Effect of milk feeding strategy and lactic acid probiotics on growth and behavior of dairy calves fed using an automated feeding system1.

Automated milk feeders offer flexibility to feed calves high milk allowances, to change the daily quantity of milk offered, and also to dispense additives like probiotics on an individual basis. Our objectives were to test the effects of 2 milk feeding protocols and a lactic acid bacterium probiotic on performance and behavior in calves. Heifer dairy calves (n = 96) were enrolled at birth in a 2 × 2 factorial study design comparing feeding (1) 2 milk feeding protocols and (2) a lactic acid bacterium-based probiotic program, or a placebo, using automated milk feeders. The early milk feeding strategy (EM) offered a maximum of 11 L/d on day 1 and a peak maximum allowance of 15 L/d on day 21. The late milk feeding strategy (LM) offered a maximum of 7 L/d on day 1 and increased slowly to its peak at 13 L/d on day 28. Both feeding strategies gradually weaned the calves after peak milk allowance until complete weaning at day 53, offering a total of 543 liters of milk. Probiotics or placebo were fed orally in a gel once after colostrum, and twice daily in the milk until weaning. Water and calf starter were provided ad libitum. The experimental period was divided into 3 periods: from day 1 on the automated feeder to day 28 (Period 1), from day 29 to day 53 (Period 2), and the week post-weaning (Period 3). For Period 1, the average daily gain (ADG) of the probiotic group was greater than that of the placebo group (0.84 ± 0.10 kg/d vs. 0.74 ± 0.10 kg/d, respectively), but was not different between milk feeding strategies. For Period 2, ADG was not affected by probiotic or milk feeding strategies. For Period 3, ADG was greater for EM compared to LM (1.27 ± 0.10 kg/d vs. 1.02 ± 0.10 kg/d, respectively), but not between probiotic and placebo groups. During the whole experimental period, LM calves consumed significantly more milk than the EM calves (431.84 ± 33.0 liters vs. 378.64 ± 34.2 liters, respectively). During Period 3, probiotics affected the frequency of visits to the calf starter feed bunk (37.72 ± 2.8 vs. 23.27 ± 2.8 visits per day for probiotic and placebo groups, respectively), but did not affect total time spent at the feed bunk. The supplementation of a lactic acid-based probiotic improved ADG during early life and altered some aspects of the feeding behavior of dairy calves. Calves receiving an early accelerated milk allowance had improved growth during post-weaning and consumed less milk in total, which may indicate better use of solid feed.

Points to Consider: Best Practices to Identify Particle Entry Routes along the Manufacturing Process for Parenteral Formulations.

During the processes involved in pharmaceutical manufacturing, particulate matter may be introduced into a product from a variety of sources and at different points in the manufacturing process. Companies design quality at the beginning of the process to ensure against defects and strive to manufacture products that meet the pharmacopeial standard of being "practically/essentially free" of particles, which can be challenging, though necessary. As particulate matter recalls are predominantly associated with parenteral products, most companies employ a quality risk management program to identify critical parameters or conditions that could affect product quality or patient safety and incorporate systemic and procedural controls to mitigate or reduce the probability of their occurrence. Yet, determining where particulates are most likely to enter the process, what types of materials are most vulnerable, and how the size and number of particles might affect product quality can be very complex. Visual inspection and sampling of the manufactured drug product are designed to control the risk of particulate contamination; building prevention controls will ensure sustainability. This concept paper highlights the necessity of a more thorough understanding of the failure mechanisms that result in particle contamination across a range of products, such as elastomeric components and glass, and processes, such as the formulation and filling of injectables. The goal is to identify process steps within the end-to-end manufacturing process that are most critical to particle generation and entering of visible particles into the final drug product.LAY ABSTRACT: This concept paper highlights the necessity of a more thorough understanding of the failure mechanisms that result in particle contamination across a range of products, such as elastomeric components and glass, and processes, such as the formulation and filling of injectables. The goal is to identify process steps within the end-to-end manufacturing process that are most critical to particle generation and entering of visible particles into the final drug product.

Achieving "Zero" Defects for Visible Particles in Injectables.

The reduction of visible particles in injectable products is an important element in the consistent delivery of high-quality parenteral products. An important part of this effort is the control of particles that may emanate from the primary packaging materials. The Parenteral Drug Association (PDA), with the support of the Pharmaceutical Manufacturers Forum (PMF), has undertaken the task of developing test methods to assess the cleanliness of primary packaging components used in the manufacturing of sterile injectable products. Further work is focused on end-to-end analysis of the supply chain to identify additional points where particles may enter the finished product workflow. This includes shipment, receipt, transfer, and fill and finishing operations. This information and appropriate corrective actions and control methods, coupled with appropriate patient risk-based acceptance limits, are intended to provide better and more consistent supply of injectable products that meet current compendial and good manufacturing practice (GMP) expectations. Aligning control limits between supplier and pharmaceutical manufacturers will offer further improvement. This paper describes the formation of a task force to address these needs and current progress to date.LAY ABSTRACT: Visible particles must be controlled in parenteral products. Such particles come from many sources including the primary packaging materials. The Parenteral Drug Association (PDA), with the support of the Pharmaceutical Manufacturers Forum (PMF), has formed a task force to review and improve particle measurement methods and perform an end-to-end analysis of how particles may enter into parenteral products. These activities are intended to lead to more consistent control limits for visible particles and ultimately more consistent supply of high quality injectable products.

Effects of tulathromycin on incidence of various diseases and growth of young heifers.

OBJECTIVE: To determine the effects of administration of 1 dose of tulathromycin on the incidence of various diseases and growth, identify risk factors for slow growth, and determine the association of Mycoplasma bovis status with the incidence of otitis media in calves. DESIGN: Randomized controlled trial and cross-sectional study. ANIMALS: 788 dairy heifer calves (median age, 3 days). PROCEDURES: Calves received tulathromycin or a saline (0.9% NaCl) solution control treatment once. Calves were observed daily for 8 weeks by farm staff to detect diseases. Nasal swab specimens were collected from some calves for Mycoplasma spp culture. RESULTS: Tulathromycin-treated calves had significantly lower odds of developing otitis media (OR, 0.41; 95% confidence interval, 0.58 to 0.82) versus control calves. Control calves had significantly higher odds of developing diarrhea (OR, 1.8; 95% confidence interval, 1.2 to 2.6) versus tulathromycin-treated calves. Control calves and those with failure of passive transfer, fever, lameness, respiratory tract disease, or diarrhea had significantly lower average daily gain versus other calves. Seventeen of the 66 (26%) calves that underwent repeated testing had positive Mycoplasma spp culture results, but positive results were not associated with otitis media. One of 42 calves with otitis media tested for Mycoplasma spp had positive results, and 1 of 43 age-matched calves without otitis media had positive results. CONCLUSIONS AND CLINICAL RELEVANCE: Tulathromycin-treated calves in this study had a lower incidence of diarrhea and otitis media versus control calves. Various diseases had negative effects on average daily gain. Mycoplasma bovis status was not associated with otitis media in calves.

Challenges and opportunities for managing respiratory disease in dairy calves.

Bovine respiratory disease (BRD) is important for the Ontario dairy industry due to the large economic and welfare costs of this disease. Practical science-based management techniques are needed to control and reduce the risk of this disease. Currently, the emphasis on BRD is focused on early detection of disease and prevention. These areas are important but it is not practical to assume this disease will be eliminated in the near future. It is necessary to determine the best practices for caring for sick animals, monitoring their recovery and making changes to their management to facilitate health and recovery. If management changes can be made for animals that are failing to thrive in a current situation, a more complete recovery may be possible and the welfare and economic costs of BRD may be minimized.