QP Services and Oversight: Releasing IMP in a Post-Brexit World

The role of a Qualified Person (QP) in pharmaceutical manufacture was introduced to European law almost 50 years ago. As new technologies, globalization, and even politics have changed the clinical landscape over time, QP responsibilities and legislation have evolved. Two recent changes, and what they mean for clinical trial sponsors, are summarized here.

First, since the United Kingdom completed its Brexit transition on December 31, 2020, QPs named on a UK manufacturing/importation authorization (MIA) license may no longer certify clinical trial batches of investigational medicinal products (IMPs) intended for EU trial sites. Sponsors need to make sure they have an EU-based site of importation and QP if receiving IMPs from the UK for EU trials. Additionally, sponsors with only an EU-based MIA holder and QP will need to enlist a UK MIA holder if they intend to manufacture and/or distribute IMP within the UK, as an EU QP certification alone would no longer be accepted. As before, QPs need to be listed on the MIA license for the site of batch release.

Second, as of January 1, 2022, the MHRA implemented a new QP oversight requirement in Great Britain regarding the importation of IMPs from an approved country (currently all EU and EEA Member States). This involves an extensive assurance system to ensure IMPs coming into Great Britain have been QP-certified before they left an approved country. While routine tasks in the verification process may be delegated to appropriate staff on the quality team, a QP named on the UK MIA license must oversee the process itself. With QP oversight of imports in place, IMPs do not require recertification, saving sponsors from additional costs and delays.

QPs are a crucial part of the clinical trial supply chain. Their certifications allow IMP to be released to clinical trial sites or depots. They ensure that batches of IMP are manufactured per specification, according to GMP standards, and in compliance with government regulations. Their work generally involves supply chain verification, production record review, and additional assessments to determine that a batch is compliant and safe for human use.

QPs have degrees in a scientific discipline, such as biology, chemistry, or pharmacy, along with practical GMP-manufacturing or pharmaceutical experience. They deeply understand the unique requirements of running clinical trials in the UK and EU.

Xerimis has a team of highly skilled QPs who can support your clinical trials in the UK and EU. Contact us to learn more.

Xerimis Partners With Area Europe on State-of-the-Art Facility in the Netherlands

We’re thrilled to be working alongside Area Europe, a UK-based construction firm specializing in workplaces, on the design and fit-out of our environmentally sustainable facility in the Netherlands. The 45,000-square-foot site marks the new location for our next global depot, enabling us to increase operations in alignment with the growing needs of our clients.

Xerimis has been helping clients run worldwide clinical trials for the past two decades. In 2016, we elevated our global capabilities by opening our packaging and distribution facility in Theale, United Kingdom. Area successfully designed and delivered that facility. In 2021, with our next major expansion unfolding in the Netherlands, we turned to Area once again. This was an easy choice given their understanding of our business and their knowledge of European workplace culture.

Opening a new facility in the Netherlands will give our clients three tremendous benefits:

  • Easier entry for clinical supplies into mainland Europe since the completion of Brexit in December 2020.
  • Increased storage and service capabilities for investigational drugs, including those with specific temperature requirements.
  • Continued advantage of Xerimis’ commitment to quality, flexibility, reliability, and responsiveness — our core values.

A new benchmark for future workplace transformation

Located within minutes of Schiphol Airport near Amsterdam, the new facility sets a benchmark for future workplace transformation. Workspaces were strategically designed to provide flexibility for different types of work to be performed. While remaining consistent with our brand identity, site design was influenced by Dutch culture and workplace expectations.

An intensive six-month design phase took place with Area’s team guiding us through a comprehensive feasibility study and schematic development. With a focus on process workflow, we created a floor plan positioning certain functions in adjacency to others, optimizing space and flow while adhering to strict GMP (Good Manufacturing Practice) standards. We also organized and tested heavy equipment in the space to ensure functionality and compatibility with the design. In addition, we constructed a mezzanine to support workflow and future development.

“This monumental expansion comes on the heels of several years of growth for our company,” says Jim LoCascio, Vice President, Global Business and Strategic Development. It also positions Xerimis well for the expected uptick in clinical research throughout Europe, following the recent launch of the EU Clinical Trials Regulation. Furthermore, as pharma and biotech increasingly expand into new treatments requiring specialized temperature control, the facility is scaled to meet these needs.

Driven by innovation, integration, and sustainability

The site is the result of two new warehouse units integrated into one production and warehouse facility. Designed to create harmony between functions, directional guidelines show the path to changing room and shower amenities, canteen, front offices, and meeting suites. Natural materials are used throughout, with matte black metal detailing seen in joinery, glazing, and feature staircase hardware. Xerimis brand color accents the space through soft furnishings and artwork. Separate air handling systems were built into the scheme for the clinical packaging, labeling, and storage areas.

On the production floor, modular ultra-cold units provide conditions required for temperature-sensitive drug storage as low as -80° C. The walk-in freezer offers abundant shelving for product storage with ample space for manoeuvring pallet jacks, and the walk-in refrigerator — large enough to drive in and operate forklifts — can accommodate over 350 pallets. The site is equipped with advanced temperature monitoring and backup systems to ensure consistent climate for inventory protection.

With significant power required to run the site, we’ve been focused on sustainable and efficient energy since early in the design stages. We leased the building’s roof and installed a solar array that will generate over 200 kVA of electricity. This solution is supported by a backup battery system, with redundant power provided by backup generators and grid electricity.

Area has been onsite since October 2021 and will carry this landmark project to completion by May 2022. “Distance has been no obstacle,” says Lee Day, Director of European Projects at Area. “Despite COVID-19 travel restrictions, we have worked collaboratively with Xerimis NL, UK, and US-based project teams to co-create this state-of-the-art facility. We are very proud to be supporting Xerimis’ growth strategy in line with the intricacies of local codes, statutory requirements and regulations.”

We’re grateful for our partnership with Area. They’ve done a remarkable job steering our construction and designing a facility bespoke to our unique business. We look forward to opening our Netherlands depot later this year.


EU Clinical Trials Regulation Is Here

The EU Clinical Trials Regulation (CTR) has been in the works since 2014, but now that it’s actually here, what are the basics you need to know?

The CTR, which went into effect on January 31, 2022, harmonizes the assessment, approval, and supervision of clinical trials throughout the EU via a central database, the Clinical Trials Information System (CTIS). The new Regulation was created to promote clinical research in the EU by streamlining the clinical trial application (CTA) process, while improving transparency on trials by making information accessible to the public.

Under the previous process, known as the Clinical Trials Directive (CTD), running a multi-country trial in the EU meant the sponsor had to send a separate CTA to the competent authorities and ethics committees of each country targeted. Then each country had to authorize the trial based on its own adaptation of the CTD into national regulations, which varied between countries. Inefficient and costly, the process ultimately hindered clinical research in the EU.

Under the new Regulation, sponsors may submit a single CTA through the CTIS, which allows for parallel review by EU/EEA Member States. The CTA is a two-part dossier: Part I involves general information about the trial, and a lead Member State (proposed by the sponsor) coordinates and reports a collective response from contributing Member States; Part II involves country-specific information, and sponsors complete a Part II for each Member State concerned. Within a set timeline, each Member State concerned must notify the sponsor of its decision via the CTIS. 

Transition period for clinical trial sponsors

From January 31, 2022 through January 30, 2023, sponsors have two choices for CTA submission: 

  • Apply using the CTD system, EudraCT (with individual submission for each targeted Member State). Approved trials may follow regulations per CTD until January 30, 2025.
  • Apply using the CTIS (simultaneous submission for up to 27 EU Member States plus Iceland, Liechtenstein and Norway). Approved trials will be immediately governed by the CTR.

Starting January 31, 2023, any sponsor seeking to run an EU/EEA trial must submit a CTA through the CTIS. 

By January 31, 2025, any ongoing trial that had been approved under the CTD must be transitioned to CTIS for governance through the new Regulation.

New considerations for sponsors

The timeline for initial CTA approval ranges from 60 to 106 days under the CTR. However, amendments may not be made until after initial approval is granted. Then, adding a country or clinical site will trigger a new review period. Therefore, sponsors are urged to select countries and clinical sites carefully when planning their submission. 

In addition, since EU countries could have simultaneous approval of Part II, all EU sites could potentially have a shipment request go live overnight, depending on the sponsor’s clinical site initiation policies and IRT management. Sponsors will need to be ready with supply and distribution in place. 

Sponsors may also consider alternate strategies for completing Parts I and II of a CTA. There may be reasons, for example, to submit Part I and Part II sequentially (within a two-year deadline), or to include only some countries in Part II initially, with plans to phase in additional countries. 

Xerimis expertise to help guide sponsors

With the CTR comes much to know about the application process, timelines, record handling, Annex VI (the stricter packaging and labeling laws coinciding with CTR), slightly different Good Manufacturing Practices (GMPs) and more. Xerimis created a webinar explaining key points of the new Regulation and Annex VI. 

For more information on how Xerimis can help your EU clinical trial stay on track, contact us today.

CMOs and CPOs: The Critical Difference

Revised on June 8, 2021

As the clinical supply industry evolves, so does its vernacular. Small molecules are making way for large ones, resulting in “genetic therapies.” We no longer work in ambient conditions; today, “controlled room temperature” best describes the handling process. Even the term “sponsor company” evolved from the fact that companies other than R&D pharmaceuticals are running trials.

One drawback to this evolution is language’s habit of lingering beyond its logical lifespan. If you still “dial” someone’s number but haven’t touched a rotary phone in decades, or “roll up” the automatic windows in your car, you understand the habit of holding onto sayings even after they stop making literal sense. In the clinical packaging industry, a memorable example is IVRS, short for Interactive Voice Response Systems. When IVRS began giving way to voiceless Interactive Response Technology (IRT) in the late 1990s, “IVRS” hung on, serving as the default terminology for years after voice features had faded.

Today, the term “CMO” is the primary offender on the nomenclature front. If the exact definition of CMO leaves you scratching your head, it’s proof positive of the problem. Today, we still — astonishingly — use “contract manufacturing organization” to describe the drug substance manufacturer, the drug product manufacturer, the fill/finish vendor, and the clinical packaging group that does not technically “manufacture” a single thing.

The misnomer traces back a few decades to when pharmaceutical companies handled packaging, labeling, and distribution in-house. Executed in close proximity to manufacturing and production (by companies best known for manufacturing and production), packaging, labeling, and distribution were lumped under the “manufacturing” umbrella. In time, pharmaceutical companies restructured and began outsourcing manufacturing, packaging, labeling, and distribution to vendors designed specifically for those highly regulated services. Erroneously, the “CMO” categorization went along with all these activities.

This ambiguity strikes at the very heart of how different stages of drug development are managed when outsourced. CMC professionals — the acronym standing, of course, for Chemistry, Manufacturing, and Controls — select, qualify, and oversee vendors that manage the drug substance manufacturers, the drug product manufacturers, and the fill/finish stages of drug development. But it is the clinical supply managers who select and actually work with the clinical packaging vendors. For this reason, a new term has emerged for providers specializing in packaging, labeling, and distribution: contract packaging organizations (CPOs). This naming breakout is in step with the clinical supply industry’s commitment to advancing drug innovation within a field that can’t afford confusion.

Xerimis is a CPO with global experience. By identifying as a CPO rather than a CMO, we distinguish ourselves from companies that don’t offer our caliber of expertise and specialization in clinical trial packaging, labeling, distribution, and related services. Contact us to learn more.

Put to the Test: Flexibility in the Pandemic Age

These are unprecedented times in our industry. The immediate need for COVID-19 treatment and vaccine has created a clinical trials scenario that would’ve been unthinkable just six months ago. Vaccine development typically takes 10-15 years. Yet reports indicate that it took about eight weeks from first receiving the Coronavirus in labs to the first dosing of a test vaccine. Nearly every pharma company examined their commercial and clinical lines to find treatment potential that could help provide relief for the growing number of COVID patients. Now the world eagerly awaits news for effective treatments and ideally a vaccine.

Hundreds of pharma companies are racing to identify treatments and vaccine for COVID-19. As early as February, Xerimis saw requests for packaging as COVID-focused trials began in earnest. These COVID studies moved though our system—from formal quote to packaged supplies—at a rapid pace unlike any before.

Flexibility and speed have been core tenets of Xerimis since our beginnings in 2001. We’ve proven that agility in clinical packaging, along with a commitment to quality, make a successful combination for meeting timelines and FPI for all studies. Following this model positions us to deliver in a high-pressure scenario marked by both volume and urgency.

The COVID-19 pandemic has tested our abilities and shown that Xerimis was built for responsiveness and urgency. Thanks to our well-established systems and experienced team, we’ve been able to turn around quotes for COVID-related projects in under 24 hours. Standard Xerimis quote turnaround time is 5 business days, while the industry standard is 2 to 3 weeks. More importantly, Xerimis has been able to facilitate contracts, supplies, packaging, labeling, batch record review and approval, release, and shipment in record time without compromising quality.

Several sponsor companies of COVID-vaccine trials selected Xerimis as their partner based on our reputation and responsiveness. We were also able to support sponsor companies who required quicker turnaround of their supplies than they would receive from a large vendor. They transferred supplies to Xerimis and we provided faster, more flexible service.

During this global crisis, we’ve been able to maintain our existing client studies to ensure no patient goes without supplies, while also meeting the demand for new and urgent COVID studies. We’ve kept true to our core values of flexibility, quality, and responsiveness. Xerimis is proud to be part of this race, providing critically needed clinical trial materials to patients for COVID-treatments and vaccine.

Focused on Your FPI

Revised on October 5, 2022

The role of clinical supply is a very crucial link in the supply chain, yet one that is often glossed over by other groups along that chain. Many decisions are made upstream that have direct impacts on what can be done once a project is handed off to you and your team, without much consideration to the management of trials in relation to dosing, formulation, delays, vendor selection, and perhaps most critically, milestones.

One main goal for the sponsor’s clinical supply group is First Patient In (FPI), that monumental first dosing of an investigational drug product to a patient enrolled in the drug’s clinical trial. FPI has become a key marker for venture capital directors and corporate heads looking to set milestones for goal achievement. Unlike many other milestones and achievements, FPI is an easy metric to track: “Did the patient receive drug on July 1st? Yes or no?” The answer has significant implications, not just on the company tracker, but all the way to Wall Street and beyond. The bonuses of the entire company often rest on meeting this target.

So why are FPIs sometimes disregarded by clinical supply groups? There may be an expectation that FPI won’t succeed in the planned timeline, given supply chain unpredictability and concerns of vendors not providing what they promise.

Anyone who has worked in small pharma can tell you: Many contract packaging organizations (CPOs) prioritize larger clients, keeping them happy at all costs — often at the expense of smaller clients’ timelines.

Every year, large CPOs with stockholders need to improve profitability over the previous year to meet corporate goals. This is a considerable factor in prioritizing how resources (such as open rooms or packaging technicians) are used. Prioritized work that was profitable “enough” a few years ago may now be deprioritized and put into less desirable slots, because the percentage of profitability no longer meets the new priority/profitability model. If a job or a shipment requires overtime, that work may not get done today. Maintaining high profitability, not just profitability, is priority.

Growth rates set by corporate are prioritized as well. Large vendors are under tremendous stress to grow sales at or beyond reasonable limits each year. Even when operations are at capacity and timelines are slipping, the sales team is pushed to close bigger and more elaborate work without consideration to available capacity. (When was the last time a large vendor turned down a Phase 3 study?)

Larger CPOs are also known to have some tolerance for delayed shipments, with roughly 10% of kits routinely delayed by a day or so. Yes, these are short delays experienced by a small number of clients, but those clients are likely operating within tight schedules already. One short delay can push their study past the FPI date.

Finally, larger companies don’t always take kindly to changes mid-process, and they won’t necessarily hustle as needed to accommodate changes inherent to clinical drug trials.

All of these realities put smaller clients’ trials at risk unnecessarily. This is why Xerimis developed our zero-miss guarantee: Assuming our clients deliver their materials on schedule, Xerimis will never be the reason an FPI is missed.

This promise stems from our thoughtful forecasting and refusal to overpromise. We assess timelines before accepting work, letting clients know if we think we cannot meet their intended FPI. With Xerimis, all jobs are based on FPI and patient-visit priority, not preferred-contract priority. No one gets deprioritized. We do what’s needed to help every client make FPI: All packaging runs are prioritized over profitability, which means we never bump shipments. If another client has an urgent need, there’s no impact on your timeline. We add resources and adjust as needed.

If our clients miss their own internal milestones during the packaging process, we do everything in our power to accommodate. We make up time for clients in a way that other companies don’t or can’t. In fact, we might be the reason they make their FPI when hiccups occur.

Xerimis’ agility is our key to meeting FPI, and this is driven by our understanding of the stakes at hand. In our industry, small studies may consist of a few hundred vials, containing a couple thousand dollars’ worth of material each. No detail can be taken for granted. So beyond hitting FPI dates, our agility means never having to sacrifice attention-to-detail or quality in completing a job.

Xerimis refuses to let our clients feel the burden of the inevitable shifts and changes that impact clinical trial timelines. Even more, we refuse to play favorites. Every Xerimis client is a client whose FPI we protect and prioritize, as reflected in our zero-miss guarantee.

Why Small and Medium-Sized Pharmaceutical Companies Must Rethink Their CPO Strategy

The clinical trial landscape is changing.

Historically, smaller pharmaceutical companies focused on preliminary research, which they sold to larger pharmaceutical companies that sponsored Phase 2 and Phase 3 trials. 

That model has shifted as large pharma has become more focused on securing venture capital. In efforts to alleviate risk, today’s big pharmaceutical companies are less likely to sponsor trials themselves, and more intent on buying smaller pharma companies with existing data derived from successful clinical studies. 

The burden of clinical trials, then, has shifted from large pharmaceutical companies to these smaller pharmaceutical companies, many of whom are sponsoring multi-continent trials for the first time. Larger trials are more complex than domestic trials in a number of ways. 

  • More regulation and moving parts
  • QPs – Qualified Persons – are needed for EU releases
  • In global trials, audits are required for facilities where drugs are manufactured and packaged
  • QP releases are needed once a drug is ready and all certifications are complete

In light of these specifics, global trials require a contract packaging organization (CPO) with extensive experience in large, multi-continent studies. Small and medium-sized pharmaceutical companies sponsoring today’s large trials turn to experienced Phase 2 and 3 CPO vendors but are learning the hard way that they’re not a priority to these businesses.    

Large CPO vendors have a tendency to prioritize big pharma over smaller pharma, regardless of the size or scope of the trial. And it makes sense – the majority of their revenue comes from big pharma. But it makes for slower and more challenging trials for smaller pharma companies.

Big pharma ex-pats now working for small and medium-sized pharmaceutical companies need to realize they’re not going to have the same relationship with larger packaging companies now that they’re with a smaller pharmaceutical company. If a large pharma trial needs extra rooms at the last minute, for example, small and medium-sized clients’ trial needs get bumped.  All in all, medium-sized pharma tends to get lost in the matrix of customer service, which can have critical consequences for trials.  

Changes in the pharma industry have created a new reality: If you’re not large pharma, you don’t want to use a large CPO vendor.

At Xerimis, we’re dedicated to small and medium-sized pharmaceutical companies. 

  • We’ll never bump your trial in favor of a larger client. That’s not how we do business.
  • We’ll help you navigate large, multi-continent studies even if you’ve never done a Phase 2 or 3 trial before. 
  • We’ll handle the complexities of global clinical supply so you can focus on the trial. You have enough on your plate as it is. 

Xerimis is the only CPO in the industry who prioritizes smaller pharma AND has the experience to navigate large, multi-continent studies. This is our niche. We welcome smaller pharmaceutical companies because it’s the small and medium-sized companies that are doing trials rather than doing venture-backed acquisitions. You can rely on our experience and our guarantee that your trial will be treated as a top priority – no matter the size of the company behind it.  

Thank you to our team and our vendors

As we continue to monitor the COVID-19 virus and its impacts, I wanted to take a moment to extend a thank you to our team and our vendors. The past weeks have been challenging for everyone around the world, but amidst those challenges, we’ve truly seen the best in all of us and what we’re all capable of together.

To our team, your commitment to our work has been an inspiration. You’ve modified processes and taken time away from family to ensure that critical trials continue to happen. You know the importance of the work we’re doing, and you know the impact it can have on the entire world.

To our vendors, none of this would be possible without the critical role you play in the supply chain. Cartons and bottles are being produced, temperature-controlled shipments maintained, and courier services are delivering. You each play an essential role in the clinical trial process, and we thank you.

We know that the future will bring its own challenges, but I feel optimistic having seen what we’ve been able to achieve over these past weeks. Thank you for dedication and hard work, and commitment to making a difference.

Carol Sue Bernardo
Chief Executive Officer and Managing Director

COVID-19 Update: Vital Operations Continue at Xerimis

On Saturday, March 21st, the Governor of New Jersey issued an Executive Order No. 107 requiring all Non-Essential Retail Businesses to close. Xerimis is not forced to close our business since Xerimis is part of the pharmaceutical supply chain responsible for providing medicines to patients, and as such is considered in the category defined as Healthcare/Life Sustaining businesses.

The ongoing efforts to contain the spread of the COVID-19 virus throughout the world make this a very dynamic time for individuals and businesses alike. Xerimis continues our commitment to the safety of our clients, patients, and team members. We have transitioned many Xerimis employees to remote working to the greatest extent possible. We continue with our on-site activities including receiving, packaging, distribution and returns accountability and have implemented aggressive cleaning procedures for all areas of the building.  Our staff is already cross trained which will allow us to perform the most critical activities at Xerimis.

We are working collaboratively with all clients to ensure supplies are packaged and dispatched as planned.  We recognize the impact of COVID-19 and the new challenges that are being presented to sponsors.  We are actively working with our partner couriers to set up direct to patient delivery when this option becomes necessary due to circumstances related to COVID-19. We will work with clients to ensure we prioritize the most critical needs for patients.

We have begun seeing countries impacted by the COVID-19 virus and shipping lanes being impacted. We continue to keep our clients updated regularly and look for alternatives as needed. The likelihood of disruption to other geographical areas cannot be ruled out with each passing day. We are committed to our partnership with you and to being here to support you and patients in this most serious time for our world.

Carol Sue Bernardo

Xerimis Coronavirus Planning Measures

Xerimis is committed to the safety of our clients, patients, and own team members while we continue to ensure that your clinical supplies are packaged, dispatched and delivered with minimal disruption.

Xerimis operates under GMPs and as such we have existing policies and procedures in place for ensuring clean environments, proper hygiene by all employees and have a written plan in place should a pandemic crisis occur. In addition, we are also following recommendations provided to the public by the Centers for Disease Control (CDC) regarding the coronavirus.

Xerimis will continue to monitor communications and statements from our approved couriers that may impact their services in specific geographic locations. In turn, we will directly notify our clients of any potential impact to their shipping lanes or if any shipment request is unable to be completed due to government-imposed travel restrictions. Currently there are no restrictions on shipments within the United States and Canada. Globally, there are restrictions to specific geographical areas within countries such as China, Italy, Iran and South Korea; however, there has been no impact to ongoing shipments from Xerimis locations to date. The likelihood of disruption to other geographical areas cannot be ruled out only passenger travel is more likely to be impacted than the approved couriers we use. This is a dynamic situation and as such the information or restriction may be subject to change without notice. Xerimis will endeavor to ensure clients that may be impacted by such restrictions are notified as early as possible.