Particles in the Spotlight – Observations from Discussions at the PDA Conference on Freeze Drying Technologies 2014

To reduce and detect particulate matter is a shared responsibility between Container Closure component suppliers and the pharmaceutical industry. Keeping the patient´s safety in mind, lively discussions about particle inspection were held in the panel session at the PDA Conference on Freeze Drying Technologies. The group focused on lyophilized presentation of drug formulations. State-of-the-art inspection techniques should be used for finished drug product that bears the risk of embedded particles or fibers within the lyophilized product, where they are hidden from detection during visual inspection procedures.

The main question focused on the feasibility and potential ways to include an opto-electronic inspection system even before the freeze drying process. At various stages, there may be sources identified to cause particulate contamination of the finished drug product. All related primary container closure systems (glass or plastic vials, elastomeric closures etc.) as well as any equipment have the potential risk to bring in particles.

Rubber closures for aseptic filling follow a manufacturing, washing and sterilization process to reduce particulate burden. Glass vials run post-washing through a heat depyrogenation tunnel in which there is a low risk that a vial may explode and shed particles into other vials. Glass containers run the risk of breakage during processing and handling, which could happen on turn tables, in the heat tunnel, on moving parts of the filling line or in the freeze dryer. Breakage can occur if the glass is under tension and mechanical stress. ETO sterilization of vials could be an alternative to the processing in the heat tunnel, but needs to be investigated to further detail.

Insight was shared that fibers will be present at the top while steel particles from the equipment accumulate at the vial base in liquid fills. The latter may be embedded in the freeze-dried drug product and could be invisible during final inspection.

Additional mechanical stress will be placed on container closure systems at the crimping stage and during labelling and application of secondary packaging material. In the case of glass containers, this requires attention to reduce glass breakage.

There is general reluctance to implement visual inspection on the liquid fill before freeze drying because the vials are spun, which causes the product to shift upwards on the inner glass walls. This may compromise the freeze drying performance and appearance of the lyophilized drug product. A suggestion was made to use vials from the Media-Fill for comparative particle inspection since these will not run through the freeze-drying cycle.

Finally, there was agreement on one important fact: finding the root cause analysis for particles is particularly complex.

Author:

Heike Kofler 2014_small

Heike Kofler, PhD
West Pharmaceutical Services

Reference and acknowledgements to the participants and organizers of the PDA Conference Freeze Drying Technologies held in Brussels Belgium on 16th and 17th September 2014

Managing Residual Moisture In Lyophilized Drugs

Parenteral drugs that are moisture sensitive are produced in a lyophilized state to protect against product degradation caused by moisture. As a result, when considering the stability and shelf life of lyophilized drugs, the residual drug moisture content is critical. It is also a crucial component in the dossier submitted for regulatory filing, which begs the question: How shall the moisture level in the lyophilized drug product cake be maintained during the drug product’s shelf life?

Generally, there are three potential sources where moisture can be introduced into a lyophilized drug cake during its shelf life: (1) through the stopper-vial interface, (2) residual moisture from the elastomeric stopper and (3) moisture permeation through the stopper. Based on this analysis, the following aspects should be considered to reduce the residual moisture in the lyophilized drugs.

Container Closure Integrity (CCI)

Moisture in the environment can ingress into a vial through the stopper-vial interface. The glass vial, stopper and aluminum crimp seal should meet strict compositional and dimensional specification with the absence of critical defects to prevent moisture from getting into the lyophilized cake through these leaks.

Leaks can be detected using a variety of CCI test methods, including dye ingress, vacuum decay and helium leak test.

Residual Moisture In Stoppers

Due to the potential for transfer of moisture from the stopper to the product during storage, stopper moisture content can have a significant impact on the stability of lyophilized drug products. It is necessary to choose a stopper formulation with low moisture retention that is easy to dry.

Steam sterilization is a typical method used in the pharmaceutical industry. During this process, the elastomeric closures will absorb the most moisture. Sufficient drying after sterilization is necessary for reducing the residual moisture content in the stopper. West recommends a minimum of 4 hours drying at 105 ℃ on the stoppers after sterilization.

Moisture Vapor Transmission Rate (MVTR)

Moisture vapor transmission rate is a measure of the tendency of an elastomeric formula to allow permeation of moisture. The moisture will migrate from the environment through the stopper and consequently to the lyophilized product cake over time, which is dependent on the MVTR of the stopper formulation. The MVTR should be low throughout the shelf-life of the product. Examples include West’s modern formulations: 4023/50 Gray and 4432/50 Gray, which have low MVTR of 0.1 g/m2·day (tested using a 0.035” thick test plate).

For more information, please contact your Technical Customer Support representative.

Author:

Lynn Yao
TCS Engineer
West Pharmaceutical Packaging (China) Company Ltd
Email: Lynn.Yao@westpharma.com

The Tech Group’s Mike Treadaway Receives Philanthropic Leadership Award

The Tech Group’s Vice President and General Manager, Mike Treadaway, was recently honored with the Spirit of Philanthropy Award at the Association of Fundraising Professionals Greater Arizona Chapter’s 30th Annual Philanthropy Leadership Awards Dinner. The celebration honors those who advance philanthropy with awards including the Spirit Award, which recognizes outstanding philanthropic contributions to nonprofit organizations.

Since 2011, The Tech Group has been fundraising for Upward for Children & Families, a nonprofit organization that aids severely disabled and/or medically fragile children and their families with skills development, learning and therapy. Upward nominated Mike and The Tech Group Arizona team for the award.

“We’ve all worked really hard for Upward, and we love doing it,” said Mike, who recently completed an Ironman triathlon that raised almost $11,000 for Upward. Tech Group team members have been helping to raise funds for the organization since 2011, when the West without Borders campaign asked facilities to select a local charity.

Mike Treadaway, who was awarded the Spirit of Philanthropy Award, recently completed an Ironman triathlon to raise money for Upward for Children & Families.

Mike Treadaway completed an Ironman triathlon to raise money for Upward.

“Our first year, we had about 12 participants run the Ragnar Relay, which is a 200 mile race, and we raised about $20,000 for Upward,” remembers Mike. “Now nearly every team member at The Tech Group’s Arizona facilities participates in a variety of fundraising activities, and over the years we’ve donated more than $250,000 to Upward.”

In addition to the monetary donation, which provides Upward with ‘unrestricted’ funds used to help with facility improvements and to create a wish-fulfillment program for the children, Tech Group team members have donated time and talent to help improve the facility.

Tech Group team members participate in the Ragnar Relay each year, a 200-mile raise to raise money for Upward.

Tech Group team members participate in the Ragnar Relay each year, a 200-mile raise to raise money for Upward.

“We’ve helped with a number of improvement projects, including replacing the tile floors, painting the buildings, putting in green space and landscaping, building storage sheds, and painting brightly colored murals on the inside and outside walls of the building for the children.”

In 2014, Tech Group team members raised over $72,000 cash for Upward, and will continue to contribute to the facility with the upcoming 2015 West without Borders campaign.

“We’ve all earned this award,” said Mike. “Every employee in the valley has an opportunity to get involved in one way or another and they’ve all jumped in to help. It’s an honor to work with so many who can be so extremely supportive to those in need.”

For more information about Upward for Children & Families, visit their website: http://www.upwardaz.org/

 

Plunger Rods: Enabling the Complete Syringe Drug Delivery System

The plunger rod is a fundamental feature of a complete syringe drug delivery system. There are three key functional characteristics that all pharmaceutical manufacturers should consider when determining the appropriate plunger rod for a specific drug product and syringe system.

  • Dimensional fit of the plunger rod to the plunger threads: The threading of the plunger and plunger rod must be compatible to ensure appropriate engagement of the plunger rod in the syringe system.
  • Break loose and gliding force: The plunger rod must be rigid, and able to support the forces associated with the process of delivering the drug product. Also, the plunger rod should not negatively impact the plunger performance, and increase the break loose and gliding forces.
  • Disengagement force: The disengagement force is the force required to pull-out (not unscrew) the plunger rod from the plunger threading. The plunger rod and plunger must be mated appropriately to ensure integrity is maintained during the patient or care-giver administration of the drug product.

Cote Plunger Rods

West and Daikyo plunger rods are designed to match the threads of a variety of plungers, while also meeting the diameter and length requirements imposed by various syringe barrels. The dimensional fit, break loose and gliding force, and disengagement force associated with each respective West plunger rod and plunger combination are desirable.  Additionally, West can provide plunger rods with alternative material options for specific durability and functional needs, as well as customized colors for differentiation.

For any questions and inquiries regarding the variety of plunger rods offered by West and Daikyo, as well as documentation highlighting studies performed to assess the key functional characteristics, please email Simon.Cote@westpharma.com or TCS.Americas@westpharma.com.

Author:

Simon Cote

Simon Côté
Senior Technical Support Engineer
Simon.Cote@westpharma.com

Particulate Matter in Injectable Drug Products – What are the Regulations?

As regulatory expectations increase, drug product manufacturers face increased pressure to produce products free of defects and minimize rejects of finished drug products. Particulate matter in finished pharmaceuticals can come from a number of sources, including the ingredients in the drug product, manufacturing equipment or the container closure system.

Regulations, such as USP <1> Injections and <788> Particulate Matter in Injections, have enhanced the complexity and confusion surrounding both visible and subvisible particulate in finished products.  For example, USP <1> Injections states that finished injectable drug products must be “essentially free from visible particulates.”1 It does not, however, clearly define the limitations on the quantity of particulate.  Referenced in USP <1> Injections, USP <788> Particulate Matter in Injections (harmonized with the corresponding European Pharmacopoeia and Japanese Pharmacopoeia text), provides limitations on particle in the ranges of 10 – 25 um and 25 um and greater. 2 More recently, however, USP <790> Visible Particulates in Injection (effective August 2014) provided some clarity to the statement “essentially free” with a more precise finished drug product sampling plan and AQL definition. 3

Novapure new 2

As a result of these regulations, greater attention to particulate load in the finished injectable drug products has resulted in increased scrutiny of the individual components constituting the packaging system. Pharmaceutical manufacturers can collaborate with packaging suppliers to reduce particulate matter in finished drug products by supplying components with a focus on minimizing loose, embedded and adhered particulate. For these customers, West offers NovaPure® components, developed under the principles of Quality by Design (QbD). West developed these components using a comprehensive quality target product profile that includes industry leading visible and subvisible particle specifications as part of the component critical quality attributes.  In turn, the use of packaging components designed to meet high-quality standards can aid in reducing the risk of rejected drug products.

Author:

Jessica Saggers

Jessica Saggers
Senior Technical Account Specialist
Jessica.Saggers@westpharma.com

References:

  1. USP 37 – NF 32. General Chapters: <1> Injections (2014), US Pharmacopeia/National Formulary
  2. USP 37 – NF 32. General Chapters: <788> Particulate Matter in Injections (2014), US Pharmacopeia/National Formulary
  3. USP 37 – NF 32. General Chapters: USP <790> Visible Particulates in Injection (2014), US Pharmacopeia/National Formulary

NovaPure® is a registered trademark of West Pharmaceutical Services, Inc., in the United States and other jurisdictions.

The Difference Between “Latex,” “Natural Rubber,” “Natural Rubber Latex” and “Dry Natural Rubber”

Allergy to natural rubber latex was first documented in the late 1970s. The condition now commonly known as “Latex allergy” is caused by the proteins produced from the rubber tree (Hevea brasiliensis) that are still present in the products manufactured from natural rubber latex. This allergy is not only caused by the proteins, but also by the chemicals and/or residues thereof.

Even though people are aware of this allergy, many do not realize that there is a difference between the various terms  “latex,” “natural rubber,” “natural rubber latex” and “dry natural rubber” and often use them interchangeably and incorrectly. This article may help medical device/drug manufacturers, medical staffs and end-users to gain some clarity on the terms, as well as West’s “natural rubber” labelling per labelling guidance by the U.S. Food and Drug Administration (FDA).

  • Latex – Latex refers to any polymer in a water-based liquid or viscous state. The word by itself does not refer to natural rubber latex.
  • Natural rubber – This term includes all materials made from or containing natural latex. In other words, it refers to natural rubber latex, dry natural rubber, and synthetic latex or synthetic rubber that contains natural rubber in its formulation.
  • Natural rubber latex – A milky fluid that consists of extremely small particles of rubber obtained from plants, mainly from the rubber tree, dispersed in an aqueous medium. Products are then formed from natural rubber latex by dipping, extruding, or coating via the natural rubber latex (NRL) process. Examples of such products are medical gloves, catheters and tracheostomy tubes.
  • Dry natural rubber – This is rubber produced by the dry natural rubber (DNR) process, which involves the use of coagulated natural latex in the form of dried or milled sheets. Products are formed from dry natural rubber by compression molding, extrusion, or by converting the sheets into a solution for dipping. Example of products that may contain dry natural rubber are syringe plungers, vial stoppers and injection ports on intravascular tubing.

At West, natural rubber latex is not used in the manufacture of our products. On the other hand, dry natural rubber is used in some West’s formulations. West certifies the absence or presence of dry natural rubber in West rubber formulations per the FDA’s guidance, by using the terminology: This Product Contains Dry Natural Rubber.

More info on the FDA’s labelling guidance could be found here.

Please contact West’s Technical Customer Support for more info about the formulation/product range available in West with/without dry natural rubber.

Author:

Boo Jia Min
Technical Support
JiaMin.Boo@westpharma.com

FortSchritt Helps Twins Along The Way

Through the global West without Borders charitable fundraising campaign, West team members around the world have raised funds for children in need in the places where we all live and work.  Often, we don’t get a chance to see the faces of those we help, but today we’re going to introduce you to two young ladies with a remarkable story.  Twins Aurelia and Charlene attend  FortSchritt, a facility in Aachen, Germany, that offers conductive education to children with movement disorders.

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The girls were born five years ago with a rare genetic condition called microdeletion syndrome. Despite a normal pregnancy, it soon became apparent that something was not right. In the newborn phase, they had problems swallowing and one of the girls needed respiratory support.  The family did not receive much encouragement from the medical staff at the hospital.

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“There was no one to turn to, and we had no official diagnosis,” recalls the mother of the twins, Barbara Haugg-Minet. The family was left to their own devices but mastered the ups and downs remarkably well. Having a low muscle tone prevented Charlene and Aurelia from sitting and standing unaided. They found other ways to move around such as crawling up the staircase while lifting their little heads from step to step.

“Each of them has a very unique personality,” says their mother. Aurelia shows some signs of autism. She needs a structured daily routine and, like her sister, she is very sensitive to noise. Charlene is very stubborn and clever. Both are loving and affectionate.

By coincidence, the family learned that FortSchritt was looking for toddlers to benefit from conductive therapy. Aurelia and Charlene were 20 months of age when they joined FortSchritt as the youngest children in the group.

“They responded really well to the therapy and made great progress within a short period of time, like walking up the stairs,” said Barbara.

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Unfortunately, the period of joy came to an abrupt end when Charlene was admitted to the hospital suffering from convulsions and fever, eventually falling into a coma. As it turned out, she had suffered a seizure. Fortunately, Charlene survived but regressed and lost all of her skills including her speech. Half a year later, her twin sister suffered the same fate. In a few months, however, the girls were back at FortSchritt where several of the children were sitting around a table. Their instructions was to push back their chairs and stand up.

“I was thinking to myself that this task is impossible for my twins, when suddenly, Charlene stood up and pushed back her chair,” recalls their mother.

The twins are living proof that good things happen when you least expect it. Aurelia and Charlene have been stable ever since and continue to make progress as FortSchritt helps them along the way.

Author:

Nadine Gerstler
Marketing Information & Communications Specialist Europe
Nadine.Gerstler@westpharma.com

West without Borders is not affiliated with Doctors Without Borders®, which is a registered service mark of Bureau International de Médecins Sans Frontières.

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