Pharma Talk

In manufacturing, where potentially hazardous substances are handled, concepts such as Occupational Exposure Bands (OEB) and Occupational Exposure Limits (OEL) play a crucial role in employee safety. The two terms, OEB and OEL, are often used interchangeably, but there are clear differences. What does OEB mean? OEB stands for Occupational Exposure Bands (OEB). This is a method of classifying substances based on their hazard potential or toxicity, particularly in relation to inhalation exposure. OEBs are usually classified on a scale of 1 to 5, with OEB 1 representing substances with the lowest hazard potential and OEB 5 representing substances with the highest hazard potential. The OEB bands are not standardized, but are defined by companies themselves. So, there can be deviations, which is important for external employees who deal with containment areas of different companies. OEBs should actually be better called iOEBs, for internal Occupational Exposure Bands. In practice, by specif

On June 18, 2024, the FDA issued a Warning Letter to the Dominican company Laboratorio Magnachem International regarding CGMP violations. The Warning Letter is based on an FDA inspection in November 2023. The company's responses dated December 1, 2023 to the complaints listed in the Form 483 were insufficient in the FDA's view. FDA Warning Letters always reference the GMP requirements set out in 21 CFR Part 211, in this case for data integrity complaints: "Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(a))" In general, comprehensive control of CGMP data is expected to ensure that all changes, deletions and additions of information to electronic records are authorized and documented. Observations The laboratory equipment used to generate analytical data for the release of finished medicinal products has

On 9 July, the FDA issued a Warning Letter to a Korean manufacturer registered as a manufacturer of over-the-counter drugs. With the Warning Letter, the FDA is responding to the documents it received from this manufacturer in response to two requests in 2022 and 2024. Since the methods, facilities or controls described in the company's response for the manufacture, processing, packaging or storage of drugs do not comply with CGMP, they are automatically considered adulterated and non-compliant. Content The Warning Letter lists a number of violations: 1. Lack of an adequate and written testing programme to assess stability properties. Only 3 months of data were available, with a shelf life of 2 years. There was therefore a lack of sufficient chemical and microbiological tests and data. This meant that there was no proof of compliance with the defined specifications and quality over the shelf life period. 2. The raw materials used had not been sufficiently tested with regard to ident

On 9 July, the FDA issued a Warning Letter to a Korean manufacturer registered as a manufacturer of over-the-counter drugs. With the Warning Letter, the FDA is responding to the documents it received from this manufacturer in response to two requests in 2022 and 2024. Since the methods, facilities or controls described in the company's response for the manufacture, processing, packaging or storage of drugs do not comply with CGMP, they are automatically considered adulterated and non-compliant. Content The Warning Letter lists a number of violations: 1. Lack of an adequate and written testing programme to assess stability properties. Only 3 months of data were available, with a shelf life of 2 years. There was therefore a lack of sufficient chemical and microbiological tests and data. This meant that there was no proof of compliance with the defined specifications and quality over the shelf life period. 2. The raw materials used had not been sufficiently tested with regard to ident

An FDA Warning Letter is a formal communication from the US Food and Drug Administration (FDA) notifying a company or individual of regulatory violations. These typically describe observations made during an inspection and list violations found (referencing the specific sections of the FD&C Act, the Code of Federal Regulations (CFR), and other applicable laws as appropriate). In addition, specific measures are listed that the recipient must take to remedy the violations. It does not go into great detail, especially not with regard to instructions on the desired procedure. In a Warning Letter issued to Sun Pharmaceutical Industries Limited (India) at the beginning of July, this is now different. It describes in great detail what the FDA considers to be appropriate CAPA measures in a specific case. What happened? The company was criticised for not adequately cleaning and maintaining the equipment used to manufacture drug products. According to the company's response, a defective

In June 2024, the U.S. FDA issued a Warning Letter to the Portuguese company "Fancystage Unipessoal, LDA" after having inspected its site in January 2024. The significant violations of CGMP regulations for drug products, which are mentioned in the Warning Letter, are listed as follows: "Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier's test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2))." "Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a))." "Your firm failed to establish laboratory controls that include scientifical

In June 2024, the U.S. FDA issued a Warning Letter to the Portuguese company "Fancystage Unipessoal, LDA" after having inspected its site in January 2024. The significant violations of CGMP regulations for drug products, which are mentioned in the Warning Letter, are listed as follows: "Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier's test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2))." "Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a))." "Your firm failed to establish laboratory controls that include scientifical

The key skills required to effectively review documents are: 1. **Analytical skills** to identify errors, inconsistencies, and gaps in information, and evaluate the importance and validity of documents[1][3]. 2. **Attention to detail** to check for spelling, grammar, punctuation, formatting, and style errors, as well as factual or logical errors[1][2].  3. **Communication skills** to write clear, concise, and professional reports summarizing document review results, and convey findings to team members and stakeholders[1][2]. 4. **Technical skills** to use document management systems, databases, search engines, and e-discovery software like Relativity, Ringtail, and Concordance[4]. 5. **Critical thinking skills** to identify biases, assess credibility, compare arguments, and synthesize information from multiple documents[1]. 6. **Ethical skills** to maintain confidentiality, privacy and security, and avoid conflicts of interest when reviewing sensitive information[1]. 7. **Editing and w

The difference between review and verification lies in their purposes and methodologies: - **Review** involves evaluating the suitability, adequacy, or effectiveness of an object to achieve established objectives. It is a process of determining whether the design or product meets the required standards. Reviews can occur throughout the design phase and at key milestones in the development process. Examples include management reviews, design and development reviews, and peer reviews[4]. - **Verification** ensures that specified requirements have been fulfilled by providing objective evidence. This can involve inspections, testing, reviewing documents, and performing alternative calculations. Verification occurs after the completion of development stages, prior to validation, to confirm that the product meets all specified design and requirement specifications[4]. In summary, review evaluates the design's ability to meet objectives, while verification confirms that the product meets

On 18th of June 2024, the EMA has issued templates for Shortage Prevention Plans (SPPs) and Shortage Mitigation Plans (SMPs). Marketing authorization holders (MAHs) in the European Union/European Economic Area are encouraged to create Shortage Prevention Plans to minimize the risk of medicinal shortages. The availability of medicinal products is a central point in the strategy of the European Medicines Agency Network until 2025 and the European Commission's pharmaceutical strategy, which led to the revision of the pharmaceutical legislation in April 2023. The draft regulation obliges MAHs to establish Shortage Prevention Plans and Shortage Mitigation Plans. In times of crisis, in form of a public health emergency or a major event, SPPs are already obligatory under Regulation 2022/123, for drugs listed in the list of critical medicines for that particular crisis. The extent of the documents should correspond to the risk level of the medicine. For this reason, the ICH Q9 guideline on