Safe and reliable filling of liquid injectables

THERE’S a great deal of risk in selecting vital equipment on short notice, and it may take several months to determine whether or not the investment is viable. In the case of a major Indian pharmaceutical company, the outcome has been a happy one.

 

The development and production of sterile injectable medicines are among the core competencies of the leading Indian pharmaceutical manufacturer Zydus Cadila, headquartered in Ahmedabad. At the end of 2011, Zydus Cadila decided to increase its production capacities for pharmaceutical liquids by investing in new equipment. Romaco’s Macofar VF 18 aseptic liquid filler was chosen to meet this challenge. The machine was shipped within six months of the order being placed and installed at the pharmaceutical company’s facilities in Ahmedabad in May 2012. Its job there is to fill sterile injectable products and vaccines into vials.

 

 

Vaccines, gastrointestinal and cardiovascular drugs as well as anti-infectives and therapies for respiratory diseases are central pillars of Zydus Cadila’s portfolio.

 

Following an extensive restructuring exercise in the mid-Nineties, Zydus has grown dramatically in the last 15 years. The company reports sales of more than a billion US dollars annually and currently employs about 13,000 staff in four continents. Eight production sites in India, the US, Brazil, South Africa, Spain, France and Japan serve pharmaceutical customers around the globe.

 

In the last year alone, the company launched 16 new products in the domestic formulations market, of which six products were the first to be launched in India. Meanwhile four new products were launched in the U.S. even as 12 were launched in emerging markets.

 

Reliable process sought

 

Brisk demand in pharmaceutical liquids drove Zydus Cadila to invest in new equipment late in 2011. The Romaco technology convinced with reliable processes where unstable containers are involved.

 

“We were looking for a high-speed machine at very short notice to fill parenteral products and help us cope with the rapidly expanding demand for our injectable preparations,” recalls Gaurang Purohit, general manager Projects and Engineering, Zydus Cadila. “Romaco was able to deliver promptly, and we’re very happy with the quality and value for money offered by the Macofar technology.”

 

Since being installed in May 2012, the Macofar VF 18 has been operating in three shifts to fill sterile injectables into vials. The aseptic liquid filler achieves a maximum filling speed of 18,000 vials an hour.

 

Immediately after filling, the sterile products are freeze-dried. This method is particularly common in the pharmaceutical industry because many APIs are more stable and have a longer shelf life after freeze-drying. Then the lyophilisate is dissolved in sterile water prior to administration and then injected directly into the body.

 

A complex challenge

 

Filling these tall, slim vials at high speed is technically very complex. The vials have to be optimally stabilised for processing on the automatic line. All this is no problem for the Macofar VF 18.

 

The Romaco machine provides multiple benefits when unstable containers are involved: an infeed screw and starwheel separate the vials on their way to the dosing and stoppering stations.

 

Pharmaceutical liquids destined for freeze-drying are first of all filled into DIN/ISO-compliant, 4R tubular glass vials in liquid form. Vials with a height of 68 millimetres, for instance, are just 16 millimetres in diameter. In this case, the filling volume is as little as 1.8 millilitres per vial. The reason for this low fill level is the downstream lyophilisation process, during which the product expands.

 

Optimum cleanroom environment

 

One Zydus operator per shift is responsible for overseeing the Macofar VF 18 aseptic liquid filler. This compact machine is installed in a cleanroom with laminar flow air conditioning. With a footprint of only three square metres, it is extremely compact and inexpensive to maintain.

 

“The Macofar technology is optimally integrated in our cleanroom environment,” notes Mr. Purohit. “What’s more, it’s very easy to retool and operate – and in pharmaceutical production that’s a crucial advantage.”

 

Strict safety and hygiene regulations intended to protect both the product and its consumers apply when processing sterile parenterals. The concentration of particles and microorganisms has to be kept to an absolute minimum during filling and stoppering. The cGMP compliant design of the Macofar VF 18 fulfils these requirements in a number of respects. A selective laminar flow prevents turbulent air movements in the vicinity of the open vials. The clean design of the machine additionally hinders particle formation in the critical zones.

 

Ultra-precise dosage made easy

 

The product is filled by means of eight rotary piston pumps, with ultra-precise dosage a defining feature of the system. For the filling volume of 1.8 millilitres, the maximum possible error is no more than ± 0.5 percent.

 

Vials are filled by means of eight rotary piston pumps

 

Then, the vials are sealed with a notched rubber stopper, which is only inserted about half-way to allow for the downstream freeze-drying process. The vials can then be transferred directly to the freeze-dryer.

 

Thanks to the positive transport system, these unstable containers are guided safely to the various stations in the aseptic filling process. Several servo systems control the transfer, filling and stoppering steps. The risk that the thin-walled glass containers could topple over or break is ruled out.

 

Good service part of the package

 

When complex technologies are introduced, reliable service is a must. On-site customer support begins when a new machine is installed and commissioned. Special technical training is recommended for all operators, and there is also maintenance and repair work to be done from time to time.

 

Income Marketing Pvt. Ltd. of Mumbai is Romaco’s representative in India. Managing director Vishesh Parekh maintains close contacts with local users of Romaco technology. Once every month on average, he flies to Zydus Cadila to discuss important matters in person. A hotline that enables Income to be reached 24/7 exists as an alternative. A qualified technician is on hand immediately if prompt action is necessary.

 

“Income’s trusty service was a key factor in our decision to award the contract to Romaco-Macofar,” Mr. Purohit confirms. “Machine downtime and other disruptions cost a lot of money. Thanks to the successful cooperation with Income and Romaco, however, that’s something we never need to worry about.”

 

No wonder then that for nearly three years, the Italian-built aseptic liquid filler has been producing parenterals for hospitals and doctor’s surgeries in India without a hitch.