Yasser Nashed-Samuel

Customer complaints due to drug product abnormalities may arise even with strict quality control measures at the manufacturing and healthcare provider levels, posing serious challenges for the manufacturers. In this paper, we report three compelling case studies which exemplify effectiveness of root cause analyses in addressing customer complaints of Amgen drug products. The three customer complaints from three different drug products reported the following issues: pink discoloration in one drug product vial, cloudy liquid with suspended particles in another drug product vial, and brown discoloration in the third drug product vial. Consequently, a comprehensive root cause analyses were performed to identify and rectify the underlying issue, thereby mitigating the recurrence of complaints. The root cause analysis of the three events ruled out manufacturing processes as the source of contamination. Instead, it was more likely that the contamination originated at the healthcare providers' facilities. Orthogonal analytical test methodologies were employed on the samples to identify any potential contaminants. The cloudy appearance, pink and brown discolorations in the three customers returned vials were caused by non-Amgen products. The first vial had cyanocobalamin injectable (vitamin B12), the second vial had fosaprepitant (a non-Amgen drug), and the third vial had iron and saline solution (likely injectable anemia drug). A possible explanation for the three complaint samples is that they were mishandled during the process of administering the drug products at the facilities of the healthcare providers. Following the identification of the likely sources of contamination, Amgen followed standard compliant-handling procedures, which may include communicating results back to complaints or health providers as appropriate. In conclusion, the pursuit of root cause determination is paramount in addressing customer complaints and ensuring the quality, safety, and efficacy of biopharmaceutical products.

A previously unreported particle type was observed during routine visual vial inspection of a liquid drug product and suspected to be the result of vial delamination. Delamination is the corrosive attack on the interior surface of a glass container resulting in the release of thin flake-like glass particles, lamellae, into solution. It is a major concern for pharmaceutical companies, especially for parenteral solutions, and drug programs with a high risk for delamination are typically monitored for lamellae formation through long term stability studies. Although these particles observed resembled lamellae (i.e. thin, reflecting light, buoyant) they were not the result of glass delamination. In this study, the authors describe a previously unreported particle type and provide a detailed comparison to known lamellae exposed to the same drug formulation. The chemical, elemental, and morphological characteristics of the particles and respective vials are described in detail. Overall, the particles′ high organic and low silica elemental signature, along with no signs of delamination on the glass vial inner surface demonstrate that this lamellae-like observation is a novel particle form that can be distinguished from lamellae formed from via glass delamination.

Glass prefilled syringes (PFS) are a container and delivery device of choice for storing and administering therapeutic protein products to patients. Addressing concerns and regulatory expectations related to the risk to biologic drug product quality and patient safety from PFS requires implementation of an extractable and leachable program based on understanding of materials, risk assessment, review of existing literature and testing based on a sound scientific foundation. Extractables and leachables data generated as part of thorough and holistic program are presented for 5 PFS systems, including glass and plastic syringes, and 12 biologic drug products encompassing the implementation of traditional and single-use biotechnology manufacturing processes. The comprehensive extractables and leachables data presented demonstrate and substantiate a holistic extractable and leachable program designed to ensure product quality and patient safety.

The European Pharmacopeia (Ph. Eur.) hydrolytic resistance method for glass vials is routinely used to screen pharmaceutical glass vial supply. Due to reliance on this method to reduce the risk of glass vial delamination in pharmaceutical drug products, it is important that the sources of method variability be understood and controlled. Several potential sources of variability in the Ph. Eur. alkalinity method have been studied for 3cc glass vials. Method parameters including vial rinsing, fill volume determination, vial covering, autoclave cycle execution, sample hold times, and titration procedure were evaluated in this study. The results of this study indicate the method parameters which require stringent control in order to achieve acceptable method precision and robustness.