Regulatory Affairs

Biopharmaceutical and Medical Device Compliance

Almost every aspect of the biopharmaceutical and medical device industries raises regulatory compliance concerns. Heightened scrutiny is required across product lifecycles — from clinical trials to manufacturing, pricing, formulary placement, and promotional practices. Those areas (as well as patient privacy and adverse event reporting) require close attention to and compliance with healthcare laws, regulations, and guidelines. Part 1 of this two-part article describes statutes, regulations, and guidances applicable to the biopharmaceutical and medical device industries. Anti-Kickback and False Claim Laws…

An Industry Perspective on Quality By Design

The US FDA’s quality by design (QbD) initiative and associated ICH Q8, Q9, and Q10 guidance documents are increasingly embraced by the biopharmaceutical manufacturing industry for ensuring consistent product quality and lower costs of development and manufacturing. One critical problem the industry faces involves understanding how to implement QbD and determine the benefit of such projects — which require the work of many groups across quality, manufacturing sciences, and engineering departments. Here we present the results from a survey of…

Meeting Regulatory Challenges for Cell-Based Therapies

    Many companies follow a general rule when assembling regulatory packages for presenting new biologics: Accentuate the aspects of your new biologic that mimic approved therapies. For companies working on cell-based therapies, however, that is a challenging task. The industry lacks established models, and the current European Medicines Agency (EMA) regulatory definition of a cell-based therapy is simply “an advanced therapy medicinal product” (ATMP) (see EMA guidance box). Regulations for cell therapies cannot always be compared directly with those…

Current Issues in Assuring Virological Safety of Biopharmaceuticals

The weakest link in the chain is also the strongest. It can break the chain.— Stanislaw Jerzy Lec, Polish writer, poet and satirist (1906–1966) Biologicals ushered in a new era for treating debilitating and life-threatening illnesses. According to a Pharmaceutical Research and Manufacturers of America (PhRMA) 2011 report, more than 900 biotech medicines and vaccines are in development that are targeting more than 100 diseases (1). Market researchers expect annual sales of biologics (now at about US$100 billion) to grow…

Ensuring Aseptic Processing Through Quality By Design

Assurance of sterility throughout drug manufacturing is paramount to patient safety. Drug products must be free of contamination from microbes, particulates, and chemicals. To that end, we see continued and increased regulatory scrutiny, with adoption of US Food and Drug Administration (FDA) and European Medicines Agency (EMA) standards outside the United States and the European Union. To consistently make microbe-free products, drug manufacturers must implement robust, validated processes that include sterilizing filtration. Sterilizing-grade filtration is used in a number of…

How QbD and the FDA Process Validation Guidance Affect Product Development and Operations, Part 2

    Earlier this year, the FDA issued its long-awaited process validation guidance document, which had been several years in development. It is well written and effectively articulates what many progressive companies have been thinking and doing for years. But many people in the industry are asking questions.   Part 1 of this article described the history of process validation before the FDA’s quality by design (QbD) initiative and discussed QbD in general. It also described the new process validation…

Addressing Image-Based Compliance and Validation Issues

    Review times for 510(k) submissions have increased by >55% since 2005 because of poor-quality submissions by medical device manufacturers, according to a US FDA July 2011 report (1). Such setbacks can debilitate research and development (R&D) budgets of medical device and pharmaceutical companies and significantly affect their return on investment. As the FDA increases scrutiny of submissions, organizations must ensure adequate controls in assessing drug and device efficacy for preclinical animal studies and clinical trials. Doing so lends…

How QbD and the FDA Process Validation Guidance Affect Product Development and Operations, Part 1

    Earlier this year, the FDA issued its long-awaited process validation guidance document, which had been several years in development. It is well written and effectively articulates what many progressive companies have been thinking and doing for years. But many people in the industry are asking questions: How will it affect our process development programs? How will it affect the submissions and licensure of our products? And how will it aid in our commercial operations? Or will it have…

Uniting Small Molecule and Biologic Drug Perspectives

    Cosponsored by CASSS (an international separation science society) and the US Food and Drug Administration (FDA), the January 2010 CMC Strategy Forum explored antibody–drug conjugates (ADCs), which are monoclonal antibodies (MAbs) coupled to cytotoxic agents. The ADC platform of products is being used more and more for clinical evaluation in oncology. More than a dozen companies are developing several types, including products conjugated with calicheamicin, auristatins, and maytansinoids. Such products use the specificity of a MAb to deliver…

Generic Biologics

      The Biologics Price Competition and Innovation (BPCI) Act of 2009 establishes an abbreviated approval pathway for biologic drugs in the United States that are demonstrated to be highly similar (biosimilar) to or interchangeable with biological products licensed by the US Food and Drug Administration (FDA). BPCI was part of the Patient Protection and Affordable Care Act (Act) that was signed into law on 23 March 2010 (1). As the name of the umbrella legislation implies, the legislative…