Regulatory Affairs

Rapid Pharmaceutical Product Development

    A Chemistry, Manufacturing, and Controls (CMC) Strategy Forum was held in January 2012 in San Francisco, CA, to examine the topic of rapid pharmaceutical product development. The purpose of this meeting was to promote an understanding of how best to increase the speed of product development, focusing on areas that improve chances of regulatory success while lessening the time it takes to get a product through development and onto the market. Participants also sought to identify and discuss…

A Framework for Process Knowledge Management

    Process development and manufacturing for biopharmaceuticals are often disjointed activities. Disconnects between groups within an organization can be aggravated by a lack of common terminology and poor data-management practices. Implementing a simple data model based on the ISA-88 standard for batch control can help companies capture process and facility data throughout their product life cycle (1). The first half of this two-part article illustrates how translating a process description to a structured electronic format could transform the bioprocessing…

Encouraging In-House Disclosures In a Whistleblower’s World

    Compliance officials have a great deal to worry about. They are judged by results and loaded with stress over the latest changes in government guidance documents and internal budget pressures. They need to continually update their programs to stay abreast of those developments, including revisions that target in-house processes to encourage disclosures from whistleblowers. Failure to provide for such revisions places both a company and individuals at risk   Whistleblower Protection Expanded and Includes Rewards   In response…

Participating in the Rx-360 Pilot Joint Audit Program

    The Rx-360 consortium has had a profoundly positive impact on pharmaceutical manufacturers and their suppliers. As an international, nonprofit, pharmaceutical supply chain group (established in 2009), its mission is to “create and monitor a global quality system that meets the expectations of industry and regulators that assures patient safety by enhancing product quality and authenticity throughout the supply chain” (1). The list of consortium members (www.rx-360.org/Membership/ListofMembers/tabid/71/Default.aspx) is diverse and presently includes both pharmaceutical manufacturers and suppliers (24 and…

Creating a Corporate Compliance Program

    Regulatory compliance is an evolving concept that must be flexible enough to adapt to both a company’s unique business climate and to changing regulatory circumstances. Although standard operating procedures (SOPs) are a compliance tool and can and should be strongly recommended, they cannot become the end of a process. Compliance is not a set of standards or procedures that sit on a shelf until something goes wrong. Instead, compliance requires thought in creating a code of conduct and…

QbD for Biologics: Learning from the Product Development and Realization (A-MAb) Case Study and the FDA OBP Pilot Program

    Cosponsored by CASSS (an international separation society) and the FDA, the 23rd CMC Strategy Forum was held in Bethesda, MD, on 19–20 July 2010. For the third time, this forum explored the topic of quality by design (QbD) for biologics. The first such forum was held in July 2007 and focused on establishing a general understanding of QbD terminology and concepts. In July 2008, the second discussed approaches for submission of QbD data and associated regulatory implications. Building…

Looking at the Recent FDA Biosimilar Guidelines

Small-molecule treatments are invaluable in providing symptomatic benefits for an array of illnesses. However, many serious conditions — ranging from cancer to autoimmune disorders — respond better to more sophisticated complex drugs such as therapeutic biologics and nonbiologic complex drugs (NBCDs). The latter are medicinal, nonbiological products in which the active substance is not a homomolecular structure, but rather consists of a number of different (closely related) structures that cannot be fully characterized. The US Food and Drug Administration (FDA)…

Spotting, Tracking, and Predicting Inspection Trends

    Compliant companies, to paraphrase Tolstoy, are all alike. Every noncompliant company seems to find its own way to fall short of compliance with good manufacturing practice (GMP) and come, as did the writer’s famous heroine Anna Karenina, to grief. One commonality of compliant firms is that most seem to have excellent self-auditing/self-inspection programs. Indeed, many inspectors say that a primary predictor of a compliant company is a rigorous self-inspection program. Such a program is appropriately focused, adequately resourced,…

Expansion of the Prior-User Rights Defense

A common reaction to some patents directed to manufacturing processes (especially of biotherapeutics) is “How did they get a patent for that when we’ve been doing the same thing for years?” But the number of patents covering biotherapeutic production processes is steadily increasing along with the realization that upstream and downstream processing events provide a potentially abundant source of so-called “second-generation” patent protection for biologics, especially those facing biosimilar competition. Although some groups are prolific patent filers claiming a wide…

Biopharmaceutical and Medical Device Compliance

Off-label marketing occurs when doctors prescribe a drug or device for a use that has not received FDA approval (1). Physicians have the unfettered right to prescribe the best drugs or devices for their patients, including approved drugs and devices for unapproved uses. Pharmaceutical and medical device manufacturers, however, cannot promote their products for such uses — even if those are supported in medical literature. Companies cross the line when their sales representatives sell physicians on the idea of using…