Publications

Closure Integrity • Packaging

Container Closure Integrity Testing (CCIT) is a critical component that must be considered in the manufacturing of a drug product or combination device, such as a prefilled syringe. The landscape of CCIT has been changing over the past 15+ years due to changes in the regulatory mindset regarding sterility testing and detection limits around CCIT. In 2008, the FDA published a guidance document “Container Closure System Integrity Testing In lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products.” This document gave clear indication that CCIT was the preferred avenue for confirming product sterility during stability studies and thus through the lifecycle of the product. While sterility testing is necessary at the release of a product to ensure that the product is sterile upon completion of manufacturing, there are limitations to using this test to indicate the product will remain sterile until the end of the lifecycle. This document did not provide testing specifics for CCIT but stated that during stability testing, sterility testing should be replaced by “properly validated physical or chemical container closure system integrity test (e.g., bubble tests, vacuum/pressure decay, trace gas permeation/leak tests, dye penetration tests, seal force of electrical conductivity and capacitance tests, etc.), or microbial container closure system integrity.

Best Practices • Testing

Data normalization is broader than data format. Normalization translates data from various sources and systems into an agreed upon ontology (i.e. nouns, verbs, and adjectives that describe data and their relationships) Organizations seek to standardize and normalize data to increase data accessibility and streamline integration of data from different systems and sources. Standardized data benefits R&D by enabling consistent data analysis, easier data exchange and collaboration, the ability to identify inconsistencies, and improve the quality of data being aggregated and used. It also allows organizations to leverage that data for AI/ML-powered innovation.

Analytical chemistry data, generated by various instruments and techniques (chromatography—CE, GC, HPLC, UHPLC, mass spectrometry [MS], nuclear magnetic resonance [NMR], infra-red [IR]/Raman/, ultraviolet [UV] spectroscopy, etc.), represents a wealth of information on the identity, properties, and behaviors of chemical compounds. Analytical instrument vendors, typically, create their own proprietary formats for data acquisition and handling. The diversity of experimental techniques and proprietary instrument vendor formats results in data that is fragmented, incompatible, and difficult to integrate into streamlined workflows. While most R&D organizations have successfully achieved some degree of digitalization of analytical workflows, data heterogeneity remains a major obstacle.

Heterogeneous analytical data: Hinders the assembly of interrelated datasets Impedes centralized data management and data accessibility Limits the use of valuable analytical data beyond its initial purpose The latest approach to scientific discovery emphasizes the use of machine learning (ML) and artificial intelligence (AI) to uncover new insights by identifying patterns and correlations in massive datasets. Data science (AI/ML) places a premium on well-curated, standardized data. Analytical chemistry, with its diverse techniques and complex datasets, epitomizes the challenges and opportunities in aligning data with the computational demands of AI/ML.

Investigations • Quality

For companies whose products are subject to regulatory requirements, especially those under the jurisdiction of agencies like the U.S. Food and Drug Administration (FDA), a corrective action/preventive action (CAPA) process is needed to address and mitigate the impact of quality events such as deviations and nonconformances. Many companies, however, are not equipped to implement an effective CAPA process. It may be that their employees lack the proper training and background to perform corrective actions. Or perhaps they don’t have access to tools and strategies that adequately support a formal CAPA process. A review of the FDA warning letters issued each year indicates that some companies only think about CAPA after the fact – when quality issues have already emerged, and they have no choice but to address them. Most organizations have some sort of CAPA system in place, but too many are woefully inadequate. This brief provides an in-depth look at each critical phase of CAPA and provides a blueprint to help life sciences companies successfully manage them.

Chambers • Preventive Maintenance

Stability Rooms play a critical role in industries like pharmaceuticals, food production, and environmental testing, where precise control of temperature and humidity is essential to maintaining product integrity. A solid preventive maintenance program is key to ensuring these rooms operate efficiently and reliably over time, reducing the risk of costly downtime or compromised results. Regularly scheduled inspections and upkeep can prevent many common issues, but it’s equally important to be prepared for unexpected equipment failures. Having the right spare parts on hand is crucial for minimizing disruptions and maintaining compliance. In this article, we’ll outline the five essential parts you should always have ready for your stability room to ensure smooth operations and quick recovery when something goes wrong.

Guidances • Regulatory

What Are the Benefits of AQbD Implementation? Analogous to QbD, a successful AQb implementation will focus on the definition of the operating ranges for the analytical method to meet the desired Analytical Target Profile, improving its robustness, and resulting in resource-efficient drug development. This approach will potentially minimize the out of specification results and consequently contribute to cost reduction. Moreover, the knowledge of the MODR increases regulatory flexibility and enables easier post-approval changes2, 3. The existence of clear guidelines is expected to encourage the use of more advanced analytical methods such as spectroscopy techniques, and to enable a robust quality oversight by drug manufacturers3

Best Practices • Chambers

Choosing the right refrigerators, freezers, and incubators for your lab is essential, but how do you know which claims to trust? Performance metrics can often feel like a puzzle with inconsistent definitions, vague data, and varying testing standards between manufacturers.

This comprehensive guide simplifies the confusion and helps provide you with the tools to decode performance claims with confidence.

Closure Integrity • Packaging

A study has investigated the challenges of freezing biological drug products with vials as a primary packaging container. In their study, Henle et al. assessed the suitability of different vial qualities in relation to the “thermally induced mechanical stresses experienced during frozen drug product preparation and storage”. The researchers stated that in recent years, novel vial types for special applications of parenteral drug products have entered the market.

Disaster • Planning

A pharmaceutical company was conducting stability testing on a new drug product intended to treat a rare, life-threatening disease. The product was in the final stage of development and on track to be submitted for regulatory approval. At one point in their ICH stability study, the company discovered that one of its stability chambers had malfunctioned due to a faulty sensor that caused the temperature and humidity levels to fluctuate erratically. The malfunction continued unnoticed for several hours, affecting hundreds of samples. The pharmaceutical company was unable to leverage its own in-house backup equipment, as all redundant chambers were already at full capacity. The pharmaceutical company faced the risk of losing valuable data and samples, delaying its regulatory filing, and compromising its product quality and patient safety.

Guidances • Regulatory

Pharmaceutical products require expiration dates and storage conditions on their labels, determined through stability studies conducted from clinical trials through post-approval. These studies ensure that any chemical, physical, or microbiological changes over time do not affect the product’s quality, safety, or efficacy. ICH Q1A(R2) provides guidance for stability programs but focuses on new drugs and lacks a comprehensive approach where prior stability knowledge can be applied...

NOTE: KENX Membership required to access article.

Methods • Testing

Introduction to a webinar video. An in-depth discussion on the influence of water activity testing on tablet and capsule quality and stability, presented by expert Mike Lally. He comprehensively explores water activity testing and shows how to utilize non-destructive headspace analysis to generate reliable water activity data.

Closure Integrity • Packaging

Brief overview introducing an embedded video. Selecting a container closure system for a sterile injectable can be a daunting task in early drug development. FDA rightly points out that “a packaging system found acceptable for one drug product is not automatically assumed to be appropriate for another.” Drug developers must ultimately prove that the container closure system and its components are suitable for intended use. The basic principles for determining that the proposed container closure system is suitable are: It adequately protects the drug product It is compatible with the drug product It is composed of materials that are considered safe for use with the drug and the route of administration Its integrity performance ensures that the drug product is safe to be administered

Testing • Types

X-ray inspection of pharmaceutical products and over-the-counter (OTC) medications are steadily increasing in use as pharmaceutical manufacturers worldwide strive to safeguard their brand reputations, protect consumers’ welfare and comply with national and international regulations and legislation. Some manufacturers, however, still have reservations about adopting x-ray inspection as a safe method of product inspection. Their primary concern is that products being inspected could be affected by radiation during the inspection process, and that their therapeutic effectiveness might be compromised. This white paper examines the potential effects of x-ray inspection on pharmaceutical products. The paper begins by exploring the nature of radiation, outlining the difference between man-made x-rays and naturally occurring radiation (‘background radiation’). The document then discusses why and how manufacturers use x-rays to inspect a wide variety of products to detect potentially harmful contaminants and defects that can damage brand reputation, potentially leading to costly recalls and lawsuits. There then follows a summary of the published research conducted on the effects of x-ray inspection on the efficacy and other physical properties of pharmaceuticals. The available research shows that the pharmaceutical and OTC products tested are not affected in terms of their chemical makeup and efficacy following exposure to x-ray in inspection systems.

Methods • Testing

Methods • Testing

Video

Best Practices • Testing

Video

Testing • Types

Guidances • Regulatory

Testing • Types

Certain sterile pharmaceutical products require deep cold storage, either at dry ice (-80°C) or even cryogenic (−196 °C) temperatures. Live viral vaccines, gene therapies, or products that contain active cells (cell therapies) often need deep cold storage to maintain stability and/or activity. These storage conditions pose a challenge to packaging components, in particular to vial/rubber stopper combinations traditionally used to fill sterile pharmaceutical product. Rubber formulations typically have glass transition temperatures (Tg’s) near -65°C meaning that rubber stoppers lose their elasticity at deep cold storage temperatures. This loss of elasticity, coupled with inappropriate capping & crimping, can result in increased risk that the vial seal integrity could be compromised. It is therefore imperative that data is generated to demonstrate the maintenance of seal integrity during deep cold storage and transport..

Laboratory Issues • Testing

Maintaining detailed records of reagents is an essential part of maintaining scientific rigor in research. The systems used by the scientific community in documenting and managing this information, however, can be highly administrative, tedious, and surprisingly prone to errors. So, for many labs, reagent record management consists of routine, repetitive tasks involving manual data entries for each of, perhaps, hundreds of chemicals, solutions, and other consumables used in large, bustling life science laboratories. On the surface, spending a few minutes locating a reagent or manually documenting its details may be perceived as insignificant, but what remains largely overlooked is the resulting time sink that diminishes the laboratory’s overall performance. Here, we discuss the main inventory management challenges faced by fast-paced biotech and pharmaceutical laboratories, highlighting how this directly impacts research outcomes, costs and regulatory compliance.

Best Practices • Shelf-Life

Best Practices • Testing

Demonstrating the compatibility of any material that comes in contact with a drug product throughout its lifecycle (manufacture, containment, and delivery) is a requirement for any regulatory submission. Agency expectations on this material evaluation, defined as extractables and leachables (E/L), continue to evolve and expand. These expectations are well beyond a check box activity that can be quickly and mindlessly completed at the end of Phase III. These newer companies are often at a disadvantage from larger companies as they do not have the ability to leverage historical E&L data or the advantage that comes with a platform approach to containment needs. Unfortunately, West sees a pattern where new and emerging pharmaceutical companies wait until the end of Phase III to start planning their E/L testing program. Waiting this late in development can lead to increased costs and delays, stemming from poor assessments that are questioned by the reviewer, or incomplete submissions that require the drug company to redo or execute additional work. In order to meet regulatory expectations, the mindset around E/L testing must change from “How quickly can we get extractable and leachables testing done?” to “Is it too soon to start my extractables and leachables assessment?”

Data Analysis • Statistics

OOT Determination is a powerful addition to any stability program and needs a clearly defined SOP to consistently apply the logic to day-to-day stability evaluation. Including an OOT protocol to stability testing and datam analysis will produce more statistically reliable stability determination and expiry prediction. OOT determination basedm on the protocol described in this paper opens the door for the automation of OOT determination and from any stability analysis and may be the best approach to systematically evaluate all time points in stability analysis.

Testing • Types

N-nitrosamines (referred throughout as “nitrosamines”) are a class of highly potent genotoxins containing a functional group (NO+) bound to an amine (see example in Figure 1), are listed as potential human carcinogens. with a growing number of drugs recalled from 2018 onwards for the presence of nitrosamines such as N-nitrosodimethylamine (NDMA) in certain receptor antagonist/sartan drugs, ranitidine, and metformin drug products, the Food and Drug Administration (FDA) has continued to release updated Guidance for Industry regarding acceptable nitrosamine levels.

Best Practices • Outsourcing

Stability storage is a vital part of the quality assurance process for pharmaceutical and medical device products, as it ensures that products meet the required standards and regulations throughout their shelf life. However, conducting stability storage in-house can be a complex and costly undertaking, requiring dedicated facilities, equipment, personnel, and resources. That is why many companies are opting to outsource their stability storage needs to a trusted and experienced partner that can offer them high-quality, flexible, and cost-effective stability storage solutions. In this whitepaper, you will discover: How outsourcing stability storage can benefit your company by reducing operational costs, increasing efficiency and productivity, enhancing innovation and compliance, and accelerating time to market. Real-life case studies using leading pharmaceutical and medical device companies that have successfully leveraged outsourcing partnerships to achieve their stability storage goals and overcome their challenges.

Best Practices • Testing

The FDA enforces a number of strict requirements regarding the calibration and maintenance of equipment. Calibration is essential not only for meeting regulatory standards but also for improving accuracy, safety, and overall quality. It should be seen as more than just routine maintenance—it’s a proactive measure for continuous quality improvement. In this webinar, we will explore common calibration findings highlighted by the FDA and offer practical insights to help you better prepare for regulatory audits. You’ll discover how implementing a comprehensive calibration program can streamline processes, enhance compliance, and significantly reduce quality risks. In this presentation, attendees will gain valuable knowledge on:

Key FDA Calibration Findings: Understand common deficiencies and pitfalls that organizations often face during inspections and learn how to avoid them. Developing a Comprehensive Calibration Program: Learn how to design and implement a robust calibration program that aligns with both FDA requirements and industry best practices. Enhancing Process Accuracy and Safety: Discover strategies for optimizing equipment calibration to improve process reliability, safety, and product quality. Real-World Examples: Explore case studies and data-driven insights to inform your approach to calibration and ensure regulatory compliance.

This webinar will equip you with the tools and strategies needed to strengthen your calibration efforts and better position your organization for success in regulatory audits.

Equipment • Testing

The FDA enforces a number of strict requirements regarding the calibration and maintenance of equipment. Calibration is essential not only for meeting regulatory standards but also for improving accuracy, safety, and overall quality. It should be seen as more than just routine maintenance—it’s a proactive measure for continuous quality improvement. In this webinar, we will explore common calibration findings highlighted by the FDA and offer practical insights to help you better prepare for regulatory audits. You’ll discover how implementing a comprehensive calibration program can streamline processes, enhance compliance, and significantly reduce quality risks. In this presentation, attendees will gain valuable knowledge on: Key FDA Calibration Findings: Understand common deficiencies and pitfalls that organizations often face during inspections and learn how to avoid them. Developing a Comprehensive Calibration Program: Learn how to design and implement a robust calibration program that aligns with both FDA requirements and industry best practices. Enhancing Process Accuracy and Safety: Discover strategies for optimizing equipment calibration to improve process reliability, safety, and product quality. Real-World Examples: Explore case studies and data-driven insights to inform your approach to calibration and ensure regulatory compliance. This webinar will equip you with the tools and strategies needed to strengthen your calibration efforts and better position your organization for success in regulatory audits.

Study Design • Study Types

Introduction to a video presentation. The successful development and approval of biosimilars hinge on the rigorous demonstration of their comparability to their reference biologics. This presentation outlines a comprehensive framework for conducting robust comparability studies that ensure biosimilars meet stringent standards for safety, efficacy, and quality.

Central to this framework is a deep understanding of regulatory expectations and guidelines. We delve into the pivotal role of comparability studies and discuss the key aspects that regulatory authorities scrutinize. Furthermore, we explore effective strategies for managing the complexities inherent in comparability studies, addressing critical considerations such as study design, analytical methods, and data interpretation. By implementing these strategies, stakeholders can contribute to the development of high-quality biosimilars that meet the needs of patients and healthcare providers worldwide while mitigating risks and enhancing the credibility of their biosimilar development programs.

Guidances • Regulatory

This article explores the significance of the FDA’s latest recommendations, explaining the nature of nitrosamine impurities, their root causes, and recommended strategies for mitigating their presence in pharmaceuticals. We also will discuss the implications of these recommendations for the global pharmaceutical industry and outline the best practices for ensuring compliance with the FDA guidelines.

Monitoring • Systems

Shipping high value and/or highly sensitive pharmaceutical products successfully requires strict adherence to procedures and policies by all parties involved. Identifying the appropriate shipping solutions, methods of transport, and transportation providers are all key aspects to ensuring that products arrive at destination on time and without degradation. The pharmaceutical supply chain must be considered as one complete entity and not as individual links in the chain. For this reason, supply chain visibility is ever paramount to the success of your shipping program.

Best Practices • Testing

It is widely recognized that gene therapy manufacturing processes result in low yields, particularly in early product development stages. Gene therapy products, however, are largely subject to many of the same regulatory requirements and expectations as other large molecule biopharmaceuticals that are produced at significantly larger scales. Often, if gene therapy manufacturers adhered to common paradigms for stability studies, the outcome would be little, if any, remaining product for patients or studies to support investigational new drug applications.

This article outlines strategies for reducing the volumes required for stability studies, with the goal of conserving product for patients, while remaining compliant and delivering data on critical quality attributes across the shelf life of gene therapy products. The recommendations include considerations for both drug substance (DS) and drug product (DP).

LIMS • Systems

Despite advancements in technology and the availability of modern LIMS platforms, many laboratories continue to cling to outdated products under the misconception that change is unnecessary or too complex. However, the high price of hanging onto rigid or feature-poor LIMS products far outweighs the cost reduction, high throughput, quality, and compliance benefits of deploying a fit-for-purpose lab platform.

Determination • Shelf-Life

In this paper ‘cumulative stability’ is defined as the concept of linking the stability of a drug substance (DS), drug product (DP) and/or of a manufacturing intermediate to the subsequent step(s) of the product manufacturing process. It may also be referred to in industry as ‘end to-end stability’. The biomanufacturing industry is facing a regulatory requirement divergence with regards to cumulative stability data in both new and major post-approval submissions. There is a lack of clarity in regulations and guidelines as to what data are required or expected to ensure successful regulatory filings. In most cases where cumulative stability is requested, regulatory expectations focus on linking the stability of the DS to that of the DP by manufacturing a batch of DP from aged DS and evaluating its stability until the end-of-shelf-life. However, additional evidence on other stability studies linking different stages of the manufacturing or lifecycle of products has also been requested. Through BioPhorum, a team of SMEs from the pharmaceutical industry (27 SMEs from 17 organizations) convened and participated in a series of workshops aimed at defining cumulative and other stability studies requested by regulators, and compiling their best practices and recommendations. To gather more data regarding the perceived differences in regulatory expectations, the team first conducted a survey. Subsequently, the team discussed and defined their recommended strategies based on risk assessment, and knowledge and understanding of the product and process.

Systems

At first glance, the laboratory of today looks remarkably like it did twenty years ago. While there is a higher level of automation particularly of routine and repetitive tasks, and there are certainly improvements to the instrument and software technology, the overall process often feels unchanged. However, a true revolution of today’s laboratory processes is on the horizon, advancing with increasing momentum with the help of groups such as BioPhorum. BioPhorum, is a collaboration across over 130 biopharmaceutical manufacturers and software and instrument vendors, which has published a manifesto envisioning the evolution of the QC (Quality Control) Lab of the Future, enabled by digital technology. Pharma 4.0 and digital transformation initiatives are transforming the manufacturing environment, but the laboratory has fallen behind. BioPhorum highlights the need to digitally enable laboratory processes and improve access and interoperability of scientific data. Laboratories rely on digital technology to support the scientific process, but these tools are often disconnected from one another. To truly harness artificial intelligence (AI) and benefit from tools like generative AI and machine learning, we must rethink how we create, curate, and access data. True digital transformation demands a reimagining of laboratory operations in the digital world.

A statistical analysis for determining an expiration date can be applied to replicates or their corresponding averages as suggested in industry guidelines. Stability data of samples of pharmaceuticals are often generated as replicate test results, typically as duplicates. A statistical analysis for determination of an expiration date can then be applied on either the replicates or their corresponding averages in line with the methodology suggested in International Council for Harmonisation (ICH) Q1A(R2) and Q1E guides. This paper aims at clarifying when a shelf-life derived from all replicates or averages is justified and correct. When replicate stability data represent preparations of the same sample, this is a case of pseudo-replication, and, therefore, the statistically derived shelf-life should be based on the averages of the replicates. However, when these replicate data represent independently and randomly selected and tested samples at each time point, a statistically derived shelf-life based on all replicate data is justifiable.

Testing • Types

Quality • Tools

In the pharmaceutical industry, the integration of artificial intelligence (AI) and machine learning (ML) into drug manufacturing processes is redefining how drugs are manufactured and controlled for quality. U.S. FDA Commissioner Califf recently stated that “AI has the potential to enable major advances in the development of more effective, less risky medical products.”1 AI and ML in good manufacturing practice (GMP) settings offer unprecedented opportunities to enhance operational precision, efficiency, accuracy, and compliance through advanced analytics and automation in a highly regulated field. However, they also introduce complex regulatory challenges that need to be navigated carefully.

This article provides insights into a variety of use cases on the application of AI and ML in GMP settings and useful considerations for manufacturers using AI in quality to demonstrate GMP compliance.

Life Cycle • Regulatory

Expiration dating and storage conditions are required on the label for all pharmaceutical products. To establish a drug product’s storage condition and expiration date, a manufacturer must conduct stability studies for all phases of the drug product, from clinical trials to manufacturing and continuing after approval. Stability studies are quality assessment tools to ensure that any chemical, physical, or microbiological changes that may occur as the product ages will not adversely impact the quality of finished products throughout the product’s lifetime. Stability data are also used to establish product specifications to monitor drug product quality, safety, and efficacy. ICH Q1A(R2) is an excellent resource for selecting the appropriate requirements for a stability program; however, ICH is a guideline for new drug substances and drug products; therefore, it is insufficient for acquiring complete knowledge of the stability behavior of a drug product. ICH Q12 has introduced the concept of product lifecycle management, in which post-approval changes are also considered to maintain and improve quality and where knowledge gained throughout the product lifecycle can provide a better understanding of the risks to the stability program. This paper will discuss how the ICH Q12 concept can be built into the stability program and how the Q12 toolbox can connect stability activities supporting product and process changes continuously from the design phase through post-approval, thus fostering continuous improvement for the entire product lifecycle.

LIMS • Systems

Methods • Testing

In recent years, cell therapy products have shown tremendous potential in regenerative medicine and the treatment of various diseases. These products are often derived through complex processes involving the isolation of human cells, particularly the expansion and manipulation of chimeric antigen receptor (CAR) T cells, which renders them vulnerable to microbial contamination. Therefore, ensuring the sterility of cell therapy products is crucial to guaranteeing product quality and safety. The traditional sterility testing method, as outlined by USP chapter , is a compendial method that relies on microbial growth–based detection. This method requires a 14-day culture, which can create difficulties in promptly releasing cell therapy products that may have a limited shelf life or require immediate administration to patients.

Guidances • Regulatory

Nitrosamines (N-nitrosamines) are organic compounds that feature a nitroso group bonded to a deprotonated amine. These mutagenic chemicals pose a concern across food and medicines since most nitrosamines are carcinogenic (in particular, connected to incidences of gastric and esophageal cancers) and several are genotoxic. Seven types of nitrosamines are considered to be potential contaminants of pharmaceutical products: Several regulatory agencies have previously issued guidelines on nitrosamines and pharmaceutical products. The World Health Organization (WHO) has added to the availability of documents with a new draft guidance (April 2024).2

Regulations • Regulatory

In March 2020, the European Commission requested an updated opinion from the European Food Safety Authority (EFSA) on titanium dioxide's safety. Although EFSA's 2016 opinion found no immediate safety concerns, it noted data gaps, especially regarding particle size, which can affect its toxicological properties. The new EFSA opinion from May 2021 doesn't definitively label E171 as harmful but doesn't dismiss health risks like genotoxicity. Since the safety cannot be confirmed, the European Commission (EC) banned titanium dioxide (E171) as a food additive in the EU, starting with a six-month phasing out period from Feb. 7, 2022, to Aug. 7, 2022, after which a full ban applied.

Regulatory agencies allow for manufacturing materials such as genome editing materials, the generation of iPS cells, and the subsequent selection process under principles of GMP or GMP-like operation instead of full GMP compliance. This article explains how to implement GMP principles in non-GMP settings, also known as GMP-like, and the quality oversight required for implementation.

Methods • Testing

Video

Guidances • Regulatory

The purpose of stability testing is to provide evidence on how the quality of a drug product varies with time under the influence of a variety of environmental factors, such as temperature, humidity, and light, shelf life for the drug product and recommended storage conditions. In cases where in-use testing is required then this best practice provides examples of how to conduct the testing. The purpose of an in-use stability study is to establish the period of time during which multi-dose products can be safely and effectively used after opening and still comply with critical quality attributes (shelf-life specifications). In-use stability is generally applicable to aqueous preparations; however, some regulatory agencies are now requesting in-use stability data for all other dosage forms, e.g., topical creams/ointments, solid dose tablets/capsules in multi-dose packaging.

Best Practices • Study Design

Conducting stability studies is a critical aspect of the drug development process, as the information gained determines key clinical development decisions and becomes an essential component of the submission package required by regulatory authorities globally. For any biological therapy, there is a set of attributes that is critical to maintaining the product’s safety and efficacy; the purpose of stability studies is to analyze these attributes at predetermined timepoints during the study to understand how they may be impacted by storage in different environmental conditions. Through understanding the links between storage and product degradation that may give rise to loss of biological activity, possible toxicity or unwanted immunogenicity that pose potential risk to patient health, stability studies generate the data necessary to specify the storage conditions required to maintain product quality and safety and justify the shelf life and expiration dates for your biological product.

Chambers • Qualification

Determining the appropriate requalification interval and testing approach used on GMP Controlled Temperature Units depends on numerous factors. The Code of Federal Regulations Title 21 §211.68(a) states that: “Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.” The “shall be routinely... checked...to assure proper performance” part of that statement clarifies that CTUs do require more than an initial qualification and expects that a lifecycle approach is implemented to maintain compliance.

Closure Integrity • Packaging

Container closure integrity (CCI) is fundamental for maintaining the sterility and stability of sterile injectable products. Regulators are therefore requiring the execution of robust CCI studies that generate data throughout the product life cycle. This will support the choice of appropriate primary packaging components, help qualify the process to fill and assemble container systems with good CCI, and help demonstrate the maintenance of CCI during transport & storage as well as over shelf life. Regulatory guidance revisions on the topic of CCI include a United States Pharmacopeia (USP) chapter implemented at the end of 2016, USP , the ongoing revision of the EU Annex 1, as well as new guidance from the regulators in China and Japan. Robust studies generating science-based CCI data to help meet these new guidances require appropriate CCI test (CCIT) methods. The language used in the slides presented in Figure 1 is an example of how regulators are asking for improved CCI test methods. The methods should be specific for the product-container closure system and should preferably move away from the traditional probabilistic tests to deterministic ones which generate analytical data and can be validated for detecting critical leaks.

Methods • Testing

The MFI system is an orthogonal technique to light obscuration and membrane microscopy for the analysis of SVPs, which are crucial in formulation development and stability studies. By letting you get information on particle size, distribution, shape, and classification on several morphological parameters, MFI lets you make informed decisions on the stability and purity of your AAV-based gene therapeutics.