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Quality Standards
Topics:
1. The Anabolic Difference
2. “Pharmaceutical made” versus “pharmaceutical grade” nutritional products
3. Failure of pharmaceutical grade supplements to meet label claims
4. Pharmaceutical made nutritional products at Anabolic Laboratories
• The manufacturing process begins
• Quarantine of raw materials
• Microbial testing
• Identification process
• Weighing and blending
• Supplement production
• Quality control steps during production
• Quality control steps after tablet compression and/or encapsulation
• Stability (shelf life) testing process
• Cleaning and the pharmaceutical manufacturing process
1. The Anabolic Difference
What is the “Anabolic Difference?” It can be summed up in two bullet points:
• As a United States federally regulated and inspected pharmaceutical manufacturer that makes nutritional products, our quality control, manufacturing and quality assurance requirements are the most stringent in the industry.
• Anabolic Laboratories has been producing “pharmaceutical made nutritional products since 1924.”
2. “Pharmaceutical made” versus “pharmaceutical grade” nutritional products
The Anabolic Laboratories’ supplements that you provide to your patients are “pharmaceutical made,” which means that an exhaustive manufacturing process has been employed to guarantee purity and potency. “Pharmaceutical made” supplements are very different from those that are “pharmaceutical grade.”
All raw materials (vitamins, minerals, herbs, etc.) that enter a nutritional supplement manufacturing facility are “pharmaceutical grade.” This is because all raw materials are powders of uniform size, such that they can flow through a tableting or encapsulating machine that was originally designed for manufacturing pharmaceuticals.
To put this terminology into perspective, recall in your mind the visual appearance of oatmeal flakes and coffee beans. Imagine putting each into a grinder; the outcome will be oatmeal powder/flour and coffee powder. You have just made pharmaceutical grade oatmeal and coffee.
The term “pharmaceutical grade” has nothing to do with purity and potency of a given nutritional product. In fact, “pharmaceutical grade” supplements commonly fail to meet label claims.
3. Failure of pharmaceutical grade supplements to meet label claims
We now have substantial third party evidence demonstrating that unless adequate quality controls are in place, it is common for nutritional supplements to not meet their label claims. This fact is being regularly published to alert consumers.
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The Food and Drug Administration (FDA) has found that manufacturing problems have been associated with dietary supplements. Products have been recalled because of microbiological, pesticide, and heavy metal contamination, and because they do not contain the dietary ingredients they are represented to contain, or they contain more or less than the amount of dietary ingredient claimed on the label.
Reference: June 22, 2007, FDA @ http://www.fda.gov/Food/DietarySupplements/GuidanceComplianceRegulatoryInformation/RegulationsLaws/ucm110863.htm |
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Of the magnesium supplements tested by ConsumerLab.com, 25% failed to meet quality standards. One magnesium supplement contained only 45.4% of labeled amount, despite boasting a “GMP” (Good Manufacturing Practices) seal on its label, and another supplement provided only 28.8% of the labeled amount.
Reference: ConsumerLab.com, Magnesium Supplement Reviews and Quality Ratings, Posted 5/19/09 |
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Tests by ConsumerLab.com have found multivitamins that were short on ingredients, failed to dissolve properly, or were contaminated with heavy metals.
Reference: ConsumerLab.com, New Product Review: Multivitamin and Multimineral Supplements, Posted 4/1/09 |
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The mean vitamin D content from 10 different commercially available brands was only 33% of what the label claimed, with the actual content ranging from less than 1% to 82% of the advertised level.
Reference: June 7, 2010. http://www.medpagetoday.com/MeetingCoverage/CMSC-ACTRIMS/20522 |
Without rigorous manufacturing standards, it is quite easy to produce contaminated supplements and/or ones that do not meet label claims. For this reason, the best choice of nutritional supplements are those that are “pharmaceutical made” by Anabolic Laboratories
4. Pharmaceutical made nutritional products at Anabolic Laboratories
As described in the company history page, Anabolic played a unique role in World War II. We already used state-of-the-art manufacturing principles, which allowed us to transform into a pharmaceutical manufacturer. We manufactured opiates for injured soldiers. This transformation allowed us to utilize pharmaceutical-type controls in manufacturing processes for the production of nutritional supplements, which has continued to this day.
It is important to emphasize the uniqueness of our company. We are a contract pharmaceutical manufacturer and this demands pharmaceutical manufacturing processes are already in place where we produce nutritional supplements to federal regulations. This process is highly intensive, redundant and regulated, which insures that label claims are met. Indeed, no supplement can leave an Anabolic manufacturing plant unless label claims have been verified.
The manufacturing process begins
Vitamin, mineral, botanical and special nutrient raw materials are received by Anabolic Laboratories from multiple pharmaceutical and nutritional manufacturers, distributors and brokers throughout the world. Most arrive as white powders that are indistinguishable from each.
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What is this white powder?
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All raw material vendors supply nutritional manufacturers with a Certificate of Analysis (C of A) stating that the delivered powder is a given vitamin, mineral, herb or other substance. However, a C of A from just any vendor is not adequate for Anabolic Laboratories. Instead, raw material vendors must meet a Supplier Qualification criteria developed by our Quality Assurance and Purchasing departments. This program establishes reliable relationships with quality suppliers, differentiating them from vendors who offer inferior or impure raw materials.
Despite this qualification process, when Anabolic receives raw materials from even a trusted vendor, a rigorous testing process begins to indentify the material and determine its purity and potency. The outcome is that every year, thousands of kilograms of raw materials are rejected because they fail to meet purity specifications or do not contain what the vendor claims.
Why does Anabolic go through this exhaustive process? Because Federal Law mandates this process for pharmaceutical manufacturing!
Quarantine of raw materials
All raw materials that enter an Anabolic manufacturing plant are first placed in quarantine. These are large rooms in which inventory is tightly monitored.
It is vital to keep untested raw materials separate from those materials in inventory that have gone through testing in our Quality Control Laboratory. Multiple tests must be performed before a raw material can be released from quarantine for supplement manufacturing.
Microbial testing
It is not uncommon for raw materials to be contaminated, particularly herbs, which arrive in the United States from all over the world. Mold, yeast, and E. coli are among the most common. For this reason, every raw material must be tested for microbial contamination.
Petri dishes contain growth media for various microbes, such as E. coli and Salmonella. A sample of the raw material is placed into the petri dish. If a microbe grows, the only source can be the raw material, which is immediately rejected.
We test hundreds of raw materials each week. To demonstrate the extensiveness of our microbial testing, even the water we use in manufacturing must first be tested.
Identification process
As most raw materials are white powders, each must be identified and then tested for purity and/or potency. Analytical equipment currently in operation at Anabolic Laboratories in the following:
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• Capillary Electrophoresis (CE)
• Gas Chromatography (GC)
• High Pressure Liquid Chromatography (HPLC)
• Atomic Absorption (AA)
• UV Spectrophotometers (UV)
• Nondestructive Infrared Spectrophotometers (IR)
• Inductively Coupled Plasma –atomic emission spectroscopy (ICP– AES)
• Near-infrared Spectrophotometers (near IR)
• Stability Chambers
• Total Organic Carbon analyzers (TOC)
• Dissolution Apparatus
• Disintegration Tanks
• Inductively Coupled Plasma -Mass Spectrometry (ICP– MS)
• Microbiological testing equipment and analysis
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After exhaustive testing, if raw materials meet Quality Control Laboratory specifications they are released from quarantine to inventory. Now the material is available for manufacturing, and the materials are weighed and compounded (blended) according to strict procedures to achieve uniform distribution of nutrients.
Important to note is that raw materials are commonly rejected due to contamination by microorganisms, heavy metals, or because of identification abnormalities, such as inadequate potency. It is not uncommon to discover 0% of stated active ingredient in a nutritional raw material.
Occasionally more interesting scenarios are encountered. For example, in 1999, Anabolic Laboratories received coenzyme Q10 from a potential new supplier. It arrives with a proper certificate of analysis (C of A), and the material was the appropriate yellow/orange colored powder. A sample passed the USP infrared identification (IR) test. However, testing with high pressure liquid chromatography revealed a substance that had characteristics not consistent with CoQ10. Further analysis with a photodiode array detector revealed that the raw material was actually folic acid and riboflavin, which is also a yellow/orange powder and mimics the IR image of CoQ10. The entire batch of raw material was returned to the supplier. Without an advanced in-house laboratory, a nutritional company could easily sell a CoQ10 product without any CoQ10 in the bottle.
Raw material issues are common and manufacturing errors occur. The difference is that Anabolic detects and corrects such errors, which allows doctors to have total confidence in the products they provide to their patients. Backorder issues may occur, and we ask doctors to please understand that very often, this is a result of holding natural ingredients to pharmaceutical-type controls.
Weighing and blending
This process of weighing and blending is quite rigorous for pharmaceutical/supplement manufacturing. Personnel are specifically trained and certified according to Federal Law to perform the various aspects of manufacturing.
After weighing, each component of a nutritional supplement is poured into one of many high volume blenders. During the blending process, manufacturing personnel will inspect the blending operation and make appropriate notations. After blending is complete, the “blend” of nutrients is emptied.
High volume V-blender Emptying a high volume blender
Not well known is that the numerous components found in a multivitamin/mineral make it the most complex and difficult of all supplements to properly manufacture; even more difficult than medications. This is because dozens of ingredients make up a large blend. The uniformity of the large blend must be consistent and reflected in the contents of a small tablet or capsule. With this in mind, it should not be surprising that nutritional supplements not manufactured with pharmaceutical-type controls, commonly fail to meet label claims.
Supplement production
Anabolic utilizes both tableting and encapsulating machines depending on the product specifications. Ingredient blends are loaded into tableting, encapsulating or other manufacturing equipment located in isolated environmentally controlled rooms, which are maintained at proper temperature and humidity with filtered air to prevent microbiological and airborne particulate cross-contamination.
Isolated Production Rooms
Quality control steps during production
Inside each manufacturing room, important quality control steps are taken. Sample tablets are removed during the tableting process and are weighed and measured for thickness and hardness, to insure they meet specifications.
Quality control steps after tablet compression and/or encapsulation
Samples of finished tablets/capsules are sent to the analytical laboratory to verify that all ingredient amounts meet label claims before the product is released for final processing (such as coating) and packaging. Insuring that label claims are met on nutritional supplements is a constant challenge due to natural ingredients. In most cases, if there is a discrepancy, the batch will be destroyed. However, dietary supplements can be modified in process to insure compliance with specification, however, pharmaceuticals are not allowed this type of in-process variation.
In 2005, a production batch of 500,000 A.V.E.D.-Kids chewable multivitamin tablets was produced. All quality specifications were met throughout production; however, post production analysis revealed significantly low levels of folic acid in many of the tablets. Our in-house quality procedures and pharmaceutical manufacturing standards required that we destroy the entire batch instead of merely re-working it.
The manufacturing process does not stop after completed batch samples meeting label claims. In order for supplements to be clinically useful, they must be digested and absorbed by the patient. Completed samples undergo disintegration testing, which mimics the digestive process. Time-release supplements go through dissolution testing to ensure nutrients are appropriately released over a prolonged period. Enteric coated products will be tested to insure they do not break down in stomach acid, but will breakdown in the intestines.
Disintegration Apparatus Dissolution testing
Only after all Quality Control specifications and procedures are passed will finished products be released to packaging. However, the extensiveness of the Anabolic quality manufacturing process does not end here.
How can you be sure that label claims of nutrient levels will be present over time? This is a question that is rarely considered.
Stability (shelf life) testing process
If you look at a supplement bottle, you will notice a manufacturing date or a“best by”/expiration date, which signifies the date into the future after which label claims may fail to be met. In most cases, expiration dates are estimations and not based on evidence. In contrast, at Anabolic Laboratories, expiration dates on our bottles are based on scientific testing.
After production is completed, bottled products are placed in stability chambers, which maintain constant high temperature and humidity to accurately assess the shelf-life of each product.
Stability chamber
After specific time intervals, supplements are removed from stability chambers and tested again by our Quality Control Laboratory for microbiological growth and to verify that nutrient values on the label (potency) will be accurate up to the best by date. Only now, after this exhaustive process are we able to place bottles of product in our shipping warehouse for delivery to doctors’ offices.
Cleaning and the pharmaceutical manufacturing process
Another underappreciated aspect of pharmaceutical manufacturing regulations is the time, money, and effort involved in cleaning. If you look at the wrapper of a nutrition bar, you will notice that most are manufactured in a plant with peanuts and other potential allergens. This statement is designed to alert consumers of the potential for cross-contamination.
In contrast, Federal Law forbids cross-contamination during pharmaceutical manufacturing and the FDA will immediately shut the business down, impose severe fines and penalties if any unsafe practice is uncovered during routine inspections and testing. If pharmaceutical material and nutritional materials mix, people could be seriously harmed, which will lead to severe penalties that may include prison time. We are a pharmaceutical manufacturer, and to prevent cross-contamination, extensive cleaning and post-cleaning laboratory testing of individual manufacturing rooms is required.
To appreciate the extent of the cleaning process, at Anabolic Laboratories approximately 30% of our total labor time and associated costs are devoted to the cleaning process. Only specially trained and certified personnel are allowed to clean, and qualified technicians must inspect and release materials and production rooms before use.
Summary
While it is impossible to develop a true “visceral” understanding for the depth and breadth of the pharmaceutical manufacturing process without visiting one of our plants, our hope is that this introductory description demonstrates the rigors associated with creating “pharmaceutical made” nutritional products.
We extend an open invitation to all health care providers to visit our Irvine, CA and Colorado Springs manufacturing facilities. If you work, or travel, near either of our facilities, please contact us to schedule a tour to experience the Anabolic Difference.
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