Quality Assurance and Quality Control for Biotech and Medtech Startups

Quality assurance and control are essential for biotech and medtech startups.

What are Quality Assurance and Quality Control?

Although the terms are sometimes used interchangeably, quality assurance and quality control are actually two different pieces of a complete quality management program.

Quality Assurance

Quality assurance consists of the policies and procedures that are implemented before or during production that help prevent problems with the finished product. In terms of FDA requirements, a problem is any deviation in processes or products. To assure the quality of a product, tools such as documentation, checklists, certificates of analysis, and validations can all play roles. The over-arching goal of quality assurance is to prevent product defects.

One example of quality assurance playing a role in a process would be a technician completing a checklist as they go, helping to ensure that all steps of the procedure were completed. The technician would also note any irregularities in the process, and depending on the severity, may pull the product out of production due to a deviation in process.

Quality Control

Whereas quality assurance involves prevention, quality control is about detecting defects and deviations. Quality control means testing the processes involved in creating a product and testing the product itself to ensure that the correct parameters are met.

Testing whether a product’s coating is the correct thickness would be an example of quality control. If the answer is no, the product would not be sold and an investigation would determine the cause of the incorrect thickness.

Why Should Biotech and Medtech Startups Consider Quality?

In regulatory affairs, there is a saying: “If it’s not documented, it didn’t happen.” In the context of producing FDA-regulated products, that means that every step in the development and manufacturing processes needs to be documented. Without such documentation, a startup might find out that their work has to be repeated in order to be valid in the eyes of the FDA.

Currently, many startups still use paper lab notebooks, which make accurate data collection and storage difficult. There are areas in the laboratory in which it is not ideal to bring a lab notebook, so scientists resort to taking notes on paper towels, lab wipes, and the backs of their gloves. Then they take these notes and transfer them to lab notebooks, sometimes hours after they have finished the procedure. As many people remember from school, notes that once made complete sense can lose their meaning entirely after a relatively short time, so record keeping that isn’t immediate and complete can be a place where errors are made. Additionally, a lab notebook has no way to automatically record the time when the notes were entered. Edits made after the fact may look like notes that were included in the first draft unless they are properly annotated. Essentially, paper records allow for too many instances of human error to constitute sufficient record keeping in a highly regulated industry.

The solution to this is to institute a quality management system with processes that require and facilitate accurate, timely, and secure record keeping. Most often this involves a digital system that time-stamps all entries, and policies that require scientists to enter information within a certain time frame after an experiment.

Quality management systems are expensive, which explains why many startups don’t use them. However, their cost pales in comparison with having to repeat experiments or losing out on potential investors who recognize the lack of quality management. Good quality management means good regulatory compliance.

The flip side of this is, a quality management system that was built for a large company is not necessarily a good idea for a startup to use. There are companies that provide quality management software for smaller companies and consultants who can help startups determine what they need at this point and what can be implemented later.

FDA Requirements for Biotech and Medtech Quality Systems

For a startup that has chosen to develop a quality management program, it is ideal to understand the FDA’s requirements for such an endeavor. As biotechnology and medical device products are regulated by different parts of the FDA, they have different regulations and guidance documents. This discussion will cover each in turn.

Biotech/Pharma

Biotech and pharma companies are regulated under 21 CFR part 210 and 211, the documents covering good manufacturing practices for these industries. For quality systems specifically, the FDA has issued multiple guidance documents. These are generally authored and utilized by both the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), so they apply to both biologics and pharmaceuticals. In 2009 the FDA released a guidance document covering ICH Q10, an internationally recognized comprehensive model for a good quality management system.

This document describes a set of requirements for a complete quality management program/system. They include:

• A commitment by management to use the quality system and evaluate its efficacy in achieving quality objectives. This essentially means that management has to “buy-in” to the quality system and make sure that everyone is actively utilizing it. No quality system can function correctly without employee training and accountability, and these come from the management’s commitment to using the system.
• Defined quality policies that describe the quality strategy and how it helps achieve regulatory compliance. If a quality system were broken down into its most basic units, most of them would look like written policies and procedures for each and every aspect of how to correctly make and test a product. Thus, clearly defining all of these policies is essential. Moreover, policies should explain how they relate to the company’s overall quality strategy and goal of achieving regulatory compliance. This allows employees to understand the reasoning behind certain policies which can not only result in easier adherence, but also allows employees to contribute to system improvements.
• Planning oversight so that quality objectives are defined and communicated, resources are available, and performance indicators are established. Because a quality program involves many parts of a company, planning out how it will be enacted requires oversight such that the what, why, and how are established and communicated to all employees. Plus, resources that are needed for the program must be made available and ways to determine whether or not employees are complying with the requirements must be established.
• Management of resources and their applications. These resources that employees must utilize in the quality management program and the applications in which they are used must themselves be managed and maintained.
• Good communication within the company ensuring that information is disseminated to the right people at the right time, and the process for handling problems as they arise is defined. Quality management is about preventing as many problems as possible, and then making sure to catch the ones that do arise. A quality management program must also define what happens when a problem occurs. Who is told, when are they told, and what has to be done next are all questions to answer.
• Periodic reviews of the quality system to determine its suitability and effectiveness. In any kind of operational process, what sounds like a good way to do things does not always turn out that way. A quality management program might look great on paper but in practice cause a lot of headache for employees. Therefore, plans to review the program and make changes if necessary should be defined within the program itself. This also allows a company to examine new technologies and products that could make their quality system easier and cheaper.
• Management of purchased materials and outsourced processes if necessary. Because most companies purchase materials to become part of their products, if a vendor changes something about a material it will affect the resulting product. Similarly, if a process is outsourced and that service provider makes a change, it can affect the end result. Therefore, it is important to communicate with vendors and service providers so any changes are accounted for.

Medical Devices

Medical devices are regulated differently depending on their class, which generally relates to the risk level conferred by the device. The “riskiest” devices require premarket approval and this discussion will cover FDA guidance on quality systems for premarket approval applications. In 2003 the FDA released a guidance document on the quality system information that must be submitted as part of a premarket approval application. This includes:

• Design Control Information. Design control is a formalized approach to design for medical devices whose goal is to make sure the device meets the needs of the user, its intended uses, and design specifications. It therefore can be considered part of or alongside a quality system and includes some of the same characteristics. The biggest one startups need to recognize is that all aspects of design control must be documented, which for medical devices begins once a prototype design is chosen for development into a manufacturable product. The aspects of design control are:
  • Documenting design procedures and development planning.
  • Identifying design input needs; developing outputs.
  • Verifying that outputs meet the design inputs.
  • Validating the design.
  • Controlling changes in design and reviewing the results of the design.
  • Conducting design reviews and risk analyses.
  • Transferring the design to be produced.
  • Compiling the device history record, design history file, and device master record.
• Manufacturing Information. Because manufacturing medical devices requires good manufacturing processes be followed, quality systems are essential to prevent product deviations and catch any product that doesn’t meet specifications before it reaches the market. The FDA wants premarket approval applications to include the following information on quality systems as they relate to manufacturing:
  • Audit procedure(s) for quality
  • Management review procedure(s)
  • Quality system documentation outline

Essential Components of a Quality Management Program

Understanding the essence of what the FDA is looking for when it comes to quality is important, but how exactly should startup biotech and medtech companies choose a system? Here are six components that make up a useful electronic quality management system:

• Document management. This keeps documents organized in a central database that includes audit trails and workflows for how the documents are to be used. As discussed above, documenting in an electronic system has many advantages over paper, not least of which is making sure that the most up-to-date version of a procedure is easily available.
• Reporting management. The ability to have data automatically compiled into useful reports can save a company a lot of time. Furthermore, being able to share these reports allows for easy communication and determination of where problems may be hiding.
• Inspection management. In order to know that procedures are being followed, equipment maintained, and data correctly recorded, quality systems incorporate inspections. Managing inspections includes not only what an inspection will cover, but also how the results of the inspection will be utilized to solve problems and improve the overall system.
• Audit management. Audits are different from inspections in that inspections solve immediate problems and audits determine the roots of these problems. Audits allow a company to “check off” that they are meeting all of their regulatory requirements. Consultants are frequently brought in to perform audits in order to ensure impartiality, so an electronic system that incorporates sophisticated security is helpful for both parties.
• Learning management. Employees have to be trained on processes and that training must be documented, so it’s important to have good management of this education. Electronic systems can automatically alert companies to when employees need to update their training, store completion certificates, and even store training videos so that all employees receive the same training.
• Product lifecycle management. This is perhaps an aspect of quality systems that a startup biotech company wouldn’t be able to take full advantage of until later in its growth. Product lifecycle management involves following a product from ideation to market to disposal. However, that doesn’t mean that it isn’t a good idea to choose a quality management software that includes it, ideally as an add-on that can be purchased down the road.

Quality Over All

Although quality systems seem cumbersome, expensive to implement, and aren’t strictly required for an early stage company, there is agreement among many investors, regulatory experts, and experienced startup CEO’s that they are necessary. Rather than waiting to consider quality management until the last minute, adopting even some of the concepts and practices outlined here can help biotech and medtech startups avoid expense and lost time down the road.

Revised 11/20/2020