We live in an aging society. Medical standards continue to develop and medicine is constantly evolving as scientists carry out research into new drugs. More and more people require medication and cases of polymedication, where people need to take numerous different types of medicine every day, are becoming more common.
The long road from development to approval
Against this backdrop, how do we ensure the safety and quality of the drugs for the patient? How is drug safety regulated nowadays and which uniform standards need to be adhered to? In this blog post, you can find out more about drug safety, drug approval, and the different approval procedures.
The concept of drug safety
Drug safety, also known as pharmacovigilance, refers to the systematic and continuous monitoring of the safety of a drug. The drugs are tested in order to identify and assess undesirable or even harmful effects for humans or animals. In order to protect patients, drugs must obtain official approval before they can be placed on the market.
The German Medicinal Products Act (AMG) came into force in 1961, establishing a standardized legal regime for the provision and safety of drugs. Due to the continuous evolution of the legislation, the act has grown over the years from 65 paragraphs to almost 200. Guidelines and measures are constantly being optimized.
In the future, drug safety will continue to be regarded as an indivisible concept comprising product safety, the safety of the distribution channels, and safe and effective drug use.
The principles of pharmacovigilance in a nutshell
In the following section, we will be looking at the objectives and scope of pharmacovigilance.
Objectives of pharmacovigilance activities:
- Optimization of patient care with a focus on drug use and improvement of medical treatments
- Assessment of the benefits and side effects of drugs and measurement of their effectiveness and risks
- Support for the promotion of information, education, and clinical training with regard to pharmacovigilance
Scope of pharmacovigilance activities:
- Products with chemical synthesis, i.e., low-molecular drugs
- Herbal medicinal products, nutritional supplements, as well as natural remedies and alternative medicine
- Blood products
- Drugs of biological origin or consisting of living cells (antigens, vaccines)
- Medical devices
- Substandard or counterfeit drugs
All new medication has to undergo an approval procedure. The regulatory authority establishes whether a pharmaceutical product is safe and effective, and whether it demonstrates the necessary pharmaceutical quality. Drug developers can use their own clinical trials when seeking to obtain approval for a new drug. These trials then help with the preparation of the necessary documentation for the approval. It is important to distinguish where a drug is to be approved.
If it is only to be approved and marketed in Germany, the relevant authority in most cases will be the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM). At the manufacturer’s request, it is possible to apply for approval in several countries simultaneously or to apply directly for approval in all countries within the European Union (EU) or the European Economic Area (EEA).
The BfArM checks whether the documents submitted with the approval application conclusively prove the effectiveness, safety, and quality of the drug.
If approval is issued, it is generally valid for five years. In special cases, it may only be valid for one year. After five years, the authority checks once again whether the medical benefits of the drug outweigh its potential risks, i.e., its side effects. The side effects can be found on the leaflet enclosed with the medication. If the holder of the approval makes a change to the drug, they must inform the BfArM.
But what kind of tests and inspections does a drug have to undergo – particularly in order to obtain approval?
Stability testing in accordance with ICH guidelines
A drug cannot obtain approval unless it successfully undergoes stability testing in accordance with the ICH guidelines in order to ascertain its effectiveness, durability, and shelf life. The stability of a drug is one of its most important features and also one of the most critical.
Anyone wanting to place a new pharmaceutical product on the market in the regions covered by the ICH guidelines must pass the same extensive tests regarding the effectiveness, durability, and shelf life of their product. It is impossible for a human drug to reach the market in these regions without passing the ICH tests. There are also corresponding ICH guidelines for veterinary products.
The four major achievements of the ICH guidelines:
- Standardizing the technical conditions and testing procedures for drug approval
- Ensuring optimum drug safety, effectiveness, and quality
- Preventing drug tests being carried out over and over again for each region
- Minimizing the need for animal testing
In order to prove that testing has been carried out in line with the ICH guidelines, reports must be produced which provide evidence of compliance with GMPs. These reports must be submitted to the drug testing authorities; for example, the FDA or the BfArM.
Good manufacturing practices (GMPs) for drugs
What factors need to be taken into account with regard to good manufacturing practices when it comes to stability testing?
The rules of good manufacturing practices for drugs are set out in national and international regulations. Among other things, GMPs stipulate strict requirements in the following areas:
The concept of GMPs is becoming more and more important in Germany due to the “Arzneimittel- und Wirkstoffherstellerverordnung” (German Ordinance on the Manufacture of Medicinal Products and Active Ingredients, AMWHV). GMPs safeguard production in the pharmaceutical industry and must therefore never be neglected.
Ongoing stability testing essential for long-term drug monitoring
It is particularly important that drugs are checked on a regular basis in order to satisfy the ever-increasing requirements set by the authorities. Once a drug has been approved, this does not mean that the tests and inspections are over. Constant monitoring and testing are essential in order to ensure patients’ well-being.
It is therefore extremely important to choose the right test chamber. A test chamber for pharmaceutics must comply with the relevant guidelines. Continuous quality monitoring is the only way to ensure that drugs comply fully with good manufacturing practices.
Ongoing stability testing should test the necessary stability of the drug in combination with the declared durability – as defined in the approval documents upon submission. Factors such as a change of supplier, for example, could have a detrimental effect on stability. These potential problems need to be identified and prevented.
Risk information –“red-hand letters”
“Red-hand letters” are letters sent by pharmaceutical companies to inform physicians and pharmacists about newly identified drug risks, recall defective drug batches, or circulate other important information. The letters are marked with a red hand symbol. If a preparation is observed to cause previously unidentified side effects, they are listed in the letter. You will know from your practical experience how important it is to keep testing medication on a long-term basis.
Dr. Reinhard Hoferichter – board spokesperson for Securpharm e.V., the German stakeholder organization – had this to say:
“Germany needs to maintain its reputation as one of the safest markets for drugs”. But this isn’t something that only affects Germany: The entire EU – in fact, the entire global pharmaceutical industry – should be putting ensuring drug safety at the top of its to-do list.”
Ongoing stability testing and stress tests are unavoidable due to the strict standards that govern this field. It is absolutely essential that the test chamber used is 100% reliable. The following key criteria must be considered when choosing the right climate chamber:
- Constant climatic conditions
- Standard-compliant operation according to ICH guidelines (Q1A/R2)
- Temperature and humidity simulation in one chamber
- Long-term stable test conditions
- FDA-compliant documentation and software
- Temperature range: 0°C – 70°C
- Humidity range: 10% – 80% RH
But do you know which test chamber is suitable for your tests and conditions? More information is provided below.