Biologics

CDMO

Process Development

Q4 2016

Regulatory

<p>In the rapidly growing but highly competitive biopharmaceutical market, drug innovators require the support of biologics contract manufacturers that offer more than just additional capacity. They must be financially stable, have an in-depth understanding of market needs and regulatory requirements, manufacturing expertise for right-first-time project implementation and a commitment to continuous improvement across all activities.</p>
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<h4>Growing market</h4>
<p>In 2015, according to BioPlan Associates the market for biopharmaceuticals was valued at $200 billion and growing at ~14% annually.<sup>1</sup> Ten to 15 new biologic treatments are expected to receive approval each year, and the top products already on the market have annual sales of over $2 billion.<sup>2</sup> Notably, 66% of the (bio)pharma professionals responding to the 2016 Nice Insight CDMO Outsourcing Survey (n=587) indicated that their current and future product pipelines include large-molecule new biological entities (NBEs). In addition, 75% to 80% of survey respondents have biologic candidates under evaluation at each phase of development from discovery through Phase IV/post-launch.<sup>3</sup></p>
<p>Given the healthy state of the biologic drug market, it is not surprising that the biopharmaceutical contract manufacturing market is also experiencing strong growth. The value of the market in 2015 was estimated by HighTech Business Decisions (HBD) to be $3 billion. HBD also predicted that biopharmaceutical contract manufacturers would increase mammalian cell culture production capacity by 14% and microbial fermentation production capacity by 16% by the end of 2016.<sup>4</sup>&nbsp;</p>
<p>As strong growth in the biopharmaceutical market continues, both innovator companies and contract development and manufacturing organizations (CDMOs) are being affected by three key trends: increasing concentrations for cell-culture and fermentation processes, which is creating the opportunity to adopt smaller-volume, single-use equipment and placing pressure on downstream processing systems; the need for increased capacity, which is driving significant investments in facilities and equipment; and a shift to parenteral formulations, which is creating demand for sterile fill/finish technologies and expertise.</p>
<h4>Challenging environment</h4>
<p>Despite the rapid growth of the market and the trends outlined above, changing market dynamics are creating challenges for sponsor companies and their contract service providers. With blockbusters being replaced by targeted/personalized medicines (e.g., antibody-drug conjugates and cell therapies), new approval pathways for biosimilars and growing expectations for treatments that provide improved outcomes over existing products at lower cost (i.e., value- or evidence-based medicine), there is more pressure than ever to be first to market. State-of-the-art manufacturing capabilities that are more efficient, more scalable and more cost-effective increasingly play a role in the ability of drug manufacturers to get life-changing treatments to patients.</p>
<h4>Need for reliable outsourcing partners</h4>
<p>While reducing costs was initially the key driver for outsourcing of biopharmaceutical manufacturing, today there are many reasons why biologic drug makers seek support from CDMOs. Improving quality, in fact, is the top goal, according to participants in the 2016 Nice Insight CDMO Outsourcing Survey.<sup>3</sup> Reducing cost is of fourth importance after reducing time to market and increasing efficiency. Sponsor companies also hope to leverage contractor regulatory expertise, gain competitive advantage and access specialized technical and operational expertise.</p>
<p>Many of those goals can only be achieved through close collaboration with a reliable outsourcing partner — the type of collaboration that requires real commitment by both parties and results in long-term strategic partnerships. Operational, methodological and therapeutic expertise combined with a strong quality record and positive regulatory history will lead to a successful relationship or outcome. A demonstrated ability to meet project deadlines and clear commercialization successes that include delivery of product on or ahead of schedule and at or under budget are essential for CDMOs desiring to participate in such relationships.</p>
<p>Good communication skills, a thorough understanding of customer requirements, knowledgeable and professional experts, transparency and a willingness to go beyond contract specifications also facilitate strategic partnerships. Successful CDMOs collaborate closely with biopharmaceutical manufacturers and continually share information through open lines of communication, allowing for the identification and resolution of any problems before they become serious.</p>
<p>All of these characteristics enable CDMOs to help their biopharmaceutical customers reduce the risk of outsourcing and simultaneously achieve their other goals. Financial stability, which has become increasingly important as a risk mitigation factor due to the turbulent conditions in the pharmaceutical market, is also vital.&nbsp;</p>
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<h4 class="callout-title">“Right first time” technology transfer, whether of an established process from a customer facility to the CDMO or from the process development lab to the production facility within the CDMO, is a crucial capability for competitive biopharmaceutical contract service providers.</h4>
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<h4>Providing capacity is insufficient</h4>
<p>An integrated CDMO that is part of a world-leading pharmaceutical firm also has the ability to provide efficient and effective process and analytical method <br /> development support, both of which are essential for achieving cost-effective, robust biopharmaceutical manufacturing operations. Processes designed with scale-up to commercial volumes in mind enable much smoother technology transfer, reduced manufacturing issues, higher product quality, lower processing costs and faster time to market.</p>
<p>“Right first time” technology transfer, whether of an established process from a customer facility to the CDMO or from the process development lab to the production facility within the CDMO, is a crucial capability for competitive biopharmaceutical contract service providers.</p>
<p>Process development begins with the expression system and continues through to biologic drug substance release, covering all of the upstream and downstream unit operations that lie in between, plus analytical and cleaning method development and validation. True biopharmaceutical CDMOs can support their clients across the entire gamut of process development activities, including cell line development and banking, scale-down, process characterization utilizing design space mapping via design of experiment (DoE) approaches, process optimization, and viral clearance studies and toxicology lot manufacture — in addition to scale-up, tech transfer, GMP manufacture and validation.</p>
<h4><strong>Conclusion</strong></h4>
<p>GSK’s focus is to deliver more products of value, both as a CDMO supporting our biopharma partners and as a world-leading drug manufacturer. The ultimate goal is to provide novel medicines to patients in need. For instance, through our agreement with Verily Life Sciences (formerly Google Life Sciences) to form Galvani Bioelectronics, we will be developing and commercializing bioelectronic medicines. We have also recently introduced several new monoclonal antibody drugs, including Benlysta (belimumab) for the treatment of active systemic lupus erythematosus (SLE or lupus), the first lupus treatment approved by the FDA in over 50 years; Nucala (mepolizumab), an add-on maintenance treatment for severe asthma; and Sirukumab (INN, USAN) for the treatment of severely active rheumatoid arthritis (RA). In Europe, GSK will also be offering Strimvelis, a first outright gene-therapy-based cure for a rare disorder, specifically ADA-SCID, a sometimes-fatal inability in children to fight infections.</p>
<p>GSK continues to invest in high-quality manufacturing. At the Upper Merion facility outside of Philadelphia, GSK is expanding its cell-culture production capabilities at the 5000 L scale to support late-phase clinical and commercial production. These investments will enable GSK to continue to accommodate the strong organic growth that the biopharma sector is experiencing.</p>
<p>These examples highlight the depth of GSK’s commitment and expertise in the development and commercialization of novel biotherapies. As a CDMO that operates as an independent group within a large pharmaceutical company, GlaxoSmithKline Biopharmaceuticals’ goal is to utilize this extensive knowledge and our global manufacturing network in order to serve as a reliable partner that delivers more products of value through world-class manufacturing and thus contributing to exceptional treatment outcomes for patients.&nbsp;&nbsp;</p>
<h4>References</h4>
<ol>
<li>BioPlan Associates Inc. “Top 15 Trends in Biopharmaceutical Manufacturing.” Contract Pharma. 11 Sept. 2015. Web.</li>
<li>Otto, Ralf, Alberto Santagostino, Ulf Schrader. “Rapid growth in Biopharma: Challenges and Opportunities.” McKinsey&amp;Company. Dec. 2014. Web.</li>
<li>The 2016 Nice Insight Contract Development &amp; Manufacturing Survey.</li>
<li>Downey, William. “Biopharmaceutical Contract Manufacturing Capacity Expansions.” Contract Pharma. 2 June 2015. Web.</li>
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Achieving Successful Treatment Outcomes Through the Delivery of Manufacturing Services