan and an effective corrective action plan. Understanding how to identify a true OOS from other types of Laboratory investigations (i.e. Invalid Assays, Known Lab Error, Atypical Events or a Lab Calibration out of Tolerance) as well as when to perform a retest based on the findings of the OOS investigation is critical to achieving compliance. It is also critical to know when and how to apply “averaging” versus an “outlier” to an original test and re-test data generated during an OOS result. This will allow a product manufacturer to achieve compliance relating to an OOS investigational process.

Audits • Best Practices • Compliance • Investigations • Laboratory Issues • Methods • Quality • Testing

Description: 90 minute paid webinar

This training program will highlight mistakes often made when corrective and preventative actions are not clearly identified and applied during a manufactured product sterility test failure investigation because an ineffective investigational procedure and tool was used to conduct a sterility test failure investigation. The webinar will also illustrate how avoiding such common mistakes will ensure that these types of products meet the sterility requirements USP and other regulatory guidelines applicable to finished products, bulk drug substance, raw materials or excipients.

Authorities • Change Control • Compliance • Guidances • Methods • Pharmacopoeia • Quality • Regulations • Regulatory • Testing

Whether involved in method development, method validation, method verification or method transfer, this 18 hour ON DEMAND accredited course will provide a broad understanding and “hands-on” knowledge of the method validation process and the difficulties encountered in validating methods to comply with today’s upgraded FDA CDER requirements. Lectures will include not only theoretical basis and practical applications, but actual validation examples of HPLC, GC, UV/Vis, AA and titration methods for small organic molecules. Some of the more common mathematical and statistical treatments of validation data will also be discussed. Because of the tremendous effort that can be expended in conducting validation studies, efficiency of experimental design and documentation will be stressed throughout the discussions.

Authorities • Guidances • Laboratory Issues • Methods • Pharmacopoeia • Regulatory • Testing

This 6 hour accredited ON DEMAND course is designed to provide training to biopharmaceutical personnel on the analytical regulations involving method validations. Regulations and how they pertain to analytics, method qualification and validation and method trending will all be course topics. Personnel with experience or just getting started will both benefit from this course. This course, divided into four segments, will go through multiple bioanalytical methods and how to examine them for validation readiness and how to perform a validation. The methods in this course will include UV-VIS, SE-HPLC, HIC HPLC, Affinity HPLC, SDS-PAGE, IEF Gels, CE-SDS, cIEE and ELISA.

Methods

Best Practices • Equipment • Methods • Testing

This course is not currently scheduled. CfPA can possibly notify you when the course is scheduled or possibly can bring this course to your location.

This basic HPLC course will benefit the personnel with some HPLC experience who are developing or optimizing HPLC methods. This 90-minute accredited course will include discussions of theory of Reversed and Normal Phase, Ion Pairing and Ion-Exchange Methods. It will also give basic starting points on method development and method evaluation these methods. The course is designed to give personnel with some HPLC experience a broader scope for how to use this invaluable analytical tool.

Best Practices • Equipment • Methods • Testing

This 90-minute accredited ON DEMAND course will include discussions of the theory of SEC, Reversed Phase, Ion-Exchange, Hydrophobic Interaction, and Protein Affinity Chromatography. It will also give basic starting points on method development and method evaluation of these methods. The course is designed to give personnel with some HPLC experience a broader scope for how to use this invaluable analytical tool.

Packaging • Primary

Maintaining and ensuring the efficacy and sustained potency of probiotics has numerous challenges. Over the years, many packaging options have been devised, but probiotics present a unique set of challenges during the formulation, blending, packaging, and transportation phases that require strict adherence to specific standards.

Packaging • Primary

Blister packaging, not long ago considered a less significant segment of the North American pharmaceutical packaging industry, is now outpacing most other industry segments. Blister packaging reduces costs for OTC and Rx drug manufacturing significantly. Blister packaging also offers tamper proof solutions in a highly competitive market. The pharmaceutical manufacturing industry has witnessed a significant increase in the number of drug approvals by the FDA over the past few years leading to several packaging innovations.

Closure Integrity • Packaging

Qualification, and demonstration of fit-for-purpose, for a drug product vial/stopper/seal primary package system comprises many factors: protection, compatibility, safety, and performance. One of the subcategories is container closure integrity (CCI), which is the topic of this article. CCI is essential to protect the drug product through shelf life, and to demonstrate an integral system to regulatory agencies.

Closure Integrity • Packaging

The visual inspection of injectable drug product has been a regulatory requirement since 19361, however, successful implementation of the standard has been challenging for many organizations. The number of recall notices issued by the U.S. Food and Drug Administration (FDA) from 2010 through 2019 for injectable products due to visible particulate have reduced since 2014 but at the current trend, will be some time before it approaches zero2. Between 2009 and 2019, the presence of visible particles in parenteral product was the second leading cause for product recalls.3 Patient safety is the main driver for requiring injectable products to meet the criteria of “essentially free of visible particulates.

Packaging • Sterile

The required quality for glass containers for pharmaceutical applications is described in global pharmacopeia, e.g., USP Chapter Containers – Glass or Ph. Eur. 3.2.1. Glass Containers for Pharmaceutical Use. Apart from pharmacopeia, the different glass types are also described in standards, such as ISO and ASTM.

USP and Ph. Eur. have classified Type I glass as Borosilicate (BS) glass and Type III glass as soda-lime (SL) glass, each one with a certain limit for hydrolytic resistance. Typical BS glasses on the market are FIOLAX®, Corning®51-D / 51-V and NSV® 51. As it is an accepted custom to treat SL glass with ammonium sulfate on the inside to increase its chemical stability, this inner surface-treated SL glass was added in pharmacopeia and classified as Type II glass. Although there are different sub types of BS glass on the market, these are not differentiated in pharmacopeia. However, ASTM E 438 does distinguish between Type I Class A which is a BS glass with a lower thermal expansion, such as DURAN® or PYREX® glass and Type I Class B, which is a BS glass with a higher thermal expansion (alumino-borosilicate glass as per ASTM), known as FIOLAX®, Corning®51-D / 51-V or NSV® 51 glass.

Data Integrity • Quality

In 2017, data integrity issues were cited in 65% of all FDA warning letters. The main reason was incomplete data. In the pharmaceutical and biotechnology industries, this can be prevented by ensuring the trustworthiness and reliability of electronic records, a process that is also known as compliance with data integrity. The highest risks, when not working in a compliant manner, lie in import bans, product recalls, or even the closing of production plants. The FDA defines the criteria under which electronic records and electronic signatures are considered trustworthy, reliable, and equivalent to paper records in Title 21 of the Code of Federal Regulations (21 CFR) Part 11.

Education • Training

In the biopharma industry, “human error” is often selected to describe a deviation for which the immediate apparent cause was the behavior, which could be through action or inaction, of the person(s) performing a task or process. Too often, “retraining” is selected as the preventive action that, hopefully, will prevent that person or persons from repeating the deviation. As anyone with significant experience working in the GMP domain knows, repetition of training may be effective for straightforward and simple work, but not for complex tasks or for activities that require the application of self-awareness, critical thinking, and real-time judgment, all of which are critical in situations that are not nominal to the process.

Change Control • Data Integrity • Facilities • LIMS • Quality • Systems

This is an article found in the E-Book, "Ensuring Data Integrity for GXP Compliance" accessible through the link, below. The book provides multiple perspectives from experts in the industry, with solutions to common challenges. This compilation of previously published material on the IVT Network website is excellent for the beginner or the experienced professional working for data integrity compliance, with papers geared towards a general understanding, as well as papers dealing with more complex issues.

Methods • Testing

Compliance • Quality

How you respond to the observations will determine if they escalate into more serious consequences, such as a warning letter or enforcement action. A review of published warning letters confirms that a significant percentage could have been avoided by a proper response to the Form 483. Our goal is to help you take appropriate actions to optimize the outcome after receipt of FDA observations.

Closure Integrity • Packaging

One major potential point of friction on the approval journey is the need to specify and verify a compatible packaging combination for your drug product. Container closure integrity (CCI) is a critical aspect of drug development, and one that demands attention and investment early in the process to avoid complications and possible harm further down the line. This point is underlined by FDA data, which reveals that around a third (34%) of injectable product recalls in recent years can be linked to particulates or a lack of sterility attributable to the container closure combination.

Best Practices • Best Practices • Extension • Methods • Parameters • Protocols • Sample Control • Shelf-Life • Storage • Study Design • Testing • Transit

Abstract: Control and prevention of unwanted aggregation for therapeutic proteins is a ubiquitous hurdle during biopharmaceutical product manufacture, storage, shipping, and administration. Methods to predict the relative or absolute rates of aggregation are therefore of great practical interest in biopharmaceutical research and development. Aggregation is often well-described as a multi-stage process involving unfolding or misfolding of free monomers, along with one or more assembly steps to form soluble or insoluble oligomers or higher-molecular-weight species. This report reviews the current state of the art in experimental and practical theoretical approaches that attempt to predict in vitro protein aggregation rates or propensities relevant to pharmaceutical proteins. Most available approaches fall within four primary categories. The principles and assumptions underlying each category are reviewed, along with advantages and limitations in each case. The importance of appropriate experimental techniques and models to probe and quantify the thermodynamics and/or dynamics of multiple steps or stages within the overall aggregation process is stressed. The primary focus is on aggregation in solution, relevant to parenteral dosage forms. Additional challenges are briefly reviewed. Keywords: protein aggregation, biophysical models, physical stability, kinetics, protein formulation

Audits • Education • Laboratory Issues • Quality • Resources

Course Description: Many QA and QC personnel in the pharmaceutical industry are not familiar with the FDA systems-based inspection model. They are also not aware of the types of 483 observations that many FDA auditors make today. One of the most scrutinized areas during these inspections is the laboratory. Because of this, it is important for lab personnel to know the techniques used the FDA inspections during these types of audits. Knowing the systems, the FDA will look at is also key so that the lab can be properly prepared for the audit.

In this 90-minute accredited training, we will discuss laboratory controls. It will focus on all of the systems that are in a laboratory that will be audited by an FDA inspector in a typical systems-based inspection. After this webinar, you will fully understand how to prepare your laboratory for the FDA.

Data Integrity • Life Cycle • Quality • Systems

Key lessons: As projects progress from pre-clinical to commercial, the amount of critical data grows as the project scales.

With the increasing complexity of treatments and intricacies of the relevant processes, there is an equally growing need for robust DI controls that allow accurate decision-making based on reliable data.

These challenges can be further compounded if digitized solutions brought in to elevate efficiency and protect data integrity are implemented without a clear understanding of the process they are trying to improve and how they could achieve this. It is therefore essential to implement a robust approach to data integrity whilst ensuring that regulatory requirements are met.

Best Practices • Parameters • Protocols • Study Design • Study Types

Introduction: Most nanoparticle formulations are in solution with a heterogeneous size distribution. These nanosuspensions can be unstable and subject to problems, such as sedimentation, agglomeration, crystal growth or chemical reactions. Lyophilization can increase the stability of these particles, which also benefits the stability of the drug products incorporated in them.

Recently, Dr. Xiuling Lu, University of Connecticut, presented a webinar describing the challenges of freeze-drying nanoparticles and how, in collaboration with Dr. Robin Bogner Ph.D., her group has designed and evaluated solutions to lyophilizing LNPs. This tech note summarizes the webinar and includes a selection of questions from the Q&A session.

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

In this three-part series, the author examines what causes protein aggregation and practical steps you can take to mitigate the risk. Key Words: Surfactant, Formulation, Headspace

Closure Integrity • Laboratory Issues • Methods • Packaging • Primary

Abstract Repeatable and proper Container Closure Integrity Testing of primary packaging’s is essential to ensure quality and effectiveness of pharmaceutical products. Blue dye test and microbial ingress are mainly used for decades. Recently, guidelines provided by regulatory organizations like USP or Annex 1 request statistical analysis and push for use of deterministic and non-destructive methods.

The following presents the results of a unique comparative study conducted on more than 500 glass vials that are prepared with leak artifacts (microtubes and glass micropipettes), which refers to Kirsch and Burrel’s studies. Each sample has been tested with different technologies: Helium Leak test, Optical Emission Spectroscopy, Mass Extraction and Blue Dye test. Depending on the needs (R&D, Production, Quality) the results can help the reader to find a suitable deterministic test method to replace the blue dye test and follow the latest guidelines.

Best Practices • Equipment • Methods • Pharmacopoeia • Testing

Introduction: The recently published general chapter USP states that water activity determination can be used to assess the level of protection provided by primary packaging for an oral solid dosage (OSD) product over its entire shelf life. Primary packaging must maintain a low relative humidity for as long as necessary to ensure the pharmaceutical product maintains its key quality attributes including potency, purity, dissolution rate, tablet hardness, and capsule swelling, up to its expiration date. During the development phase, data must be acquired to determine if an existing package can provide adequate protection, or if new technologies are required for new formulations. For commercial products, a replacement package must be assessed to determine if it has equivalent, inferior, or superior performance. Water activity (aw) measurements provide unique information, and therefore expand and complement the data collected from USP Auxiliary Packing Components and USP Containers - Performance Testing.

Sample Control • Storage • Transit

Introduction: As “living treatments” continue to serve an increasingly significant role in medicine, finding cryopreservation approaches that offer an alternative to toxic, suboptimal solvents is critical to improving their commercial and therapeutic potential. Non-toxic alternatives to DMSO have shown promise in the lab, particularly products that mimic the natural antifreeze proteins (AFPs) found in certain species dodging the effects of freezing temperatures.

Best Practices • Chamber Space • Chambers • Planning • Resources • Sample Control • Storage

Conclusion: Conventional ULT freezers are used for freezing and storage of biopharmaceutical bulk DS, but they are not always the optimal solution. ULT freezers are designed for storing frozen material and have limited capacity for freezing liquid DS.

For freezing bulk DS, forced air convection freezers that are designed for the application provide much faster freezing rates, much more consistent freezing rates, and greater mechanical reliability.

For storage of bulk DS, there are now three options available – conventional ULT freezers, large custom freezers, and a newer option of midsize ULC freezers. There are pros and cons to each option, and one tool to find the optimal solution is an economic evaluation. The results of an example evaluation show the optimum solution varies with the amount of freezer capacity required. For a small freezer capacity requirement (around five ULT freezers or fewer), ULT freezers provide the lowest overall cost. For very large applications where more than 100 ULT freezers would be required, the large custom freezers are optimal. And when freezer capacity of between five and 100 ULT freezers is required, the ULC freezer option gives the lowest overall cost. Key Words: Design, Strategies, Blast

Best Practices • Guidances • Methods • Regulatory • Testing

Introduction: Toward the end of 2022, the FDA issued guidance on the validation of biological assays, titled M10 Bioanalytical Method Validation and Study Sample Analysis.1 The guidance was originally issued in draft form in 2019; a little over three years was required to develop the final guidance document, and it was approved by ICH in May 2022. Hence, the FDA adoption completes international acceptance of a unified approach to biological assays. The objective of issuing the document was to address some concerns with regulatory submissions, and the document provides a set of recommendations for method validation for bioanalytical assays for nonclinical and clinical studies. As well as full validation, the guidance extends to partial validation where modifications are undertaken for previously validated assays. There is an additional intention centered on reducing the numbers of animals used in drug research and development.

This article considers the core objectives of the guidance and how it applies to both GMP and GLP activities.

Extrapolation • Specifications • Testing • Tools • Types

One of the reported methods to estimate the probability of passing the USP dissolution test uses Mathematica software for calculation. The goal of this article is to calculate the probability of passing the USP dissolution test from that method using Microsoft Excel.

Dissolution testing is performed to provide in vitro drug release information and to accurately predict the in vivo drug release. Dissolution tests are performed at different stages of the drug manufacturing process to ensure that the drug product meets the standards as specified in the United States Pharmacopoeia (USP). USP provides requirements for sampling, testing, and acceptance criteria for tests like content uniformity and dissolution.1,2 A manufacturing process is said to be in regulatory compliance only if it meets the acceptance criteria for all the tests specified in USP. To ensure there is a high probability of passing these tests, sponsors establish in-house specification limits to ensure there is a high probability of meeting these acceptance criteria. Different methods are reported in the literature to calculate the probability of passing the dissolution test.

Best Practices • Best Practices • Packaging • Parameters • Primary • Protocols • Sample Control • Storage • Study Design • Transit

In this three-part series, the author examines what causes protein aggregation and practical steps you can take to mitigate the risk. Key Words: Manufacture, Container, Pathway

Closure Integrity • Guidances • Methods • Primary • Regulatory • Testing

Opening Paragraphs: The revised EU Annex 1 contains new requirements for ensuring the container closure integrity (CCI) of sterile pharmaceutical products, causing pharmaceutical companies to reassess their CCI policies for compliance.

Learn in detail how the new requirements of the revised EU Annex 1 may impact your strategy for ensuring CCI of sterile pharmaceutical products. Gain an understanding of the advantages and disadvantages of CCI testing methods and why a science-based holistic approach to ensure good CCI is important. Explore how cold chain storage and transport can impact the CCI of sterile pharmaceutical products.

Audits • Investigations • Quality • Tools

What you'll find inside: - Root cause analysis and CAPA basics - Strategies for overcoming common challenges such as defining your CAPA process or determining when CAPA is appropriate - CAPA's connection to other parts of your QMS - Practical perspectives on shifting to a prevention mindset - Firsthand experiences from a former FDA official - How third-party specialists can play a vital role in remediation projects.

Guidances • Regulatory

Introductory Paragraph: Revision of the ICH Stability Guideline Series Q1A-F and Q5C is recommended to a) streamline the series by combining the various guidelines into a single guideline focused on core stability principles; b) promote harmonised interpretation by addressing potential gaps and areas of ambiguity; c) address additional technical issues, including relevant stability strategies and innovative tools that strengthen the application of risk management; and d) consider inclusion of new topics, such as stability considerations for advanced therapies. The informal working group proposes to establish these updates through the Revision procedure. The envisioned result is a combined guideline, ICH Q1, with integrated annexes and/or appendices that address specific topics beyond the core principles on stability recommendations and to address product type1 specific recommendations, as required. It is also recommended to update and supplement current training material.

Best Practices • Chambers • Excursions • Monitoring • Qualification • Storage

Abstract: This article describes the use of temperature mapping as a process to qualify storage areas to maintain temperature for the storage of drugs, which is an effective strategy to identify risks as part of a quality management system.

The authors point out that maintaining temperature during storage is an important aspect to make sure that the safety, efficacy, and expiry of drugs are kept. This, of course, includes avoiding temperature excursions during storage. To evaluate if storage areas can adequately maintain the appropriate temperature, temperature mapping studies are necessary.

Packaging • Primary • Secondary

Conclusion: As manufacturers develop more advanced therapeutics, especially cell and gene therapies, solutions that support reliable cold chains will become central. Biopharmaceuticals culminate in complex design decisions requiring substantial research, resources, and time investment.

Oftentimes, manufacturers will misguidedly look to improve end-user training and secondary packaging before first evaluating the most durable primary solutions to prevent product loss. Many recognize the critical aspect and value, both in cost and to patients, of container integrity. The key takeaway for manufacturers is that by choosing the most durable and innovative primary packaging, they can eliminate potential issues that might occur through subsequent phases of supply chain transportation.

Authorities • Guidances • Regulations • Regulatory

Introductory Paragraph: To accommodate changing requirements and encourage the adoption of new technology, India’s Ministry of Health and Family Welfare released a draft bill in July 2022 to replace the existing Drugs and Cosmetics Act 1940. This act governs drug importation, production, and distribution across the country. The act's main goal is to ensure that all drugs and cosmetics sold in India are safe, effective, and meet international standards.1 It also focuses on ensuring the quality, safety, efficacy, and performance of new drugs, as well as on the clinical investigation of investigational medical devices. Finally, it adds regulations and restrictions on drug imports aimed at protecting public health interests. Below are some of the areas most highly impacted by this new bill.

Audits • Quality

Introduction: Gearing up for a quality audit is no small feat. Whether it’s your organization’s first time being audited or the 100th, there’s always room for improvement when it comes to your quality management system. An internal quality audit is an important tool for any company that wishes to assess its quality procedures, compare performance against external standards, or prepare for an external audit. By conducting an internal audit, organizations can identify areas where they need to make changes or improvements. We'll review the benefits of and responsibilities within an internal audit, as well as the 4 steps you should follow to make sure your audit is successful. Key Words: Systematic, Planning, Corrective

Closure Integrity • Equipment • Packaging • Testing

Introduction: The quality and effectiveness of drugs significantly depends on their proper packaging: It needs to be unscathed and of the highest quality. Otherwise, serious consequences might occur. This was proven by a serious incident in the 1970´s: During this period, contaminated intravenous fluids packaged in glass bottles - which were typical at the time for packaging such dosage forms - caused an estimated 2,000 to 8,000 episodes of bloodstream infection, resulting in the deaths of about 10% of the patients. This severe package-integrity failure incident has triggered a heightened awareness of package integrity.

Change Control • Change Control • Data Integrity • Quality • SOPS • Systems • Tools

Key strategies for change control -Having a strong change control process in place is critical for compliance. -Developing a regulatory notification decision flowchart or matrix now can make your life much easier later. -Don’t forget to document everything! You’ll need to document every piece of the change control process from identification through to approval and implementation. -Using a software system for tracking the MANY moving pieces during a change control process can minimize chaos and ensure that steps are not skipped. -Quality or engineering cannot complete the change control process in a silo, it is a team effort that functions best when it has input from everyone. -Don’t forget the follow-up activities to make sure that the change was effective and didn’t introduce any other problems. Key Words: Risk, 9001, Regulation

Best Practices • Shelf-Life • Statistics

The role of sampling and measurement uncertainty in assessing production process capability is examined, using content uniformity testing as an example. An expanded components of variance model is proposed for consideration during risk assessment and mitigation studies, with emphasis that either empirical (“top-down”) or model-based (“bottom-up”) approaches to estimation of uncertainty can be equally valuable in completing an expanded production process characterization (PPC) study.

Closure Integrity • Equipment • Methods • Packaging • Testing

Automated laser-based headspace inspections systems are now implemented and validated for 100% container closure inspection of sterile pharmaceutical containers at production speeds. Such implementations give insight into the process, ensure the maintenance of sterility for finished product after capping, and can be seen as a tool for meeting current regulatory guidance. Download this White Paper to get an introduction to laser-based headspace inspection and the application to 100% container closure inspection of sterile pharmaceutical containers.

Best Practices • Data Analysis • Methods • Specifications • Submissions

This presentation, in light of ICH Q1/Q5C reviews a Predictive Stability Strategy implemented at AstraZeneca, including some recent developments and routine application. This is supported by four case studies across the stages of development. Key Words: Astra, Case, Q5C

Packaging • Parameters • Primary • Protocols • Sample Control • Storage • Study Design • Transit

In this three-part series, the author examines what causes protein aggregation and practical steps you can take to mitigate the risk. Key Words: Sterile, Prefilled, Vials

Auditing • Best Practices • Communications • Outsourcing

Opening Paragraph: When reviewing health agency citations, it is clear that a common area of focus by investigators during inspections is the stability program and the data that is generated by the program. Why is this? Obviously, there can be numerous reasons such as that stability studies are frequently on the critical path when seeking agency approval and the resource demands associated with stability testing and the competing priorities. But one of the issues, I believe, is that stability testing is commonly outsourced, which puts a focus on the vendor qualification/oversight program, along with the associated quality agreements, adding a complexity/risk that investigators are aware of.

Compliance • Guidances • Life Cycle • Parameters • Protocols • Quality • Regulatory • Study Design • Submissions

Abstract We have summarized five high impact issues related to the stability studies for drug substances that are documented in the Type II drug master files (DMFs) supporting Abbreviated New Drug Applications (ANDAs). We intend to provide the scientific considerations for the regulatory policies which bear upon such high-impact issues. We have also provided our perspective to avoid such issues, to reduce the DMF review time, and subsequently to accelerate the approvals of the supporting ANDAs.