Regulatory Affairs

Cell Culture Media: An Active Pharmaceutical Ingredient or Ancillary Material?

Cell-based therapies are used to treat diseases that require the replacement of diseased, dysfunctional, and injured cells (1). To produce these therapies, a wide range of reagents and materials such as antibodies, growth factors, and enzymes are used in their manufacturing processes. Such necessary materials are administered through a cell culture medium. Active pharmaceutical ingredients (APIs) are the main ingredients that make products therapeutic. Ancillary materials (AMs) and raw materials (RMs) are essential components used during production but are not…

Trends in Chemistry, Manufacturing, and Controls: Next-Generation Technologies and Product Modalities

New technologies bring new regulatory challenges. The biopharmaceutical industry must be cautious in its implementation of new scientific ideas and technology platforms — no matter how promising those might be. Regulators will look skeptically on any claim that isn’t backed up by good data, and with no solid history of successful use to build on, a company must have all the answers itself. How do compliance professionals anticipate what kinds of questions reviewers will ask when the time comes —…

Seamless Transition from R&D to Manufacturing

Fast and cheap: These criteria are becoming ever more urgent drivers for manufacturers of biologics, faced with increased scrutiny on the costs of developing novel drugs, the lengthy timelines for delivering these drugs to patients, and the tightening competition to capitalize on new targets. The challenge for manufacturers is further heightened by the expectations to deliver on quality as well. Although development and production of molecules such as monoclonal antibodies (MAbs) have greatly benefited from the “platformization” of core technologies…

Methods on the Move: Addressing Method Transfer Challenges for the Biopharmaceutical Industry

Analytical method transfers are essential components of the current global biotechnology environment. Analytical method transfer can be defined as “a documented process that qualifies a laboratory (the receiving laboratory) to use a validated analytical test procedure that originated in another laboratory (sending laboratory), thus ensuring that the receiving laboratory has the procedural knowledge and ability to perform the transferred analytical procedure as intended” (1). The goal is to ensure that a method continues to perform in the validated state regardless…

Innovators and Biosimilar Companies: Experts Predict Intense Conflicts Ahead

CPhI Worldwide (organized by UBM) announced last fall the final section findings of the fifth edition of the CPhI Annual Report. Presented live at the meeting in Frankfurt, Germany, the report is now available online. It highlights immediate and long-term trends in pharmaceutical data, regulation, generics, and biosimilars. Four experts gave their views. They warned that the US Food and Drug Administration’s (FDA) approach to achieving six-sigma (nearly perfect or 99.9997% defect-free) quality is failing in respect to the pharmaceutical…

Sourcing Clinical-Grade Human Tissue: Considerations for Supporting Cell Therapy Development and Production

The rapidly developing global cell therapy market poses numerous industry challenges for drug development, process scalability, commercialization, and patient safety. The processes of procuring donated human tissue for clinical applications are fraught with many technical, ethical, and legal issues. Allogeneic cell therapies involving primary cell types such as bone marrow mesenchymal stromal/stem cells (BM-MSCs), hematopoietic stem and progenitor cells (HSPCs), and T and natural killer (NK) cells for immunotherapy applications are especially challenging because of the vigorous process of screening…

Back to Basics for Biotech: Driving a Culture of Quality and Compliance with Practical Communication Techniques

The robust regulatory environment surrounding biotechnology and bioprocessing demands a comprehensive current good manufacturing practice (CGMP) culture of quality, compliance, and absolute adherence to policy. Employees need to be engaged in their work, with a laser focus on meeting stringent specifications and operating under tight controls. A misstep in quality or compliance can lead to hefty fines, legal concerns, regulatory retaliation, and reputational damage. Communication and stakeholder engagement are critical to aligning organizations and driving the right culture in highly…

Beyond Compliance: Serialization Has More to Offer

As the global pharmaceutical industry implements serialization (track and trace from manufacturing to dispensing) to meet governmental regulatory requirements, other opportunities arise for drug companies. The main driver here is to improve the integrity of the overall drug supply chain, but other meaningful business benefits can come from serialization. Generally accomplished through automated, electronic means, it involves such practices as recording, authenticating, maintaining, and sharing accurate records of products. Outside-the-Box Benefits In addition to tightening up the supply chain and…

Postapproval CMC Changes: Increasingly a Fact of Biopharmaceutical Life

The manufacture of vaccines and therapeutic proteins has suffered from a reputation of being part art and part science, with heavy doses of regulatory uncertainty thrown in. Postapproval changes (PACs) to chemistry, manufacturing, and controls (CMC) were initiated reluctantly and carefully in the era of “the process is the product.” Today, CMC PACs are a normal part of the biopharmaceutical industry business. Emma Ramnarine (head of global biologics quality control at Hoffmann-La Roche in South San Francisco, CA) notes that…

eBook: Challenges Facing Biosimilar Entries into US Markets

Since the 2009 enactment of the Biologics Price Competition and Innovation Act (BPCIA) (1), the US Food and Drug Administration (FDA) has licensed six biosimilar products under PHS 351(k) and approved one product under FD&C 505 (b)(2). It also provided complete response letters (CRLs) to four biologics license application (BLA) filings (Table 1) (2). By comparison, the European Medicines Agency (EMA) has approved 31 biosimilar products (3) and refused or withdrawn about five. There is no doubt that US market…