Archive for the 'Manufacturing' Category

Meeting Technical and Regulatory Requirements for Organic Impurity Control and Analysis

Patricia Van Arnum PharmTech editorProduct quality is of paramount importance to pharmaceutical manufacturers, and implementing a strategy for impurity control is crucial. Organic impurities cover a wide spectrum of compounds that have varying structures, behaviors, and characteristics. Organic impurities can result from the manufacturing process, storage conditions, or degradation resulting from light, heat, and other external factors. Deciding what technology or analytical methods to use to detect and measure organic impurities is a challenge. Pharmaceutical Technology will hold a live educational webcast, “Meeting Regulatory and Technical Requirements for Organic Impurity Analysis, on Tuesday Sept. 24 at 11:00 AM EDT to 12:00 PM EDT to provide insight on the regulatory, compendial, and ICH requirements for organic impurity control and analysis as well as best practices in analytical method development, method selection, and method validation for detecting and quantifying organic impurities in drug substances and drug products.

The panelists for the webcast will be: Timothy Watson, PhD, and research fellow in the GCMC Advisory Office at Pfizer and a member of the PhRMA Expert Working Group on the ICH Q11 regulatory guidance document for drug substances; Mark Argentine, PhD, senior research advisor, analytical sciences R&D with Eli Lilly; and Hildegard Bruemmer, PhD, operational laboratory manager, SGS Life Science Services, Berlin. The panelists will provide insight on the regulatory and compendial requirements for organic impurity control and analysis in drug substances and drug products. They will also share insight on selecting the appropriate analytical methods for the detection, analysis, and quantification of organic impurities and offer related case studies on how best to ensure product quality.

Audience members may ask questions of the panelists during the live webcast. Information on how to register for the webcast, “Meeting Regulatory and Technical Requirements for Organic Impurity Analysis” for Tuesday Sept. 24 at 11:00 AM EDT to 12:00 PM EDT and for on-demand viewing is available here.

Examining Containment Strategies in High-Potency Manufacturing

With the increasing use of high-potency APIs, it is more important than ever to have an appropriate containment strategy to protect both the quality of your product and the safety of your personnel. Many important questions should be asked. Have you considered environmental, health, and safety (EH&S) issues early in your product development process? What are OELs and how should you evaluate industrial hygiene exposure? How can you prevent exposure? What elements are crucial for containment?

To examine these questions and others, Pharmaceutical Technology will host a complimentary, educational, live webcast, Containment Strategies in High-Potency Manufacturing, on Thursday, September 12 at 11:00 AM EDT. This 30-minute webcast will focus on current best practices and strategies for containment in high-potency manufacturing.

The webcast will be presented by John Farris, a Certified Industrial Hygienist and president & CEO of SafeBridge Consultants.  John is a recognized expert in the safe handling of potent pharmaceutical compounds.

Audience members will be able to ask questions for additional insight during the live webcast on Thursday, September 12. Additional information and registration for the live webcast and on-demand viewing may be found at

True Pharma Innovation Lies in Quality, not Quantity, of Approvals, say FDA Analysts

We’re already embroiled in the annual speculation game about whether FDA approvals this year will keep pace with last year’s near-record of 39 new molecular entities (NMEs) brought to market. The tally is closely watched as a sign of the state of biopharmaceutical innovation and the health of the pharmaceutical industry and biomedical research enterprise.

But this focus on the quantity of new drug approvals is misleading, according to FDA analysts, because it fails to distinguish between truly innovative new therapies and those that are similar to medicines already on the market, explains Mike Lanthier, operations research analyst on the economics staff of FDA’s Office of Planning. While all NMEs offer some therapeutic advantage, those that are “first-in-class” and “advance-in-class” medicines represent important advances, he explains. Alternatively, “addition-to-class” therapies may provide useful options for patients, but not substantial advances over existing products. And it is this last category that has experienced the much-hyped decline in approvals in recent years, while more vital therapies are holding steady or increasing in number, Lanthier points out in an FDA Voice blog posted Aug. 6, 2013. This “more nuanced and informative” assessment of NME categories thus refutes fears of an “innovation gap” that threatens drug discovery.

One factor may be a rise in small biopharma companies developing more innovative drugs, while large drug companies have focused on refining blockbuster drugs for large patient populations. NMEs from small companies have increased notably since 1996 and now account for 50% of approvals, compared to roughly one-third in the past, Lanthier and colleagues explain more fully in an article in the August 2013 issue of Health Affairs.

FDA initiatives also may support these developments. Most innovative NMEs have benefited from priority review treatment, and the new breakthrough drug program and added incentives for new antibiotics and pediatric treatments promise to expedite the development of innovative therapies. It’s also possible, the authors say, that the increased influence of large pharmacy benefit management firms reduces reimbursement for pricey drugs that lack proven benefits.

Another measure of biopharma innovation may be the number of new drug applications filed with FDA, although the quantity-over-quality measure also may apply here.

Risk-Mitigation Strategies in Drug Manufacturing for Emerging Markets

Patricia Van Arnum PharmTech editorRisk and reward. It is a balance that has to be achieved in any business endeavor and is of utmost importance for pharmaceutical and biopharmaceutical companies managing their growth and manufacturing in emerging markets. Emerging markets are a crucial part of pharmaceutical companies’ growth strategies, but in serving those markets, pharmaceutical and biopharmaceutical manufacturers must align that strategy with partners that can facilitate access to local markets, manage complex supply chains, meet global and national regulatory standards for quality, and secure production for local as well as established markets in North America and Western Europe. Read more »

Quality Focus: Ensuring Raw Material Transparency

Patricia Van Arnum PharmTech editor Quality is of utmost importance in drug development and manufacturing. The increased globalization of the pharmaceutical and biopharmaceutical industries, resulting in more complex and elongated supply chains on a raw material and ingredients basis, obligates suppliers and pharmaceutical and biopharmaceutical companies to develop ways to achieve greater transparency and understanding of those supply chains to ensure product quality and regulatory compliance.  Read more »

Manufacturers Seek Strategies for Life-Cycle Approach to Process Validation

The US Food and Drug Administration and industry have been working to incorporate process validation as an integral component of drug development and production, and to avoid divergent policies in the US and Europe. A good deal of progress has been made in this area, but manufacturers continue to feel uncertain about the details in revising existing systems and updating long-held practices to fit new approaches, as seen in the discussion at the PDA/FDA Process Validation Workshop in Bethesda, Md., May 20-21. Participants assessed FDA’s Process Validation guidance, which was published in January 2011, and the corresponding PDA technical report on “A Lifecycle Approach to Process Validation” (TR 60) issued in January 2013 [available at].

The aim is to help manufacturers who are wrestling with and working to implement the FDA guidance, explained Harold Baseman, chief operating office of ValSource and co-chair of the PDA process validation interest group. The workshop program followed FDA’s three stages for process validation, starting with process design and moving through process qualification to achieve continued process validation to provide ongoing assurance that a production process remains in a state of control.

Workshop attendees discussed the importance of gaining extensive knowledge about a process early in design and development stages to ensure that the system is well controlled. Patrick Swan, deputy director of the Division of Monoclonal Antibodies, Office of Biotechnology Products (OBP) in the Center for Drug Evaluation and Research (CDER), highlighted the value of tapping prior knowledge to support process validation activities, noting that this may expedite product development for lifesaving breakthrough therapies.
Process qualification involves identifying and interpreting information from process design functions to establish testing and acceptance criteria. Methods for equipment and facility assessment are important, as are sound process qualification sampling plans.

The lifecycle approach also involves linking process validation activities to a manufacturer’s Quality Risk Management system. While manufacturers and regulators are looking to shift away from assessing a set number of batches, questions remain about how much data is needed to show that something is or is not in control, Baseman explained.

Similar efforts by the European Medicines Agency (EMA) to update policies on these issues were discussed, with an emphasis on the importance of achieving similar approaches to validation requirements. Concerns were raised that EMA doesn’t consider process development part of process validation, that different terms are emerging, and that divergent regulatory approaches may cause confusion. Manufacturers filing applications in some 150 countries emphasized the importance of common formats and systems.

OBP deputy director Jeffrey Baker explained that FDA and EMA officials discuss these and other issues at “cluster meetings,” held to address topics such as biosimilar evaluation, good manufacturing practices and differences in review policies. Regulatory authorities at these sessions don’t consider specific companies or applications, Baker noted, but address general policy approaches, with an eye to gaining alignment on regulatory guidance.

Baker and others suggested that questions about data collection and regulatory requirements can be addressed by focusing on the science, which is key to appropriate terminology, data formats and determining what information is needed to assure product quality.

Yet, legacy products raise challenges, as manufacturers have to determine what would be involved in updating process validation data to support manufacturing changes or address safety issues.

One benefit of revised process validation policy that reduces the volume of unnecessary testing is to streamline the development and approval of important, life-saving therapies. Future FDA guidance on its regulatory approach to “breakthrough” therapies should explain further how the agency will address manufacturing and quality assurance issues for such products, Baker noted. But he pointed out that companies request the breakthrough designation and thus should be able to explain how they will supply a quality product efficiently and quickly for sick patients.

PharmTech Webcast: QbD in Solid Dosage

Patricia Van Arnum PharmTech editor Quality by Design (QbD) is changing drug development and manufacturing. The science- and risk-based approach inherent in a QbD paradigm increases process understanding and leads to better drug development and manufacturing. Sharing lessons learned and strategies for applying QbD in solid dosage development and manufacturing is valuable. Pharmaceutical Technology will address this topic in a webcast,A Pragmatic Application of QbD: Turning Theory into Tangible Success” this Thursday May 2 from 11:00 to 12:00 PM EST.

Two industry experts will share their experience with QbD and offer insight into how the practical application of QbD contributed to the success of their projects. Through several case studies, these experts will provide lessons learned and advice on the measures they took that enabled the success of their projects; steps that can be universally applied to other projects.

Don Barbieri, associate director of formulation and process development at Patheon, will present case studies demonstrating different aspects of the QbD approach, including identifying CQAs (critical quality attributes) and CPPs (critical process parameters) as well as how to perform risk assessment, incorporate risk mitigation into a process, and how to develop a design of experiments (DoE).

David Smith, pharmaceutical specialist, formulation and process development at Patheon, will present a case study where the pragmatic application of QbD enabled a successful technology transfer of a film-coated tablet from Phase III to commercial scale.

Further information, including how to register for the complimentary webcast, may be found  here.

Efficient Equipment Displayed at INTERPHEX

As I visited the exhibits and attended the conference sessions at INTERPHEX 2013 last week, I noticed a focus on equipment flexibility and ease-of-cleaning and changeover that enables manufacturing efficiency. Read more »

EC Releases Revisions of GMP Guidelines

The European Commission (EC) has released the draft revision for four chapters of its good manufacturing practice (GMP) guidelines—chapters 3, 5, 6 and 8.  A public consultation was launched earlier this year with comments due on 18 July 2013. The EC stated that these revisions were needed to reflect the latest thinking relating to best practices. Read more »

The Next Horizon: Single-Use Technologies for Finished Drug Product Manufacturing

Patricia Van Arnum PharmTech editor Biopharmaceutical production is an often discussed application for single-use technologies, but single-use technologies also have application for small-scale finished drug-product manufacturing for producing clinical-trial materials. An educational webcast by Pharmaceutical Technology, “Accelerate Sterile and Non-Sterile Clinical Trial Manufacturing with Single-Use Technologies,” on Wednesday Mar. 6th examines this application. Read more »

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