3.2: Quality Systems in Companies

Quality Systems in Companies which are Regulated

The goal of government regulation is to protect public health. Any company producing drugs or medical devices is governed by the FDA. Serious injury and even death can result from product contamination, deviation, failure, and errors in manufacturing and packaging. These types of events may be reduced or avoided altogether when a company follows federally mandated quality guidelines, known as Current Good Manufacturing Practices (CGMPs).

These guidelines for product manufacturing and testing represent a formal quality system that describes the general principles that must be observed during manufacturing. It is the company’s responsibility to ensure GMP compliance and to do so efficiently and effectively. To this end, regulations are relatively flexible. It is up to the manufacturer to establish design procedures, processing methods, and testing procedures. This flexibility gives companies room to experiment and innovate.

Additionally, it should be noted that CGMPs represent only the currently accepted minimum standards for manufacturing, testing, and packaging drugs and medical devices. Most companies go above and beyond minimum guidelines to assure a customer a high-quality product. They frequently employ multiple quality systems, including voluntary ones, which provide the consumer peace of mind and a level of trust in the safety of the product.

GMP Guidelines Follow a Few Basic Principles:

1. Define, control, and validate all critical manufacturing processes.
2. Changes to the manufacturing process must be evaluated and approved.
3. Instructions and procedures must be written clearly and easy to understand.
4. Production operators must receive thorough training on all processes and documentation of processes.
5. The company must maintain accurate records demonstrating their adherence to guidelines and regulations. Any deviations in product quality or quantity must be documented and investigated.
6. Records must be comprehensive, complete, and easily accessible.
7. A recall system is in place so that any batch of a drug may be easily recalled
8. The company responds to complaints, quality defects are investigated, and appropriate measures are taken to prevent future defects.

Explore!

Explore the nutraceuticals company NuLab’s website.

Watch the video on CGMP quality procedures: https://www.youtube.com/watch?v=kvICQiMFVi4 & https://www.youtube.com/watch?v=oRsZihZa4CQ

In what ways has NuLabs incorporated quality principles into its manufacturing facility?

Good Laboratory Practices (GLPs)

In 1975, FDA inspection of several pharmaceutical testing laboratories revealed poorly designed and carelessly executed experiments on animals, inaccurate record keeping, poorly maintained animal facilities and a variety of other problems. These deficiencies led the FDA to institute the Good Laboratory Practices (GLP) regulations to govern animal studies of pharmaceutical products. GLPs require that testing laboratories follow written protocols, have adequate facilities, provide proper animal care, record data accurately, and conduct valid toxicity tests. GLPs regulate all non-clinical safety studies that support investigative new drugs and new drug applications, biologics that are drugs, veterinary drugs, and some food additives.

GLP laboratories are organized in a particular manner in seven general areas:

1. Organization and personnel (study director, quality assurance unit)
2. Testing facility (there are specific requirements for animal care)
3. Testing facility operation (each laboratory must base its functioning on Standard Operating Procedures (SOPs)
4. Test and control article characterization
5. The protocol and the conduct of the nonclinical laboratory study (a document, a plan, which indicates objectives and methods for the conduct of the study)
6. Records and reporting (periodic audits and final report)
7. Equipment design (equipment must be appropriately designed and well maintained).

Good Clinical Practice (GCP)

Good clinical practice (GCP), for hospital & clinician’s clinical studies on new drugs in humans; regulations meant to ensure the quality of data submitted to the FDA on a new pharmaceutical to be marketed has been properly conceived and tested. These regulations also protect the welfare of human volunteers in clinical trials:

1. To protect volunteers participating in a clinical study, they must be informed about the study and treatment they are to receive so they can make an informed decision whether to participate.
2. To protect the rights and welfare of clinical subjects, the FDA requires that clinical trials be reviewed by a committee independent of the study sponsor called an Institutional Review Board (IRB).
3. Another regulation defines the responsibilities of the trial sponsors and investigators during the conduct of a trial.
4. The FDA “Guideline for the Monitoring of Clinical Investigations” also explains the monitoring needed during a clinical trial, and how to document the process.

Enforcement

The U.S. Food and Drug Administration (US FDA) enforces Good Manufacturing Processes under Section 501(B) of the 1938 Food, Drug, and Cosmetic Act (21USC351). Inspections are sometimes scheduled but may also occur unannounced as long as they are conducted at a “reasonable time” as outlined in Section 704(A) of the FD&C Act (21USC374). Any time the company is open for business is the accepted definition of a “reasonable time.” It is interesting to note that a product may be considered “adulterated” if the manufacturer failed to produce it by industry standards, even if the manufacturer did not violate any specific regulatory requirement. More on FDA enforcement in a later chapter!

Quality Systems in Companies with Voluntary Standards

Not all biotechnology companies produce regulated products. It makes good business sense for companies to impose some form of the established quality system. They may choose to follow CGMPs or certain federal guidelines – but what most of these companies do is voluntarily adopt quality systems that are not government regulated.

International Organization for Standardization (ISO)

One of the most prominent international quality systems is ISO. ISO is a quality system that can be applied to a wide range of products. Participation is voluntary, and oversight is conducted through outside auditors paid for by the participating company. ISO standards can apply to more than just product design and specifications. There are also standards that outline things such as design methods and production processes based on currently accepted ‘good practices.' The ISO system is so well-known and respected that most companies who can voluntarily follow it do follow it. Below we will dive into a more in-depth discussion of the ISO system and how it applies in bioscience and biotechnology companies. The mission of the ISO is: “to facilitate the international coordination and unification of industrial standards." (www.iso.org)

Explore!

Visit the ISO website: http://www.iso.org/iso/home.html and learn about The International Organization of Standards.

1. What is ISO?
2. Who is responsible for the ISO 9000 quality standards?
3. What’s new this year for ISO standards (hint: read their news!)

The need for a global standard arose because of the uneven progress of industrial development throughout the world. As manufacturing technology spreads, many countries develop their standards. Different processes and even different methods of measuring and testing made for vastly different outcomes in quality. Recognizing these differences as a barrier to trade, a group of delegates from 25 countries met to create the ISO, and the organization officially began operation on February 23, 1947. Each member nation participates through its national standards organization. The United States is a member of the ISO through the American National Standards Institute (ANSI) (www.ansi.org). The collective efforts of ISO members have helped to make the development and production of products and services safer and more efficient.

Explore!

Visit the ANSI website: http://www.ansi.org.

1. What is the mission of ANSI?
2. Why is ANSI relevant to quality systems?