Pharma Talk

If a pressure gauge is not calibrated within its scheduled date, it can lead to several quality risks:  * Inaccurate Measurements: An uncalibrated gauge may provide readings that are significantly different from the true pressure. This can result in errors in processes, calculations, and decision-making.  * Non-Compliance: Many industries have regulations or standards that require regular calibration of pressure gauges. Non-compliance can lead to fines, penalties, and damage to the organization's reputation.  * Product Defects: Inaccurate pressure measurements can lead to product defects, especially in processes that rely on precise pressure control. This can result in wasted materials, rework, and customer dissatisfaction.  * Safety Hazards: Inaccurate pressure readings can pose safety hazards, particularly in applications involving hazardous materials or equipment. For example, a faulty gauge might indicate a lower pressure than is actually present, leading to an unsafe operating

Specificity in a potentiometric assay refers to the ability of the method to measure the analyte of interest without interference from other substances. This is crucial to ensure accurate and reliable results. Methods to Assess Specificity Here are some common methods to evaluate the specificity of a potentiometric assay:  * Blank Analysis:    * Purpose: To determine the baseline signal or response in the absence of the analyte.    * Procedure: Prepare a blank sample containing all the reagents and solvents used in the assay except for the analyte. Measure the potential or response.    * Evaluation: If the blank signal is significantly low compared to the signal obtained with the analyte, it indicates good specificity.  * Matrix Effect Study:    * Purpose: To investigate how different matrices (e.g., excipients, impurities) can affect the assay's response.    * Procedure: Prepare samples with varying concentrations of the analyte in different matrices. Measure the potential or resp

On 05 August, the FDA issued a warning letter to the US company LS Promotions Inc. in Hicksville. The warning letter is the result of a review of the company's responses to a 483 letter from the FDA. It summarises the violations of Current Good Manufacturing Practice (CGMP) for finished drug products under Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 21) found during the inspection as follows. Laboratory Testing Adequate laboratory testing was not performed on each batch of manufactured drug product prior to release to ensure compliance with specifications, including the identity and strength of the active ingredients. Similarly, microbiological testing was not carried out, although this is required for certain products, such as SPF 15 lip balm, SPF 30 sunscreen and hand sanitiser. The lack of testing means that it is not certain whether the products meet the specifications. The FDA therefore expects the company to provide a list of chemical a

In July 2024, the  nitrosamine Q&A document  "Nitrosamines EMEA-H-A5(3)-1490 - Questions and answers for marketing authorization holders / applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products" of the EMA/CMDh was revised again and published on the EMA website under "Questions and answers". This list of questions and answers was first published in 2020. The new version 21 now contains updates and changes in the following questions and their answers: 8. How should confirmatory tests be conducted by MAHs and manufacturers? 9. What are the requirements of the analytical method(s)? 10. Which limits apply for nitrosamines in medicinal products? 14. What is the approach for new and ongoing marketing authorisation applications (MAA)?  15. When should a test for nitrosamines be included in the MA dossier? 16. What are the responsibilities of MAHs for APIs with CEPs or ASMFs? The

From 1 July 2024, the Australian TGA will introduce, at least temporarily,  new regulations for GMP inspections  of domestic and foreign manufacturers of medicinal products, active pharmaceutical ingredients (APIs), biological products and blood products, so-called surveillance inspections. These are repeat inspections of manufacturers with a shorter duration, but according to the TGA with full scope. This means that the inspection should cover all aspects of the pharmaceutical quality system (PQS) and the operations, but be reduced by around 50 % of the usual inspection time. The GMP certificates issued after the inspection will then state that a surveillance inspection has been carried out. Who is eligible for this? Both domestic and foreign manufacturers who received a " good " or " satisfactory " rating (A1 or A2) in their last TGA inspection. However, there are also clearly defined exceptions where shortened inspections are not possible. Objectives The primary

advantage is that the increased temperature also reaches areas that are difficult to access, such as branch pipes, if the duration of the thermal sanitization is long enough. Temperatures of 70-80 °C are common. Hot systems are therefore self-sanitizing. Conclusion The removal of biofilms from pharmaceutical water systems is difficult. Therefore, the measure should not be the removal of a biofilm, but the prevention of such a biofilm. An appropriate system design is essential for this (no dead leg, stub lines, cold spots, etc.). Ozonization of the system is very helpful in preventing biofilm. Regular heating of the entire system is also a good prevention strategy. The most important aspect, however, is to avoid stagnant water. This applies to the entire system as well as to individual components, which should be able to be drained. The water system should therefore not be left standing over the weekend, but should rather be producing water in the design. The motto is: "keep it run

The topic of revalidation is rarely mentioned in the regulations. Ongoing/continued process verification has replaced regular revalidation (with exceptions in the sterile area). But what can happen after a change control? Read the FDA's opinion below. In a Warning Letter, the FDA describes what it expects in the event of a change in the process. What is it about? The lack of sufficient validation was criticised. In addition, as a result of customer complaints regarding the viscosity of the product, the company changed two ingredients without change control. The new process was not (re)validated. The FDA does not explicitly refer to revalidation here, but only validation. With reference to its process validation guideline, the FDA then explains what it understands by process validation. The company's response that it had initiated a structured approach to process validation was not sufficient for the FDA. The authority requires the demonstration of appropriate process validation

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