Covid variants fast driving injectables demand

The imminent approval of Omicron-specific vaccines globally and the increasing presence of market approved advanced biologics will drive demand for injectables and will continue to provide lucrative contracts for CMOs beyond 2022.

On August 15, the UK became the first country to approve an Omicron-specific vaccine. The Medicines and Healthcare Products Regulatory Agency (MHRA) conditionally approved Moderna’s bivalent vaccine for use in adults. Moderna’s bivalent Covid-19 vaccine targets both the original version of SARS-CoV-2 and the Omicron BA.1 variant and will be rolled out alongside the original Moderna, Pfizer, and Novavax Covid-19 vaccines as part of the autumn booster program.

Packaging has created bottlenecks in producing injectable drugs, as the industry had lacked capacity to make and fill enough vials in the face of high volumes of Covid-19 vaccine production. But other packaging types are growing in popularity: injectable drug approvals are trending towards self-administrations via auto-injector syringes. Meanwhile, ampoule-packaging facilities are common globally but account for a very small percentage of FDA and EMA innovative approvals as they have largely been replaced in North America and Western Europe, but are still extensively used in emerging markets because of their low cost.

Pfizer’s and Moderna’s Omicron-specific vaccines are in late-stage development or conditionally approved across most of the seven major markets (7MM: the US, France, Germany, Italy, Spain, the UK, and Japan), have demonstrated good efficacy against the Covid-19 variant, and will likely be available to citizens in the developed markets in the autumn to provide an additional booster and increase demand for injectable manufacturing.

Despite the advanced stage of covid-19 vaccination programs in richer countries, which would suggest an approaching drop-off in contract manufacturing demand, there is still considerable need for variant-specific boosters. Once new vaccines for the Omicron variant are approved, they will partly make up for the waning interest in older Covid boosters in developed markets. The Omicron variant spreads more easily than earlier variants of the virus that cause Covid-19, including the Delta variant, and also has the ability to sometimes evade immunity from vaccines, previous infection, or both. The first case of Omicron was announced on November 24, 2021 by South Africa, with the first positive sample dating back to November 9. Vaccines were developed from the original SARS-CoV-2 strain but the variants that exist today are very different.

On June 25, 2022, Pfizer and BioNTech reported pivotal Phase II/III data demonstrating the safety, tolerability, and immunogenicity of two Omicron-adapted vaccine candidates. This data has been shared with regulators, including the FDA, and a request for US emergency use authorization (EUA) is planned. Pfizer completed a submission to the EMA for an Omicron-adapted bivalent COVID-19 vaccine candidate, based on the BA.1 sub-lineage on July 19, 2022.

On July 11, Moderna announced Phase II/III clinical data for its bivalent Omicron booster candidate, named mRNA 1273.214. It is an adapted version of Moderna’s approved Spikevax vaccine. The booster dose elicited a significantly higher neutralizing antibody response against Omicron subvariants BA.4 and BA.5, compared to the currently authorized Moderna booster, regardless of prior infection status or age. On June 27, the EMA started a rolling review for this Omicron-adapted vaccine and the FDA plans to review the vaccine for EUA.

On August 4, the US Department of Health and Human Services declared monkeypox a public health emergency, a move required to grant EUAs. On the same day, the FDA granted an EUA to Bavarian Nordic’s Jynneos vaccine. The drug was already approved for subcutaneous use in adults at risk of monkeypox or smallpox, but the EUA will allow more people to be treated with a smaller dose by giving it to adults intradermally, which requires only one fifth of the volume of a subcutaneous injection.

Advanced biologics are also driving injectables demand. Certain innovative products like cell and gene therapies have a limited pool of staff and expertise that can engage with their production; large CMOs have been acquiring these capabilities in recent years and, even large and mega cap sponsors will require these services. Larger sponsor companies can also choose to dual-source their manufacture (using both in-house and outsourced production) and can use contractors as an additional site in a multi-site supply strategy that increases supply chain security and offers backup capacity. This is especially the case in an age of supply chain disruption caused by the pandemic and the Russia-Ukraine war. Outsourcing may also be pursued if it is more favorable in terms of time and/or cost. Contract packaging of cell and gene therapies also requires specialist capabilities, and contractors manufacturing doses often also provide the packaging as part of an integrated approach.

Increasing self-administration for injectables
The majority of biologics are delivered through intravenous infusion or by subcutaneous injections. Innovative FDA auto-injector products are primarily biologics, and tend towards self-administration and patient-centricity. Injectable CMOs and CPOs with capabilities to manufacture and/or package this class of products and in packaging that allows for self-administration will be at an advantage in the future.

Subcutaneous injectables are far more common in the pipeline than among marketed products. Subcutaneous injections are more readily self-administered compared to intravenous and other types of injectable routes of administration. The number of marketed auto-injector products is currently low, but about half of those have been approved since 2017, indicating the packaging type will gain more popularity in future. Increasing evidence has shown how patients tend to opt for auto-injectors over prefilled syringes or conventional syringes. In the last 10 years, patients’ waiting times for an appointment have sometimes been excessive, and hospital-administered injectables add burden to typically overstretched clinicians. Injections that are self-administered and are as convenient as possible also encourage higher levels of patient compliance, thereby improving treatment outcomes.

Contract packaging leaders by FDA and EMA contracts
In the “Contract Injectable Packaging Trends in the Bio/Pharma Industry” publication, GlobalData assessed packaging contracts for US and EU innovator and biosimilar injectables approved between 2012–21. The top contract packaging organizations for injectables are well-known dedicated CPOs like PCI and Sharp, along with large CMOs such as Patheon, Catalent, and Vetter, which are more renowned for their commercial dose manufacturing but also offer integrated packaging services. Apart from Pfizer CentreOne (the contract manufacturing arm of Pfizer Inc), all the top contract packagers for injectables have a dedicated contract business model.

Since 2016, PCI Pharma Services has acquired manufacturing facilities in North American, EU, and Asia-Pacific markets, and has expanded its packaging business through acquisitions of Sherpa Clinical Packaging, Pharmaceutical Packaging Professionals, Millmount Healthcare, LSNE, and Bellwyck Pharma Services, and has boosted its capacity for packaging. PCI’s 10 commercial packaging and 12 clinical packaging facilities are in the US, UK, Canada, Germany, Ireland, and Australia. These facilities serve the US, EU, and Asia-Pacific markets. A high number of clinical packaging and containment facilities add to the value of the company’s service offering. Clinical packages are typically customized for specific clinical trials and only a small number of batches are produced to meet the need of the clinical trial. Clinical packaging requires specialized capabilities that commercial packagers do not typically possess.

Overall, Thermo Fisher Scientific (Patheon) has 17 sites offering some form of commercial packaging and 32 sites offering some form of clinical packaging. In January 2021, Thermo Fisher Scientific acquired Henogen SA, a provider of contract manufacturing services for vaccines and therapies to biotechnology companies, from Novasep Holding SAS. Henogen has two locations in Seneffe and Gosselies, Belgium. The transaction has allowed Thermo Fisher Scientific to expand global capacity and address growing demand for cell and gene therapy, including viral vectors.

In May 2022, Catalent started investing $350 million in biologics API and dose manufacturing at its facility in Bloomington, Indiana, US. Catalent will add 2,000L single-use bioreactors, QC laboratories, and fill-finish and packaging space for cartoning, auto-injectors, syringe filling, barrier isolation filling, and lyophilized vials. When completed in Q4 2024, the site will offer clinical and commercial fill-finish. Overall, Catalent has 24 sites offering some form of commercial packaging and 24 sites offering some form of clinical packaging.

The top sponsors for commercial injectable packaging contracts are some of the largest pharma companies worldwide, even though large or mega cap companies are less likely than smaller companies to outsource to contractors. Larger bio/pharma companies have the funds to invest in their own injectable packaging facilities. CPOs will have to find ways of enticing larger cap pharma companies, which often have the largest portfolio of products to outsource. There has been considerable supply chain disruption caused by the pandemic, and large cap sponsors use additional sites in multi-site supply strategies to increase supply chain security and offer backup capacity, which can be an advantage for CPOs looking to increase their business with larger customers.