Good practice quality guidelines & regulations: pharma industry
The role of pharmaceutical companies in today’s global village is unparalleled. They develop, produce and deliver a wide range of medications, from vaccines to over-the-counter drugs. Because of their unmatched role in healthcare, the pharmaceutical industry must meet numerous guidelines and regulations.
Aside from complying with Good Manufacturing Practices (GMP) and Good Distribution Practices (GDP), pharmaceutical companies must also monitor and adapt their internal and external processes to match the guidelines set by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the U.S. Food and Drug Administration (FDA).
Learn more below about the ICH and FDA’s guidelines for pharmaceuticals, as well as how to meet them.
The ICH and the Pharmaceutical Industry
Founded in 1990, the ICH is the result of efforts by the FDA and European Community — now known as the European Union (EU) — to unify the world’s regulatory standards for the pharmaceutical industry. The goal is to provide patients around the world with registered medicines that are safe, effective and high-quality. Because of its international presence, more than 10 organizations support the ICH, including:
- The Pharmaceutical Research and Manufacturers of America (PhRMA)
- The Center for Drug Evaluation and Research (CDER)
- The Center for Biologics Evaluation and Research (CBER)
- The European Commission
- Health Canada
- European Free Trade Area (EFTA)
- World Health Organization (WHO)
- The European Federation of Pharmaceutical Industries Association
- The Japanese Ministry of Health, Labor and Welfare
- The Japanese Pharmaceutical Manufacturers Association
- The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA)
While respected by pharmaceutical companies and referenced by the FDA, the ICH does not enforce its standards for the pharmaceutical industry. Instead, the organization serves as an international reference point for businesses and governing bodies like the FDA, thus streamlining regulatory standards for pharmaceuticals.
ICH Guidelines for Pharmaceuticals
With its worldwide reach, the ICH’s guidelines for pharmaceuticals are extensive, encompassing four categories:
- Multi-disciplinary handling
While it’s essential to review each of these sectors, there are a few guidelines to emphasize, including:
Q1A(R2): Stability Testing of New Drug Substances and Products
A significant influencer in the pharmaceutical industry is stability. Without a stable environment, medicines undergo changes that can affect their safety and efficacy, which is why it’s essential businesses understand how environmental factors such as temperature, light and humidity can impact a medication’s shelf life and influence its ideal storage conditions. Guideline Q1A(R2) provides pharmaceutical companies with a stability data package, detailing the following:
- Test type
- Test frequency
- Test conditions
- Test parameters
Using your results, you can develop accurate and appropriate labels for your drug products and substances.
Q5C: Stability Testing of Biotechnological or Biological Products
While similar to Q1A(R2), this ICH guideline addresses stability testing for biological or biotechnological products — medications with active components that are either proteins or polypeptides. Due to their makeup, these items tend to be more sensitive to environmental conditions, which influences their recommended storage conditions. Per Q5C, pharmaceutical companies should test and analyze the following product factors:
- Dissolution time
If involved with biological or biotechnological products, it’s essential to examine how the medication interacts with its container and that container’s closure features. Some products, for example, may be delivered via a single-use or multiple-dose vial based on these results.
Q6A: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products
When developing this guideline, the ICH wanted to provide the pharmaceutical industry with a universal set of specifications, which include tests, analytical procedures and acceptance criteria. Via Q6A, the ICH hopes to enhance quality assurance and production consistency among pharmaceutical companies. Specifications vary between the following types of medicines:
- Drug substances
- Drug products
- Oral liquids
- Parenteral drug products
For example, drug substances should undergo testing to determine their disintegration time while the dissolution time of oral liquids should undergo assessment. Depending on your company’s product, some of the recommended tests may not be applicable. To help determine which ones are, the ICH provides several decision trees.
Q6B: Test Procedures and Acceptance Criteria for Biotechnological or Biological Products
Like Q5C, the Q6B guideline is for biological or biotechnological products. Instead of stability tests, Q6B focuses on specifications for biotechnological or biological medicines, which makes it similar to Q6A. It includes decision trees as well. Due to biological and biotechnological product variances, you should set your specifications based on the following:
- Physiochemical properties
- Biological activity
- Immunochemical properties
After considering these factors, you can determine which tests to conduct, such as those for potency and identity. It’s essential to note that specifications focus on confirming the quality of your batches versus building their characterization.
The reason the above ICH guidelines — Q1A(R2), Q5C, Q6A and Q6B — are often cited is due to their influence on the cold-supply-chain processes within the pharmaceutical industry. An appropriate and accurate assessment of your products provides your in-house team, as well as shippers and distributors, with critical information about how to ship and store your medications.
The FDA and the Pharmaceutical Industry
Founded in 1906, the FDA plays a substantial role in the pharmaceutical industry. The federal agency regulates not only drugs and biologicals but also medical devices. Like the ICH, it carries a mission of ensuring patients receive safe, effective and affordable medicines.
Pharmaceutical companies with an interest in the U.S. market must meet the FDA’s standards, which include several statutes from the Code of Federal Regulations (CFR). The most substantial statutes are within Title 21, such as 21 CFR Part 11.
FDA Guidelines for Pharmaceuticals
Due to the rising role of the cold supply chain — it’s expected to become an industry worth $16.7 billion in 2020 — FDA guidelines for cold supply chains in the pharmaceutical sector are becoming a significant focus for pharmaceutical companies with a U.S. market. In 21 CFR, there are several FDA guidelines for pharmaceuticals that involve cold supply chains, including:
21 CFR Part 11: Electronic Records and Electronic Signatures
Today, many companies use electronic records and electronic signatures to conduct business. Due to the widespread use of digital data, the FDA has implemented 21 CFR Part 11. The goal of this statute is to verify the authenticity, reliability and validity of your electronic records and signatures. To confirm these three factors, you or a third party must provide proof of the following controls:
- Audit trails
- User levels
- Record generation, modification and protection
- System validation, operation and accessibility
- Staff training
Due to the features of this regulation, as well as its testing standards, it’s now critical for pharmaceutical companies to use 21 CFR-compliant programs and devices such as data loggers. Otherwise, the process of testing the above controls will consume more of your time and resources.
21 CFR Part 203.32: Drug Sample Storage and Handling Requirements
With this FDA guideline for pharmaceuticals, the focus is on the appropriate storing and handling of drug samples, as well as compliance with labeling standards. As a result, 21 CFR Part 203.32 builds on the ICH’s testing recommendations, which provide critical information on how your products should be labeled, stored and handled.
It’s essential to note that 21 CFR Part 203.32 applies not only to pharmaceutical manufacturers but also to your authorized distributors and any other representative of your product. If your medicines are contaminated, deteriorated or show evidence of alterations due to mishandling, you are in violation of this FDA standard.
21 CFR Part 203.36: Fulfillment Houses, Shipping and Mailing Services, Co-marketing Agreements and Third-Party Recordkeeping
Another critical FDA requirement for pharmaceuticals is 21 CFR Part 203.36, which discusses the responsibility of manufacturers and authorized distributors. Per the two-part regulation, they must complete the following:
- Meet Prescription Drug Marketing Act (PDMA) and Parenteral Drug Association (PDA) requirements
- Maintain requests, receipts, forms, reports and records per PDMA, PDA and 21 CFR Part 203.36
- Provide reports, forms and records within two business days to the FDA or another regulatory agency
If your company does not use any third party in your operations, such as a fulfillment house or shipping and mailing service, you are considered exempt from this standard. Note that 21 CFR Part 203.36 does apply to co-marketing agreements.
21 CFR Part 211.142: Warehousing Procedures
In cold supply chains, 21 CFR Part 211.142 is significant. It details the need for written procedures that explain how to store, quarantine and release drug substances. Like 21 CFR Part 203.32, this FDA requirement for pharmaceuticals builds off the ICH’s recommendation to assess your products’ environmental reactions. Factors your written procedures should consider or note include:
Many warehouses will use temperature data loggers to make sure they store your products under the appropriate conditions, as well as ensure both their compliance and your compliance with the FDA. Due to the use of data loggers in the pharmaceutical industry, it has become critical for companies to carry FDA-compliant ones.
21 CFR Part 211.150: Distribution Procedures
Ensuring a seamless distribution and recall process for pharmaceutical products is another focus of the FDA. It happens via 21 CFR Part 211.150, the FDA’s established requirements for pharmaceutical companies and their distributors. The primary standard is that you provide your distributors with a written procedure for distributing drug products. Additional requirements include:
- Distribution of oldest approved stock before newer batches
- Recall of drug product batches via an established system
In some instances, the FDA permits the distribution of newer batches first — if temporary and warranted.
While achieving compliance with the FDA’s 21 CFR standards is a time-consuming process, it does ensure you implement the necessary measures across your cold supply chain. It also makes you consider potential logistical hurdles so you can preserve the quality, safety and efficacy of your products.
Good Practice Quality Standards for Meeting ICH and FDA Guidelines for Pharmaceuticals
Expanding your knowledge on the standards of the ICH and guidelines of the FDA for pharmaceuticals provides your company with the opportunity to create and integrate good practice (GxP) quality standards into your internal and external operations, including your cold supply chain. Develop your GxP quality standards by considering three components:
Log. Track. Monitor. Documentation is everything in the pharmaceutical sector — and it’s essential for compliance. For many pharmaceutical companies, recording and maintaining in-house products is a hassle-free process. Ensuring that supply-chain members do the same is the challenge.
The global presence of pharmaceutical companies makes recording a priority issue. Drug products, as well as biological medicines, are traveling through numerous climate zones to reach their destination, which increases their risk of becoming unsuitable for use. As a result, it’s essential to not only implement standard operating procedures (SOPs) for monitoring and recording products and conditions at your facility, but also at your testing laboratories, distribution centers, wholesaler warehouses, pharmacies and other locations involved in your cold supply chain.
With evolving ICH and FDA guidelines for pharmaceuticals, it’s vital you review your GxP quality standards. Annual assessments, or even more frequent ones, offer your team the opportunity to develop smarter solutions to new or existing problems.
From your GMP to your GDP, evaluate all your procedures. Are all of your SOPs compliant with FDA requirements, such as 21 CFR Part 211.142? Do your distributors frequently submit requests for additional information on storing products? How are you monitoring the location and storage conditions of your goods?
Since members of your cold supply chain play a significant role in the quality of your medicines, consider providing them with a survey to assess your performance as their supplier. Every member, or link of your chain, can offer valuable information when reviewing and modifying your SOPs.
Adapting your GxP quality standards is essential — they need to grow with the newest ICH and FDA guidelines for pharmaceuticals. By reviewing your documentation processes within your cold supply chain, you can ensure your company’s operations remain optimal.
Begin by referencing your assessment, and rank potential actions by priority. Which procedures require updates to comply with standards? Which changes offer the most return on investment (ROI)? Which measures provide a more efficient, higher-quality cold supply chain? Potential action plans developed by your team may include:
- Purchasing new monitoring devices for accurate and compliant readings across your supply chain
- Developing new SOPs for more concise and compliant instructions for supply-chain members
- Implementing new flows of transportation for faster delivery to supply-chain links
Depending on your conclusions, you may also find it necessary to seek out different distributors, wholesalers or shipping providers. If multiple instances of product contamination have occurred at one of your many distribution centers, for example, it’s likely due to negligence, not a confusing SOP. In some cases, however, it may be due to faulty products like inaccurate, low-quality data loggers.
Good Practice Quality Standards and Data Loggers for Pharmaceuticals
Data loggers, like documentation, are an essential component of GxP quality standards. When assessing your practices, it’s vital that you evaluate your loggers and ensure they’re delivering accurate readings, providing your company with the means to meet the FDA’s requirements for temperature monitoring in pharmaceuticals. The ideal, good-practice standard for data loggers is to deploy them in the following supply-chain links:
- Store: Every refrigeration unit, whether in your wholesaler’s warehouse or distribution center, should be equipped with data loggers designed for pharmaceutical applications. Loggers, such as the Cobalt 2, provide insight into your facility’s temperatures as well as humidity, carbon dioxide and more.
- Manufacture: While transportation often poses a significant contamination risk, your biological or drug substances can also become compromised during manufacturing, which is why many pharmaceutical companies install data loggers at their manufacturing plants, ensuring optimal environmental conditions.
- Transport: By monitoring your products during transportation, your team can pinpoint where and when contamination occurred, thus creating the opportunity to fix the issue. With Bluetooth® data loggers for pharmaceuticals, such as Emerald, it’s convenient and hassle-free for drivers to check conditions.
- Research: Your laboratories are the basis for your SOPs for storage conditions, which shape your compliance with FDA regulations. That’s why it’s critical these facilities are equipped with data loggers, whether on refrigerators, incubators or lab spaces.
With appropriate data loggers for your pharmaceutical applications, as well as the deployment of them across your cold supply chain, your company can ensure it meets the standards of the ICH and FDA, plus reduce your product losses, which can lead to noticeable savings.
How to Choose FDA-Compliant Data Loggers for the Pharmaceutical Industry
As a part of your GxP quality standards, it’s essential you select a reliable, durable and accurate logger. Data loggers for the pharmaceutical industry are numerous. With so many options, companies often enter a time-consuming process of comparing models, specifications and prices. To shorten this process without sacrificing the quality of your choice, consider these questions:
What Measurements Do You Need?
Measurements play a substantial role in your purchase decision. Do you need to monitor more than the temperature of your products, such as their light exposure? Many data loggers for pharmaceuticals, such as the Cobalt 2, take multiple measurements from differential pressure to carbon dioxide. Make a list of your must-have measurements before you decide.
What Are Your Work-Environment Conditions?
For every link in your supply chain, you’ll likely have a different answer. Aim to assess the environmental extremes of each facility. Do your research labs, for instance, feature environments that can reach temperatures of -80 degrees Celsius? What climate zones do your shipments pass through? Determine each center’s parameters before moving forward.
What Is Your Ideal Data-Logger Resolution?
The deployment period of your data logger, as well as your preference for the frequency of reports, influence your ideal data-logger resolution. Again, analyze your cold supply chain and each member’s unique features. Do you want your data logger to record values every 10 seconds during a one-hour transportation period? With a data logger like the Emerald, which stores 16,000 readings on its internal memory, that need would not be an issue.
What Is Your Budget?
Another influential factor to consider when browsing data loggers for pharmaceutical companies is your budget. Often, this varies by which cold-supply-chain member you’re considering. While you may invest in a long-term monitoring solution for your research labs, you may instead choose a disposable temperature recorder for your logistics provider due to the risk of loss or damage during shipment.
Which Regulations Must You Meet?
Due to FDA requirements for pharmaceutical temperature monitoring, such as 21 CFR Part 211.142 and 21 CFR Part 203.32, it has become essential to purchase FDA-compliant data loggers. Depending on your markets, you may also need to meet the standards of other regulatory bodies. List these organizations before beginning your search. Examples of compliant monitoring solutions include the Cobalt L3 and its software, CobaltView, which has been developed to meet GMP, 21 CFR Part 11 and more.
What Software Programs Do You Use?
A critical component of data loggers for pharmaceuticals is their software. When comparing models of data loggers, investigate their software. Is it easy to use? Does it export documents to other formats like XLS or PDF? Is it compliant with federal and international statues, such as 21 CFR Part 11? OCEAView is an example of a web-based program — with a mobile application — that has been designed to meet regulations and offers fast access to vital information.
What Level of Experience Does Your Team Have?
From your research laboratories to your manufacturing facilities, a wide variety of users are handling your data loggers. In most cases, data loggers for the pharmaceutical industry must meet various experience levels. That’s why it’s smart to choose a user-friendly model, which provides an intuitive setup, data retrieval and data analysis. With this type of temperature data logger, you can decrease the chance of user error in gathering data.
How Would You Like to Download Measurements?
Offloading measurements can consume time and risk losing vital data-logger components such as their internal storage. Think about what’s convenient and efficient for your team. While wired connections are still available, it has become more common for businesses to choose USB or Bluetooth-enabled data loggers for their pharmaceutical applications.
By answering the above questions, your staff should be able to build a GxP quality standards plan for data loggers across your company’s cold supply chain. With the appropriate data loggers, your team can decrease product losses, maximize productivity and comply with ICH and FDA guidelines.
Learn More About Data Loggers for the Pharmaceutical Industry
At Dickson, we’ve become a trusted partner of the pharmaceutical industry. Our innovative software and data loggers for the pharmaceutical industry deliver smart solutions to constant challenges in the sector. From complying with evolving regulations to collaborating with supply-chain links to ensure product quality, our monitoring solutions provide the data, convenience and simplicity you need.