Tag Archives: biotechnology

FDA Researchers Explore Fundamental Chemical Reaction that Could Threaten the Quality of Therapeutic Protein Products

In a recent news release the FDA described research it has conducted regarding detection of protein carbonylation, an oxidative reaction that may occur in therapeutic protein drug products during manufacture, storage, use, and transport potentially causing structural alterations and threatening stability, quality, and clinical efficacy of such products. FDA scientists have refined an antibody-binding assay with high sensitivity to detect protein carbonylation allowing many samples to be studied in a short period of time under a variety of conditions. The assay is being used to study the tendencies of various protein products to undergo oxidative carbonylation and whether containers and chemicals that contact proteins may start or speed up these reactions. The goal is to develop methods such as addition of stabilizing agents to counteract protein carbonylation in order to maintain stability, purity, and potency of therapeutic protein products and to avoid any harmful adverse reactions such as unwanted immune responses.

See https://www.fda.gov/Drugs/NewsEvents/ucm571068.htm

 

Full FDA Story:

The potential for biotechnology to transform medicine remains immense, with several therapeutic protein products already having come into widespread clinical use and hundreds of proteins under clinical investigation. For the FDA, the regulatory oversight of therapeutic protein development poses a great challenge, not only because of the increasing number of products, but also because proteins, by their very nature, are highly variable, and compared to small-molecule drugs, more likely to undergo chemical reactions over time. Chemical reactions that occur in these proteins (for example, during storage in vials before administration to patients) can have a significant impact on protein function. For FDA scientists in the CDER Office of Biotechnology Products (OBP), these reactions are of great interest because they can directly impact the quality, safety, and efficacy of protein products.

For decades—before the biotechnological revolution and the rise of therapeutic proteins—FDA drug reviewers focused primarily on small-molecule drugs. Aspirin, for example, contains only nine carbon atoms, whereas the modern protein product bevacizumab contains well over 6,000 carbon atoms. In general, proteins also contain sulfur atoms (bevacizumab has 44!), and biochemists have long known that sulfur-containing molecules are prone to undergo reactions related to the presence of unstable oxygen and other atoms in our environment. (Proteins are not the only molecules that undergo such oxidative reactions. The rusting of iron tools and statues, where iron atoms interact with oxygen atoms in the air and water, is also oxidative.) In some instances, oxidized proteins can be damaged in various ways, which could in turn trigger an unwanted immune response in patients. This feature is a unique concern with therapeutic proteins.

Recently, biochemists have begun to investigate the exact locations of oxidative reactions within large intact protein molecules. Laboratory researchers in OBP, for example, have published important new information (see References) concerning protein carbonylation, which entails the addition of a single atom of oxygen, originating from the environment, to discrete carbon atoms (rather than sulfur atoms) within protein molecules. Although protein carbonylation has been recognized within the context of disease and age-related conditions, its occurrence during the manufacture, storage, use, and transport of therapeutic proteins is a relatively new area of study. For pharmaceutical quality scientists, key issues include: understanding the different tendencies of various protein products to undergo oxidative carbonylation; identifying the role that containers and chemicals that contact proteins may have in these reactions; and discovering reliable methods for specifically and consistently detecting and controlling carbonylation.

To detect protein carbonylation, the OBP team has refined an antibody-binding assay that takes advantage of the reactivity of the “carbonyl group,” which is the name given to the carbon- and oxygen-atom grouping that occurs upon protein carbonylation. Carbonyl groups that form in proteins can make the entire protein molecule less stable and lead to damage after degradation or aggregation. By exposing the carbonyl groups that are formed in proteins to a laboratory reagent known as DNPH, the OBP team found that different proteins undergo carbonylation at different levels and at specific sites. The rate and site of carbonylation can depend on temperature, time, and other variables, such as the presence of small amounts of metals that accelerate protein oxidation reactions. The laboratory also investigated the tendency for certain additives in drug formulations to start or speed up these reactions. The methods developed by the team allow many samples, under a variety of conditions, to be studied in a short period of time. Moreover, the method is sensitive enough to detect as little as a single carbonylation modification within a large protein molecule.

The findings of the OBP team may help protein drug developers produce therapeutic proteins under optimized manufacturing conditions, potentially with structural alterations or by adding stabilizing additives that could prevent harmful carbonylation reactions. More stable protein drugs could offer a longer shelf life, reduced risk of quality problems, and more predictable clinical performance. Understanding reactions such as protein carbonylation may result in improved versions of current drugs or new drugs with superior stability, purity, and potency. Above all, the goal is to have safe and effective high-quality protein products available for patients. 

Sentry BioPharma Services offers temperature sensitive biological product management to pharmaceutical companies, hospitals and organizations with need for validated  GMP storage, labeling, kitting and temperature-sensitive drug distribution services.  For more information about how Sentry’s GMP services can help protect the integrity and delivery of your biological products to patients, contact Sentry via email or by phone at 1-866-757-7400.

Sentry’s Controlled Substance Program Strengthens the Reliable and Secure Pharmaceutical Drug Supply Chain

Regulatory oversight shapes every dimension of controlled substances: licensing, registration, storage, security, use, inventory and controlled drug disposal. Finding a Drug Enforcement Administration (DEA) licensed partner to store, distribute and manage returns and destruction of Schedule III-V controlled substances while maintaining regulatory and quality standards required for a secure pharmaceutical supply chain can be a challenge. Sentry BioPharma Services provides seamless product management required to safeguard controlled substances which are brought into Sentry’s custody and care.

pills2

Features & Benefits of Sentry’s Controlled Substance Program

DEA Regulation Secure Storage – Inspected and approved by the Drug Enforcement Administration  in 2014, Sentry’s state-of-the-art controlled substance capacity provides secure and reliable storage to support your pharmaceutical supply chain needs.

Controlled Substance Importation/Exportation – Sentry’s controlled substance importation and controlled substance exportation capabilities provide pharmaceutical organizations unique flexibility in the drug supply chain. This coupled with Sentry’s high quality standards affords pharmaceutical companies a competitive advantage throughout the drug development process.

Redundant Systems and Extensive Security Measures Product safety, identity, strength, purity and quality (SISPQ) remain intact.  Sentry features which support this agenda include:

  • Auxiliary power feeds and back-up systems
  • Continuous (24/7) security monitoring
  • Foreign Trade Zone (FTZ) status which allows controlled substances to be internationally shipped directly to Sentry where DEA, Customs & Border Patrol (CBP) and FDA clearances can be obtained within the security provided by Sentry’s GMP facility
  • Physical plant security
  • Redundant HVAC systems
  • Secure data and document programs

Pharmaceutical Labeling and Packaging – Sentry’s light pharmaceutical manufacturing capabilities help streamline clinical trial distribution and commercial drug distribution with one stop shop GMP labeling and GMP secondary packaging.

Drug Product Return and Drug Disposal Services – Sentry completes the controlled substance supply chain with a full-service approach to product guardianship.  Our drug product return and drug destruction program ensures project integrity, reliable inventory tracking and public safety from development to launch.

For more information about how Sentry can provide controlled substance supply chain solutions for your project, contact Sentry via email or by phone at 1-866-757-7400.

Sentry Raises Public Awareness for DEA’s National Prescription Drug Take-Back Day Initiative

As part of the U.S. Drug Enforcement Administration’s (DEA’s) National Prescription Drug Take-Back Day Initiative (NTBI), people will be able to dispose of expired, unwanted or unused prescription drugs on Saturday, October 22, 2016 from 10:00 a.m. to 2:00 p.m. at numerous collection sites around the U.S.

The DEA collected a record amount of meds during the 11th annual National Prescription Drug Take-Back Day on April 30, 2016.  According to the DEA’s May 6, 2016 press release, the DEA and over 4,200 of its state, local, and tribal law enforcement partners collected 893,498 pounds of unwanted medicines—about 447 tons—at almost 5,400 sites spread through all 50 states, beating its previous high of 390 tons in the spring of 2014 by 57 tons, or more than 114,000 pounds.

dea-take-back-day

The top five states with the largest collections, in order, were:

  1. Texas (almost 40 tons)
  2. California (32 tons)
  3. Wisconsin (31 tons)
  4. Illinois (24 tons)
  5. Massachusetts (24 tons)

“I am very proud of our state officials and residents,” said Ms. Jennifer Marcum, Sentry BioPharma Services’ chief executive officer.  Ms. Marcum continued, “Indiana’s authorities collected 29,125 pounds (14.6 tons).  That’s an enormous amount of unwanted prescription drugs and controlled substances to be safely removed from the pharmaceutical supply chain.  The statistics best illustrate how much the people of Indiana care about this important matter; no question about it.”

Marcum continued, “During the event, people can anonymously bring unwanted prescription pharmaceuticals and over-the-counter (OTC) medications to a participating drop-off site for proper drug disposal by law enforcement authorities with no questions asked.  The service is free and an ideal way to preserve the environment from pharmaceutical contamination.  This is a terrific opportunity to safely dispose of accumulated prescription drugs and medications that may have expired or are simply unwanted.”

The FDA’s Ilisa Bernstein, Pharm.D., J.D., offers a few more helpful tips when discarding drugs:

  1. Scratch out all identifying information on the prescription label to make it unreadable. This will help protect your identity and the privacy of your personal health information.
  2. Do not give your medicine to friends. Doctors prescribe medicines based on your specific symptoms and medical history. Something that works for you could harm another person.
  3. When in doubt about proper drug disposal, ask your pharmacist.

For more information about the DEA’s National Prescription Drug Take-Back Day Initiative, general public inquiries can be made by calling the DEA toll free at: 1-800-882-9539.

If you would like to learn more about Sentry’s pharmaceutical drug destruction services, please contact Sentry via email or by phone at 1-866-757-7400.

Features & Benefits of a Pharmaceutical Foreign Trade Zone

What is a Foreign Trade Zone?

The U.S. Foreign Trade Zone program was established by the Foreign Trade Zone Act of 1934 to “expedite and encourage foreign commerce” in the United States. Certain geographical areas, in or adjacent to Customs Ports of Entry, can obtain foreign-trade zone (FTZ) status and receive commercial merchandise under the same Customs standards as if it were outside the commerce of the United States. Any merchandise, including pharmaceutical products, admitted and held in a foreign trade zone can be exempt of any Customs duties, tariffs and other ad valorem taxes. No duty or back taxes are charged on “value-added,” or foreign-sourced parts or materials incorporated into a finished product using U.S. parts and labor until the product is officially imported into the U.S. Commerce. This tariff and tax relief lowers the costs of U.S.-based organizations engaged in international trade while creating and retaining employment and capital investment opportunities that result from those operations.

Benefits to the Biopharmaceutical Industryshutterstock_367703690

Pharmaceutical and biopharmaceutical companies can take advantage of Sentry’s GMP temperature-sensitive pharmaceutical storage and light manufacturing facility, which  resides in a foreign trade zone.  Sentry’s zone allows drug product to reside within the product’s designated temperature range, (such as API, biologics, controlled substances, etc.), while awaiting clearance for importation by the CBP and approved for distribution by the Food & Drug Administration (FDA).

During its stay in the FTZ, the biopharmaceutical  product can be further labeled and secondarily packaged  while greatly mitigating the numerous logistic and economic challenges encountered throughout the  drug importation and development process.

Logistic Benefits 

Unlimited Storage Terms Term of pharmaceutical material storage in an FTZ is indefinite.
Eliminated U.S. Quota Restrictions Product previously subject to quota limitations is now exempt from such restrictions.
Strengthened Foreign Pharmaceutical Supply Chain Eliminate administrative and importation hold-ups at Customs and ports of entry by bringing product straight to our GMP pharmaceutical storage environments ensuring product integrity: safety, identity, strength, purity and quality (SISPQ) along the drug supply chain.
Uninterrupted Local Manufacture Prior to Importation Product can be labelled, kitted and packaged and stored in the United States until need for importation into U.S. Commerce and Customs Clearance.
Expedited Release to Market Product can be held in an FTZ until FDA approval, greatly reducing time and logistic hassle from manufacturer to end-user.

Economic Benefits 

Duty Deferral or Duty Aversion  Import, admit and hold product without paying U.S. Customs duties.
Zero Inventory Taxes All materials held in an FTZ are exempt from state, county and local ad valorem taxes.
Country of Origin Marking and Labeling Country-of-origin labels are non-required on product admitted to an FTZ freeing companies from this expense.

Sentry BioPharma Services’ pharmaceutical supply chain management expertise and FTZ status across all storage environments ensures product integrity and project management flexibility.

For more information about how Sentry’s Foreign Trade Zone can help you optimize your medical and pharmaceutical import/export process, contact Sentry via email or by phone at 1-866-757-7400.

Read more about the Greater Indianapolis Foreign Trade Zone: inzone.org

Sentry’s Leaders Attend Exclusive FedEx® Freight Lunch Event

Today, Sentry’s Ms. Jennifer Marcum and Mr. Dwayne Marcum attend an exclusive lunch event hosted by FedEx® at the Indianapolis FedEx® Freight Terminal located at 4750 Decatur Blvd, Indianapolis, 46241. 370_FedExGate

FedEx® Freight now offers two sizes of standard boxes for less-than-truckload (LTL) shipments.  Ms. Jennifer Marcum, Sentry’s Chief Executive Officer, recognizes the ease of use a flat-rate box option by saying, “The larger pallet box (48” x 40” X 38”) is ideal for small businesses needs as it simplifies the negotiation and shipping of freight under 1,200 pounds within the continental United States.  By removing the National Motor Freight Classification® (NMFC®) from the equation, FedEx® is further standardizing a shipment’s transportability while ensuring cargo is adequately protected to withstand the normal variabilities of the LTL environment.  The added FedEx® brand security and quality reputation appeals to Sentry’s tailored small business model and can satisfy our pharmaceutical clients with a stable formulation in an effective container closure system at ambient conditions.”

“Sentry BioPharma Services ships to all eight of the FedEx® Freight Zones,” adds Mr. Dwayne Marcum.  He continues, “The pallet service is also ideal for transporting marketing supplies to/from pharmaceutical and biotechnology industry conferences like BIO 2017 which will be hosted in San Diego, California.  For example, to ship one pallet of marketing materials from Indianapolis, Indiana to San Diego, California using the FedEx Priority Solution results will cost a flat $248.00 one way.  The online tool makes it easy to know the rate and expected delivery time for a Zone 7 shipment.  Because FedEx® Freight has a solid reputation for on-time delivery and the logistics are transparent, this makes our strategic planning and budgeting much easier.”

For more information about how outsourcing can increase the efficiency of your company’s pharmaceutical supply chain, contact Sentry via email or by phone at 1-866-757-7400.

Find out more information here: https://smallbusiness.fedex.com/freightbox.html

Melanoma: A Preventable Killer

Moles to Melanoma: Recognizing the ABCDE Features by the National Cancer Institute

Sentry BioPharma Services provides oncology product management, global drug distribution, GMP storage and specialized services like pharmaceutical labeling, packaging and kitting.  Sentry plays a critical role in protecting temperature-sensitive product safety, identity, strength, purity and quality (SISPQ) for both cancer clinical trials and commercial drug distribution for a wide range of pharmaceutical and biotechnology clients. 

The focus of our post this week is preventable cancer.  Therefore, we are sharing this article from the National Cancer Institute (NCI) concerning a multi-year study of skin lesions and moles which resulted in melanoma.

Skin Cancer: Body Mole Map

Skin Cancer: Body Mole Map

Key Points
  • Melanoma incidence rates have doubled from 1982 to 2011.
  • In 2011, in the United States, there were 65,647 cases of melanoma and 9,128 deaths.
  • The annual cost of treating newly diagnosed melanomas is projected to triple by 2030.
  • Melanoma can be prevented by reducing ultraviolet radiation exposure from sunbathing and indoor tanning and increasing the use of sun protection.
  • A comprehensive national skin cancer prevention program could avert 230,000 melanoma cases and $2.7 billion in initial year treatment costs from 2020 to 2030.
  • Additional information available at https://www.cdc.gov/vitalsigns.

Introduction

Skin cancer is the most common form of cancer in the United States, and melanoma is responsible for the most skin cancer deaths with over 9,000 each year. An individual dying from melanoma loses an average of 20.4 years of potential life. Total melanoma treatment costs are about $3.3 billion annually in the United States. Melanoma is the fifth most common cancer for men, and is the seventh most common cancer for women. More than 90% of melanoma cases in the United States are attributed to skin cell damage from ultraviolet (UV) radiation exposure.

The National Cancer Institute has collected photographs of 29 different pigmented skin lesions, presented as case studies, to help patients and other individuals recognize common moles, dysplastic nevi (DN), and melanomas that started from DN. Each case series shows changes in an individual pigmented lesion (mole) over time and across the various mole changes typically seen in individuals from U.S. melanoma-prone families.

What are moles, dysplastic nevi and melanoma?

  • Common MolesA non-cancerous growth on the skin that is formed by a cluster of melanocytes (cells that make a substance called melanin, which gives color to skin and eyes). A mole may be dark or flesh-colored and may be raised from the skin.
  • Dysplastic Nevi (DN) – A type of mole that may develop into a type of skin cancer called malignant melanoma. They look different from common moles. A DN is often larger with borders that are not easy to see. Its color is usually uneven and can range from pink to dark brown. Parts of the mole may be raised above the skin surface.
  • MelanomaA form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

Who is the intended audience?

  • The pictures used in this article were taken over more than a 35-year period. They show moles and melanomas from participants enrolled in the NCI Familial Melanoma Study.
  • The pictures show examples of the variability in pigmented lesions in U.S. melanoma-prone families.
  • Because most of the study participants are Caucasian, the nevi and melanomas shown are not representative of those found in individuals with darker skin.
  • Melanomas and lesions suspicious for melanoma vary widely in appearance; these pictures should not be used to diagnose melanoma.
  • NCI does not provide medical advice to users of its website.
  • Consult with a qualified health care provider if you have concerns about your skin.

About the photos

  • The photographs have variations in color due to differences in photography equipment, lighting, and skin color of the individual (e.g. sunburned or suntanned).
  • Photographs are standardized to ease viewing.
  • Rulers show size of the moles and melanomas in millimeters.

This study only includes individuals in U.S. melanoma-prone families who are at high-risk of developing this form of skin cancer. As shown in Figure 1, Caucasians are at the highest risk of developing melanoma. To date, this study has not identified or enrolled any non-Caucasian families.  Therefore, this tool does not provide images representative of other ethnicities.

Figure 1: Melanoma incidence by race/ethnicity in the U.S. Surveillance, Epidemiology and End Results Program 1975-2012

chart

Reference: Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2012, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2012/ , based on November 2014 SEER data submission, posted to the SEER web site, April 2015
Data points are not included for clarity of presentation, but may be found at https://seer.cancer.gov/csr/1975_2012/sections.html Figure 16.2.

Where can I find information on Skin Cancer in other Ethnicities?

  • National Cancer Insititure – “Anyone Can Get Skin Cancer”, includes images of skin cancer in people with darker skin
  • Skin Cancer Foundation – “Skin Cancer and Skin of Color”

Where can I find information about Non-Melanoma Skin Cancer?

This collection does not include any pictures of non-melanoma types of skin cancer (e.g. basal cell or squamous cell), since they arise from different cell types in the skin they look very different from melanoma. For information on those types of skin cancer, visit the following websites: https://www.cancer.gov/types/skin & https://www.cancer.org/cancer/cancercauses/sunanduvexposure/skin-cancer-facts.

What information does this resource provide?

This resource provides information about and examples of: common moles, dysplastic nevi (atypical moles) and melanoma. This collection does not include any pictures of non-melanoma types of skin cancer (e.g. basal cell or squamous cell). Since they arise from different cell types in the skin, they look very different from melanoma. Additional information, including resources for other types of non-melanoma skin cancer, can be found in the Intended Audience section.

The “ABCDE” rule describes the features of early melanoma. These features are:

Asymmetry – The shape of one half does not match the other half.

Asymmetry

Border that is irregular – The edges are often ragged, notched, or blurred in outline. The pigment may spread into the surrounding skin.

Border

Color that is uneven – Shades of black, brown, and tan may be present. Areas of white, gray, red, pink, or blue may also be seen.

Color

Diameter – There is a change in size, usually an increase. Melanomas can be tiny, but most are larger than 6 millimeters wide (about 1/4 inch wide).

Diameter

Evolving – The mole has changed over the past few weeks or months.

Evolving

A common mole is a non-cancerous growth on the skin that is formed by a cluster of melanocytes (cells that make a substance called melanin, which gives color to skin and eyes). A mole may be dark or flesh-colored and may be raised from the skin. Most adults have between 10 and 40 common moles. These growths are usually found above the waist on areas exposed to the sun. Common moles are seldom found on the scalp, breast, or buttocks.

  • Common moles are growths on the skin that develop when pigment cells (melanocytes) grow in clusters; also called “common nevi” or “common acquired nevi”.
  • Appearance (using ABCDE rules)
    • Asymmetry: Usually symmetrical, round or oval.
    • Border: Usually have a distinct edge that separates it from the rest of the skin.
    • Shape: Usually round or oval.
    • Color: Usually have an even color; may be pink, tan, brown, black (in deeply pigmented individuals), or a color that is very close to a person’s normal skin tone.
    • Diameter: Usually less than 5 millimeters or about ¼ inch (smaller than a pencil eraser).
    • Evolving: Moles go through a life-cycle. Often they start as small freckle-like spots; gradually round up and form a bump; may lighten, become flesh-colored; become less elevated, flatten and eventually disappear. Life-cycle is a gradual process typically over many years. Some moles do not go through the entire life-cycle. Vast majority are stable and then disappear; rarely develop into melanoma (or cancer).

Mole Case 1: Stable normal mole

Over thirty years, this common mole remained the same size (about 6 millimeters), color, shape, and elevation (height) above the skin.

“ABCDE” features:

  • Asymmetry none
  • Border no irregularity
  • Color even
  • Diameter 6 millimeters
  • Evolving not changing

Clinical Diagnosis Common acquired nevus

M1M2

M3

This picture shows a large mole which is slightly bigger than a pencil eraser. The mole is a smooth light tan and pink bump with normal skin markings (lines) present on the entire surface. Unlike most moles, there are some hairs growing from the center and edges of the mole. All of the features of this mole are normal.

Recognizing the ABCDE Features

Common Moles

Dysplastic Nevi (DN)

Melanomas

A dysplastic nevus (DN) is a mole that may develop into malignant melanoma, a skin cancer starting in pigment cells. DN look different from common moles. DN are often larger than common moles (more than 5 millimeters) and have borders that are not easy to see. Their color is usually uneven and can range from pink to dark brown. Similar to common moles, parts of the DN may be raised above the skin surface. Some doctors use the term “atypical mole” to refer to DN.

  • The word “dysplastic” in its name refers to the look and pattern of cells in the nevi as they appear under a microscope.
  • Appearance (according to ABCDE rules)
    • Asymmetry: irregular shape
    • Border: indistinct (blurry) borders
    • Color: mixture of colors (tan, brown, and red or pink shades)
    • Diameter: greater than 5 millimeters or ¼ inch and have a flat part
    • Evolving: Majority are stable and then disappear; typically start to show these features when small and show all features by the time they reach the size of most moles; become larger than most moles and eventually disappear.
  • The “ABCDE” rules were made for identifying early melanoma, but can also be used to describe DN.
  • Clinicians use the number of DN to identify some individuals who are at increased risk of developing melanoma.
  • DN most likely found on sun-exposed areas, especially intermittently exposed, such as the back, but are also frequent on chest, arms and legs.
  • Approximately 10% of adult populations of northern European descent have at least one DN.
  • DN are frequently found in melanoma-prone families in North America, Europe, and Australia.
  • Melanomas may develop from DN.
  • Risk of melanoma is high for people who have a large number of DN; especially high for people with a family history of both DN and melanoma.

All Cases

Stable and Fading

Evolving Toward Melanoma

Examples

Case 1

case1

Over five years, this dysplastic nevus more than doubled in size, increasing from 3 millimeters to 10 millimeters wide. The color lightened from dark brown to very light in the center and reddened around the edges. The shape became more irregular and the borders became more indistinct. The mole was mostly flat but slightly raised in the center, and then became flatter. The mole was removed because it continued to change in color and the patient reported that it had been itching.

Case 2

case2

Over seventeen years, this DN increased in size to 8 millimeters and then decreased to 4 millimeters. The nevus went from reddish brown, partially flat with an irregular outline and indistinct borders to light tan and barely visible. The large papule (bump) in the center flattened.

Case 3

case3

Over twenty-six years, this DN grew from 14 millimeters wide to about 17 millimeters, and then decreased to 14 millimeters. The mole contained shades of tan to dark brown, red and pink, but as the mole became smaller it faded considerably to light pink. The lighter area in the right lower portion became a flesh-colored almost flat bump that was barely visible. The irregular scalloped-shaped outline filled in as the nevus grew into a more irregular shape. Later the mole started fading and became less irregular.

Case 4

case4

Over twenty-two years, these two mostly flat DN with irregular and indistinct outlines were stable and then regressed (faded). Both nevi were approximately 5 millimeters wide, and after several years, decreased to about 4 millimeters. Both nevi had slight mixtures of tan, brown, and red shades which became more uniform. Both nevi faded; the “B” nevus became flat and barely visible.

Case 5

case5

Over eight years, this DN increased in diameter from 4 millimeters to 7 millimeters. The mixture of tan to dark brown colors lightened and then darkened. The partially flat mole with indistinct borders had a slightly irregular outline which became more irregular. The mole was removed because it was getting darker (after having lightened) and was growing slightly larger.

Case 6

case6

Over four and a half years, this DN increased in diameter from 8 millimeters to 9 millimeters. The mole is partially flat and has an irregular shape and indistinct border. It contains a mixture of tan to dark brown colors which lightened and then darkened. The upper central and right side lightened considerably with an arc of very light color across the central portion. The shape became more irregular as the pigment receded (color faded). Then, much of the nevus darkened considerably and a new area of very dark brown color developed that extends inwardly at the 4 o’clock to 5 o’clock position. The mole was removed because it had changed in color over the past year.

Melanomas

Melanoma is a form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but infrequently can also begin in other pigmented tissues, such as in the eye or the intestines. Melanoma is potentially dangerous because it can spread to nearby tissues and other parts of the body, such as the lung, liver, bone, or brain. The earlier that melanoma is detected and removed, the more likely that treatment will be successful.

  • A type of skin cancer that begins in melanocytes (cells that make the pigment melanin).
  • Early, thin melanomas are curable by minimal surgery alone.
  • Advanced melanomas may spread to others parts of the body; treatments such as additional surgery, chemotherapy, radiation therapy, immunotherapy and/or new types of treatment being tested in clinical trials may be used.
  • Appearance of early melanoma (according to ABCDE rules)
    • Asymmetry: Often irregular and asymmetrical (the shape of one half does not match the other half).
    • Border: Usually irregular. Edges often ragged, notched, or blurred in outline. The pigment may spread into the surrounding skin.
    • Color: Usually uneven in color. Shades of black, brown, and tan may be present. May also have areas of white, gray, red, pink, or blue.
    • Diameter: Change in size, usually an increase. Melanomas can be tiny, but most are larger than 6 millimeters wide (about ¼ inch wide). The surface may appear scaly.
    • Evolving: The mole has changed in size, shape, and/or color over the past few weeks or months. Development of a new mole that has any of the ABCDE features in an area of previously normal skin.
  • Melanomas can vary greatly in how they look. Many show all of the “ABCDE” features; however, some may show only one or two of those features.

Warning Signs

Guidelines for Individuals at Increased Risk of Melanoma

Examples

Case 1

case1a

A new and unusual mole developed on the arch of the foot in an area of skin that was previously normal. The mole steadily increased in size and irregularity. It was 10 millimeters in diameter, and larger and more irregular than any of the moles nearby. The mole was mostly flat with an irregular darker border, and a mixture of light brown to very dark brown with some lighter color in the center. It was removed because it displayed several of the warning signs for melanoma (changes in size, color, and shape).

Case 2

case2a

Over two years, this DN changed in size, color, shape and surface. It was predominantly flat with some tiny bumps in the center, and uniformly tan with a triangular shape and indistinct borders. The nevus then enlarged slightly to 6 millimeters by 5 millimeters and developed a new black slightly raised area and a fine scale on the surface. The mole was removed because it was changing in ways highly suspicious for melanoma.

Case 3

case3a

Two relatively small nevi were on the left abdomen at about 4 o’clock from the navel. Two years later, the mole closer to the navel had become very prominent and was circled as #60. (The smaller, more distant mole did not change.) The nevus was 8 millimeters in diameter. It had very indistinct borders, an irregular outline, and an asymmetric shape. The color varied from reddish dark brown to a very dark brown in the center portion. The lesion was removed because it was changing in ways very suspicious for melanoma (rapid growth, dark coloration, and asymmetric shape).

Case 4

case4a

The patient reported that the mole was new and had grown much larger during the previous six months. The mole is large (7 millimeters in diameter), and contains a mixture of reds and browns. The area of very dark brown color in the right central part is especially concerning in a patient with very fair skin. The borders are indistinct and quite irregular. The mole is larger, darker, and more irregular than any of the moles nearby. The mole was removed because it was new, and had changed in size, color, and shape during a very short period of time.

Case 5

case5a

The DN of interest (marked with an arrow and then circled as #30) was stable and appeared mainly unchanged for many years. The DN was partially flat and had an irregular outline and indistinct borders. It contained multiple shades of tan and brown. After a long period of relative stability, over two years, it increased in size to about 8 millimeters in diameter and darkened when most other moles had faded. The mole was removed five months after the picture shown in image 5 because it continued to darken over a short period of time.

Case 6

case6a

Over two and a half years, the small tan mole of interest developed into a DN which changed in size, color, shape and surface. It grew to about 8 millimeters in diameter. A very dark brown portion developed at top of the mole. Then most of the rest of the mole darkened considerably while the central area lightened greatly. It was darker than all of the other moles and quite irregular in shape. The mole was removed because it was changing in ways suspicious for melanoma.

Conclusion

While cancer of the skin is the most common form of cancer, it is also the most preventable.  One can reduce one’s risk of skin damage and skin cancer by seeking shade under an umbrella, tree, or other shelter before you need relief from the sun. Your best practice to protect your skin is to use sunscreen or wear protective clothing when you’re outside—even when you’re in the shade.  Prevention practices, regular self-exams and having one’s doctor exam any mole changes are the keys to living a skin cancer free life.

Sentry BioPharma Services offers temperature-sensitive biological product management to pharmaceutical companies, hospitals and organizations with need for validated  GMP storage, labeling, kitting and temperature-sensitive drug distribution services.  For more information about how Sentry’s GMP services can help protect the integrity and delivery of your biological products to patients, contact Sentry via email or by phone at 1-866-757-7400.

Sentry Goes Purple in June for Alzheimer’s & Brain Awareness Month

Sentry is going purple! On Friday, June 24, 2016 Sentry BioPharma Services invites employees to wear the color purple in recognition of Alzheimer’s and brain awareness month.

SBS-Approved-Logo-High-Res-With-Trademark__03.10.11Orange-Purple

Alzheimer’s disease is the sixth leading cause of death in the United States; it kills more citizens annually than prostate and breast cancer combined. Worst of all, there presently is no cure for Alzheimer’s disease. Researchers possess great hope that there will be treatments that can stop or slow Alzheimer’s in the near future.

The National Institute on Aging (NIA), one of the 27 Institutes and Centers of the National Institutes of Health (NIH), leads a broad scientific effort to understand the nature of aging and to extend the healthy, active years of life. NIA is the primary Federal agency supporting and conducting Alzheimer’s disease research. For more information about Alzheimer’s disease, please watch the video below.

Several medications are approved by the U.S. Food and Drug Administration to treat symptoms of Alzheimer’s. Donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Razadyne®) are used to treat mild to moderate Alzheimer’s (donepezil can be used for severe Alzheimer’s as well). Memantine (Namenda®), is used to treat moderate to severe Alzheimer’s.

These drugs work by regulating neurotransmitters, the brain chemicals that transmit messages between neurons. They may help maintain thinking, memory, and communication skills and help with certain behavioral problems. However, these drugs don’t change the underlying disease process. They are effective for some but not all people and may help only for a limited amount of time.

For more information about how Sentry can implement a custom solution to meet your unique GMP storage and pharmaceutical cold chain challenges, contact Sentry via email or by phone at 1-866-757-7400, for a complimentary, no obligation phone call with one of Sentry’s problem-solving experts.

WHO’s World Blood Donor Day 2016: Blood Connects Us All

The World Health Organization (WHO) has declared Tuesday, June 14, 2016 as World Blood Donor Day.  The theme is “Blood Connects Us All”.

shutterstock_419643730  wallpaper-girl

In May 2005, at the Fifty-Eighth Session of the World Health Assembly, 192 Member States of the WHO adopted resolution WHA58.13 to establish World Blood Donor Day as an annual event, to be celebrated each year on 14 June.

According to the WHO, “The safest blood donors are voluntary, non-remunerated blood donors from low-risk populations. In the key global fact and figures of 2011 (Fact sheet number 279), in 62 countries, national blood supplies are based on 100% or almost 100% (more than 99.9%) voluntary unpaid blood donations. Forty countries collect less than 25% of their blood supplies from voluntary unpaid blood donors. The primary goal of the WHO is for all countries to obtain all blood supplies from voluntary unpaid donors by 2020 in accordance with World Health Assembly resolution 28.72, which was adopted in 1975.”

Ms. Jennifer Marcum, Sentry BioPharma Services’ CEO, acknowledges the significance of the international event by scheduling an appointment to donate whole blood at the American Red Cross on June 17, 2016.  Ms. Marcum offers, “The National Institutes of Health (NIH) says approximately five million Americans require blood transfusions every year.  The need is continuous.  To this day blood cannot be manufactured on an industrial scale.  There is some research being done at The University of Edinburgh to create blood type O red blood cells using pluripotent stem cells, but a true biological blood substitute has not been commercially approved by the FDA.   So, in the absence of a safe and effective blood surrogate, we donate.  A blood donation not only forges a bond between human beings, but it also creates links to our local and global community.  It is the one common denominator among us all.”

Ms. Marcum continues, “Protecting the integrity of the entire blood cold chain should be an integral part of the global blood distribution system.”  The WHO says, “Deviations from specified temperature ranges and conditions during storage and transportation of blood and blood products can seriously affect the viability of the constituents of blood, thus leading to reduced clinical benefits. It can also increase the risk of bacterial proliferation in blood components during storage and may cause potentially life-threatening transfusion reactions, such as septic shock and even death.”

The WHO notes, “A break in the blood cold chain leads to wastage and discard of unsuitable blood units, which may adversely affect the supply of blood and blood products for transfusion. An effective blood cold chain is essential for the countries to implement strategies to expand safe blood transfusion services to cover wider geographic areas and achieve universal access to safe blood transfusion for all patients who need transfusion.”

Sentry BioPharma Services offers biological product storage to pharmaceutical companies, hospitals and organizations with need for validated refrigerated (+2°C to +8°C) storage and temperature-sensitive product shipping services.  For more information about how Sentry’s GMP warehouse can help protect the integrity of the blood cold chain and biological products in general, contact Sentry via email or by phone at 1-866-757-7400.

NIH: Increased Physical Activity Associated with Lower Risk of 13 Types of Cancer

Sentry BioPharma Services provides oncology product management, global drug distribution, GMP storage and specialized services like pharmaceutical labeling, packaging and kitting.  Sentry plays a critical role in protecting temperature-sensitive product safety, identity, strength, purity and quality (SISPQ) for both cancer clinical trials and commercial drug distribution for a wide range of pharmaceutical and biotechnology clients.  With this in mind, the most successful cancer drugs are no match for avoidance of cancer altogether.  Therefore, we are sharing this article from the National Institute for Health (NIH) concerning a new study which links physical exercise with lower cancer rates. 

A new study of the relationship between physical activity and cancer has shown that greater levels of leisure-time physical activity were associated with a lower risk of developing 13 different types of cancer. The risk of developing seven cancer types was 20 percent (or more) lower among the most active participants (90th percentile of activity) as compared with the least active participants (10th percentile of activity). These findings, from researchers at the National Cancer Institute (NCI), part of the NIH, and the American Cancer Society (ACS), confirm and extend the evidence for a benefit of physical activity on cancer risk and support its role as a key component of population-wide cancer prevention and control efforts. The study, by Steven C. Moore, Ph.D., NCI, and colleagues, appeared May 16, 2016, in JAMA Internal Medicine.

Hundreds of previous studies have examined associations between physical activity and cancer risk and shown reduced risks for colon, breast, and endometrial cancers; however, results have been inconclusive for most cancer types due to small numbers of participants in the studies. This new study pooled data on 1.44 million people, ages 19 to 98, from the United States and Europe, and was able to examine a broad range of cancers, including rare malignancies. Participants were followed for a median of 11 years during which 187,000 new cases of cancer occurred.

The investigators confirmed that leisure-time physical activity, as assessed by self-reported shutterstock_426808351surveys, was associated with a lower risk of colon, breast, and endometrial cancers. They also determined that leisure-time physical activity was associated with a lower risk of 10 additional cancers, with the greatest risk reductions for esophageal adenocarcinoma, liver cancer, cancer of the gastric cardia, kidney cancer, and myeloid leukemia. Myeloma and cancers of the head and neck, rectum, and bladder also showed reduced risks that were significant, but not as strong. Risk was reduced for lung cancer, but only for current and former smokers; the reasons for this are still being studied.

“Leisure-time physical activity is known to reduce risks of heart disease and risk of death from all causes, and our study demonstrates that it is also associated with lower risks of many types of cancer,” said Moore. “Furthermore, our results support that these associations are broadly generalizable to different populations, including people who are overweight or obese, or those with a history of smoking. Health care professionals counseling inactive adults should promote physical activity as a component of a healthy lifestyle and cancer prevention.”

Leisure-time physical activity is defined as exercise done at one’s own discretion, often to improve or maintain fitness or health. Examples include walking, running, swimming, and other moderate to vigorous intensity activities. The median level of activity in the study was about 150 minutes of moderate-intensity activity per week, which is comparable to the current recommended minimum level of physical activity for the U.S. population.

There are a number of mechanisms through which physical activity could affect cancer risk. It has been hypothesized that cancer growth could be initiated or abetted by three metabolic pathways that are also affected by exercise: sex steroids (estrogens and androgens); insulin and insulin-like growth factors; and proteins involved with both insulin metabolism and inflammation. Additionally, several non-hormonal mechanisms have been hypothesized to link physical activity to cancer risk, including inflammation, immune function, oxidative stress, and, for colon cancer, a reduction in time that it takes for waste to pass through the gastrointestinal tract.

Most associations between physical activity and lower cancer risk changed little when adjusted for body mass index, suggesting that physical activity acts through mechanisms other than lowering body weight to reduce cancer risk. Associations between physical activity and cancer were also similar in subgroups of normal weight and overweight participants, and in current smokers or people who never smoked.

The study was a large-scale effort of the Physical Activity Collaboration of NCI’s Cohort Consortium, which was formed to estimate physical activity and disease associations using pooled prospective data and a standardized analytical approach.

“For years, we’ve had substantial evidence supporting a role for physical activity in three leading cancers: colon, breast, and endometrial cancers, which together account for nearly one in four cancers in the United States,” said Alpa V. Patel, Ph.D., a co-author from the American Cancer Society. “This study linking physical activity to 10 additional cancers shows its impact may be even more relevant, and that physical activity has far reaching value for cancer prevention.”

The National Cancer Institute leads the National Cancer Program and the NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at https://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reference

Moore SC, et al. Leisure-time physical activity and risk of 26 types of cancer in 1.44 million adults. JAMA Internal Medicine. May 16, 2016. DOI:10.1001/jamainternmed.2016.1548.

Sentry BioPharma Services offers temperature sensitive biological product management to pharmaceutical companies, hospitals and organizations with need for validated  GMP storage and temperature-sensitive drug distribution services.  For more information about how Sentry’s GMP storage can help protect the integrity of your biological products in general, contact Sentry via email or by phone at 1-866-757-7400.

Clinical Trial of Chikungunya Vaccine

Safeguarding the health of clinical trial participants and the progression of trial results demands strict adherence to protocols.  Sentry BioPharma Services specializes in vaccine drug product storage, labeling, kitting and effective distribution for clinical trials worldwide.   Please see the following article concerning the National Institute of Health’s (NIH) phase 2 clinical trial of Chikungunya Vaccine which is now open and seeking patients.

NIH-Sponsored Clinical Trial of Chikungunya Vaccine Opens

This digitally-colorized transmission electron micrograph (TEM) depicts numerous chikungunya virus particles, which are composed of a central dense core that is surrounded by a viral envelope.
Credit: CDC
TEM

An experimental vaccine to protect against the mosquito-borne illness chikungunya is being tested in a Phase 2 trial sponsored by the National Institutes of Health. Results from an initial trial of the vaccine, which was developed by scientists at the NIH National Institute of Allergy and Infectious Diseases (NIAID), were reported in 2014. In that study, all 25 vaccine recipients developed robust immune responses and no safety concerns were noted. The new trial is designed to enroll 400 healthy adult volunteers aged 18 to 60 years old at six sites in the Caribbean. It will continue to gather data on the candidate vaccine’s safety and ability to elicit immune responses, including antibodies.
The hallmark symptoms of chikungunya are severe joint pain accompanied by fever and headache. The pain typically eases after about a week but can persist for months or years in some cases. There are no specific treatments for chikungunya infection and no vaccine to prevent it.
Since its appearance in the Western Hemisphere in late 2013, cases of chikungunya have skyrocketed. So far in 2015, more than 621,000 suspected and confirmed cases have been reported throughout the Americas.
“The recent re-emergence of chikungunya virus in this hemisphere has rapidly become a significant health burden,” said NIAID Director Anthony S. Fauci, M.D.  “Our chikungunya vaccine development efforts are part of a broader research effort to prevent, diagnose, treat and ultimately control this painful illness, which can strike anyone unlucky enough to be bitten by an infected mosquito.”
The experimental vaccine, developed by investigators at NIAID’s Vaccine Research Center, uses virus-like particles (VLPs) instead of either inactivated or weakened whole virus. VLP vaccines can stimulate immune responses comparable to those resulting from naturally acquired immunity following infection and, because virus is not needed to produce VLP vaccines, they do not need to be prepared in high-level biocontainment facilities.
Eligible volunteers will be randomly assigned to enroll into one of two groups of 200 people each. Study participants will receive either two doses of the candidate vaccine spaced 28 days apart or two doses of an inactive placebo. Blood samples will be drawn at multiple time points following the injections to assess whether the candidate vaccine prompted the production of antibodies to chikungunya virus.

Additional details about the trial can be found at ClinicalTrials.gov  using the identifier NCT02562482.

References:

L-J Chang et al. Chikungunya virus-like particle vaccine elicits neutralizing antibodies in healthy adults in a phase I dose escalation clinical trial. The Lancet DOI: 10.1016/S0140-6736(14)61185-5 (2014).

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Strict adherence to clinical material management protocols, in combination with proven GMP storage, secondary packaging, distribution, and shipping expertise allow Sentry to provide a variety of flexible services to our clinical trial outsourcing clients.

For more information about how Sentry can integrate your requirements into a scalable, secure, value-added clinical trial logistics solution, contact Sentry via email or by phone at 1-866-757-7400.