Daniel Prince No Comments

Understanding how the sterilization temperature and sterilization exposure time are developed.

Understanding how the sterilization temperature and sterilization exposure time are developed.

By Daniel Prince

Commercially prepared bacterial spores known as biological indicators (BI) are the preeminent tools used to verify and validate that items subjected to steam or dry heat sterilization are sterile to a very high level of probability. This is because they are used as standards to allow measurements of multiple replicates that are repeated which can be followed by critical statistical examination. In a validated sterilization process when, for example, one million (106) items from a homogenous population are loaded into a sterilizer not more than one item is expected to be non-sterile. This outcome is referred to a one in one million (10-6) probability of a non-sterile unit (PNSU) or alternatively as a sterilization assurance level (SAL). BIs are commercially available with known numbers of spores present (N0) and a known inherent resistance of that spore to heat. The temperature in which the resistance of the spore to the lethal process changes by a factor of ten is known as the DT value. The change in temperature that causes a tenfold change in the DT value is known as the zT value.

The maximum number of spores present on a BI is usually limited to 1 -2 million. The BI is placed in the sterilizer and subjected to the sterilization process. When using moist steam heat the sterilization reference temperature (T) is 121C. For dry heat it is usually greater than or equal to 200C. Once the sterilization cycle is completed the BI is cultured to determine the number of survivors, if any. When N0 is one million and there are 1,000 (103) survivors the spore reduction is 1,000. For moist steam heat 121C is referred to as the reference temperature. For example Geobacillus stearothermophilus has a DT value of 2 minutes at 121C (D121 = 2 minutes). After exposure to 2 minutes at 121C the number of surviving spores is expected to be N0/10. The theoretical time needed to destroy all one million spores subjected to sterilization at 121C is given by

D121 x Log N0 = 2 x 6 = 12 minutes.

When the number of survivors is transformed to log 10 a linear plot is obtained on semi-log paper against the sterilization temperature DT values are accepted as a measure of the microbial destruction rate as inputs for determining the z value. The graph of log D versus temperature is called the thermal resistance (TR) curve.

A thermal death-time (TDT) curve is a graph of Lethality (log F) versus temperature. The TR curve differs from the TDT curve in that a TR curve is, by definition, the time (D value) at a range of temperatures necessary to destroy 90% of the organisms in a homogeneous microbial population, whereas the TDT curve is the time (F value) at a range of temperatures necessary to produce some given or specified level of microbial destruction (FT = DT × SLR, where SLR is the spore-log reduction). For the same homogeneous microbial spore population and substrate, the TR and TDT curves are parallel.

Again with respect to a homogeneous commercially prepared BI manufactured under cGMP the D value of a given organism is influenced by other factors. When a given factor such as temperature causes a tenfold change on the D value this is known as a z value. Thus at 131C or 111C the D value of Geobacillus stearothermophilus is D121/10 = 0.2 minutes and D121 x 10 = 20 minutes, respectively.

In liquid preparations pH can combine with temperature to influence the D value. For example, for Geobacillus stearothermophilus placed in food at 115C at pH 2.7 D115 was reduced by a factor of ten. Thus, zpH115 = 2.7. At 135C a pH of 4.7 caused a tenfold reduction in the D value and thus, 135 = 4.7.

Derek Prince No Comments

FDA FINAL RULE: Consumer Antiseptic Washes Are Neither Safe nor Effective.

 

FDA FINAL RULE: Consumer Antiseptic Washes Are Neither Safe nor Effective.

Written by: Derek Prince

On September 6, 2017 the Food and Drug administration (FDA) final rule banning a list of 29 consumer antiseptic wash ingredients officially became in effect. This rule strictly bans the usage of certain ingredients commonly used in the manufacturing of products intended to be applied and rinsed off with water.  It should be noted that this final rule has no effect on the manufacturing of consumer antiseptic rubs, commonly referred to as “hand sanitizers, “hand rubs” or “antibacterial wipes”. Similarly, this rule has no bearing on health care antiseptics, first aid antiseptics or antiseptics used in the food industry.

Although certain ingredients were temporarily deferred from this ruling, it is most likely only a matter of time before all consumer antiseptic wash products are banned.

Because of the stimulation of interest that the new rule has and will engender, Gibraltar has composed a paper on aspects of antiseptic science and have chosen to discuss four antiseptics of the many presented in the Federal Register. If you’d like to learn more about this topic and some common antiseptic/disinfectant ingredients we encourage you to get a copy of the article: “A review of consumer antiseptic wash ingredients undergoing FDA challenge” published in the Contract Pharma – September 2017 print and online edition. The digital version can be viewed by following the link below:

https://www.contractpharma.com/contents/view_features/2017-09-06/fda-otc-antiseptics/

 

Daniel Prince No Comments

The Importance of Clean Glass Containers and Stoppers for Pharmaceutical Applications

The Importance of Clean Glass Containers and Stoppers for Pharmaceutical Applications

8/17/2017 by Daniel Prince

 

FDA has published guidance for industry to assure patient safety public that glass containers such as vials, beakers and rubber stoppers be clean. Gibraltar provides vials that meet these requirements and is an outsourcing destination for the washing of containers and closures with USP/EP Water for Injection (WFI) as well as being a FDA registered laboratory to certify that the materials processed at Gibraltar are pyrogen-free and particulate–free.

            Containers/Closures: For an example of products that are certified to meet this requirement see, https://www.gibraltarlabsinc.com/sterikit-product/

Section 211.94 (drug product containers and closures) states that “drug product containers and closures shall be clean and, where indicated by the nature of the drug, sterilized and processed to remove pyrogenic properties to assure that they are suitable for their intended use.” It also states that “Standards or specifications, methods of testing, and, where indicated, methods of cleaning, sterilizing and processing to remove pyrogenic properties shall be written and followed for drug product containers and closures.”

 

Section 211.113(b) requires “validation of any sterilization process” as part of designing procedures “to prevent microbiological contamination of drug products purporting to be sterile.”

1.         Preparation

Containers and closures should be rendered sterile and, for parenteral drug products, pyrogen-free.  The type of processes used will depend primarily on the nature of the material comprising the container and/or closure.  The validation study for any such process should be adequate to demonstrate its ability to render materials sterile and pyrogen-free.  Written procedures should specify the frequency of revalidation of these processes as well as time limits for holding sterile, depyrogenated containers and closures.

Presterilization preparation of glass containers usually involves a series of wash and rinse cycles. These cycles serve an important role in removing foreign matter.  Rinse water should be of high purity so as not to contaminate containers.  For parenteral products, final rinse water should meet the specifications of Water for Injection, USP. 

The adequacy of the depyrogenation process can be assessed by spiking containers or closures with known quantities of endotoxin, followed by measuring endotoxin content after depyrogenation.  The challenge studies should be performed with a reconstituted endotoxin solution applied directly onto the surface being tested and air-dried.  Positive controls should be used to measure the percentage of endotoxin recovery by the test method.  Validation study data should demonstrate that the process reduces the endotoxin content by at least 99.9% (3 logs).

Glass containers are generally subjected to dry heat for sterilization and depyrogenation.  Validation of dry heat sterilization/depyrogenation should include appropriate heat distribution and penetration studies as well as the use of worst-case process cycles, container characteristics (e.g., mass), and specific loading configurations to represent actual production runs. For example, This service is offered at Gibraltar https://www.gibraltarlabsinc.com/services/microbiology/depyrogenation-services/

Pyrogen on plastic containers can be generally removed by multiple WFI rinses.  Plastic containers can be sterilized with an appropriate gas, irradiation or other suitable means.   For gases such as EtO, the parameters and limits of the EtO sterilization cycle (e.g. temperature, pressure, humidity, gas concentration, exposure time, degassing, aeration, and determination of residuals) should be specified and monitored closely.  Biological indicators are of special importance in demonstrating the effectiveness of EtO and other gas sterilization processes.

Rubber closures (e.g., stoppers and syringe plungers) are cleaned by multiple cycles of washing and rinsing prior to final steam or irradiation sterilization.  At minimum, the initial rinses for the washing process should employ Purified Water USP of minimal endotoxin content, followed by final rinse(s) with WFI for parenteral products.  Normally, depyrogenation is achieved by multiple rinses of hot WFI.  The time between washing and sterilizing should be minimized because moisture on the stoppers can support microbial growth and the generation of endotoxins.  Because rubber is a poor conductor of heat, extra attention should be given to the validation of processes that use heat to sterilize rubber stoppers.  Validation data should also demonstrate successful endotoxin removal from rubber materials.

A potential source of contamination is the siliconization of rubber stoppers.  Silicone used in the preparation of rubber stoppers should be rendered sterile and should not have an adverse effect on the safety, quality, or purity of the drug product.

Contract facilities, such as Gibraltar, that perform sterilization and depyrogenation of containers and closures are subject to the same CGMP requirements as those established for in-house processing.  The finished dosage form manufacturer is responsible for the review and approval of the contractor’s validation protocol and final validation report.

Reference: Sterile Drug Products Produced by Aseptic Processing Draft.  See Appendix for full guidance.

Danina Rinaldi No Comments

Discussions about Total Organic Carbon

Discussions about Total Organic Carbon

By Danina Rinaldi

Testing bulk, sterile, purified, DI, or sterile water for pharmaceutical purposes is important for manufacturing, production and analytical applications.

Total organic carbon, or simply TOC, provides an indirect measurement of all the organic molecules in a water sample. The test method is very sensitive, providing results in ppb (parts per billion).  A major advantage to in using this test is that it accurately quantifies most organic materials that may be present in only trace amounts. Accordingly this methodology is well suited to verify cleaning in between manufacturing campaigns.

Because of its advantages TOC is one of the tests considered to be most critical for final water quality per the USP chapter <1231> Water for Pharmaceutical Purposes.   It is purposed to provide critical feedback to determine product quality and performance as well as immediate use and suitability.

In addition, there are many examples in the USP that require this test to be performed as a quality attribute. For example, Pure Steam, Water for Injection, Sterile Water for Inhalation, Sterile Water for Injection, Purified Water, Sterile Purified Water and Water for Hemodialysis.

Other USP general chapters containing requirement for this test to be performed  are <1051> Cleaning Glass Apparatus, <1059> Excipient Performance, <1661> Evaluation of Plastic Packaging Systems and their Materials of Construction with Respect to their User Safety Impact, <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems, <661.1> Plastic Materials of Construction and <661.2> Plastic Packaging Systems for Pharmaceutical Use.

When submitting samples, sponsors should be careful to note that the use of plastic materials may contribute to the TOC levels.  Other contaminating factors may be presence of alcohol or detergents and microbial contaminates.  The total organic carbon test is not a substitute for a routine microbiological monitoring practice.  To monitor the microbial quality of water a heterotrophic plate count and coliform tests are necessary to be performed.

Samples should be sent refrigerated, overnight in a 40 ml I-Chem Low Level Certified Vial.

Contact Gibraltar Laboratories, Inc. to begin testing today or for more information click here.

Kate Slezak No Comments

Why Should You Change Your Contacts Often?

Why Should You Change Your Contacts Often?

Written by Kate Slezak

These days, it’s safe to say that everyone either wears contact lenses or knows someone who does and understands that it’s important to change your contacts frequently. As if it isn’t annoying enough to have to dig your fingers into your eyeballs each morning and night, you also have to stay on top of keeping the contact solution fresh and the supply of new contacts steady. Regardless of whether someone has one-day-use or another type of contacts that can be left in longer, doctors warn of the importance of switching pairs regularly. But why change them so often? Why not just save money and wear the contacts a little longer, especially if they aren’t scratched? Is it really so bad to have irritated eyes for a few days?

Irritation is not the only effect of leaving contact lenses in too long- it can also lead to the growth of an organism called Pseudomonas aeruginosa. Though P. aeruginosa primarily affects patients in hospitals or with weakened immune systems, it can also cause problems in healthy patients, like rashes on the skin when hot tubs are inadequately chlorinated and eye infections with extended-use contact. Only requiring acetate and ammonia as its source of carbon and nitrogen, P.aeruginosa is an opportunistic pathogen, meaning it can easily adapt to survive in many different environmental conditions and can make use of a wide range of available nutrients. Though it commonly affects plants like lettuce, tomatoes, and tobacco, P.aeruginosa forms slime-enclosed communities called biofilms that allow it to survive and grow within human tissues. These biofilms prevent antimicrobial agents and other antibiotics from entering the community of bacteria within. This form of defense allows the organism to be resistant to antimicrobial agents found in hand creams, and certain cleaning solutions, like those in contact solutions.

Irritation from wearing contact lenses for an extended period of time can lead to inflammation and infection, called microbial keratitis. Though many bacterial organisms’ growth can lead to microbial keratitis, the most common source is P. aeruginosa. Once in the eye, P. aeruginosa has the ability invade and kill corneal cells. It can also activate several pathways in the immune system which are used to alert the body of the source of inflammation and recruit white blood cells. Despite the fact that white blood cells usually fight infection within the body, the buildup of white blood cells can lead to the destruction of healthy corneal cells and other tissues within the eye, ultimately leading to scarring and vision loss.

Pseudomonas aeruginosa is not only responsible for causing eye irritation from the use of old contacts, it also has the ability to withstand varying environmental conditions with minimal nutrients allowing it to grow and multiply in environments practically devoid of nutrients. This includes distilled water and anaerobic environments, as well as those with higher temperatures of up to 42°C (107.2°F). The elevated temperature levels and churning water of hot tubs causes the chlorine levels in the water to drop and allow the resulting higher pH of the water to reduce the antibacterial effect of the halogens in the chlorine. If the chlorine level drops below <1mg/L P. aeruginosa  can multiply up to 1,000,000 organisms per milliliter of water in as short a window as 24hours. The organism can enter the body through the gastrointestinal tract due to the accidental ingestion of water and spread to warmer moist areas of the body, like the perineum and armpits, and form a rash.

Laboratories like Gibraltar Laboratories use the antimicrobial effectiveness test to test the antimicrobial properties of hand creams and optic solutions such as contact solutions over time. This helps to prove how strong the antimicrobial agents in these products are in preventing the growth of harmful bacteria like P. aeruginosa. Though there are antibiotics like fluoroquinolone that can be used to combat P. aeruginosa, the organism is known for its ability to resist antibiotics and to even mutate to survive once an antibiotic has already been introduced. That being said, it’s not a pleasant organism to contract.

So the doctors are right- spend the extra money and make sure you and your friends aren’t keeping contacts in for too long and are changing the solutions regularly.

 

References:

Breidenstein, E. B., De la Fuente-Nunez, C., & Hancock, R. E. (2011, August). Pseudomonas aeruginosa: all roads lead to resistance. Trends in Microbiology, 19(8), 419-426. doi:10.1016/j.tim.2011.04.005.

Crnich, C. J., Gordon, B., & Andes, D. (2003, February 1). Hot tub-associated necrotizing pneumonia due to Pseudomonas aeruginosa. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 36(1), 55-57. doi:10.1086/345851.

Fujitani, S., Moffett, K. S., & Yu, V. L. (n.d.). Pseudomonas aeruginosa. Retrieved August, 2016, from http://www.antimicrobe.org/new/b112.asp.

Klockgether, J., Cramer, N., Wiehlmann, L., Davenport, C. F., & Tummler, B. (2011, July 13). Pseudomonas aeruginosa genomic structure and diversitty. Frontiers in Microbiology, 2(150). doi:10.3389/fmicb.2011.00150.

Pseudomonas aeruginosa in Healthcare Settings. (2013, April 2). Retrieved August, 2016, from http://www.cdc.gov/hai/organisms/pseudomonas.html.

Schaber, J. A., Triffo, W. J., Suh, S., Oliver, J. W., Hastert, M., Griswold, J. A., . . . Rumbaugh, K. P. (2007, August). Pseudomonas aeruginosa forms biofilms in acute infection independent of cell-to-cell signaling. Infection and Immunity, 75(8), 3715-3721. doi:10.1128/IAI.00586-07.

Wilcox, M. D. (2007, April). Pseudomonas aeruginosa infection and inflammation during contact lens wear: A review. Optometry and Vision Science: Official Publication of the American Academy of Optometry, 84(4), 273-278. doi:10.1097/OPX.0b013e3180439c3e.

Daniel Prince No Comments

Call for Collaboration: Terminal Sterilization for Aseptic Manufactured Products Based on Bioburden, Sterilization Temperature F0 to accomplish a PNSU ≥ 10-6

Sterilization services

Call for Collaboration: Terminal Sterilization for Aseptic Manufactured Products Based on Bioburden, Sterilization Temperature F0 to accomplish a PNSU ≥ 10-6

Liquid filled products manufactured aseptically are usually assumed to be inappropriate for steam sterilization due to possible heat liability of the finished product. However, these products must be sterile. Data is needed to verify that new approaches in the current USP <1229.2> can provide due diligence to justify standard practices or to supplement aseptic manufacturing practices with terminal sterilization.

As written in USP <1238> Vaccines for Human Use – Bacterial Vaccines, vaccines, like other aseptically manufactured finished products, rely on filtration to remove any organisms. After filtration, the finished products are filled under classified conditions into pre-sterilized vials, stoppered and sealed. Manufacturing relies on the use of a controlled clean environment and verification of the process cleanliness by testing 3,000 to 5,000 units by media fill. Sterility testing is used to justify that the aseptic manufacturing is under control.

A critical deficit of media fill based aseptic manufacturing is there is no assurance of sterility based on probability. A critical advantage of terminal sterilization is that it does provide a probability of sterilization.  Therefore, it is well accepted that the best practice is to follow aseptic manufacturing with terminal sterilization whenever possible.

As per USP <1229> Sterilization of Compendial Articles, “…a specimen is deemed sterile only when there is a complete absence of viable microorganisms (bacteria, yeasts, and molds). Sterility can be accomplished only by the use of a validated sterilization process under appropriate current good manufacturing practices and cannot be demonstrated by reliance on aseptic manufacturing, media fills or sterility testing.

Because of new thinking [USP 1229.2> a fresh look can be taken for products aseptically manufactured that is both realistic and practical.  By using bioburden as the basis of the challenge and lower temperatures more products than before can be successfully terminally steam sterilized.

Terminal sterilization alone is able to define the probability of a non-sterile unit [PNSU]. Liquids in sealed containers are steam sterilized in programmable air over pressure steam sterilizers and maintain package integrity without leaks or damage.  Development cycles are performed to ensure both product potency and sterilization effectiveness is maintained.

New thinking does not rely upon high populations of highly resistant spores like Geobacillus stearothermophilus to assure sterilization nor excessively high sterilization temperatures.

Instead for heat labile products that cannot withstand the extreme conditions imposed on products by “overkill” sterilization USP <1229.2> discusses  product bioburden with the specification of obtaining ≥ 10-6 PNSU.

Utilizing a product’s bioburden dramatically reduces the exposure time for a given sterilization temperature because the natural bioburden is usually less resistant than bacterial spores used in overkill cycles. For example, a typical Geobacillus stearothermophilus spore D value is 1.0 minute. As per USP <1229.2> one may test the resistance of the product’s natural bioburden. If it survives boiling at 100°C for one minute and not for 10 minutes then, by definition, its D121 value is taken to be 100 times lower than Geobacillus stearothermophilus, i.e., 0.01 minutes.

The application and utility of steam sterilization at 121.1C is illustrated as follows. When F0 is 8 and the product’s natural bioburden is 100 CFUs, the calculation of the PNSU is:

Log Nu = −F + Log N0
D

Nu = PNSU
D = D-value of the natural bioburden
F0 = F0-value of the process (lethality)
N0 = bioburden population per container

 

Log Nu = −8 + 2 = −798
0.01

Therefore, the PNSU = 10-798.  Product potency is critical for heat labile products. Clearly this level of assurance is excessive and is not justified if product integrity is compromised, e.g., diminished potency.

Potency can be examined after exposure to development cycles designed to be consistent with sterility and product integrity. Thus, a product may or may not maintain its potency and purity if exposed to 121.1C.

However, by lowering the sterilization exposure temperature from 121.1°C the D value will become 0.1 because Z = 10.  Thus, to minimize possible damage to the product, whilst in the sterilizer, the sterilization temperature can be lowered to 111.1°C and still achieve [more than] acceptable PNSU of 10-78.

 

 

Still there are more options to protect the product and achieve the required PNSU. Specifically, by lowering the temperature from 121.1 to 101.1 one obtains the desired PNSU of 10-6

Log Nu = −8 + 2 = −6
1

Therefore, the PNSU = 10-6

Sterilization Temperature F D Log N0 PNSU
121.1 8 0.01 2 10-798.
111.1 8 0.1 2 10-78
101.1 8 1.0 2 10-6
All three approaches achieve a valid sterilization process.

 

As seen in the table below, tools available to the sterilization practitioner now include lower sterilization temperatures, longer cycles and bioburden based parameters, all of which may permit a much greater number of aseptically manufactured products to be terminally sterilized  at a PNSU of ≥ 10-6 to the benefit of all.

In summary, a PNSU of 10-6 is essential for regulatory and consumer confidence and has never been scientifically assignable with respect to aseptic processing. However, using terminal sterilization and the approaches discussed a PNSU assignment is available for aseptically manufactured products and other heat sensitive products at relatively low sterilization exposure temperatures.

As a community we can explore together the potential application of the terminal sterilization strategies. Gibraltar Laboratories invites your participation to submit products to be evaluated under defined temperature, bioburden, N0 and F0 limits versus heat lability and overall product integrity.

 

You may contact,

Daniel Prince,Ph.D.

973 227 6882 x. 519

danielprince@gibraltarlabsinc.com

www.gibraltarlabsinc.com

 

 

 

Daniel Prince No Comments

Gibraltar Laboratories Heritage- “The Journey” By Dr. Daniel Prince

Gibraltar Laboratories Heritage- “The Journey” By Dr. Daniel Prince

My role at Gibraltar now involves looking to the future as I begin to ponder a transition towards a lesser role and eventual retirement. I am busy leading our succession planning and developing the future leaders of organization. My greatest wish is for Gibraltar Laboratories to continue in the future without me and still  be known as the excellent company it is even while it increases its market share and diversifies its offerings.  I invite you to view a short video that is a rare example of three generations of a scientific contract testing laboratory, all being featured at the same time about their feelings on the company.

Even as I look forward I also remember my beginnings at Gibraltar. As a family operated business I was fortunate to gain employment and work under my father, Dr. Herbert Prince. He and my mother, Leah Prince, BA, established our company at great risk and his  superior knowledge of bacteriology, virology, chemistry and toxicology provided a strong foundation and wide breadth of services to offer to pharmaceutical, medical devices and cosmetic companies. I was trained by my father and I learned a lot on my own working many hours for many, many years — even today. When my dad decided to retire he consulted with a professional firm to guide him about selecting his successor. At that time my two younger brothers were also working at Gibraltar. Fortunately, after about a 1½ years process, I was selected to be the president.

Now my son Derek Prince, MS, is completing a Ph.D. to prepare him with the same strong scientific heritage of my father and myself. I need to assure that he is properly prepared. I am so proud to work beside him and see his vision of the company through his enthusiastic eyes.

Working at Gibraltar for almost 40 years I can honestly say it has been a privilege to work with my parents and many other family members including Derek. The video I mentioned is very special because it lets you, our customers, employees, colleagues have a glimpse of our family’s story — The Gibraltar Labs Journey through three generations. A story involving three generations of management all holding scientific Ph.D.’s. I hope that this video will inform our customers and employees about the history of our company and the journey we have taken to become the highly respected organization that we are today. Please leave a comment about the video or something about Gibraltar that you can share.

 

Daniel Prince, Ph.D.

President

 

Mike Venanzi No Comments

Application of Terminal Sterilization for Aseptic Manufactured Products

Sterilization services

Application of Terminal Sterilization for Aseptic Manufactured Products

USP <1238> Vaccines for Human Use – Bacterial Vaccines states: “Tests required for each lot-release protocol include potency, general safety, sterility, purity, identity, and constituent materials. Potency and potency-related tests are different for each bacterial vaccine. The inclusion of these tests makes each bacterial vaccine lot-release protocol unique.” Vaccines, like other aseptically manufactured finished products, rely on filtration to remove any organisms. After filtration, the finished products are filled under classified conditions into pre-sterilized vials, stoppered and sealed. At this point aseptically manufactured products are usually assumed to be inappropriate for steam sterilization due to possible heat liability of the finished product.

However, due diligence must be followed in order for the manufacturer to comply with cGMP because with newer thinking and technology – this assumption may be incorrect.  It is well accepted that the best practice is to follow aseptic manufacturing with terminal sterilization whenever possible.

As per USP <1229> Sterilization of Compendial Articles, “…a specimen is deemed sterile only when there is a complete absence of viable microorganisms (bacteria, yeasts, and molds)…”.  However, sterility cannot be demonstrated with respect to compendial articles and other materials because of the inherent limitations of the current test (see USP <71> Sterility Tests). Sterility can be accomplished only by the use of a validated sterilization process under appropriate current good manufacturing practices and cannot be demonstrated by reliance on aseptic manufacturing, media fills or sterility testing.

Terminal sterilization alone is able to define the probability of a non-sterile unit [PNSU]. Liquids in sealed containers are steam sterilized in programmable air over pressure steam sterilizers. Development cycles are performed to ensure both product potency and sterilization effectiveness are maintained. New thinking does not rely upon high populations of highly resistant spores like Geobacillus stearothermophilus to assure sterilization nor excessively high sterilization temperatures. For example, less resistant spores and/or product bioburden are discussed in USP <1229.2> with the specification of obtaining ≤ 10-6 PNSU.

Utilizing a product’s bioburden dramatically reduces the exposure time for a given sterilization temperature and obtains an acceptable PNSU. For example, a typical Geobacillus stearotherpmophilus spore D value is 1.0 minute. If the natural bioburden for a product survives boiling at 100°C for one minute and not for 10 minutes then its D value is 100 times lower than Geobacillus stearotherpmophilus , i.e., 0.01 minutes.

The accessibility of steam sterilization is illustrated as follows. When F0 is 8 and the bioburden is 100 CFUs, the calculation of the PNSU is:

 

Log Nu = −F/D + log N0

Nu = PNSU
D = D-value of the natural bioburden
F0 = F0-value of the process (lethality)
N0 = bioburden population per container

 

Log Nu = −8/0.01 + 2 = −78

 

Therefore, the PNSU = 10-78.

Product potency can be examined after exposure to development cycles designed to be consistent with sterility and product integrity.

In this example, in addition to sterilizing at 121.1°C, because Z = 10 the D value will rise or fall by a factor of ten when the sterilization temperature is raised or lowered, respectively.  To minimize heat lability the sterilization temperature can be lowered to 111.1°C achieving an acceptable PNSU of 10-7.8 when D = 0.1.

In practice, tools available to the sterilization practitioner now include lower sterilization temperatures, longer cycles and bioburden based parameters, all of which may permit a much greater number of aseptically manufactured products to be terminally sterilized to the benefit of all.

 

Kate Slezak No Comments

Importance of Microbiological Food Safety Testing

Importance of Microbiological Food Safety Testing

Written by Kate Slezak

When we first start going to the grocery store with a parent or family member, we all get taught the same things; don’t get the expired milk, check the tomato for bruises, don’t take the dented or bulging cans. Some things are straightforward – no one wants to eat a rotten tomato or suffer the nasty stench of curdled milk, but why avoid the bulging cans? Who decided that was a thing we had to do? Does it not mean that it’s just stuffed with extra food? People throw around the word “Botulism” but what does it mean?
Clostridium botulinium, the organism that causes Botulism, leads to problems in the nervous system that may result in muscle and chest weakness, difficulty seeing, and can even be fatal. It’s considered a thermophilic anaerobic organism, meaning it can withstand extreme temperatures and mostly exists in environments without oxygen. But it’s only one example of the different thermophilic anaerobic organisms that affect the food consumers purchase on a daily basis.- There are some foods and contaminants that people aren’t even aware of, and most people don’t know where it all comes from. Here at Gibraltar Laboratories, Microbiological Food Safety Testing is performed in order to detect thermophilic anaerobic microorganisms similar to that which causes Botulism. These types of bacteria and spores are responsible for 60-80% of the spoilage of canned foods, and can present problems in things like infant formula, dehydrated milk, starch, flour, cereals, soy proteins, and even sugar.
Contaminants like the spores we test for usually grow on the handling equipment throughout the canning process, the skin of the handlers, in the soil, and on the raw materials themselves. The affected foods can be contaminated at several points during processing. For example, many canned foods such as vegetables and meats go through a process of sterilization that involves the use of extreme heat. This heat is used to hermetically seal the product and kill any bacteria incapable of withstanding such temperatures, thus making it safer for consumption. The cans are then cooled by being placed in water, which despite often being treated with chlorine to prevent bacterial growth, is the source of most canned food contamination. Organisms growing in the cooling water can leak through any failing hermetic seals due to dents in cans or an incorrect sealing process, contaminating the food within. In the case of infant formula, if thermophilic organisms are present in the raw milk, the high temperatures attained during the pasteurization process can cause the spores to grow and contaminate the formula.
A shopper can sometimes avoid buying these contaminated foods by doing what we were taught to do- avoid swollen or dented cans. Many of the thermophilic anaerobic spores and bacteria that contaminate canned food produce carbon dioxide and hydrogen, which react with the acids in the food and the metals in the can, causing it to swell and indicating that contamination is occurring. On the other hand, some organisms don’t produce gas or are packaged differently. This makes it much more difficult for the average person to find contaminated products like sugar or cereals, which are sold in boxes and bags. That’s what the FDA and laboratories like Gibraltar are here for. Companies will check their finished products by performing routine Microbiological Food Safety Testing with Gibraltar Laboratories, Inc. to keep consumers safe. The FDA enforces strict rules and methods of detection that Gibraltar uses to test products such as infant formula, starch, flour, cereals, and other related products for all of those hard-to-see contaminants that can hide in food and make you sick.
So Mom was right- avoid those swollen or dented cans, but we’ll are here to help make sure what you’re consuming is safe. For more information on our testing services and how our microbiological food testing services as well as our sterilization services can help your business contact us today at 973-227-6882.

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Gibraltar Laboratories Receives ACIL Customer Quality Service Award

We’re excited to announce that we have received confirmation that Gibraltar Laboratories has received the ACIL Customer Quality Service Award for the fourth year in a row!

The American Council of Independent Laboratories (ACIL) has been awarding the ACIL Customer Quality Service Award on a yearly basis since 1996. The purpose of the award is to provide a system with which to evaluate laboratories and compare the quality of their operations. It’s the only program in the laboratory services industry that both ranks customer satisfaction as well as requires the participating laboratories to commit to a data integrity program.

During the evaluation process, participating laboratories provide customer satisfaction surveys to their clients, as well as deliver proof of their annual ethics-training program, systems designed to detect suspicious analytical practices early on, and a code of ethics the laboratory has agreed to. The 2015 round of evaluations was highly competitive, as the participating laboratories had an average of 3.5 out of a possible 4.0 in the timeliness category, and an average of 3.7 out of a possible 4.0 in the overall customer satisfaction category.

Despite the high standards and expertise of the laboratories participating, in addition to being awarded the ACIL Customer Quality Service Award, for the fourth year in a row Gibraltar Laboratories was also ranked in the top fifth of the participants for both timeliness and overall customer satisfaction. We’ll be heading over to sunny Florida to accept our award at the ACIL Annual Meeting that takes place from October 6th to October 9th.

We believe that our consistent success with the ACIL Customer Quality Service, as well as other recognitions we’ve been awarded and our reputation for excellence, are a direct result of everyone at the company committing to the principle of outstanding customer service. We at Gibraltar Laboratories have high standards for our staff, only hiring the most experienced and motivated experts in the field, and we are extremely appreciative of their hard work and dedication that makes us one of the leading testing laboratories in the country.

Moving forward, we want to continue to live up to our mission and quality policy statements, not only upholding, but ever improving, the quality of our operations, facilities and customer service. We believe you can’t be one of the best providers of a large variety of services from rapid sterility testing to medical device cleaning validation without constant diligence and willingness to go above and beyond to find the right solutions for every one of our customers.