Jeffrey D. Hofer
Eli Lilly and Company
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Jeffrey D. Hofer.
Journal of Pharmaceutical and Biomedical Analysis | 1998
Matthew W Borer; Xiangji Zhou; Donna M Hays; Jeffrey D. Hofer; Kevin White
Potential sources of variability in the measurement of solid oral drug products by near infrared reflectance spectroscopy were evaluated with statistical experimental design. Spectra were collected for two different tablet types according to the data collection and treatment parameters defined by the experimental design. Each tablet had three different dose-levels. Libraries were constructed using second-derivative spectra. Key figures-of-merit generated during internal and external library validation were used to calculate which parameters most strongly influence the library performance for dose-level discrimination. These responses and their corresponding experimental conditions were evaluated with the screening model in the JMP program. Segment value used for the second-derivative calculation was an an influential factor and had a complex effect. Orientation on the sampling platform also had an influential effect for embossed tablets. Collection of spectra over fewer days decreased variability within the library. More frequent reference spectrum collection improved the performance of libraries to a small degree. A larger sample population increased the range of spectral variability within a dose-level but apparently not the overall performance of the library. The number of scans averaged per spectrum was not an influential factor in this study. These results are summarized and used to recommend an approach to dose-level discrimination.
Journal of Pharmaceutical and Biomedical Analysis | 1998
P.K.S Tsang; J.S.A Larew; L.A Larew; T.W Miyakawa; Jeffrey D. Hofer
Assessment of analytical variability is recognized as an important factor for the establishment of specifications. Estimation of the variance for an analytical procedure can be accomplished using a variety of approaches. The approach of variance component analysis was applied retrospectively, as well as prospectively, to estimate analytical variance. The prospective approach also included the use of experimental design. Recent new drug substance examples illustrating these approaches are presented. In these examples, the analytical property of potency was evaluated. Factors examined in the experimental design include laboratory, day, analyst, instrument and column. Process variability can also be determined by variance component analysis. For a stable drug substance, combining the analytical and process variances provides an estimate on the total variance for the analytical property of potency. With the total variability statistically derived, an appropriate specification that is consistent with process and analytical capability can be established.
Journal of Pharmaceutical Sciences | 2017
Wyatt J. Roth; Ahmad Almaya; Timothy T. Kramer; Jeffrey D. Hofer
The purpose of this work was to assess the impact of continuous mixing on tablet critical quality attributes (CQAs) manufactured using a continuous, direct compression process. A 9-run design of experiments (DoE) that bracketed the range of commercially relevant mixer speeds, mixer orientations, and mass flow rates was executed using a formulation containing a cohesive drug substance at relatively low drug load. Drug substance dispensed concentration using loss-in-weight feeders was within 1% of target for each experiment with 30-s mass flow relative standard deviation values of 3.5% or less. Higher mass flow rates resulted in first off tablets closer to target potency, a shorter tablet potency startup phase, and greater assurance of passing content uniformity testing. Dissolution profiles from the DoE runs that bracketed mixer shear conditions were similar, indicating mixing had minimal impact on drug substance release from the tablets. None of the DoE parameters had a practical impact on the description CQA (tablet breaking force, friability, and appearance). Collectively, these results highlight that for this study continuous mixing within a direct compression process is robust and is assessed as low risk of adversely impacting drug product CQAs provided there is appropriate control of the continuous feeders.
Drug Information Journal | 2002
John R. Murphy; Jeffrey D. Hofer
Recent international harmonization efforts such as the International Conference on Harmonization (ICH) Harmonized Tripartite Guideline: Q6A, Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances have provided general guidance for setting specifications for new drug substances and drug products, but have not provided statistical methods for integrating stability results into the process. The only statistical methods are those provided in the ICH Harmonized Tripartite Guideline: Q1(R), Stability Testing of New Drug Substances and Products (Revised guideline), which are essentially the same as those contained in the 1987 U.S. Food and Drug Administration (FDA) Guidelines for Submitting Documentation for the Stability of Human Drugs and Biologics. Although these methods are widely used, they have continued to be a source of controversy, and they are unsuitable for establishing specifications at the time of submission. This paper provides a new computational method for determining shelf life, expiry limits, and release limits using random slopes based upon Least Squares ANOVA Estimators. Examples are provided to illustrate how the new method may be used to assist in setting specifications according to the recommendations in Q6A.
Journal of Pharmaceutical and Biomedical Analysis | 2000
Jeffrey D. Hofer; John R. Murphy
In the pharmaceutical industry, the process of measuring a products attributes can be very complicated and the potential for an analytical mistake can be quite high. Often, an unexpected result leads to an investigation to assess the possibility that a mistake was made in the laboratory. Traditionally, the data generated in these investigations has been used, along with various outlier tests, to attempt to negate the original data. Sometimes, historical estimates of the S.D. of the analytical method are not available for use in outlier testing and the power of the outlier tests to detect true mistakes without such historical estimates is often very low due to the small amount of data available. This leads to a great deal of inconsistency in the amount of data that is further generated and how the data is ultimately handled in making a decision. Recently, FDA demands for consistent and objective laboratory investigations have raised concerns about these practices. An alternative approach, involving a systematic investigation strategy and data handling via the structured use of the median, is proposed in this paper. The operating characteristics of the traditional and proposed approaches are compared to show their similarity and the advantages of the proposed approach. It is strongly believed by the authors that the structured use of the median will lead to more consistent investigations and data handling, which will benefit industry, the FDA and ultimately, the consumer, by allowing more accurate decisions to be made more efficiently.
Pda Journal of Pharmaceutical Science and Technology | 2018
Galen H. Shi; Sharon L. Shinkle; Ganapathy Gopalrathnam; Xia Dong; Jeffrey D. Hofer; Eric Jensen; Natarajan Rajagopalan
Use of prefilled syringes to self-administer biologics via subcutaneous administration provides convenience to patients. The barrel interior of prefilled syringes is typically coated with silicone oil for lubrication to aid plunger movement at the time of administration. This study intended to evaluate the impact of formulation variables on the silicone oil on the barrel interior surface. Characterization techniques including syringe glide force, break loose force, Schlieren imaging, contact angle, inductively coupled plasma spectrometry, and thin film interference reflectometry were used in assessing the interactions. Data indicated that formulation variables such as pH, buffer/tonicity agent type and concentration, and surfactant present in the formulation can effect silicone oil lubrication of prefilled syringes, leading to changes in functional properties of the syringe over time. Syringe samples containing acetate and histidine buffers showed an increase in glide force at accelerated storage temperature conditions, but the change was minimal at 5 °C. The samples with the highest glide force correlated with the presence of mannitol in combination with sodium acetate buffer. Sodium chloride had lesser impact on glide force than mannitol. Samples with higher glide force exhibited a substantial change in the silicone oil layer of the syringe, as observed with Schlieren imaging, as well as a significant reduction in surface hydrophobicity, as demonstrated through contact angle measurement. These data indicated that the structure of the siliconized surface can change over time in contact with different formulations. During formulation development of drug products in prefilled syringes, in addition to potential impact on molecule stability, the selection of formulation variables should also be guided by assessing the impact to syringe functionality with the glide force as one of the key parameters. LAY ABSTRACT: Self-administering drug products packaged in prefilled syringes provides convenience to patients. The interior of a prefilled glass syringe is typically lubricated with silicone oil for easy plunger movement during injection. This article discusses the impact of formulation excipients on silicone oil coating inside the syringe. Characterization techniques were used to assess the ease of plunger movement and structure of the silicone coating. Data indicate formulation excipients can affect silicone oil distribution of prefilled syringes, leading to an increase in plunger glide force at accelerated storage temperature conditions. The increase in glide force within a prefilled syringe with or without an auto-injector can have an impact on dose accuracy and user experience. Syringes with a higher plunger glide force appeared to exhibit a change over time in surface energy and structure of the silicone oil layer in contact with particular formulations.
Journal of Pharmaceutical Sciences | 2017
Jeffrey D. Hofer; Adam P. Rauk
The purpose of this work was to develop a straightforward and robust approach to analyze and summarize the ability of content uniformity data to meet different criteria. A robust Bayesian statistical analysis methodology is presented which provides a concise and easily interpretable visual summary of the content uniformity analysis results. The visualization displays individual batch analysis results and shows whether there is high confidence that different content uniformity criteria could be met a high percentage of the time in the future. The 3 tests assessed are as follows: (a) United States Pharmacopeia Uniformity of Dosage Units <905>, (b) a specific ASTM E2810 Sampling Plan 1 criterion to potentially be used for routine release testing, and (c) another specific ASTM E2810 Sampling Plan 2 criterion to potentially be used for process validation. The approach shown here could readily be used to create similar result summaries for other potential criteria.
Pharmaceutical technology | 2003
Jeffrey D. Hofer
Journal of Pharmaceutical and Biomedical Analysis | 2007
Jeffrey D. Hofer; Bernard A. Olsen; Eugene C. Rickard
Pharmaceutical technology | 2001
Jeffrey D. Hofer; Eugene C. Rickard