Life Extension Magazine

Life Extension Magazine September 2013

Report

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

By Life Extension

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
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.