Publications

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.

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.

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.

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

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.

In mid-October 2023, the WHO published a paper titled Regulatory Considerations on Artificial Intelligence for Health,1 identifying the key principles that international regulatory frameworks for artificial intelligence (AI) should address and are, in fact, starting to coalesce around. The paper was developed in consultation with WHO’s Working Group on Regulatory Considerations (WG-RC) on AI for Health, whose members include regulatory authorities, policy makers, academics, and representatives from industry. The document is intended to serve as a resource for regulators, providing a list of 18 regulatory considerations to address in their emerging regulatory frameworks. It should be noted that the scope of the document extends beyond medical product development and is also intended to inform healthcare delivery.

Best Practices • Shelf-Life

mRNA-based treatments have already shown great promise as a potent therapeutic agent for cancer immunotherapy. As additional mRNA-based cancer immunotherapies vaccines enter clinical development, operational and supply chain challenges must be addressed to reduce turnaround times and COGS. Cell & Gene Chief Editor Erin Harris hosted expert panelists J. Andrew Case, Head of Supply Chain Cell and Gene Therapies at Genentech/Roche and Daniel Getts, CEO & Co-Founder of Myeloid Therapeutics for a breakdown of ways to address uncoordinated and inefficient processes to promote greater stability and immunogenicity.

Methods • Parameters • Protocols • Study Design • Testing

Introduction:

In the absence of definitive guidance on microbial testing in R&D and Marketed Product Stability Programs for Drug Substances and Drug Products, the pharmaceutical industry makes inconsistent and sometimes misguided choices with respect to microbiology. These choices are further confounded by the fact that stability programs are almost always managed by analytical chemists or pharmacists without training and limited experience in the field of microbiology.

This article will review the current regulatory guidance and provide recommendations on the role of microbial testing as stability test parameters, and when other physicochemical tests will be preferred to microbiological tests. To be comprehensive, a product life cycle approach will be taken for drug substances and both sterile and non-sterile drug products.

Best Practices • Testing

Adeno-associated virus (AAV) gene therapies that are designed to deliver a therapeutic transgene to patients are complex products that can be challenging to manufacture. Because of their complexity, a variety of analytical methods are required to ensure that these viral vectors are of high quality and purity, will function as intended, and have batch-to-batch consistency. This requires confirming the vector’s identity, titer, purity, and safety using a variety of analytical methods.

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.