A Look Ahead at Manufacturing and Regulation - Pharmaceutical Technology

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PharmTech Europe

A Look Ahead at Manufacturing and Regulation
FDA talks about the changing scope of regulatory science and its effect on drug reviews, site inspections, overall approaches.

Pharmaceutical Technology Europe

Microbial contamination

PTE: Priority 3 of the August 2011 strategic plan calls for reducing microbial contamination of medical products. What specific goals does FDA have in this area?

FDA: FDA has attempted to identify and study specific gaps in pharmaceutical manufacturing. Studies are ongoing on sterilising filtration, effects of terminal- sterilisation energies on classes of products, and methods for detection of elusive microorganisms in drug components and manufacturing environments.

Filtration studies have included microbial penetration rates based on the cell's size and filter matrix composition as well as penetration due to time on various filters with two sizes of growing microorganisms. The goal of these studies is to improve filter-validation studies that previously were shown to have vulnerabilities. Future steps in the research will look into solution conditions that encourage miniaturisation of the cells, neutralise cells or filter surface charges that enhance cell entrapment on filter membranes.

Many products are manufactured using aseptic processing, which may be less effective than terminal sterilisation. Some other surgical products are not manufactured to be sterile at all, also posing risk. Each of these situations is the result of risk assessments that are based on the nature of the product and its vulnerability to sterilising energy or other conditions. FDA and NIPTE [National Institute for Pharmaceutical Technology and Education] have initiated studies of products (the initial focus is surgical antiseptics) to assess the effects of sterilising energy on selected products. The goal of these studies is to define conditions that may allow manufacturing to use processes intended to produce a sterile product, which is safer for use in surgical procedures.

Nonsterile products often require a demonstration that microorganisms, normally expected to be in the product, will not grow or are killed. A similar demonstration is expected of sterile products that may be used several times (e.g., multidose vials). However, there exist microbial strains that can resist preservatives used to control contamination and some of these strains even grow in the presence of the antimicrobial agents. If allowed to grow, large numbers of microorganisms may reach a potentially infectious dose upon exposure to patients. Among these species are common water bacteria that CDC [Centres for Disease Control and Prevention] have shown to be difficult to detect using compendial methods. In collaboration with CDC and with help from the University of Michigan [US], we are examining culture methods for recovering these organisms from pharmaceutical water and products. Alternative technologies for their detection are also being considered. The goal of these studies is the development of methods to reliably detect these potential contaminants.

Role of CERSIs

PTE: One way to improve regulatory science (from a drug review standpoint) is to work with the industry directly to identify and fill in scientific and technological gaps that exist across drug development and manufacturing. FDA has created a few grant-based CERSIs, specifically with Georgetown University (GU) [US], the University of Maryland (UMD) [US], and the State of Arkansas [US]. Will the agency be opening any additional centres of excellence?

FDA: We hope in future to fund one to two additional CERSIs, outside the region, but if and when depends on availability of funding.

PTE: Can you comment on the staff training workshops held to date with these centres and their benefit to agency reviewers?

FDA: Agency reviewers have had the opportunity to participate in training events sponsored by both UMD and GU CERSIs. These events have provided continuing medical education to staff and opportunities to network with leading researchers from around the country [US]. Additionally, agency reviewers have also had the opportunity to maintain their scientific and medical skills by participating in clinical work, research or teaching opportunities at UMD and GU CERSI.

Advancing regulatory science

PTE: Section 1124 of FDASIA states that the US HHS Secretary should have a strategy and implementation plan 'for advancing regulatory science for medical products in order to promote the public health and advance innovation in regulatory decision-making' by July 2013. What is FDA's role?

FDA: FDA is taking the lead in developing the Strategy and Implementation Plan for Medical Products, as required in Section 1124 of FDASIA.

PTE: Are any additional major goals expected beyond FDA's current strategic plan surrounding regulatory science?

FDA: No, FDA expects to stay within the framework outlined in the Strategic Plan for Regulatory Science. The major areas of focus outlined in the Strategic Plan for Regulatory Science identify broad areas where advances in regulatory science are needed and are thus quite comprehensive. It is expected that the annual progress reports, which will follow in 2014 and 2016, will include more detailed information on specific accomplishments related to regulatory science.


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