Pharmaceutical Serialization: Looking beyond Regulatory Compliance

By: ACG North America

Counterfeiting of medications is a major problem faced by the global pharmaceutical industry. As per the WHO estimates around 30% of the medicines sold in developing countries are counterfeit.[i] Owing to globalization, the supply chain for medicines has become lengthier with every step offering another opportunity for counterfeiters. As a result, global track and trace requirements have become stringent putting tremendous pressure on the supply chain’s transparency.

Using Serialization as a Business Strategy

The pharmaceutical companies do believe that counterfeiting can be reduced significantly by implementing product serialization. However, serialization requires a comprehensive system to track and trace the passage of prescription drugs through the entire supply chain. Therefore, serialization is often looked upon as an effort and cost-intensive process and often a regulatory mandate. However, pharmaceutical companies are now increasingly adopting a strategic business view for overall adoption of serialization. They have started developing packaging and information technology to not only ensure regulatory compliance, but also use this for their own business gain: safeguarding brand reputation and ensuring patient safety to name a few. Serialization and traceability can also be used for effective management of the supply chain and management of medicine inventory at wholesale and retail levels.

The following are some additional benefits that companies can reap by implementing effective serialization processes:

Protecting brand reputation

Counterfeit drugs pose a huge risk to pharmaceutical companies. It not only affects potential sales, but also leads to deterioration of brand reputation and brand value. Brand reputation is of utmost importance for the pharmaceutical industry, as compromised drugs can potentially harm the patients’ health. Therefore, serialization and traceability allow pharmaceutical companies curb counterfeiting and protect the brand image.

Improved processes

Serialization and traceability can standardize and harmonize operational processes in across manufacturing units, warehouses and distribution hubs, resulting in smooth operations. It also assists in scanning and removing expired, faulty or damaged product, ensuring that only genuine product reaches the consumer. Further, it helps manufacturer by preventing revenue loss occurring due to recall of faulty or damaged product.

Ensures better control over parallel trading

Parallel trading is when goods are bought in low price and sold in the market when their price increases. This is considered as an illegal process in certain industries where the cost of the product is a cumulative of the actual cost and additional import and export taxes. Track and trace is quite useful to curb parallel trading.

Serialization is a cost-saving exercise

Serialization and track and trace projects are often perceived cost-intensive exercises owing to complex serialization framework and equipment handling. However, pharmaceutical companies often tend to overlook the amount of revenue lost due to counterfeit medicines that serialization projects can help curtail. Currently, the global counterfeit drug market allegedly makes for approximately USD 200 Billion.

Serialization also helps eliminate manual errors, such as incorrect entry of GTIN or batch numbers (prevalent in manually operated machines), that are linked with loss of productivity. Furthermore, loss of time due to human intervention adds to the loss of production and revenue. Automation in the serialization machines can minimize the loss of productivity.

In conclusion, an efficiently implemented serialization and traceability processes can offer benefits that are beyond regulatory compliance. Serialization and traceability processes can be complex to develop and implement. However, there are companies that have experience in both pharmaceutical and inspection technologies that can smoothen the process and ensure cross-country regulatory compliance. It is essential for particular pharmaceutical companies to partner with trusted and experienced solutions provider to achieve successful serialization and traceability.

ACG provides a comprehensive range of serialization and track and trace solutions that help you get ready to meet the global serialization demands. The innovative machine vision systems of ACG are designed to inspect quality, while helping maintain traceability and eliminate possible loss of revenue & reputation.

[i] Bansal D, Malla S, Gudala K, Tiwari P. Anti-Counterfeit Technologies: A Pharmaceutical Industry Perspective. Scientia Pharmaceutica. 2013;81(1):1-13. doi:10.3797/scipharm.1202-03.

Posted in Uncategorized | Leave a comment

Is Continuous Manufacturing Really New?

By Ed Godek
Manager, Process Technology
Glatt Air Techniques, Inc.

Some 25+ years ago, I graduated from college with a Chemical Engineering degree, armed with the knowledge of process modeling, flow sheet analysis and statistical process control…important skills for continuous manufacturing in the chemical industry. At that time, I chose to venture into the world of Pharmaceutical Manufacturing for a career and found one.  Unfortunately, the industry was rigidly stuck in a world of batch manufacturing.  It was almost like we just took the unit operations from the old compounding pharmacists’ benches and made them bigger, while adding technology from the food and baking industry.  Not as cutting edge and revolutionary as I was hoping for.  Fast forward to the present.  We are finally trying to move the Pharma Industry into the world of Continuous Manufacturing at the urging of FDA and other Regulatory agencies.  It is a known fact that the ability to manufacture product of a very high quality hinges on complete process understanding, the ability to analyze the product “in-process”, and have the flexibility to adjust process parameters to maintain quality.  Sounds like the skills I once possessed 25 years ago.  We need to reach back into our engineering past to help bring us fully into the Continuous Manufacturing space of the future.  This is what we are trying to do at Glatt: to provide the best and most flexible continuous manufacturing systems in the industry.

Posted in Uncategorized | Leave a comment

Disposable Hopper: A small unit to improve ease of work and ergonomics while reducing man power

bsBy: Bausch + Stroebel

Portable vibrating system for dispensing components (stoppers and caps)

At first sight, the disposable hopper – type BZV 8110 might look rather unspectacular. The unit might be small, but it packs a punch. The small unit actually becomes a real workhorse piece of equipment and savings for both, the process and operator.  Basically, the BZV8110 is a portable vibrating system to hold ready-to-use or ready-to-sterilize component bags and with the vibrating system dispensing the components into the bowls for processing. The bright idea behind it: we would dispense the components into large hoppers to hold a large number of components.  The hoppers were located inside the RABS or inside the isolator.  The hopper would vibrate upon demand and dispensed the components into the bowls for processing. The component bags now become the hopper to hold a large number of components.  Hence, we are eliminating the hopper and vibration mechanism from inside the aseptic filling area.  A study according to DIN EN 14644-1 ISO 5 sterility compliance was performed which resulted in an improved compliance when compared to operator handling vs the automated vibration.

Even as the BZV 8110 is serving a critical and sophisticated function it is simple to operate and integrate with a great variety of systems. The transportable system is pushed in front of the dedicated sterile port or RABS opening. Next, the unit automatically elevates to a position where the operator can comfortably place the bag from the ergonomic point of view. At the press of a button, the unit elevates to a programed position. The operator then simply connects the bag to the alpha-beta-port system for the sterile connection without the need of stairs or straining activity.

The disposable hopper – type BZV 8110 is exactly tailored to the requirements of the VarioSys flexible production modules (see VarioSys.com).

In the sterile production environment space is at a premium. The VarioSys system is a compact yet highly flexible system and is designed to make best use of the available clean room real estate. The BZV hopper system plays in to this concept and works automatically as part of a fully integrated solution. Sensors ensure constant and controlled supply of the stoppers. Excess or insufficient supply of closures is reliably avoided, thereby significantly enhancing process reliability.

The disposable hopper was originally designed for small batch operation in connection with this system; however it can be used in combination with any machines that would benefit from a reduced hopper and sorting bowl size, or an environment where reducing operator handling and time spent on this task is of interest.

The disposable hopper is suitable for all bag types and sizes available on the market.

Features and advantages in a nutshell:

  • Hopperless component feeding
  • Reduces parts that need to be sterilized.
  • Automate the component bag to bowl dispensing
  • Portable and adaptable to all existing machines
  • Dispenses components directly from the “Ready-to-use” and “Ready-to-sterilize” RTP port component bags to the sorting bowl
  • Plug and play connection to any VarioSys L-flange and other machines as a standard design
  • The vibratory unit is linked to the level sensor of the sorting bowl ensuring continuous dispensing of the stoppers and caps without the need of an operator
  • Capable of using multiple sizes of component bags from different vendors
  • Slim design, which allows two units to be connected side by side to one L-flange filler
  • A maximum of two BZV units is needed to cover all flexible filling line needs for vials, syringes, cartridges etc.
  • Electric motor-driven telescoping lift column for operator-friendly ergonomics, eliminates/reduces lifting and above shoulder operations.
  • Maximizes operator efficiency (one bag to last multiple hours or a full batch)
  • DIN EN 14644-1 ISO 5 compliant (study on particle generation available)
  • The BZV vibrator is outside of the aseptic filling line whether it is a RABS or isolator

 

imagee.png

 

Posted in Uncategorized | Leave a comment

Formulation Factors Affecting Capsule Brittleness

By: ACG North America

Gelatin capsules are a popular dosage form for numerous reasons, including faster speed to market and improved patient compliance. Brittleness is one of the common challenges associated with capsule performance. Capsule manufacturers often implicate poor performance of a capsule to manufacturing processes or storage conditions. However, it is important to realize that formulation parameters play an important role in overall capsule performance, including its tendency to become brittle.

Here’s looking at 4 major formulation factors that may have an impact on brittleness of capsule:

  1. Type of gelatin used

Gelatin is the main component of hard shell capsules and is derived from the chemical degradation of collagen. It behaves very differently depending on whether its macromolecules are in the collagen-like helical or coiled conformation. In the former case, the gelatin exhibits properties suitable for use at ordinary temperatures. However, in the latter case, gelatin is a typical rigid-chain polymer and behaves as a brittle impractical material. It does so because of the absence of water. Information about the performance of gelatin in terms of brittleness can be obtained by analyzing glass transition temperature and polymer crystallinity. Higher the crystallinity, the higher is the tendency of the gelatin to become brittle.

  1. Pigments

Pigments cause opacity and create a protective barrier to harmful radiation. However, they also play a significant role on mechanical properties of capsules; higher the pigment content, the higher is brittleness. Therefore, it is critical to formulate the capsule with optimum pigment content.

  1. Molecular weight

It is well known that molecular weight and molecular weight distribution can markedly affect the mechanical properties of a polymer. It is important to use the polymer of an optimum molecular weight: high enough for delivering good mechanical properties, but not too high that renders processability difficult.

Subjecting gelatin to higher temperatures for a long duration can cause polymer chains to fragment, reducing the molecular weight and deteriorating the capsule performance in terms of brittleness.  Therefore, it is important that processes that need gelatin to be heated are performed in the shortest possible time.

  1. Use of plasticizers

Plasticizers are often used to reduce the stiffness of a polymer by reducing the cohesive intermolecular forces along the polymer. The amount and choice of the plasticizer contribute to the hardness of the final product and may even affect its dissolution or disintegration characteristics, as well as its physical and chemical stability. For hard gelatin capsules, water acts as a plasticizer. Therefore, at low relative humidity, these capsules lose moisture and become brittle. Softgels capsules are more elastic owing to plasticizers such as glycerol or sorbitol and propylene glycol used in combination with glycerol.

In conclusion, numerous formulation parameters can affect the mechanical properties of raw materials and the capsule itself.  Extensive experience in the field of capsule manufacturing is needed to identify core fundamental properties that affect capsule performance. Therefore, it is important for manufacturers to also be cognizant of and have a stringent check over these parameters to improve the hard gelatin capsule performance.

With over fifty years of industry expertise, ACG is an integrated processing, manufacturing and packaging solutions provider to the global pharmaceutical industry. It is the world’s second largest manufacturer of high quality empty hard capsules. ACG’s capsule range is designed to provide customized solutions to the pharmaceutical and nutraceutical industry. 

 

Posted in Uncategorized | Leave a comment

NJM to Exhibit Compact Filling & Closing Pharmaceutical Packaging Machine in NYC

By Marla, Marketing Manager, NJM Packaging

We’re always excited to showcase the latest in pharmaceutical packaging equipment at Interphex in NYC. This year, we’re bringing the Dara SX-310-PPD filling station down to the Javits Center next month to demonstrate how it handles automatic infeed, filling, and closing of injection vials.

The Dara SX-310-PP/D is a compact vial aseptic packaging machine that is suitable for cylindrical vials, both RTU (ready-to-use) and supplied in bulk, in glass, plastic, or metal. It can fill them with liquid, semisolid, and powder products in sterile areas or a clean room. Since the machine has been designed in compliance with cGMP and US FDA regulations, and in special accordance with industries that require the utmost accuracy and precision, it’s ideal for the pharmaceutical, biotech, and cosmetic packaging applications.

The versatile SX-310-PP filling station can be equipped with either stainless steel or ceramic valveless rotary piston pumps, or with SpeedFill® peristaltic pumps for liquid products, and with vacuum-pressure fill guns for powders. It features fully servo-driven automation and a compact footprint, and it offers accurate filling and precise stoppering and capping. The low-maintenance Dara SX-310-PP/D is easy to set up for new containers and achieves fast and easy changeover. When using CIP / SIP construction elements, it is not necessary to remove the product contact parts for their cleaning or sterilization.

At NJM Packaging, we’re proud to have this machine as part of our pharmaceutical packaging lineup, and we can’t wait to show you how you can integrate it onto your packaging floor.  Learn more about the Dara SX-310-PP/D aseptic filling, stoppering, and capping machine for vials on our website, or visit us at Booth #2353 at Interphex NYC 2017 at the Jacob Javits Center from March 21-23. 

Register for Interphex for free here, and come check out the new Dara SX-310-PP/D or learn more about how NJM Packaging’s machines can improve your packaging line.

fakjld.jpg

 

Posted in Uncategorized | Leave a comment

A Vision for Full Scale, Isolator-Based Aseptic Filling Systems

By Paul Valerio
Director, Process Technology/ Associate
IPS-Integrated Project Services, LLC

It will be possible to design a large proportion of full scale, isolator-based aseptic filling lines with most required systems and utilities under the typical 10 feet (3 meters) clean room ceiling in the near future.

Will you join me in this vision? I am sure other stakeholders in aseptic fill-finish manufacturing share this desire.

Such an achievement will be highly valuable to the pharmaceutical industry. Current solutions and trends in process technology indicate it is feasible, and perhaps around the corner.

The industry has benefitted greatly from early pioneers of advanced aseptic technology: companies and individuals that pushed the envelope in the past. New filling lines provide greater flexibility, reliability, and higher yields through improved component handling, more accurate dosing, advanced automation, and minimization of waste. Isolator systems provide a quality environment that separates people from aseptic processes and the systems perform automated bio-decontamination cycles, now under two hours. An isolated filling line with state-of-the-art functionality has become feasible for more and more companies, whether they are branded, CMO or generic injectable drug manufacturers.

More progress is needed.

There are still many pharma manufacturing sites, some say hundreds to thousands worldwide, that perform aseptic manufacturing in traditional Grade A clean rooms, relying on fully gowned operators to perform their trained aseptic technique with consistency. They have limited capital, or perhaps limited knowledge of today’s possibilities. World regulatory agencies are applying pressure for barrier technology to make this history. Today, manufacturers with legacy facilities planning upgrades are often looking past Restricted Access Barriers (RABS) and choosing isolator technology once they understand how much isolator design robustness and affordability have improved.

Despite advances in isolator-based filling lines, the need to position significant air handling equipment above the machine adds cost and required space, making this option out of reach for some companies.

I see equipment suppliers already embarked on the vision for more compact full-scale lines. Significant strides in aseptic processing and filling technology are flashing before the pharma industry quite rapidly these days. Transformation of leading suppliers from pure equipment builders to solution providers has a lot to do with the significant progress. Gone are the days when a supplier would react with an attitude of, “you want me to make your machine do what?” Instead, suppliers understand the quality and process requirements of the pharma industry. Not only are they eager to meet the challenges requested of them today but they also have stepped up to proactively advance process technology in collaboration with drug manufacturers.

One such collaboration spawned the development of small-scale, modular systems with a ‘plug and play’ approach. Bausch + Stroebel partnered with isolator supplier, SKAN, to develop VarioSys®. The initial concept used a sterility testing isolator platform designed to fit into lab spaces, i.e. below the ceiling, allowing companies to fill vials one day and syringes the next, all on one platform. A new solution was born. Filler supplier, groninger, and Franz Ziel now offer a similar combined product, called FlexPro. Vanrx Pharmasystems designed its small-scale robotic and isolator-based filler from the ground up, neatly designed for easy installation.

Meanwhile, advances in isolator design for full-scale lines have resulted in more efficient and compact air handling. Bus-sized air handlers from the past have become compact modules. Some solutions already incorporate all air handling on top of the isolator footprint, albeit above the ceiling.

One can see a natural progression, making isolators for full-scale lines look more and more like those used for the smaller scale systems. There are technical challenges to make the full scale filler/isolator systems even more compact, but recent developments clearly show that solution providers are up to the task. Just as the modular systems have opened up isolator-based filling to many companies on a smaller scale, the proposed step change for more compact full-scale lines will also have a significantly positive impact on the industry.

The vision I put forth is not a ‘man on the moon’ moment. My colleagues and I have a few ideas of our own, and the star wheels are already in motion with current design trends. It is simply a matter of time and priority. Let’s do what our industry does best and collaborate to make it happen.

Join my colleagues and me to meet the innovators of the small scale/modular system suppliers mentioned above at the Advanced Small-Scale Aseptic Technology Tour, hosted by IPS at INTERPHEX in New York on 22 March 2017.

Posted in Uncategorized | Leave a comment

USP Chapter 41 Updates and Breakdown

image

By: Fred Algieri Jr., Atlantic Scale Company

USP Chapter 41 has updated their testing requirements to determine the suitability of balances. Here is a quick reference on the important aspects and updates:

Chapter 41 is a REQUIREMENT for QC analysis measurements.

There are two required tests in Chapter 41, Accuracy and Repeatability. Both tests have tolerances of 0.10%.

The Accuracy requirement is applicable between 5% and 100%.

Calibration weights being used in the Accuracy check must have an accuracy of NMT 1/3 of the balance tolerance for that respective test point. This can be the tolerance of the nominal value of the weight or it can be the uncertainty of measurement for the weight when applying the actual weight value from the certificate.

The Repeatability test consists of 10 replicate weighings. The resulting standard deviation is to be used in the following calculation:

(2 × SD) ÷ Desired Minimum Sample Weight ≤ 0.10%

The coverage factor is now 2. Previously it was 3.

The denominator in the calculation is now stated as the “Desired Minimum Sample Weight”, not the weight applied as previously stated.

There is also now a “standard deviation floor” of 0.41d (d being the scale interval or the readability of the unit). This means if the determined standard deviation from the replicate test is less than the 0.41d value then the 0.41d value will need to be used in the assessment calculation.

The 0.41d (standard deviation floor) limits the low end measuring range to the below:

  • 8.2 mg minimum sample weight (lowest possible) 5-place (0.00001 g) analytical balances
  • 82 mg minimum sample weight (lowest possible) 4-place (0.0001 g) semi-analytical balances
  • 820 mg minimum sample weight (lowest possible) 3-place (0.001 g) toploading balances
  • 8.2 g minimum sample weight (lowest possible) 2-place (0.01 g) toploading balances

Again, the above values are the lowest possible minimum weights. The determined standard deviation needs to be at or lower than the 0.41d value to obtain the above results. This usually requires a very good environment. Most test results for on-site repeatability testing is as follows:

  • 10 mg – 20 mg minimum sample weight (commonly determined) 5-place (0.00001 g) analytical balances
  • 100 mg – 200 mg minimum sample weight (commonly determined) 4-place (0.0001 g) semi-analytical balances
  • 1 g – 2 g minimum sample weight (commonly determined) 3-place (0.001 g) toploading balances
  • 10 g – 20 g minimum sample weight (commonly determined) 2-place (0.01 g) toploading balances

Successful repeatability testing mostly depends on the balance quality, the controlled environment it is in, and also the balance operator’s dexterity and experience in performing the repeatability test.

Posted in Uncategorized | Leave a comment