Dietary Supplement Safety-Control Compared to FDA-regulated Drug Factories

Can you imagine having a business where you charge customers
$200 each month for something that cost you only $2.10 !
That’s a markup of about 100 times and it’s not for a patented product.

In 2010, drug companies were charging around $7 for each 500 mg tablet of a generic medicine called valacyclovir. The brand name Valtrex^® was priced slightly higher. People with frequent oral or genital herpes outbreaks needed to take one valacyclovir tablet each day to reduce the number of outbreaks they’d suffer.

The annual cost to these consumers was $2,400, yet drug companies paid only $25.20 to produce it. (Valacyclovir is also used in higher doses to treat shingles.)

You would think that with these obscene profits, drug factories would bend over backward to ensure the strictest quality-control standards so as not to jeopardize this lucrative cash cow, much of it guaranteed by your tax dollars.

Instead, with quasi-monopoly status provided by federal regulators who stomp out competition, some pharmaceutical companies ran 24-hour-a-day assembly lines to make as many of these outrageously priced drugs as possible, knowing they had little downside risk by ignoring even rudimentary safety standards.

Over the past 33 years, Life Extension^® has inspected hundreds of supplement makers. While some do not meet our exacting standards, we have never seen anything close to the deplorable conditions that have been uncovered inside some of America’s largest drug factories.

One difference between supplement makers and drug factories is that owners of supplement companies often take their own products daily, whereas some pharmaceutical owners apparently live in a state of denial that they will ever need the polluted drugs they sell to others.

The FDA pretends to protect the public against contaminated drugs. The sordid facts reveal an agency incapable of acting in a consistent and logical manner.

Such is the case of a company that made contaminated injectable drugs that have killed and sickened many Americans. The FDA identified problems with this manufacturer as early as 2002, but dropped the ball into a state pharmacy board’s lap that failed to act. The FDA again identified dangerous problems in 2006, but once more failed to take actions other than sending a “warning letter.” The FDA now says it needs more power and money to do its job.

An increasing number of supplement companies are being bought out by pharmaceutical companies. These corporate behemoths have historically shown little regard for their customer’s health and longevity, as demonstrated by the cover-ups of deadly side effects of drugs like Vioxx^® that killed tens of thousands of Americans.

This article describes the quality-control mandates for products that carry the Life Extension^® brand name.

Since June 2007, there have been strict federal rules in outlining requirements for manufacturing, packaging, labeling and holding dietary supplement products in the United States.

Long before this, however, Life Extension insisted that its manufacturing and packaging partners follow these types of stringent quality control practices to ensure product purity and potency.

Life Extension stays ahead of government mandates by proactively defining and managing quality systems internally with an emphasis on qualification of materials and suppliers, mandating meticulous facility cleanliness, and insisting on rigorous finished goods specification/testing programs.

FDA Inspections of Life Extension

In the year 2000, an FDA inspector showed up at Life Extension and demanded samples of products for the FDA to assay.

The FDA agent was initially belligerent, perhaps expecting a legal challenge to his demand for product samples. Instead, Life Extension’s quality control supervisor provided the FDA with all the requested samples, but let him know that the identical lot numbers would be sent out to two independent assay laboratories to verify any findings the FDA came back with.

During this initial inspection, the FDA agent repeatedly threatened to imprison Life Extension personnel if any problems were found. Life Extension responded that the products had already been assayed and, therefore, we had no concern about what the FDA would find.

Within ten days, the assays from the two independent labs came back on all the products. Upon submitting these assays to the FDA inspector, along with file cabinets full of quantitative analysis results, the FDA agent stated he was calling off the inspection because the quality control procedures employed, as he stated, are “analogous to those of drug companies.” At the time, we took that as a compliment, until recent reports showed how poorly certain drug factories operate.

The FDA inspector indicated that he did not expect that a supplement maker would operate under high quality standards. When the FDA agent was asked if the samples taken ten days earlier met the FDA’s standards, he indicated that they were not yet submitted for assay and would not be because the two independent testing labs had already documented that they met label potency.

The FDA inspected again in 2012. The inspection resulted in zero findings of non-compliance.

NSF^® International Registration

 

Life Extension’s fulfillment facility recently earned cGMP (current Good Manufacturing Practices) registration from NSF International, an organization that provides third party certification programs using state-of-the-art analytical laboratories and a highly skilled staff of chemists and microbiologists.

NSF International registration was based on a demanding two-day audit conducted by NSF International which included an evaluation of Life Extension’s Warehouse & Distribution center, including facility cleanliness and sanitation, as well as various quality systems such as complaint handling/investigations, product returns, training, deviation management and product recall handling. The NSF International registration is widely recognized as an objective “seal of approval” signifying the meeting or exceeding of cGMP requirements and industry standards/best practices for quality.

ConsumerLab and International Fish Oil Standards

Life Extension continues to participate in the voluntary ConsumerLab testing program. The program includes an annual evaluation of various product families for potency and label claim verification. For example, over the past year products were submitted in a variety of categories including Multivitamins, Bone Health, Cancer, B-Vitamins, CoQ10/Ubiquinol and Memory. In 2012, all submitted products met all testing requirements.

ConsumerLab in late 2012 evaluated a wide range of green coffee bean extract supplements and found that 50% failed to meet their label claims. As usual, Life Extension green coffee bean extract, which contains the identical ingredient used in successful clinical studies, came out flawlessly.

Life Extension also continues to participate in the International Fish Oil Standards (IFOS™) testing program for fish oil products. In 2012, over 10 batches were submitted which met or exceeded the industry standards requirements for purity and potency. This is especially important for delicate fish oils that can oxidize and lose their EPA/DHA potency, and/or contain toxic levels of mercury and other heavy metals.

Supplier Management / External Audit Program

Life Extension places high emphasis on the management and evaluation of outside providers … including contract manufacturers and packagers, contract laboratories and raw material suppliers. The evaluation process consists of an assessment of completed regulatory questionnaires as well as an aggressive on-site audit program based on our stringent criteria for manufacturing, packaging, labeling and holding dietary supplement products in the United States. Items of special interest include: cleaning and sanitation procedures, pest control, manufacturing and packaging controls, testing, training and documentation practices.

In 2011, we conducted 13 audits including on-site evaluations of Life Extension’s top contract manufacturers, packagers and laboratories. Audit findings were documented and reported to the suppliers and corrective and preventive actions were requested from each supplier. In several instances, follow-up audits were performed to evaluate the effectiveness of corrective actions. In some cases, suppliers were disqualified for not meeting Life Extension’s exacting quality standards.

In 2012, 26 audits were conducted. These audits include evaluations of new suppliers and/or existing supplier follow-up. This aggressive audit schedule will continue to ensure cGMP compliance and drive continuous improvement initiatives with our manufacturing partners.

Roughly 90% of Life Extension branded products are manufactured in NSF International cGMP registered facilities and the combination of NSF International registration along with Life Extension on-site inspections helps ensure that the products manufactured on our behalf have been produced in accordance with the highest standards.

Internal Audit Program

To ensure compliance with applicable regulations, policies and procedures, the Life Extension Quality Unit maintains a documented system for self-inspections which includes internal audits conducted at the corporate location as well as the distribution center in Coram, NY. Although these internal audits are required annually, they are actually conducted more frequently by choice. Since late 2011, a total of four internal audits have been conducted at corporate and four have been conducted at the distribution center. The findings of these audits are captured under a documented quality-control program which ensures that processes and procedures are constantly being reviewed and evaluated as part of the company’s continuous improvement initiatives.

Raw Material Qualification Program

Before new Life Extension-purchased raw materials can be considered for use in branded products they must undergo an extensive, documented review process to ensure that they meet requirements for identity, potency and purity. These materials are tested at contract analytical laboratories which have been qualified by the Life Extension Quality Unit. Materials are typically assayed for potency via advanced analytical chemistry techniques like high performance liquid chromatography (HPLC) or gas chromatography (GC) and are screened for contaminants such as heavy metals via inductively coupled plasma-mass spectrometry (ICP-MS) and microbes utilizing advanced United States Pharmacopeia (USP) methodology.

Botanical ingredients undergo a higher level of scrutiny, with identity (genus/species) verified through comparison to reference standards utilizing high performance thin layer chromatography (HPTLC) and microscopy methods.

Botanical ingredients are also screened for pesticides as defined in USP <561>, Articles of Botanical Origin. In some cases residual solvents will also be evaluated to ensure that raw materials purchased by Life Extension meet appropriate requirements for safety, purity and efficacy. Based on these qualification activities, raw material specifications are developed for each ingredient which are reviewed and approved by the Quality Unit. Life Extension partners with contract manufacturers to ensure that all incoming test results on these materials meet Life Extension specifications and have been reviewed and approved by the Life Extension Quality Unit before use.

Finished Product Specifications / Testing Requirements

Requirements for the formulation, manufacturing, packaging and testing of all Life Extension branded finished goods are defined in each product’s Finished Product Specification Packet (FPSP). This comprehensive document is developed, reviewed and approved by Life Extension’s Product Development, Purchasing and Quality experts to ensure that Life Extension finished goods are manufactured, packaged and tested the same way every time. The process begins with the development of formulation and testing requirements by Product Development and Quality Control. These requirements are communicated to the contract manufacturer of choice and become the basis for what eventually becomes the Finished Product Specification Package. Contract manufacturers are required to acknowledge the approved specifications in writing and must notify Life Extension of any changes before implementation. Life Extension’s specifications are reflected in the manufacturers’ Master Manufacturing Records (MMRs) ensuring that the manufacturing, packaging and testing processes can be replicated on each run.

The finished product testing requirements are rigorous, including specifications for the testing of active ingredients (label claim) as well as potential contaminants including heavy metals and microbes. These tests are conducted using state of the art equipment such as HPLC, GC and ICP-MS at Life Extension’s approved contract manufacturers and laboratories. Each lot of finished product received by Life Extension is held in quarantine pending a physical inspection of the goods along with a review of the product’s Certificate of Analysis, which must accompany each shipment. The result of this incoming inspection is documented by Life Extension’s Quality Control group. Any finished products not meeting these exacting standards are rejected by the Quality Control group and are not released for distribution.

Pharmaceutical cGMP Standards Not Always Adhered to by Drug Makers

The FDA’s current Good Manufacturing Practices (cGMP) requirements are, in general, stricter for pharmaceuticals than either food cGMP or dietary supplement cGMP standards. Dietary supplement cGMP can be accurately characterized as a combination of food cGMP and pharmaceutical cGMP.

In 2003, the FDA implied that food cGMP should be followed for dietary supplements. In fact, food cGMP focuses upon product safety and sanitation, not quality. In contrast, pharmaceutical cGMP focuses upon safety, sanitation, and quality.

In 2007, the FDA passed 21 Code of Federal Regulations (CFR) Part 111 to ensure the identity, purity, quality, strength, and composition of dietary supplements. The FDA proceeded with enforcement under a “rolling” approach tiered for company employee number.

Tragedy that could have been prevented

The public learned in late 2012 that not all pharmaceutical makers are following sanitary procedures and other mandated cGMP practices to make injectable prescription drugs. Fungal meningitis causes inflammation of the lining of
the brain and spinal cord that results in dreadful sickness and sometimes death.

A drug factory made large quantities of a steroid (methylprednisone) that was injected into the joints and spines of aging humans in chronic pain. It provided immediate but temporary relief.

The problem was that almost 800 Americans contracted fungal infections that caused severe meningitis. Use of the contaminated drug has been linked to 58 deaths.¹ The underlying culprit was a black mold that was allowed to grow in the supposedly sterile vials of injectable steroid (methylprednisone).² Since injectable drugs bypass the natural barriers afforded by an intact digestive/immune system, they have to be manufactured and maintained in a sterile environment to avoid killing patients.

FDA inspections in 2002 and 2006 revealed injectable drugs being made under substandard (non-sterile) conditions. It was not until hundreds fell ill and scores died that the FDA took meaningful action.

How the FDA bungled the investigation

The name of the company that made the fungus-laced injectable drug is New England Compounding Center (NECC). It pretended to be a compounding pharmacy, but instead functioned as a large drug factory.

The FDA claims that it lacks adequate regulatory authority over compounding pharmacies, but the FDA’s inspection of NECC in year 2002 revealed problems with record keeping, sterility, and other issues. That same year the FDA informed the Massachusetts State Board of Pharmacy of an adverse reaction to methylprednisone, which is the same drug that in 2012 caused the fungal-meningitis outbreak.

Had the FDA done their job back in 2002, they would have forced NECC to register as a drug manufacturer and subjected them to stricter regulatory oversight … which may not have prevented the problems since FDA-registered drugmakers were later found to have similar unsanitary facilities.

The FDA and Massachusetts State Board of Pharmacy’s most blatant failure, however, were to uncover horrific conditions inside NECC and then take no practical steps to enforce safety compliance or shut down its facilities before tragedy struck.

Independent Assays

All of Life Extension’s raw material qualification samples are sent out to independent labs for assay, heavy metals, micro and other contaminants during the qualification process. Likewise, a large percentage of finished product assay work and most finished product heavy metals testing is performed by qualified independent labs which are mandated and approved by Life Extension.

This independent testing, along with our participation in the ConsumerLab and International Fish Oil Standards programs, provides a very high level of confidence that Life Extension products meet all requirements for potency and purity.

Deviation / Change Control Management

An important part of a robust Quality System is developing and managing a process for identifying, documenting, justifying and approving changes which could affect an approved process or system impacting a product’s safety, purity and efficacy.

Life Extension has developed internal processes and procedures for documenting one-time occurrences (deviations) and permanent changes (change control). These systems cover changes to formulations, procedures, specifications, labels and any other cGMP-related system which could impact the quality of a finished product.

Life Extension’s suppliers are required to notify Life Extension in writing of any proposed changes to formulations or processes and these changes cannot be implemented without the written approval of the Life Extension Quality Unit.

Current Good Manufacturing Practices / Standard Operating Procedures Training

Life Extension maintains a documented internal cGMP (current Good Manufacturing Practices) training program for colleagues involved in the formulation, purchasing or holding of dietary supplements. This program includes a summary review of safety mandates and is presented to new hires in Quality Assurance and Quality Control, Product Development, Purchasing and Distribution Operations. Annual refresher training is provided to existing employees.

Life Extension’s Quality Unit has also developed a training matrix per position defining Standard Operating Procedure (SOP) training requirements for these colleagues based on their job function and description. Relevant training is performed for new hires or when SOPs are issued or revised. These training efforts ensure that Life Extension colleagues are well-versed on cGMP requirements and have the training to effectively execute their specific job functions.

Complaint Handling / Continuous Improvement

All dietary supplement companies in the United States are obligated to document and investigate customer complaints.

Life Extension’s complaint management system far exceeds these requirements in that all complaints are tracked and trended to drive Continuous Improvement initiatives internally and at our contract manufacturers. These complaints are vigorously documented and investigated to ensure that products in the field meet or exceed high quality standards for our supplement customers.

As part of the complaint management system, quarterly reports are compiled and reviewed to spot trends in problematic products or suppliers. The reports are shared with Life Extension’s contract manufacturers as a means to identify areas for improvement in products and processes. These “continuous improvement” efforts have been fruitful, with a robust 50% decrease in quality customer complaints in 2012 compared to those received in 2011.

Member-Ready Certificates of Analysis (COA)

Life Extension makes member-ready Certificates of Analysis (COAs) available to our customers upon request. These COAs are representations of the analytical reports received from the contract manufacturers and laboratories and contain all of the required tests as defined in the Finished Product Specification Packets (FPSP), including potency, heavy metals and micro. This transparency provides additional confidence that Life Extension’s products meet high quality standards for purity and potency.

Summary

This report describes the step-by-step processes Life Extension has in place to ensure cleanliness, purity, active ingredient status and overall integrity of finished products. These quality control standards exceed FDA mandates in order to ensure consumers the highest quality finished products.

Life Extension has taken steps to produce nutritional supplements made under far safer conditions from a potency and purity standpoint than many expensive prescription drugs.

References

1. Available at: http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html. Accessed July 1, 2013.
2. Available at: http://www.nejm.org/doi/full/10.1056/nejmra1212617?query=featured_meningitis. Accessed June 13, 2013.

IFOS™ certification mark is a registered trademark of Nutrasource Diagnostics, Inc. These products have been tested to the quality and purity standards of the IFOS™ program conducted at Nutrasource Diagnostics, Inc.