Overcoming the Challenges of Developing Generic and Inhalation Technologies

Sirdupla (salmeterol xinafoate/fluticasone propionate), a product from Mylan, represents the first commercialized generic of its kind produced at science technology company 3M’s modernized Loughborough, UK facility.

3M’s new cold filling line for inhalation products includes the fill head and can handling equipment.
3M’s new cold filling line for inhalation products includes the fill head and can handling equipment.

In many areas of the healthcare industry, the devices used to administer drugs are becoming almost as significant as the drugs themselves. This is making the field of developing generic versions of off-patent pharmaceutical technologies increasingly important.

In 2015, 3M partnered with Mylan to launch a generic version of the Seretide® Evohaler® (salmeterol xinafoate/fluticasone propionate), an inhaler made by GlaxoSmithKline (GSK). The product, named Sirdupla™, is now available throughout the UK, where it is endorsed by some 150 of the country’s more than 236 Clinical Commissioning Groups (CCGs) and health boards.

Key to Sirdupla’s success is a recent investment in 3M’s state-of-the-art facilities in Loughborough, UK. The 150,000 sq-ft Derby Road site houses a factory, distribution center, packaging facilities and an R&D laboratory. A nearly 500-person staff focuses on producing inhalers, liquids, creams and capsules. The company recently spent millions of pounds developing a third inhalation production line inside the factory.

 

Wayne Jarvis, 3M’s Global Marketing Manager for Inhalation Drug Delivery, says, “Sirdupla was the first of 3M’s inhaled generics to be commercialized, together with Mylan. However, we have several additional inhaled generic opportunities currently in the pipeline.”

Describing the line

3M’s new manufacturing line incorporates the latest technologies for batching, filling line and fill head equipment, all designed to overcome the challenges of producing modern inhalers. A key benefit of the new line is that it automates as much of the process as possible, helping to increase productivity, efficiency, product quality, all of which helps to improve worker safety. Safety is of paramount importance to 3M, particularly as each batch of Sirdupla inhalers contains thousands of units, with operators handling kilograms of the drugs at a time.

Automation is evident during aerosol filling, during which a sophisticated tap weighs out precisely the right quantity of the chilled formulation into each vial. A valve is then crimped onto every canister, with each unit weighed. If required by the market, each unit is then heat-stress tested in a temperature-controlled water bath to ensure the canisters can withstand the necessary pressure. Each canister is also laser-marked with its batch number and the date and time of production.

The new fill line runs with minimal stops, producing thousands of units/hr. Even when stoppages do occur, the new fill head design reduces the issues that cause units to be rejected.

After filling, a machine transfers the cans from the production line into trays. If the machine drops even one unit as it is packed into the tray, it immediately stops production in order to let operators solve the problem. The apparatus does not include any gaps that the canisters could drop through, and design features make clearing the line quicker, permitting production of the next batch to begin sooner.

On the packaging line, a function tester machine checks each unit’s dose level and weight to make sure none have leaked over time. Automated robots (who supplies the robots?) pick up the actuators and align them correctly so that the aerosol can be dropped into them.

Factoring in serialization

For products packaged on 3M’s upgraded packaging line there is the option to include serialization data. Information is printed on each carton, bundle, case and pallet, creating a unique identifier for each. This enables each unit to be traced in the unlikely event of a problem, providing increased product security. Customers can scan their pallet to receive codes for each carton inside.

Aisling Bradley, 3M’s Engineering Group Leader, says, “In the case of a recall, we would know exactly where that particular product is, which is a huge benefit. We would know precisely how many are on customers’ shelves and where these are.”

3M spent six years developing Sirdupla, getting the product approved, setting up the systems needed for commercial manufacture, and establishing everything required for efficient distribution, including complying with varying regulatory requirements. Those efforts ultimately resulted in the 3M-Mylan partnership.

During the recent visit to the 3M site, Enis Otuk, Head of Marketing at Mylan, said, “At Mylan, the patient is always our first thought and how we can provide them with better access to high-quality medicines. Our collaboration with 3M combines this quality with innovation—a perfect match.”

Positive UK National Health Service Visit

Last November, Mylan and 3M invited leading industry experts to the Derby Road manufacturing facility to watch how Sirdupla is made, and to attend interactive presentations from 3M technical experts.

Layo Ogunremi, a clinical pharmacist at Crossroads Medical Practice in Lincoln, said: “I was particularly impressed with the serialization, because by doing such they are able to reduce forgery of medication. It was great to see how they merge innovation and product quality.”

Professor Anna Murphy, Consultant Respiratory Pharmacist at the University Hospitals of Leicester NHS Trust, added: “3M is at the forefront of technology and serialization. The staff is so passionate, so I was very impressed to see what was going on and how it all works together.”

Garry MacDonald, Respiratory Specialist and a Consultant for Scotland’s NHS Boards, said, “The technology has just moved on and 3M is listening to the operators about what makes their job easier and safer. I see the pride in efficiency and the pride in their final product, so it’s not just getting it out of there, it’s pushing boundaries and using new technology to its maximum effect. I’m extremely excited that the future of respiratory and inhalers isn’t stagnating, and I see 3M’s role in that as innovation. We have never seen this before.”

(Seretide® and Evohaler® are registered trademarks of GlaxoSmithKline Group. Sirdupla is a trademark of Mylan EV.)

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